Elsayed Z. Soliman

Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e3 1. About These Statistics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e7 2. American Heart Association's 2020 Impact Goals. . . . . . . . . . . . . . . . .e10 3. Cardiovascular Diseases . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . .e21 4. Subclinical Atherosclerosis . . . . . . . . . . . . . . . . . . . . .e45 5. Coronary Heart Disease, Acute Coronary Syndrome, and Angina Pectoris . . . . . . . . .e54 6. Stroke (Cerebrovascular Disease) . . . . . . . . . . . . . . . . . . . . . . . . . . . .e68 7. High Blood Pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . .e88 8. Congenital Cardiovascular Defects . . . . . . . . . . . . . . . . . . . . . . . . . . . .e97 9. Cardiomyopathy and Heart Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . .e102 10. Disorders …

HomeCirculationVol. 125, No. 1Heart Disease and Stroke Statistics—2012 Update Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessResearch ArticlePDF/EPUBHeart Disease and Stroke Statistics—2012 UpdateA Report From the American Heart Association Writing Group Members Véronique L. Roger, MD, MPH, FAHA, Alan S. Go, MD, Donald M. Lloyd-Jones, MD, ScM, FAHA, Emelia J. Benjamin, MD, ScM, FAHA, Jarett D. Berry, MD, William B. Borden, MD, Dawn M. Bravata, MD, Shifan Dai, MD, PhD, Earl S. Ford, MD, MPH, FAHA, Caroline S. Fox, MD, MPH, Heather J. Fullerton, MD, Cathleen Gillespie, MS, Susan M. Hailpern, DPH, MS, John A. Heit, MD, FAHA, Virginia J. Howard, PhD, FAHA, Brett M. Kissela, MD, Steven J. Kittner, MD, FAHA, Daniel T. Lackland, DrPH, MSPH, FAHA, Judith H. Lichtman, PhD, MPH, Lynda D. Lisabeth, PhD, FAHA, Diane M. Makuc, DrPH, Gregory M. Marcus, MD, MAS, FAHA, Ariane Marelli, MD, MPH, David B. Matchar, MD, FAHA, Claudia S. Moy, PhD, MPH, Dariush Mozaffarian, MD, DrPH, FAHA, Michael E. Mussolino, PhD, Graham Nichol, MD, MPH, FAHA, Nina P. Paynter, PhD, MHSc, Elsayed Z. Soliman, MD, MSc, MS, Paul D. Sorlie, PhD, Nona Sotoodehnia, MD, MPH, Tanya N. Turan, MD, FAHA, Salim S. Virani, MD, Nathan D. Wong, PhD, MPH, FAHA, Daniel Woo, MD, MS, FAHA and Melanie B. Turner, MPHon behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Writing Group Members Search for more papers by this author , Véronique L. RogerVéronique L. Roger Search for more papers by this author , Alan S. GoAlan S. Go Search for more papers by this author , Donald M. Lloyd-JonesDonald M. Lloyd-Jones Search for more papers by this author , Emelia J. BenjaminEmelia J. Benjamin Search for more papers by this author , Jarett D. BerryJarett D. Berry Search for more papers by this author , William B. BordenWilliam B. Borden Search for more papers by this author , Dawn M. BravataDawn M. Bravata Search for more papers by this author , Shifan DaiShifan Dai *The findings and conclusions of this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. Search for more papers by this author , Earl S. FordEarl S. Ford *The findings and conclusions of this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. Search for more papers by this author , Caroline S. FoxCaroline S. Fox Search for more papers by this author , Heather J. FullertonHeather J. Fullerton Search for more papers by this author , Cathleen GillespieCathleen Gillespie *The findings and conclusions of this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. Search for more papers by this author , Susan M. HailpernSusan M. Hailpern Search for more papers by this author , John A. HeitJohn A. Heit Search for more papers by this author , Virginia J. HowardVirginia J. Howard Search for more papers by this author , Brett M. KisselaBrett M. Kissela Search for more papers by this author , Steven J. KittnerSteven J. Kittner Search for more papers by this author , Daniel T. LacklandDaniel T. Lackland Search for more papers by this author , Judith H. LichtmanJudith H. Lichtman Search for more papers by this author , Lynda D. LisabethLynda D. Lisabeth Search for more papers by this author , Diane M. MakucDiane M. Makuc *The findings and conclusions of this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. Search for more papers by this author , Gregory M. MarcusGregory M. Marcus Search for more papers by this author , Ariane MarelliAriane Marelli Search for more papers by this author , David B. MatcharDavid B. Matchar Search for more papers by this author , Claudia S. MoyClaudia S. Moy Search for more papers by this author , Dariush MozaffarianDariush Mozaffarian Search for more papers by this author , Michael E. MussolinoMichael E. Mussolino Search for more papers by this author , Graham NicholGraham Nichol Search for more papers by this author , Nina P. PaynterNina P. Paynter Search for more papers by this author , Elsayed Z. SolimanElsayed Z. Soliman Search for more papers by this author , Paul D. SorliePaul D. Sorlie Search for more papers by this author , Nona SotoodehniaNona Sotoodehnia Search for more papers by this author , Tanya N. TuranTanya N. Turan Search for more papers by this author , Salim S. ViraniSalim S. Virani Search for more papers by this author , Nathan D. WongNathan D. Wong Search for more papers by this author , Daniel WooDaniel Woo Search for more papers by this author and Melanie B. TurnerMelanie B. Turner Search for more papers by this author and on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Originally published15 Dec 2011https://doi.org/10.1161/CIR.0b013e31823ac046Circulation. 2012;125:e2–e220is corrected byCorrectionsOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2011: Previous Version 1 Table of ContentsSummary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e3About These Statistics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e7American Heart Association's 2020 Impact Goals. . . . . . . . . . . . . . . . .e10Cardiovascular Diseases . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . .e21Subclinical Atherosclerosis . . . . . . . . . . . . . . . . . . . . .e45Coronary Heart Disease, Acute Coronary Syndrome, and Angina Pectoris . . . . . . . . .e54Stroke (Cerebrovascular Disease) . . . . . . . . . . . . . . . . . . . . . . . . . . . .e68High Blood Pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . .e88Congenital Cardiovascular Defects . . . . . . . . . . . . . . . . . . . . . . . . . . . .e97Cardiomyopathy and Heart Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . .e102Disorders of Heart Rhythm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e107Other Cardiovascular Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . .. . .e122Risk Factor: Family History and Genetics . . . . . . . . . . . . . . . . . . . . . . . .e130Risk Factor: Smoking/Tobacco Use . . . . . . . . . . . . . . . . . . . . . . . . . . .e134Risk Factor: High Blood Cholesterol and Other Lipids . . . . . . . . . . . . . . . . . . . .e139Risk Factor: Physical Inactivity . . . . . . . . . . . . . . . . . . . . . . . . . . . .e145Risk Factor: Overweight and Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . .e152Risk Factor: Diabetes Mellitus . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e160End-Stage Renal Disease and Chronic Kidney Disease . . . . . . . . . . . . . . . . . . . .e170Metabolic Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e175Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e180Quality of Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. .e193Medical Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e204Economic Cost of Cardiovascular Disease . . . . . . . . . . . . . . . . . . . . . .. . . . .e209At-a-Glance Summary Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e213Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e218Roger Véronique L., MD, MPH, FAHATurner Melanie B., MPHand On behalf of the American Heart Association Statistics Committee and Stroke Statistics SubcommitteeSummaryEach year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay public, and many others who seek the best national data available on disease morbidity and mortality and the risks, quality of care, medical procedures and operations, and costs associated with the management of these diseases in a single document. Indeed, since 1999, the Statistical Update has been cited more than 8700 times in the literature (including citations of all annual versions). In 2010 alone, the various Statistical Updates were cited ≈1600 times (data from ISI Web of Science). In recent years, the Statistical Update has undergone some major changes with the addition of new chapters and major updates across multiple areas. For this year's edition, the Statistics Committee, which produces the document for the AHA, updated all of the current chapters with the most recent nationally representative data and inclusion of relevant articles from the literature over the past year and added a new chapter detailing various disorders of heart rhythm. Also, the 2012 Statistical Update is a major source for monitoring both cardiovascular health and disease in the population, with a focus on progress toward achievement of the AHA's 2020 Impact Goals. Below are a few highlights from this year's Update.Rates of Death Attributable to CVD Have Declined, Yet the Burden of Disease Remains HighThe 2008 overall rate of death attributable to cardiovascular disease (CVD) (International Classification of Diseases, 10th Revision, codes I00–I99) was 244.8 per 100 000. The rates were 287.2 per 100 000 for white males, 390.4 per 100 000 for black males, 200.5 per 100 000 for white females, and 277.4 per 100 000 for black females.From 1998 to 2008, the rate of death attributable to CVD declined 30.6%. Mortality data for 2008 show that CVD (I00–I99; Q20–Q28) accounted for 32.8% (811 940) of all 2 471 984 deaths in 2008, or 1 of every 3 deaths in the United States.On the basis of 2008 mortality rate data, more than 2200 Americans die of CVD each day, an average of 1 death every 39 seconds. About 150 000 Americans killed by CVD (I00–I99) in 2008 were <65 years of age. In 2008, 33% of deaths due to CVD occurred before the age of 75 years, which is well before the average life expectancy of 77.9 years.Coronary heart disease caused ≈1 of every 6 deaths in the United States in 2008. Coronary heart disease mortality in 2008 was 405 309. Each year, an estimated 785 000 Americans will have a new coronary attack, and ≈470 000 will have a recurrent attack. It is estimated that an additional 195 000 silent first myocardial infarctions occur each year. Approximately every 25 seconds, an American will have a coronary event, and approximately every minute, someone will die of one.Each year, ≈795 000 people experience a new or recurrent stroke. Approximately 610 000 of these are first attacks, and 185 000 are recurrent attacks. Mortality data from 2008 indicate that stroke accounted for ≈1 of every 18 deaths in the United States. On average, every 40 seconds, someone in the United States has a stroke. From 1998 to 2008, the stroke death rate fell 34.8%, and the actual number of stroke deaths declined 19.4%.In 2008, 1 in 9 death certificates (281 437 deaths) in the United States mentioned heart failure.Prevalence and Control of Traditional Risk Factors Remains an Issue for Many AmericansData from the National Health and Nutrition Examination Survey (NHANES) 2005–2008 indicate that 33.5% of US adults ≥20 years of age have hypertension (Table 7-1). This amounts to an estimated 76 400 000 US adults with hypertension. The prevalence of hypertension is nearly equal between men and women. African American adults have among the highest rates of hypertension in the world, at 44%.Among hypertensive adults, ≈80% are aware of their condition, 71% are using antihypertensive medication, and only 48% of those aware that they have hypertension have their condition controlled.Despite 4 decades of progress, in 2010, among Americans ≥18 years of age, 21.2% of men and 17.5% of women continued to be cigarette smokers. In 2009, 19.5% of students in grades 9 through 12 reported current cigarette use.The percentage of the nonsmoking population with detectable serum cotinine (indicating exposure to secondhand smoke) declined from 52.5% in 1999 to 2000 to 40.1% in 2007 to 2008, with declines occurring, and was higher for those 3 to 11 years of age (53.6%) and those 12 to 19 years of age (46.5%) than for those 20 years of age and older (36.7%).An estimated 33 600 000 adults ≥20 years of age have total serum cholesterol levels ≥240 mg/dL, with a prevalence of 15.0% (Table 14-1).In 2008, an estimated 18 300 000 Americans had diagnosed diabetes mellitus, representing 8.0% of the adult population. An additional 7 100 000 had undiagnosed diabetes mellitus, and 36.8% had prediabetes, with abnormal fasting glucose levels. African Americans, Mexican Americans, Hispanic/Latino individuals, and other ethnic minorities bear a strikingly disproportionate burden of diabetes mellitus in the United States (Table 17-1).The 2012 Update Expands Data Coverage of the Obesity Epidemic and Its Antecedents and ConsequencesThe estimated prevalence of overweight and obesity in US adults (≥20 years of age) is 149 300 000, which represents 67.3% of this group in 2008. Fully 33.7% of US adults are obese (body mass index ≥30 kg/m2). Men and women of all race/ethnic groups in the population are affected by the epidemic of overweight and obesity (Table 16-1).Among children 2 to 19 years of age, 31.7% are overweight and obese (which represents 23.6 million children), and 16.9% are obese (12.6 million children). Mexican American boys and girls and African American girls are disproportionately affected. Over the past 3 decades, the prevalence of obesity in children 6 to 11 years of age has increased from ≈4% to >20%.Obesity (body mass index ≥30 kg/m2) is associated with marked excess mortality in the US population. Even more notable is the excess morbidity associated with overweight and obesity in terms of risk factor development and incidence of diabetes mellitus, CVD end points (including coronary heart disease, stroke, and heart failure), and numerous other health conditions, including asthma, cancer, degenerative joint disease, and many others.The prevalence of diabetes mellitus is increasing dramatically over time, in parallel with the increases in prevalence of overweight and obesity.On the basis of NHANES 2003–2006 data, the age-adjusted prevalence of metabolic syndrome, a cluster of major cardiovascular risk factors related to overweight/obesity and insulin resistance, is ≈34% (35.1% among men and 32.6% among women).The proportion of youth (≤18 years of age) who report engaging in no regular physical activity is high, and the proportion increases with age. In 2009, among adolescents in grades 9 through 12, 29.9% of girls and 17.0% of boys reported that they had not engaged in 60 minutes of moderate-to-vigorous physical activity, defined as any activity that increased heart rate or breathing rate, even once in the previous 7 days, despite recommendations that children engage in such activity ≥5 days per week.Thirty-three percent of adults reported engaging in no aerobic leisure-time physical activity.Data from NHANES indicate that between 1971 and 2004, average total energy consumption among US adults increased by 22% in women (from 1542 to 1886 kcal/d) and by 10% in men (from 2450 to 2693 kcal/d; see Chart 20-1).The increases in calories consumed during this time period are attributable primarily to greater average carbohydrate intake, in particular, of starches, refined grains, and sugars. Other specific changes related to increased caloric intake in the United States include larger portion sizes, greater food quantity and calories per meal, and increased consumption of sugar-sweetened beverages, snacks, commercially prepared (especially fast food) meals, and higher energy-density foods.The 2012 Update Provides Critical Data About Cardiovascular Quality of Care, Procedure Utilization, and CostsIn light of the current national focus on healthcare utilization, costs, and quality, it is critical to monitor and understand the magnitude of healthcare delivery and costs, as well as the quality of healthcare delivery, related to CVDs. The Statistical Update provides these critical data in several sections.Quality-of-Care Metrics for CVDsChapter 21 reviews many metrics related to the quality of care delivered to patients with CVDs, as well as healthcare disparities. In particular, quality data are available from the AHA's “Get With The Guidelines” programs for coronary artery disease and heart failure and from the American Stroke Association/AHA's “Get With The Guidelines” program for acute stroke. Similar data from the Veterans Healthcare Administration, national Medicare and Medicaid data, and Acute Coronary Treatment and Intervention Outcomes Network–“Get With The Guidelines” Registry data are also reviewed. These data show impressive adherence with guideline recommendations for many, but not all, metrics of quality of care for these hospitalized patients. Data are also reviewed on screening for cardiovascular risk factor levels and control.Cardiovascular Procedure Utilization and CostsChapter 22 provides data on trends and current usage of cardiovascular surgical and invasive procedures. For example, the total number of inpatient cardiovascular operations and procedures increased 22%, from 6 133 000 in 1999 to 7 453 000 in 2009 (National Heart, Lung, and Blood Institute computation based on National Center for Health Statistics annual data).Chapter 23 reviews current estimates of direct and indirect healthcare costs related to CVDs, stroke, and related conditions using Medical Expenditure Panel Survey data. The total direct and indirect cost of CVD and stroke in the United States for 2008 is estimated to be $297.7 billion. This figure includes health expenditures (direct costs, which include the cost of physicians and other professionals, hospital services, prescribed medications, home health care, and other medical durables) and lost productivity resulting from mortality (indirect costs). By comparison, in 2008, the estimated cost of all cancer and benign neoplasms was $228 billion ($93 billion in direct costs, $19 billion in morbidity indirect costs, and $116 billion in mortality indirect costs). CVD costs more than any other diagnostic group.The AHA, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current data available in the Statistics Update.Finally, it must be noted that this annual Statistical Update is the product of an entire year's worth of effort by dedicated professionals, volunteer physicians and scientists, and outstanding AHA staff members, without whom publication of this valuable resource would be impossible. Their contributions are gratefully acknowledged.Véronique L. Roger, MD, MPH, FAHAMelanie B. Turner, MPHOn behalf of the American Heart Association Statistics Committee and Stroke Statistics SubcommitteeNote: Population data used in the compilation of NHANES prevalence estimates is for the latest year of the NHANES survey being used. Extrapolations for NHANES prevalence estimates are based on the census resident population for 2008 because this is the most recent year of NHANES data used in the Statistical Update.AcknowledgmentsWe wish to thank Thomas Thom, Michael Wolz, Dale Burwen, and Sean Coady for their valuable comments and contributions. We would like to acknowledge Karen Modesitt for her administrative assistance.DisclosuresWriting Group DisclosuresWriting Group MemberEmploymentResearch GrantOther Research SupportSpeakers' Bureau/HonorariaExpert WitnessOwnership InterestConsultant/Advisory BoardOtherVéronique L. RogerMayo ClinicNoneNoneNoneNoneNoneNoneNoneEmelia J. BenjaminBoston University School of MedicineNIH†NoneNoneNoneNoneNIH†NoneJarett D. BerryUT Southwestern Medical SchoolAHA†; NHLBI†NoneMerck†NoneNoneNoneNoneWilliam B. BordenWeill Cornell Medical CollegeNoneNoneNoneNoneNoneNoneThe Dr. Robert C. and Veronica Atkins Foundation provided an educational grant to develop a curriculum in Metabolic Diseases; Dr Borden receives salary support from that†Dawn M. BravataUniversity of IowaNoneNoneNoneNoneNoneNoneNoneShifan DaiCenters for Disease Control and PreventionNoneNoneNoneNoneNoneNoneNoneEarl S. FordCenters for Disease Control and PreventionNoneNoneNoneNoneNoneNoneNoneCaroline S. FoxNHLBINoneNoneNoneNoneNoneNoneNoneHeather J. FullertonUniversity of California, San FranciscoNIH/NINDS†NoneCincinnati Children's Hospital*; Toronto Hospital for Sick Children*NoneNoneDSMB for Berlin Heart*NoneCathleen GillespieCenters for Disease Control and PreventionNoneNoneNoneNoneNoneNoneNoneAlan S. GoThe Permanente Medical GroupGlaxoSmithKline†; Johnson & Johnson†NoneNoneNoneNoneNoneNoneSusan M. HailpernIndependent ConsultantNoneNoneNoneNoneNoneNoneNoneJohn A. HeitMayo ClinicNoneNoneNoneNoneNoneNoneNoneVirginia J. HowardUniversity of Alabama at Birmingham School of Public HealthNIH/NINDS†NoneNoneNoneNoneNoneNoneBrett M. KisselaUniversity of CincinnatiNexstim*NoneAllergan*Expert witness for defense in 1 stroke-related case in 2010†NoneAllergan*NoneSteven J. KittnerUniversity of Maryland School of MedicineNoneNoneNoneNoneNoneNoneNoneDaniel T. LacklandMedical University of South CarolinaNoneNoneNoneNoneNoneNoneNoneJudith H. LichtmanYale School of MedicineNoneNoneNoneNoneNoneNoneNoneLynda D. LisabethUniversity of MichiganNHLBI†; NINDS†NoneNoneNoneNoneNoneNoneDonald M. Lloyd-JonesNorthwestern UniversityNoneNoneNoneNoneNoneNoneNoneDiane M. MakucNational Center for Health Statistics, CDCNoneNoneNoneNoneNoneNoneNoneGregory M. MarcusUCSFAstellas*; Baylis Medical*NoneNoneNoneNoneNoneNoneAriane MarelliMcGill University Health CenterNoneNoneNoneNoneNoneNoneNoneDavid B. MatcharDuke-NUS Graduate Medical SchoolNoneNoneNoneNoneNoneBoehringer Ingelheim*NoneClaudia S. MoyNational Institutes of HealthNoneNoneNoneNoneNoneNoneNoneDariush MozaffarianDivision of Cardiovascular Medicine, Brigham and Women's Hospital/Harvard School of Public HealthNIH†; Genes and Environment Initiative at Harvard School of Public Health†; Gates Foundation/World Health Organization†; GlaxoSmithKline†; Pronova†; Searle Scholar Award from the Searle Funds at the Chicago Community Trust†; Sigma Tau†NoneAramark*; the Chicago Council*; International Life Sciences Institute*; Norwegian Seafood Export Council*; Nutrition Impact*; SPRIM*; Unilever*; UN Food and Agricultural Organization*; US Food and Drug Administration*; World Health Organization*NoneHarvard has filed a provisional patent application that been assigned to Harvard, listing Dr Mozaffarian as a coinventor for use of trans-palmitoleic acid to prevent and treat insulin resistance, type 2 diabetes, and related conditions*; royalties from UpToDate for an online chapter*FoodMinds*NoneMichael E. MussolinoNational Heart, Lung, and Blood InstituteNoneNoneNoneNoneNoneNoneNoneGraham NicholUniversity of WashingtonAsmund S. Laerdal Foundation for Acute Medicine†; Medtronic Inc†; NHLBI†; NIH†NoneNoneNoneNoneGambro Renal Inc*; LIFEBRIDGE Medizintechnik AG*; Sotera Wireless*NoneNina P. PaynterBrigham and Women's HospitalCelera Corp†; NIH/NHLBI†NoneNoneNoneNoneNoneNoneElsayed Z. SolimanWake Forest University School of MedicineNoneNoneNoneNoneNoneNoneNonePaul D. SorlieNational Heart, Lung and Blood Institute, NIHNoneNoneNoneNoneNoneNoneNoneNona SotoodehniaUniversity of WashingtonNoneNoneNoneNoneNoneNoneNoneTanya N. TuranMedical University of South CarolinaNIH/NINDS†AstraZeneca supplied drug for SAMMPRIS study†; Stryker Co supplied stents for SAMMPRIS study†NoneNoneNoneBoehringer Ingelheim*; CardioNet*; WL Gore*NoneMelanie B. TurnerAmerican Heart AssociationNoneNoneNoneNoneNoneNoneNoneSalim S. ViraniDepartment of Veterans AffairsMerck†; NFL Charities†; NIH†; VA†NoneNoneNoneNoneNoneNoneNathan D. WongUniversity of California, IrvineBristol-Myers Squibb†; Merck†NoneNoneNoneNoneAbbott Pharmaceuticals*NoneDaniel WooUniversity of CincinnatiNIH†NoneNoneNoneNoneNoneNoneThis table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be “significant” if (a) the person receives $10 000 or more during any 12-month period, or 5% or more of the person's gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10 000 or more of the fair market value of the entity. A relationship is considered to be “modest” if it is less than “significant” under the preceding definition.*Modest.†Significant.1. About These StatisticsThe American Heart Association (AHA) works with the Centers for Disease Control and Prevention's (CDC's) National Center for Health Statistics (NCHS); the National Heart, Lung, and Blood Institute (NHLBI); the National Institute of Neurological Disorders and Stroke (NINDS); and other government agencies to derive the annual statistics in this Heart Disease and Stroke Statistical Update. This chapter describes the most important sources and the types of data we use from them. For more details, see Chapter 25 of this document, the Glossary.The surveys used are: Behavioral Risk Factor Surveillance System (BRFSS)—ongoing telephone health survey systemGreater Cincinnati/Northern Kentucky Stroke Study (GCNKSS)—stroke incidence rates and outcomes within a biracial populationMedical Expenditure Panel Survey (MEPS)—data on specific health services that Americans use, how frequently they use them, the cost of these services, and how the costs are paidNational Health and Nutrition Examination Survey (NHANES)—disease and risk factor prevalence and nutrition statisticsNational Health Interview Survey (NHIS)—disease and risk factor prevalenceNational Hospital Discharge Survey (NHDS)—hospital inpatient discharges and procedures (discharged alive, dead, or status unknown)National Ambulatory Medical Care Survey (NAMCS)—physician office visitsNational Home and Hospice Care Survey (NHHCS)—staff, services, and patients of home health and hospice agenciesNational Hospital Ambulatory Medical Care Survey (NHAMCS)—hospital outpatient and emergency department (ED) visitsNationwide Inpatient Sample of the Agency for Healthcare Research and Quality—hospital inpatient discharges, procedures, and chargesNational Nursing Home Survey (NNHS)—nursing home residentsNational Vital Statistics System—national and state mortality dataWorld Health Organization—mortality rates by countryYouth Risk Behavior Surveillance System (YRBSS)—health-risk behaviors in youth and young adultsAbbreviations Used in Chapter 1AHAAmerican Heart AssociationAPangina pectorisARICAtherosclerosis Risk in Communities StudyBPblood pressureBRFSSBehavioral Risk Factor Surveillance SystemCDCCenters for Disease Control and PreventionCHSCardiovascular Health StudyCVDcardiovascular diseaseDMdiabetes mellitusEDemergency departmentFHSFramingham Heart StudyGCNKSSGreater Cincinnati/Northern Kentucky Stroke StudyHDheart diseaseHFheart failureICDInternational Classification of DiseasesICD-9-CMInternational Classification of Diseases, Clinical Modification, 9th RevisionICD-10International Classification of Diseases, 10th RevisionMEPSMedical Expenditure Panel SurveyMImyocardial infarctionNAMCSNational Ambulatory Medical Care SurveyNCHSNational Center for Health StatisticsNHAMCSNational Hospital Ambulatory Medical Care SurveyNHANESNational Health and Nutrition Examination SurveyNHDSNational Hospital Discharge SurveyNHHCSNational Home and Hospice Care SurveyNHISNational Health Interview SurveyNHLBINational Heart, Lung, and Blood InstituteNINDSNational Institute of Neurological Disorders and StrokeNNHSNational Nursing Home SurveyPADperipheral artery diseaseYRBSSYouth Risk Behavior Surveillance SystemSee Glossary (Chapter 25) for explanation of terms.Disease PrevalencePrevalence is an estimate of how many people have a disease at a given point or period in time. The NCHS conducts health examination and health interview surveys that provide estimates of the prevalence of diseases and risk factors. In this Update, the health interview part of the NHANES is used for the prevalence of cardiovascular diseases (CVDs). NHANES is used more than the NHIS because in NHANES, angina pectoris (AP) is based on the Rose Questionnaire; estimates are made regularly for heart failure (HF); hypertension is based on blood pressure (BP) measurements and interviews; and an estimate can be made for total CVD, including myocardial infarction (MI), AP, HF, stroke, and hypertension.A major emphasis of this Statistical Update is to present the latest estimates of the number of people in the United States who have specific conditions to provide a realistic estimate of burden. Most estimates based on NHANES prevalence rates are based on data collected from 2005 to 2008 (in most cases, these are the latest published figures). These are applied to census population estimates for 2008. Differences in population estimates based on extrapolations of rates beyond the data collection pe

Chronic kidney disease (CKD) is a public health epidemic that increases risk of death due to cardiovascular disease.Left ventricular hypertrophy (LVH) is an important mechanism of cardiovascular disease in individuals with CKD.Elevated levels of FGF23 have been linked to greater risks of LVH and mortality in patients with CKD, but whether these risks represent causal effects of FGF23 is unknown.Here, we report that elevated FGF23 levels are independently associated with LVH in a large, racially diverse CKD cohort.FGF23 caused pathological hypertrophy of isolated rat cardiomyocytes via FGF receptor-dependent activation of the calcineurin-NFAT signaling pathway, but this effect was independent of klotho, the coreceptor for FGF23 in the kidney and parathyroid glands.Intramyocardial or intravenous injection of FGF23 in wild-type mice resulted in LVH, and klotho-deficient mice demonstrated elevated FGF23 levels and LVH.In an established animal model of CKD, treatment with an FGF-receptor blocker attenuated LVH, although no change in blood pressure was observed.These results unveil a klotho-independent, causal role for FGF23 in the pathogenesis of LVH and suggest that chronically elevated FGF23 levels contribute directly to high rates of LVH and mortality in individuals with CKD.

HomeCirculationVol. 125, No. 1Executive Summary: Heart Disease and Stroke Statistics—2012 Update Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBExecutive Summary: Heart Disease and Stroke Statistics—2012 UpdateA Report From the American Heart Association Writing Group Members Véronique L. Roger, MD, MPH, FAHA, Alan S. Go, MD, Donald M. Lloyd-Jones, MD, ScM, FAHA, Emelia J. Benjamin, MD, ScM, FAHA, Jarett D. Berry, MD, William B. Borden, MD, Dawn M. Bravata, MD, Shifan Dai, MD, PhD, Earl S. Ford, MD, MPH, FAHA, Caroline S. Fox, MD, MPH, Heather J. Fullerton, MD, Cathleen Gillespie, MS, Susan M. Hailpern, DPH, MS, John A. Heit, MD, FAHA, Virginia J. Howard, PhD, FAHA, Brett M. Kissela, MD, Steven J. Kittner, MD, FAHA, Daniel T. Lackland, DrPH, MSPH, FAHA, Judith H. Lichtman, PhD, MPH, Lynda D. Lisabeth, PhD, FAHA, Diane M. Makuc, DrPH, Gregory M. Marcus, MD, MAS, FAHA, Ariane Marelli, MD, MPH, David B. Matchar, MD, FAHA, Claudia S. Moy, PhD, MPH, Dariush Mozaffarian, MD, DrPH, FAHA, Michael E. Mussolino, PhD, Graham Nichol, MD, MPH, FAHA, Nina P. Paynter, PhD, MHSc, Elsayed Z. Soliman, MD, MSc, MS, Paul D. Sorlie, PhD, Nona Sotoodehnia, MD, MPH, Tanya N. Turan, MD, FAHA, Salim S. Virani, MD, Nathan D. Wong, PhD, MPH, FAHA, Daniel Woo, MD, MS, FAHA and Melanie B. Turner, MPHon behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Writing Group Members , Véronique L. RogerVéronique L. Roger , Alan S. GoAlan S. Go , Donald M. Lloyd-JonesDonald M. Lloyd-Jones , Emelia J. BenjaminEmelia J. Benjamin , Jarett D. BerryJarett D. Berry , William B. BordenWilliam B. Borden , Dawn M. BravataDawn M. Bravata , Shifan DaiShifan Dai , Earl S. FordEarl S. Ford , Caroline S. FoxCaroline S. Fox , Heather J. FullertonHeather J. Fullerton , Cathleen GillespieCathleen Gillespie , Susan M. HailpernSusan M. Hailpern , John A. HeitJohn A. Heit , Virginia J. HowardVirginia J. Howard , Brett M. KisselaBrett M. Kissela , Steven J. KittnerSteven J. Kittner , Daniel T. LacklandDaniel T. Lackland , Judith H. LichtmanJudith H. Lichtman , Lynda D. LisabethLynda D. Lisabeth , Diane M. MakucDiane M. Makuc , Gregory M. MarcusGregory M. Marcus , Ariane MarelliAriane Marelli , David B. MatcharDavid B. Matchar , Claudia S. MoyClaudia S. Moy , Dariush MozaffarianDariush Mozaffarian , Michael E. MussolinoMichael E. Mussolino , Graham NicholGraham Nichol , Nina P. PaynterNina P. Paynter , Elsayed Z. SolimanElsayed Z. Soliman , Paul D. SorliePaul D. Sorlie , Nona SotoodehniaNona Sotoodehnia , Tanya N. TuranTanya N. Turan , Salim S. ViraniSalim S. Virani , Nathan D. WongNathan D. Wong , Daniel WooDaniel Woo and Melanie B. TurnerMelanie B. Turner and on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Originally published3 Jan 2012https://doi.org/10.1161/CIR.0b013e3182456d46Circulation. 2012;125:188–197is corrected byCorrectionsTable of ContentsSummary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e3About These Statistics. . . . . . . . . . . . . . . . . . . . . . . . . .e7American Heart Association's 2020 Impact Goals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e10Cardiovascular Diseases . . . . . . . . . . . . . . . . . . . . . . .e21Subclinical Atherosclerosis . . . . . . . . . . . . . . . . . . . . .e45Coronary Heart Disease, Acute Coronary Syndrome, and Angina Pectoris . . . . . . . . . . . . . . . . . .e54Stroke (Cerebrovascular Disease). . . . . . . . . . . . . . . . .e68High Blood Pressure . . . . . . . . . . . . . . . . . . . . . . . . . .e88Congenital Cardiovascular Defects. . . . . . . . . . . . . . . .e97Cardiomyopathy and Heart Failure. . . . . . . . . . . . . . .e102Disorders of Heart Rhythm . . . . . . . . . . . . . . . . . . . .e107Other Cardiovascular Diseases. . . . . . . . . . . . . . . . . .e122Risk Factor: Family History and Genetics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e130Risk Factor: Smoking/Tobacco Use . . . . . . . . . . . . . .e134Risk Factor: High Blood Cholesterol and Other Lipids. . . . . . . . . . . . . . . . . . . . . . . . . . . .e139Risk Factor: Physical Inactivity . . . . . . . . . . . . . . . . .e145Risk Factor: Overweight and Obesity. . . . . . . . . . . . .e152Risk Factor: Diabetes Mellitus. . . . . . . . . . . . . . . . . .e160End-Stage Renal Disease and Chronic Kidney Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . .e170Metabolic Syndrome . . . . . . . . . . . . . . . . . . . . . . . . .e175Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e180Quality of Care. . . . . . . . . . . . . . . . . . . . . . . . . . . . .e193Medical Procedures. . . . . . . . . . . . . . . . . . . . . . . . . .e204Economic Cost of Cardiovascular Disease . . . . . . . . .e209At-a-Glance Summary Tables . . . . . . . . . . . . . . . . . .e213Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e218Roger Véronique L., MD, MPH, FAHATurner Melanie B., MPHand On behalf of the American Heart Association Statistics Committee and Stroke Statistics SubcommitteeSummaryEach year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay public, and many others who seek the best national data available on disease morbidity and mortality and the risks, quality of care, medical procedures and operations, and costs associated with the management of these diseases in a single document. Indeed, since 1999, the Statistical Update has been cited more than 8700 times in the literature (including citations of all annual versions). In 2010 alone, the various Statistical Updates were cited ≈1600 times (data from ISI Web of Science). In recent years, the Statistical Update has undergone some major changes with the addition of new chapters and major updates across multiple areas. For this year's edition, the Statistics Committee, which produces the document for the AHA, updated all of the current chapters with the most recent nationally representative data and inclusion of relevant articles from the literature over the past year and added a new chapter detailing various disorders of heart rhythm. Also, the 2012 Statistical Update is a major source for monitoring both cardiovascular health and disease in the population, with a focus on progress toward achievement of the AHA's 2020 Impact Goals. Below are a few highlights from this year's Update.Rates of Death Attributable to CVD Have Declined, Yet the Burden of Disease Remains HighThe 2008 overall rate of death attributable to cardiovascular disease (CVD) (International Classification of Diseases, 10th Revision, codes I00–I99) was 244.8 per 100 000. The rates were 287.2 per 100 000 for white males, 390.4 per 100 000 for black males, 200.5 per 100 000 for white females, and 277.4 per 100 000 for black females. Table 1 contains complete details for males; Table 2 for females.From 1998 to 2008, the rate of death attributable to CVD declined 30.6%. Mortality data for 2008 show that CVD (I00–I99; Q20–Q28) accounted for 32.8% (811 940) of all 2 471 984 deaths in 2008, or 1 of every 3 deaths in the United States.On the basis of 2008 mortality rate data, more than 2200 Americans die of CVD each day, an average of 1 death every 39 seconds. About 150 000 Americans killed by CVD (I00–I99) in 2008 were <65 years of age. In 2008, 33% of deaths due to CVD occurred before the age of 75 years, which is well before the average life expectancy of 77.9 years.Coronary heart disease caused ≈1 of every 6 deaths in the United States in 2008. Coronary heart disease mortality in 2008 was 405 309. Each year, an estimated 785 000 Americans will have a new coronary attack, and ≈470 000 will have a recurrent attack. It is estimated that an additional 195 000 silent first myocardial infarctions occur each year. Approximately every 25 seconds, an American will have a coronary event, and approximately every minute, someone will die of one.Each year, ≈795 000 people experience a new or recurrent stroke. Approximately 610 000 of these are first attacks, and 185 000 are recurrent attacks. Mortality data from 2008 indicate that stroke accounted for ≈1 of every 18 deaths in the United States. On average, every 40 seconds, someone in the United States has a stroke. From 1998 to 2008, the stroke death rate fell 34.8%, and the actual number of stroke deaths declined 19.4%.In 2008, 1 in 9 death certificates (281 437 deaths) in the United States mentioned heart failure.Table 1. Males and CVD: At-a-Glance TableDiseases and Risk FactorsBoth SexesTotal MalesWhite MalesBlack MalesMexican American MalesTotal CVD Prevalence, 2008*82.6 M (36.2%)39.9 M (37.4%)37.4%44.8%30.7% Mortality, 2008†811.9 K392.2 K335.2 K46.8 KN/ACHD Prevalence, CHD, 2008*16.3 M (7.0%)8.8 M (8.3%)8.5%7.9%6.3% Prevalence, MI, 2008*7.9 M (3.1%)4.8 M (4.3%)4.3%4.3%3.0% Prevalence, AP, 2008*9.0 M (3.9%)4.0 M (3.8%)3.8%3.3%3.6% New and recurrent CHD‡§1.26 M740.0 K675.0 K70.0 KN/A New and recurrent MI§935.0 K565.0 KN/AN/AN/A Incidence, AP (stable angina)‖500.0 K320.0 KN/AN/AN/A Mortality, 2008, CHD†405.3 K216.2 K189.4 K21.4 KN/A Mortality, 2008, MI†134.0 K72.4 K63.8 K6.9 KN/AStroke Prevalence, 2008*7.0 M (3.0%)2.8 M (2.7%)2.4%4.5%2.0% New and recurrent strokes†795.0 K370.0 K325.0 K45.0 KN/A Mortality, 2008†134.1 K53.5 K44.5 K7.2 KN/AHBP Prevalence, 2008*76.4 M (33.5%)36.5 M (34.1%)33.9%43.0%27.8% Mortality, 2008†61.0 K26.8 K19.6 K6.4 KN/AHF Prevalence, 2008*5.7 M (2.4%)3.1 M (3.0%)2.7%4.5%2.3% Mortality, 2008†56.8 K23.0 K20.3 K2.4 KN/ASmoking Prevalence, 2010¶44.1 M (19.3%)23.7 M (21.2%)23.0%23.4%15.2%#Blood cholesterol Prevalence, 2008 Total cholesterol ≥200 mg/dL*98.8 M (44.4%)45.0 M (41.8%)41.2%37.0%50.1% Total cholesterol ≥240 mg/dL*33.6 M (15.0%)14.6 M (13.5%)13.7%9.7%16.9% LDL cholesterol ≥130 mg/dL*71.3 M (31.9%)35.3 M (32.5%)30.5%34.4%41.9% HDL cholesterol <40 mg/dL*41.8 M (18.9%)30.8 M (28.6%)29.5%16.6%31.7%PA** Prevalence, 2010¶20.7%25.1%26.7%24.6%N/AOverweight and obesity Prevalence, 2008 Overweight and obesity, BMI ≥25.0 Kg/m2*149.3 M (67.3%)78.0 M (72.4%)72.3%70.8%77.5% Obesity, BMI ≥30.0 Kg/m2*75.0 M (33.7%)34.9 M (32.4%)32.1%37.0%31.4%DM Prevalence, 2008 Physician-diagnosed DM*18.3 M (8.0%)8.3 M (7.9%)6.8%14.3%11.0% Undiagnosed DM*7.1 M (3.1%)4.4 M (4.1%)3.9%4.8%6.3% Prediabetes*81.5 M (36.8%)48.1 M (44.9%)45.4%31.6%44.9% Incidence, diagnosed DM*1.6 MN/AN/AN/AN/A Mortality, 2008†70.6 K35.3 K28.6 K5.5 KN/ACVD indicates cardiovascular disease; M, millions; K, thousands; N/A, data not available; CHD, coronary heart disease (includes heart attack, angina pectoris chest pain, or both); MI, myocardial infarction (heart attack); AP, angina pectoris (chest pain); HBP, high blood pressure; HF, heart failure; LDL, low-density lipoprotein; HDL, high-density lipoprotein; PA, physical activity; BMI, body mass index; and DM, diabetes mellitus.*Age ≥20 y.†All ages.‡New and recurrent MI and fatal CHD.§Age ≥35 y.‖Age ≥45 y.¶Age ≥18 y.#Hispanic.**Met 2008 Federal PA guidelines for adults.Table 2. Females and CVD: At-a-Glance TableDiseases and Risk FactorsBoth SexesTotal FemalesWhite FemalesBlack FemalesMexican American FemalesTotal CVD Prevalence, 2008*82.6 M (36.2%)42.7 M (35.0%)33.8%47.3%30.9% Mortality, 2008†811.9 K419.7 K360.4 K49.8 KN/ACHD Prevalence, CHD, 2008*16.3 M (7.0%)7.5 M (6.1%)5.8%7.6%5.6% Prevalence, MI, 2008*7.9 M (3.1%)3.1 M (2.2%)2.1%2.2%1.1% Prevalence, AP, 2008*9.0 M (3.9%)5.0 M (4.0%)3.7%5.6%3.7% New and recurrent CHD‡§1.26 M515.0 K445.0 K65.0 KN/A New and recurrent MI§935.0 K370.0 KN/AN/AN/A Incidence, AP (stable angina)‖500.0 K180.0 KN/AN/AN/A Mortality, 2008, CHD†405.3 K189.1 K164.5 K20.5 KN/A Mortality, 2008, MI†134.0 K61.5 K53.3 K6.9 KN/AStroke Prevalence, 2008*7.0 M (3.0%)4.2 M (3.3%)3.3%4.4%2.7% New and recurrent strokes†795.0 K425.0 K365.0 K60.0 KN/A Mortality, 2008†134.1 K80.6 K68.8 K9.5 KN/AHBP Prevalence, 2008*76.4 M (33.5%)39.9 M (32.7%)31.3%45.7%28.9% Mortality, 2008†61.0 K34.2 K26.3 K7.0 KN/AHF Prevalence, 2008*5.7 M (2.4%)2.6 M (2.0%)1.8%3.8%1.3% Mortality, 2008†56.8 K33.8 K30.2 K3.1 KN/ASmoking Prevalence, 2010¶44.1 M (19.3%)20.4 M (17.5%)20.5%16.7%9.0%#Blood cholesterol Prevalence, 2008 Total cholesterol ≥200 mg/dL*98.8 M (44.4%)53.8 M (46.3%)47.0%41.2%46.5% Total cholesterol ≥240 mg/dL*33.6 M (15.0%)19.0 M (16.2%)16.9%13.3%14.0% LDL cholesterol ≥130 mg/dL*71.3 M (31.9%)36.0 M (31.0%)32.0%27.7%31.6% HDL cholesterol <40 mg/dL*41.8 M (18.9%)11.0 M (9.7%)10.1%6.6%12.2%PA** Prevalence, 2010¶20.7%16.4%19.1%11.2%N/AOverweight and obesity Prevalence, 2008 Overweight and obesity, BMI ≥25.0 Kg/m2*149.3 M (67.3%)71.3 M (62.3%)59.3%77.7%75.1% Obesity, BMI ≥30.0 Kg/m2*75.0 M (33.7%)40.1 M (35.2%)32.8%51.0%43.4%DM Prevalence, 2008 Physician-diagnosed DM*18.3 M (8.0%)10.0 M (8.2%)6.5%14.7%12.7% Undiagnosed DM*7.1 M (3.1%)2.7 M (2.3%)1.9%4.0%3.8% Prediabetes*81.5 M (36.8%)33.4 M (28.8%)27.9%27.1%34.3% Incidence, diagnosed DM*1.6 MN/AN/AN/AN/A Mortality, 2008†70.6 K35.2 K27.3 K6.6 KN/ACVD indicates cardiovascular disease; M, millions; K, thousands; N/A, data not available; CHD, coronary heart disease (includes heart attack, angina pectoris chest pain, or both); MI, myocardial infarction (heart attack); AP, angina pectoris (chest pain); HBP, high blood pressure; HF, heart failure; LDL, low-density lipoprotein; HDL, high-density lipoprotein; PA, physical activity; BMI, body mass index; and DM, diabetes mellitus.*Age ≥20 y.†All ages.‡New and recurrent MI and fatal CHD.§Age ≥35 y.‖Age ≥45 y.¶Age ≥18 y.#Hispanic.**Met 2008 Federal PA guidelines for adults.Prevalence and Control of Traditional Risk Factors Remains an Issue for Many AmericansData from the National Health and Nutrition Examination Survey (NHANES) 2005–2008 indicate that 33.5% of US adults ≥20 years of age have hypertension (Chapter 7, Table 7-1). This amounts to an estimated 76 400 000 US adults with hypertension. The prevalence of hypertension is nearly equal between men and women. African American adults have among the highest rates of hypertension in the world, at 44%. Table 3 contains complete details by race/ethnicity.Among hypertensive adults, ≈80% are aware of their condition, 71% are using antihypertensive medication, and only 48% of those aware that they have hypertension have their condition controlled.Despite 4 decades of progress, in 2010, among Americans ≥18 years of age, 21.2% of men and 17.5% of women continued to be cigarette smokers. In 2009, 19.5% of students in grades 9 through 12 reported current cigarette use. Table 4 contains complete details for children and youth.The percentage of the nonsmoking population with detectable serum cotinine (indicating exposure to secondhand smoke) declined from 52.5% in 1999 to 2000 to 40.1% in 2007 to 2008, with declines occurring, and was higher for those 3 to 11 years of age (53.6%) and those 12 to 19 years of age (46.5%) than for those 20 years of age and older (36.7%).An estimated 33 600 000 adults ≥20 years of age have total serum cholesterol levels ≥240 mg/dL, with a prevalence of 15.0% (Chapter 14, Table 14-1).In 2008, an estimated 18 300 000 Americans had diagnosed diabetes mellitus, representing 8.0% of the adult population. An additional 7 100 000 had undiagnosed diabetes mellitus, and 36.8% had prediabetes, with abnormal fasting glucose levels. African Americans, Mexican Americans, Hispanic/Latino individuals, and other ethnic minorities bear a strikingly disproportionate burden of diabetes mellitus in the United States (Chapter 17, Table 17-1).Table 3. Race/Ethnicity and CVD: At-a-Glance TableDiseases and Risk FactorsBoth SexesWhitesBlacksMexican AmericansHispanics/LatinosAsians: Both SexesAmerican Indian/Alaska Native: Both SexesMalesFemalesMalesFemalesMalesFemalesMalesFemalesTotal CVD Prevalence, 2008*82.6 M (36.2%)37.4%33.8%44.8%47.3%30.7%30.9%N/AN/AN/AN/A Mortality, 2008†811.9 K335.2 K360.4 K46.8 K49.8 KN/AN/AN/AN/AN/AN/ACHD Prevalence, CHD, 2008*16.3 M (7.0%)8.5%5.8%7.9%7.6%6.3%5.6%5.2%‖4.9%‖5.9%‖# Prevalence, MI, 2008*7.9 M (3.1%)4.3%2.1%4.3%2.2%3.0%1.1%N/AN/AN/AN/A Prevalence, AP, 2008*9.0 M (3.9%)3.8%3.7%3.3%5.6%3.6%3.7%N/AN/AN/AN/A New and recurrent CHD‡§1.26 M675.0 K445.0 K70.0 K65.0 KN/AN/AN/AN/AN/AN/A Mortality, CHD, 2008†405.3 K189.3 K164.5 K21.4 K20.5 KN/AN/AN/AN/AN/AN/A Mortality, MI, 2008†134.0 K63.8 K53.3 K6.9 K6.9 KN/AN/AN/AN/AN/AN/AStroke Prevalence, 2008*7.0 M (3.0%)2.4%3.3%4.5%4.4%2.0%2.7%2.6%‖2.0%‖5.9%‖# New and recurrent strokes†795.0 K325.0 K365.0 K45.0 K60.0 KN/AN/AN/AN/AN/AN/A Mortality, 2008†134.1 K44.4 K68.8 K7.2 K9.5 KN/AN/AN/AN/AN/AN/AHBP Prevalence, 2008*76.4 M (33.5%)33.9%31.3%43.0%45.7%27.8%28.9%24.7%‖20.5%‖30.0%‖ Mortality, 2008†61.0 K19.6 K26.3 K6.4 K7.0 KN/AN/AN/AN/AN/AN/AHF Prevalence, 2008*5.7 M (2.4%)2.7%1.8%4.5%3.8%2.3%1.3%N/AN/AN/AN/A Mortality, 2008†56.8 K20.3 K30.2 K2.4 K3.1 KN/AN/AN/AN/AN/AN/ASmoking Prevalence, 2010‖44.1 M (19.3%)23.0%20.5%23.4%16.7%12.0%15.2%9.0%9.3%26.6%Blood cholesterol Prevalence, 2008 Total cholesterol ≥200 mg/dL*98.8 M (44.4%)41.2%47.0%37.0%41.2%50.1%46.5%N/AN/AN/AN/A Total cholesterol ≥240 mg/dL*33.6 M (15.0%)13.7%16.9%9.7%13.3%16.9%14.0%N/AN/AN/AN/A LDL cholesterol ≥130 mg/dL*71.3 M (31.9%)30.5%32.0%34.4%27.7%41.9%31.6%N/AN/AN/AN/A HDL cholesterol <40 mg/dL*41.8 M (18.9%)29.5%10.1%16.6%6.6%31.7%12.2%N/AN/AN/AN/APA¶ Prevalence, 2010‖20.7%21.3%17.2%13.2%14.4%17.8%12.5%Overweight and obesity Prevalence, 2008 Overweight and obesity, BMI ≥25.0kg/m2*149.3 M (67.3%)72.3%59.3%70.8%77.7%77.5%75.1%N/AN/AN/AN/A Overweight and obesity, BMI ≥30.0kg/m2*75.0 M (33.7%)32.1%32.8%37.0%51.0%31.4%43.4%N/AN/AN/AN/ADM Prevalence, 2008 Physician-diagnosed DM*18.3 M (8.0%)6.8%6.5%14.3%14.7%11.0%12.7%N/AN/AN/AN/A Undiagnosed DM*7.1 M (3.1%)3.9%1.9%4.8%4.0%6.3%3.8%N/AN/AN/AN/A Prediabetes*81.5 M (36.8%)45.4%27.9%31.6%27.1%44.9%34.3%N/AN/AN/AN/A Incidence, diagnosed DM*1.6 MN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A Mortality, 2008†70.6 K28.6 K27.3 K5.5 K6.6 KN/AN/AN/AN/AN/AN/ACVD indicates cardiovascular disease; M, millions; N/A, data not available; K, thousands; CHD, coronary heart disease (includes heart attack, angina pectoris chest pain, or both); MI, myocardial infarction (heart attack); AP, angina pectoris (chest pain); HBP, high blood pressure; HF, heart failure; LDL, low-density lipoprotein; HDL, high-density lipoprotein; PA, physical activity; BMI, body mass index; and DM, diabetes mellitus.*Age >20 y.†All ages.‡New and recurrent MI and fatal CHD.§Age ≥35 y.‖Age ≥18 y.¶Met 2008 Federal PA guidelines for adults.#Figure not considered reliable.Table 4. Children, Youth, and CVD: At-a-Glance TableDiseases and Risk FactorsBoth SexesTotal MalesTotal FemalesNH WhitesNH BlacksMexican AmericansMalesFemalesMalesFemalesMalesFemalesCongenital cardiovascular defects Mortality, 2008*3.4 K1.8 K1.6 K1.4 K1.2 K0.3 K0.3 KN/AN/ASmoking, % High school students, grades 9–12 Current cigarette smoking, 200919.519.819.122.322.810.78.419.4†16.7† Current cigar smoking, 200914.018.68.821.08.013.911.515.8†9.5†Blood cholesterol, mg/dL Mean total cholesterol Ages 4–11 y164.5163.8165.2163.9165.6165.7162.3160.7161.5 Ages 12–19 y159.2156.3162.3155.9162.3157.7163.6156.9161.3 Mean HDL cholesterol Ages 4–11 y54.755.653.654.752.861.458.153.651.1 Ages 12–19 y51.649.354.048.153.354.656.948.353.5 Mean LDL cholesterol Ages 12–19 y88.587.189.987.689.888.892.688.488.8PA‡ Prevalence, grades 9–12, 2009§ Met currently recommended levels of PA, %37.045.627.747.331.343.321.941.3†24.9†Overweight and obesity Prevalence, 2008 Children and adolescents, ages 2–19 y, overweight or obese23.6 M (31.7%)12.2 M (32.1%)11.4 M (31.3%)29.5%29.2%33.0%39.0%41.7%36.1% Children and adolescents, age 2–19 y, obese§12.6 M (16.9%)6.8 M (17.8%)5.8 M (15.9%)15.7%14.9%17.3%22.7%24.9%16.5%CVD indicates cardiovascular disease; NH, non-Hispanic; K, thousands; N/A, data not available; HDL, high-density lipoprotein; LDL, low-density lipoprotein; PA, physical activity; and M, millions.Overweight indicates a body mass index in the 95th percentile of the Centers for Disease Control and Prevention 2000 growth chart.*All ages.†Hispanic.‡Regular leisure-time PA.§Data derived from Eaton DK, Kann L, Kinchen S, Shanklin S, Ross J, Hawkins J, Harris WA, Lowry R, McManus T, Chyen D, Lim C, Whittle L, Brener ND, Wechsler H; Centers for Disease Control and Prevention (CDC). Youth risk behavior surveillance—United States, 2009. MMWR Surveill Summ. 2010;59:1–142.The 2012 Update Expands Data Coverage of the Obesity Epidemic and Its Antecedents and ConsequencesThe estimated prevalence of overweight and obesity in US adults (≥20 years of age) is 149 300 000, which represents 67.3% of this group in 2008. Fully 33.7% of US adults are obese (body mass index ≥30 kg/m2). Men and women of all race/ethnic groups in the population are affected by the epidemic of overweight and obesity (Chapter 16, Table 16-1).Among children 2 to 19 years of age, 31.7% are overweight and obese (which represents 23.6 million children), and 16.9% are obese (12.6 million children). Mexican American boys and girls and African American girls are disproportionately affected. Over the past 3 decades, the prevalence of obesity in children 6 to 11 years of age has increased from ≈4% to >20%.Obesity (body mass index ≥30 kg/m2) is associated with marked excess mortality in the US population. Even more notable is the excess morbidity associated with overweight and obesity in terms of risk factor development and incidence of diabetes mellitus, CVD end points (including coronary heart disease, stroke, and heart failure), and numerous other health conditions, including asthma, cancer, degenerative joint disease, and many others.The prevalence of diabetes mellitus is increasing dramatically over time, in parallel with the increases in prevalence of overweight and obesity.On the basis of NHANES 2003–2006 data, the age-adjusted prevalence of metabolic syndrome, a cluster of major cardiovascular risk factors related to overweight/obesity and insulin resistance, is ≈34% (35.1% among men and 32.6% among women).The proportion of youth (≤18 years of age) who report engaging in no regular physical activity is high, and the proportion increases with age. In 2009, among adolescents in grades 9 through 12, 29.9% of girls and 17.0% of boys reported that they had not engaged in 60 minutes of moderate-to-vigorous physical activity, defined as any activity that increased heart rate or breathing rate, even once in the previous 7 days, despite recommendations that children engage in such activity ≥5 days per week.Thirty-three percent of adults reported engaging in no aerobic leisure-time physical activity.Data from NHANES indicate that between 1971 and 2004, average total energy consumption among US adults increased by 22% in women (from 1542 to 1886 kcal/d) and by 10% in men (from 2450 to 2693 kcal/d; see Chart 20-1).The increases in calories consumed during this time period are attributable primarily to greater average carbohydrate intake, in particular, of starches, refined grains, and sugars. Other specific changes related to increased caloric intake in the United States include larger portion sizes, greater food quantity and calories per meal, and increased consumption of sugar-sweetened beverages, snacks, commercially prepared (especially fast food) meals, and higher energy-density foods.The 2012 Update Provides Critical Data About Cardiovascular Quality of Care, Procedure Utilization, and CostsIn light of the current national focus on healthcare utilization, costs, and quality, it is critical to monitor and understand the magnitude of healthcare delivery and costs, as well as the quality of healthcare delivery, related to CVDs. The Statistical Update provides these critical data in several sections.Quality-of-Care Metrics for CVDsChapter 21 reviews many metrics related to the quality of care delivered to patients with CVDs, as well as healthcare disparities. In particular, quality data are available from the AHA's “Get With The Guidelines” programs for coronary artery disease and heart failure and from the American Stroke Association/AHA's “Get With The Guidelines” program for acute stroke. Similar data from the Veterans Healthcare Administration, national Medicare and Medicaid data, and Acute Coronary Treatment and Intervention Outcomes Network–“Get With The Guidelines” Registry data are also reviewed. These data show impressive adherence with guideline recommendations for many, but not all, metrics of quality of care for these hospitalized patients. Data are also reviewed on screening for cardiovascular risk factor levels and control.Cardiovascular Procedure Utilization and CostsChapter 22 provides data on trends and current usage of cardiovascular surgical and invasive procedures. For example, the total number of inpatient cardiovascular operations and procedures increased 22%, from 6 133 000 in 1999 to 7 453 000 in 2009 (National Heart, Lung, and Blood Institute computation based on National Center for Health Statistics annual data).Chapter 23 reviews current estimates of direct and indirect healthcare costs related to CVDs, stroke, and related conditions using Medical Expenditure Panel Survey data. The total direct and indirect cost of CVD and stroke in the United States for 2008 is estimated to be $297.7 billion. This figure includes health expenditures (direct costs, which include the cost of physicians and other professionals, hospital services, prescribed medications, home health care, and other medical durables) and lost productivity resulting from mortality (indirect costs). By comparison, in 2008, the estimated cost of all cancer and benign neoplasms was $228 billion ($93 billion in direct costs, $19 billion in morbidity indirect costs, and $116 billion in mortality indirect costs). CVD costs more than any other diagnostic group.The AHA, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current data available in the Statistics Update.Finally, it must be noted that this annual Statistical Update is the product of an entire year's worth of effort by dedicated professionals, volunteer physicians and scientists, and outstanding AHA staff members, without whom publication of this valuable resource would be impossible. Their contributions are gratefully acknowledged.Véronique L. Roger, MD, MPH, FAHAMelanie B. Turner, MPHOn behalf of the American Heart Association Statistics Committee and Stroke Statistics SubcommitteeNote: Population data used in the compilation of NHANES prevalence estimates is for the latest year of the NHANES survey being used. Extrapolations for NHANES prevalence estimates are based on the census resident population for 2008 because this is the most recent year of NHANES data used in the Statistical Update.AcknowledgmentsWe wish to thank Thomas Thom, Michael Wolz, Dale Burwen, and Sean Coady for their valuable comments and contributions. We would like to acknowledge Karen Modesitt for her administrative assistance.DisclosuresWriting Group DisclosuresWriting Group MemberEmploymentResearch GrantOther Research SupportSpeakers' Bureau/ HonorariaExpert WitnessOwnership InterestConsultant/Advisory BoardOtherVéronique L. RogerMayo ClinicNoneNoneNoneNoneNoneNoneNoneEmelia J. BenjaminBoston University School of MedicineNIH†NoneNoneNoneNoneNIH†NoneJarett D. BerryUT Southwestern Medical SchoolAHA†; NHLBI†NoneMerck†NoneNoneNoneNoneWilliam B. BordenWeill Cornell Medical CollegeNoneNoneNoneNoneNoneNoneThe Dr. Robert C. and Veronica Atkins Foundation provided an educational grant to develop a curriculum in Metabolic Diseases; Dr Borden receives salary support from that†Dawn M. BravataUniversity of IowaNoneNoneNoneNoneNoneNoneNoneShifan DaiCenters for Disease Control and PreventionNoneNoneNoneNoneNoneNoneNoneEarl S. FordCenters for Disease Control and PreventionNoneNoneNoneNoneNoneNoneNoneCaroline S. FoxNHLBINoneNoneNoneNoneNoneNoneNoneHeather J. FullertonUniversity of California, San FranciscoNIH/NINDS†NoneCincinnati Children's Hospital*; Toronto Hospital for Sick Children*NoneNoneDSMB for Berlin Heart*NoneCathleen GillespieCenters for Disease Control and PreventionNoneNoneNoneNoneNoneNoneNoneAlan S. GoThe Permanente Medical GroupGlaxoSmithKline†; Johnson & Johnson†NoneNoneNoneNoneNoneNoneSusan M. HailpernIndependent ConsultantNoneNoneNoneNoneNoneNoneNoneJohn A. HeitMayo ClinicNoneNoneNoneNoneNoneNoneNoneVirginia J. HowardUniversity of Alabama at Birmingham School of Public HealthNIH/NINDS†NoneNoneNoneNoneNoneNoneBrett M. KisselaUniversity of CincinnatiNexstim*NoneAllergan*Expert witness for defense in 1 stroke-related case in 2010†NoneAllergan*NoneSteven J. KittnerUniversity of Maryland School of MedicineNoneNoneN

Background Tools for the prediction of atrial fibrillation ( AF ) may identify high‐risk individuals more likely to benefit from preventive interventions and serve as a benchmark to test novel putative risk factors. Methods and Results Individual‐level data from 3 large cohorts in the U nited S tates (Atherosclerosis Risk in Communities [ ARIC ] study, the Cardiovascular Health Study [ CHS ], and the Framingham Heart Study [ FHS ]), including 18 556 men and women aged 46 to 94 years (19% A frican A mericans, 81% whites) were pooled to derive predictive models for AF using clinical variables. Validation of the derived models was performed in 7672 participants from the Age, Gene and Environment—Reykjavik study ( AGES ) and the Rotterdam Study ( RS ). The analysis included 1186 incident AF cases in the derivation cohorts and 585 in the validation cohorts. A simple 5‐year predictive model including the variables age, race, height, weight, systolic and diastolic blood pressure, current smoking, use of antihypertensive medication, diabetes, and history of myocardial infarction and heart failure had good discrimination (C‐statistic, 0.765; 95% CI , 0.748 to 0.781). Addition of variables from the electrocardiogram did not improve the overall model discrimination (C‐statistic, 0.767; 95% CI , 0.750 to 0.783; categorical net reclassification improvement, −0.0032; 95% CI , −0.0178 to 0.0113). In the validation cohorts, discrimination was acceptable ( AGES C‐statistic, 0.664; 95% CI , 0.632 to 0.697 and RS C‐statistic, 0.705; 95% CI , 0.664 to 0.747) and calibration was adequate. Conclusion A risk model including variables readily available in primary care settings adequately predicted AF in diverse populations from the U nited S tates and E urope.

Background— Atrial fibrillation (AF) is an important risk factor for stroke and overall mortality, but information about the preventable burden of AF is lacking. The aim of this study was to determine what proportion of the burden of AF in blacks and whites could theoretically be avoided by the maintenance of an optimal risk profile. Methods and Results— This study included 14 598 middle-aged Atherosclerosis Risk in Communities (ARIC) Study cohort members. Previously established AF risk factors, namely high blood pressure, elevated body mass index, diabetes mellitus, cigarette smoking, and prior cardiac disease, were categorized into optimal, borderline, and elevated levels. On the basis of their risk factor levels, individuals were classified into 1 of these 3 groups. The population-attributable fraction of AF resulting from having a nonoptimal risk profile was estimated separately for black and white men and women. During a mean follow-up of 17.1 years, 1520 cases of incident AF were identified. The age-adjusted incidence rates were highest in white men and lowest in black women (7.45 and 3.67 per 1000 person-years, respectively). The overall prevalence of an optimal risk profile was 5.4% but varied according to race and gender: 10% in white women versus 1.6% in black men. Overall, 56.5% of AF cases could be explained by having ≥1 borderline or elevated risk factors, of which elevated blood pressure was the most important contributor. Conclusion— As with other forms of cardiovascular disease, more than half of the AF burden is potentially avoidable through the optimization of cardiovascular risk factors levels.

Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death. We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 × 10(-8)). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.

To define the incidence and cumulative risk of atrial fibrillation (AF) in a population-based cohort of whites and African Americans. African-Americans reportedly have a lower risk of AF than whites despite their higher exposure to AF risk factors. However, precise estimates of AF incidence in African Americans have not been previously published. We studied the incidence of AF in the Atherosclerosis Risk in Communities (ARIC) study, which has followed up 15,792 men and women 45 to 65 years of age at baseline from 4 communities in the United States since 1987. Atrial fibrillation cases were identified from electrocardiograms conducted at baseline and 3 follow-up visits, and from hospitalizations and death certificates through the end of 2004. During follow-up, 1,085 new cases of AF were identified (196 in African Americans, 889 in whites). Crude incidence rates of AF were 6.7, 4.0, 3.9, and 3.0 per 1,000 persons per year in white men, white women, African-American men, and African-American women, respectively. Increasing age was exponentially associated with an elevated risk of AF. Compared to whites, African-Americans had a 41% (95% CI: 8%-62%) lower age- and sex-adjusted risk of being diagnosed with AF. The cumulative risk of AF at 80 years of age was 21% in white men, 17% in white women, and 11% in African-American men and women. In this population-based cohort, African Americans presented a lower risk of AF than whites. Still, the burden of AF among the former is substantial, with 1 in 9 receiving a diagnosis of AF before 80 years of age.

Chronic kidney disease is associated with the incidence of cardiovascular disease. Chronic kidney disease may also increase the risk of atrial fibrillation (AF), but existing studies have reported inconsistent results.We estimated cystatin C-based glomerular filtration rate (eGFR(cys)) and measured urinary albumin-to-creatinine ratio (ACR) in 10 328 men and women free of AF from the Atherosclerosis Risk in Communities (ARIC) Study in 1996 to 1998. Incidence of AF was ascertained through the end of 2007. During a median follow-up of 10.1 years, we identified 788 incident AF cases. Compared with individuals with eGFR(cys) ≥90 mL · min(-1) · 1.73 m(-2), multivariable hazard ratios and 95% confidence intervals (CIs) of AF were 1.3 (95% CI, 1.1 to 1.6), 1.6 (95% CI, 1.3 to 2.1), and 3.2 (95% CI, 2.0 to 5.0; P for trend <0.0001) in those with eGFR(cys) of 60 to 89, 30 to 59, and 15 to 29 mL · min(-1) · 1.73 m(-2), respectively. Similarly, the presence of macroalbuminuria (ACR ≥300 mg/g; hazard ratio, 3.2; 95% CI, 2.3 to 4.5) and microalbuminuria (ACR, 30 to 299 mg/g; hazard ratio, 2.0; 95% CI, 1.6 to 2.4) was associated with higher AF risk compared with those with ACR <30 mg/g. Risk of AF was particularly elevated in those with both low eGFR(cys) and macroalbuminuria (hazard ratio, 13.1; 95% CI, 6.0 to 28.6, comparing individuals with ACR ≥300 mg/g and eGFR(cys) of 15 to 29 mL · min(-1) · 1.73 m(-2) and those with ACR <30 mg/g and eGFR(cys) ≥90 mL · min(-1) · 1.73 m(-2)).In this large population-based study, reduced kidney function and presence of albuminuria were strongly associated with the incidence of AF independently of other risk factors.

Patrick Ellinor and colleagues report a genome-wide association study identifying variants in KCNN3 associated to lone atrial fibrillation. Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF. This condition affects a subset of individuals without overt heart disease and with an increased heritability of AF. We report a meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF (cases) and 12,844 unaffected individuals (referents). Cases were obtained from the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and Massachusetts General Hospital. We identified an association on chromosome 1q21 to lone AF (rs13376333, adjusted odds ratio = 1.56; P = 6.3 × 10−12), and we replicated this association in two independent cohorts with lone AF (overall combined odds ratio = 1.52, 95% CI 1.40–1.64; P = 1.83 × 10−21). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization.

The electrocardiographic PR interval (or PQ interval) reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation. We report a meta-analysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N = 28,517). We identified nine loci associated with PR interval at P < 5 x 10(-8). At the 3p22.2 locus, we observed two independent associations in voltage-gated sodium channel genes, SCN10A and SCN5A. Six of the loci were near cardiac developmental genes, including CAV1-CAV2, NKX2-5 (CSX1), SOX5, WNT11, MEIS1, and TBX5-TBX3, providing pathophysiologically interesting candidate genes. Five of the loci, SCN5A, SCN10A, NKX2-5, CAV1-CAV2, and SOX5, were also associated with atrial fibrillation (N = 5,741 cases, P < 0.0056). This suggests a role for common variation in ion channel and developmental genes in atrial and atrioventricular conduction as well as in susceptibility to atrial fibrillation.

While black-white and regional disparities in U.S. stroke mortality rates are well documented, the contribution of disparities in stroke incidence is unknown. We provide national estimates of stroke incidence by race and region, contrasting these to publicly available stroke mortality data.This analysis included 27,744 men and women without prevalent stroke (40.4% black), aged ≥45 years from the REasons for Geographic And Racial Differences in Stroke (REGARDS) national cohort study, enrolled 2003-2007. Incident stroke was defined as first occurrence of stroke over 4.4 years of follow-up. Age-sex-adjusted stroke mortality rates were calculated using data from the Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiological Research (WONDER) System.There were 460 incident strokes over 113,469 person-years of follow-up. Relative to the rest of the United States, incidence rate ratios (IRRs) of stroke in the southeastern stroke belt and stroke buckle were 1.06 (95% confidence interval [CI], 0.87-1.29) and 1.19 (95% CI, 0.96-1.47), respectively. The age-sex-adjusted black/white IRR(black) was 1.51 (95% CI, 1.26-1.81), but for ages 45-54 years the IRR(black) was 4.02 (95% CI, 1.23-13.11) while for ages 85+ it was 0.86 (95% CI, 0.33-2.20). Generally, the IRRs(black) were less than the mortality rate ratios (MRRs) across age groups; however, only in ages 55-64 years and 65-74 years did the 95% CIs of IRRs(black) not include the MRR(black) . The MRRs for regions were within 95% CIs for IRRs.National patterns of black-white and regional differences in stroke incidence are similar to those for stroke mortality; however, the magnitude of differences in incidence appear smaller.

The epidemiology of atrial fibrillation (AF) has been mainly investigated in patients with end-stage renal disease, with limited data on less advanced chronic kidney disease (CKD) stages. A total of 3,267 adult participants (50% non-Hispanic blacks, 46% women) with CKD from the Chronic Renal Insufficiency Cohort were included in this study. None of the study participants had been on dialysis. Those with self-identified race/ethnicity other than non-Hispanic black or white (n = 323) or those without electrocardiographic data (n = 22) were excluded. Atrial fibrillation was ascertained by a 12-lead electrocardiogram and self-report. Age-, sex-, and race/ethnicity-specific prevalence rates of AF were estimated and compared between subgroups. Cross-sectional associations and correlates with prevalent AF were examined using unadjusted and multivariable-adjusted logistic regression analysis. The mean estimated glomerular filtration rate was 43.6 (±13.0) mL/(min 1.73 m2). Atrial fibrillation was present in 18% of the study population and in >25% of those ≥70 years old. In multivariable-adjusted models, 1-SD increase in age (11 years) (odds ratio 1.27, CI 95% 1.13-1.43, P < .0001), female sex (0.80, 0.65-0.98, P = .0303), smoking (former vs never) (1.34, 1.08-1.66, P = .0081), history of heart failure (3.28, 2.47-4.36, P < .001), and history of cardiovascular disease (1.94, 1.56-2.43, P < .0001) were significantly associated with AF. Race/ethnicity, hypertension, diabetes, body mass index, physical activity, education, high-sensitivity C-reactive protein, total cholesterol, and alcohol intake were not significantly associated with AF. An estimated glomerular filtration rate <45 mL/(min 1.73 m2) was associated with AF in an unadjusted model (1.35, 1.13-1.62, P = .0010), but not after multivariable adjustment (1.12, 0.92-1.35, P = .2710). Nearly 1 in 5 participants in Chronic Renal Insufficiency Cohort, a national study of CKD, had evidence of AF at study entry, a prevalence similar to that reported among patients with end-stage renal disease and 2 to 3 times of that reported in the general population. Risk factors for AF in this CKD population do not mirror those reported in the general population.

Myocardial infarction (MI) is an established risk factor for atrial fibrillation (AF). However, the extent to which AF is a risk factor for MI has not been investigated.To examine the risk of incident MI associated with AF.A prospective cohort of 23,928 participants residing in the continental United States and without coronary heart disease at baseline were enrolled from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort between 2003 and 2007, with follow-up through December 2009.Expert-adjudicated total MI events (fatal and nonfatal).Over 6.9 years of follow-up (median 4.5 years), 648 incident MI events occurred. In a sociodemographic-adjusted model, AF was associated with about 2-fold increased risk of MI (hazard ratio [HR], 1.96 [95% CI, 1.52-2.52]). This association remained significant (HR, 1.70 [95% CI, 1.26-2.30]) after further adjustment for total cholesterol, high-density lipoprotein cholesterol, smoking status, systolic blood pressure, blood pressure-lowering drugs, body mass index, diabetes, warfarin use, aspirin use, statin use, history of stroke and vascular disease, estimated glomerular filtration rate, albumin to creatinine ratio, and C-reactive protein level. In subgroup analysis, the risk of MI associated with AF was significantly higher in women (HR, 2.16 [95% CI, 1.41-3.31]) than in men (HR, 1.39 [95% CI, 0.91-2.10]) and in blacks (HR, 2.53 [95% CI, 1.67-3.86]) than in whites (HR, 1.26 [95% CI, 0.83-1.93]); for interactions, P = .03 and P = .02, respectively. On the other hand, there were no significant differences in the risk of MI associated with AF in older (≥75 years) vs younger (<75 years) participants (HR, 2.00 [95% CI, 1.16-3.35] and HR, 1.60 [95% CI, 1.11-2.30], respectively); for interaction, P = .44.AF is independently associated with an increased risk of incident MI, especially in women and blacks. These findings add to the growing concerns of the seriousness of AF as a public health burden: in addition to being a well-known risk factor for stroke, AF is also associated with increased risk of MI.

We conducted meta-analyses of genome-wide association studies for atrial fibrillation (AF) in participants from five community-based cohorts. Meta-analyses of 896 prevalent (15,768 referents) and 2,517 incident (21,337 referents) AF cases identified a new locus for AF (ZFHX3, rs2106261, risk ratio RR = 1.19; P = 2.3 x 10(-7)). We replicated this association in an independent cohort from the German AF Network (odds ratio = 1.44; P = 1.6 x 10(-11); combined RR = 1.25; combined P = 1.8 x 10(-15)).

The QRS interval, from the beginning of the Q wave to the end of the S wave on an electrocardiogram, reflects ventricular depolarization and conduction time and is a risk factor for mortality, sudden death and heart failure. We performed a genome-wide association meta-analysis in 40,407 individuals of European descent from 14 studies, with further genotyping in 7,170 additional Europeans, and we identified 22 loci associated with QRS duration (P < 5 × 10(-8)). These loci map in or near genes in pathways with established roles in ventricular conduction such as sodium channels, transcription factors and calcium-handling proteins, but also point to previously unidentified biologic processes, such as kinase inhibitors and genes related to tumorigenesis. We demonstrate that SCN10A, a candidate gene at the most significantly associated locus in this study, is expressed in the mouse ventricular conduction system, and treatment with a selective SCN10A blocker prolongs QRS duration. These findings extend our current knowledge of ventricular depolarization and conduction.

Rationale Recent data suggest that a thrombogenic atrial substrate can cause stroke in the absence of atrial fibrillation. Such an atrial cardiopathy may explain some proportion of cryptogenic strokes. Aims The aim of the ARCADIA trial is to test the hypothesis that apixaban is superior to aspirin for the prevention of recurrent stroke in subjects with cryptogenic ischemic stroke and atrial cardiopathy. Sample size estimate 1100 participants. Methods and design Biomarker-driven, randomized, double-blind, active-control, phase 3 clinical trial conducted at 120 U.S. centers participating in NIH StrokeNet. Population studied Patients ≥ 45 years of age with embolic stroke of undetermined source and evidence of atrial cardiopathy, defined as ≥ 1 of the following markers: P-wave terminal force &gt;5000 µV × ms in ECG lead V 1 , serum NT-proBNP &gt; 250 pg/mL, and left atrial diameter index ≥ 3 cm/m 2 on echocardiogram. Exclusion criteria include any atrial fibrillation, a definite indication or contraindication to antiplatelet or anticoagulant therapy, or a clinically significant bleeding diathesis. Intervention: Apixaban 5 mg twice daily versus aspirin 81 mg once daily. Analysis: Survival analysis and the log-rank test will be used to compare treatment groups according to the intention-to-treat principle, including participants who require open-label anticoagulation for newly detected atrial fibrillation. Study outcomes The primary efficacy outcome is recurrent stroke of any type. The primary safety outcomes are symptomatic intracranial hemorrhage and major hemorrhage other than intracranial hemorrhage. Discussion ARCADIA is the first trial to test whether anticoagulant therapy reduces stroke recurrence in patients with atrial cardiopathy but no known atrial fibrillation.

A risk score for atrial fibrillation (AF) has been developed by the Framingham Heart Study; however, the applicability of this risk score, derived using data from white patients, to predict new-onset AF in nonwhites is uncertain. Therefore, we developed a 10-year risk score for new-onset AF from risk factors commonly measured in clinical practice using 14,546 subjects from the Atherosclerosis Risk In Communities (ARIC) study, a prospective community-based cohort of blacks and whites in the United States. During 10 years of follow-up, 515 incident AF events occurred. The following variables were included in the AF risk score: age, race, height, smoking status, systolic blood pressure, hypertension medication use, precordial murmur, left ventricular hypertrophy, left atrial enlargement, diabetes, coronary heart disease, and heart failure. The area under the receiver operating characteristics curve (AUC) of a Cox regression model that included the previous variables was 0.78, suggesting moderately good discrimination. The point-based score developed from the coefficients in the Cox model had an AUC of 0.76. This clinical risk score for AF in the Atherosclerosis Risk In Communities cohort compared favorably with the Framingham Heart Study's AF (AUC 0.68), coronary heart disease (CHD) (AUC 0.63), and hard CHD (AUC 0.59) risk scores and the Atherosclerosis Risk In Communities CHD risk score (AUC 0.58). In conclusion, we have developed a risk score for AF and have shown that the different pathophysiologies of AF and CHD limit the usefulness of a CHD risk score in identifying subjects at greater risk of AF. A risk score for atrial fibrillation (AF) has been developed by the Framingham Heart Study; however, the applicability of this risk score, derived using data from white patients, to predict new-onset AF in nonwhites is uncertain. Therefore, we developed a 10-year risk score for new-onset AF from risk factors commonly measured in clinical practice using 14,546 subjects from the Atherosclerosis Risk In Communities (ARIC) study, a prospective community-based cohort of blacks and whites in the United States. During 10 years of follow-up, 515 incident AF events occurred. The following variables were included in the AF risk score: age, race, height, smoking status, systolic blood pressure, hypertension medication use, precordial murmur, left ventricular hypertrophy, left atrial enlargement, diabetes, coronary heart disease, and heart failure. The area under the receiver operating characteristics curve (AUC) of a Cox regression model that included the previous variables was 0.78, suggesting moderately good discrimination. The point-based score developed from the coefficients in the Cox model had an AUC of 0.76. This clinical risk score for AF in the Atherosclerosis Risk In Communities cohort compared favorably with the Framingham Heart Study's AF (AUC 0.68), coronary heart disease (CHD) (AUC 0.63), and hard CHD (AUC 0.59) risk scores and the Atherosclerosis Risk In Communities CHD risk score (AUC 0.58). In conclusion, we have developed a risk score for AF and have shown that the different pathophysiologies of AF and CHD limit the usefulness of a CHD risk score in identifying subjects at greater risk of AF.

<h3>Importance</h3> Coronary artery calcification (CAC) is highly prevalent in dialysis-naive patients with chronic kidney disease (CKD). However, there are sparse data on the association of CAC with subsequent risk of cardiovascular disease and all-cause mortality in this population. <h3>Objective</h3> To study the prospective association of CAC with risk of cardiovascular disease and all-cause mortality among dialysis-naive patients with CKD. <h3>Design, Setting, and Participants</h3> The prospective Chronic Renal Insufficiency Cohort study recruited adults with an estimated glomerular filtration rate of 20 to 70 mL/min/1.73 m²from 7 clinical centers in the United States. There were 1541 participants without cardiovascular disease at baseline who had CAC scores. <h3>Exposures</h3> Coronary artery calcification was assessed using electron-beam or multidetector computed tomography. <h3>Main Outcomes and Measures</h3> Incidence of cardiovascular disease (including myocardial infarction, heart failure, and stroke) and all-cause mortality were reported every 6 months and confirmed by medical record adjudication. <h3>Results</h3> During an average follow-up of 5.9 years in 1541 participants aged 21 to 74 years, there were 188 cardiovascular disease events (60 cases of myocardial infarction, 120 heart failures, and 27 strokes; patients may have had &gt;1 event) and 137 all-cause deaths. In Cox proportional hazards models adjusted for age, sex, race, clinical site, education level, physical activity, total cholesterol level, high-density lipoprotein cholesterol level, systolic blood pressure, use of antihypertensive treatment, current cigarette smoking, diabetes status, body mass index, C-reactive protein level, hemoglobin A_1clevel, phosphorus level, troponin T level, log N-terminal pro–B-type natriuretic peptide level, fibroblast growth factor 23 level, estimated glomerular filtration rate, and proteinuria, the hazard ratios associated with per 1 SD log of CAC were 1.40 (95% CI, 1.16-1.69;<i>P</i> &lt; .001) for cardiovascular disease, 1.44 (95% CI, 1.02-2.02;<i>P</i> = .04) for myocardial infarction, 1.39 (95% CI, 1.10-1.76;<i>P</i> = .006) for heart failure, and 1.19 (95% CI, 0.94-1.51;<i>P</i> = .15) for all-cause mortality. In addition, inclusion of CAC score led to an increase in the C statistic of 0.02 (95% CI, 0-0.09;<i>P</i> &lt; .001) for predicting cardiovascular disease over use of all the above-mentioned established and novel cardiovascular disease risk factors. <h3>Conclusions and Relevance</h3> Coronary artery calcification is independently and significantly related to the risks of cardiovascular disease, myocardial infarction, and heart failure in patients with CKD. In addition, CAC improves risk prediction for cardiovascular disease, myocardial infarction, and heart failure over use of established and novel cardiovascular disease risk factors among patients with CKD; however, the changes in the C statistic are small.

Background and Purpose— The paradox of the reported low prevalence of atrial fibrillation (AF) in blacks compared with whites despite higher stroke rates in the former could be related to limitations in the current methods used to diagnose AF in population-based studies. Hence, this study aimed to use the ethnic distribution of ECG predictors of AF as measures of AF propensity in different ethnic groups. Methods— The distribution of baseline measures of P-wave terminal force, P-wave duration, P-wave area, and PR duration (referred to as AF predictors) were compared by ethnicity in 15 429 participants (27% black) from the Atherosclerosis Risk in Communities (ARIC) study by unpaired t test, χ 2 , and logistic-regression analysis, as appropriate. Cox proportional-hazards analysis was used to separately examine the association of AF predictors with incident AF and ischemic stroke. Results— Whereas AF was significantly less common in blacks compared with whites (0.24% vs 0.95%, P &lt;0.0001), similar to what has been reported in previous studies, blacks had significantly higher and more abnormal values of AF predictors ( P &lt;0.0001 for all comparisons). Black ethnicity was significantly associated with abnormal AF predictors compared with whites; odds ratios for different AF predictors ranged from 2.1 to 3.1. AF predictors were significantly and independently associated with AF and ischemic stroke with no significant interaction between ethnicity and AF predictors, findings that further justify using AF predictors as an earlier indicator of future risk of AF and stroke. Conclusions— There is a disconnect between the ethnic distribution of AF predictors and the ethnic distribution of AF, probably because the former, unlike the latter, do not suffer from low sensitivity. These results raise the possibility that blacks might actually have a higher prevalence of AF that might have been missed by previous studies owing to limited methodology, a difference that could partially explain the greater stroke risk in blacks.

Background— Despite a higher burden of standard atrial fibrillation (AF) risk factors, African Americans have a lower risk of AF than whites. It is unknown whether the higher risk is due to genetic or environmental factors. Because African Americans have varying degrees of European ancestry, we sought to test the hypothesis that European ancestry is an independent risk factor for AF. Methods and Results— We studied whites (n=4543) and African Americans (n=822) in the Cardiovascular Health Study (CHS) and whites (n=10 902) and African Americans (n=3517) in the Atherosclerosis Risk in Communities (ARIC) Study (n=3517). Percent European ancestry in African Americans was estimated with 1747 ancestry informative markers from the Illumina custom ITMAT-Broad-CARe array. Among African Americans without baseline AF, 120 of 804 CHS participants and 181 of 3517 ARIC participants developed incident AF. A meta-analysis from the 2 studies revealed that every 10% increase in European ancestry increased the risk of AF by 13% (hazard ratio, 1.13; 95% confidence interval, 1.03 to 1.23; P =0.007). After adjustment for potential confounders, European ancestry remained a predictor of incident AF in each cohort alone, with a combined estimated hazard ratio for each 10% increase in European ancestry of 1.17 (95% confidence interval, 1.07 to 1.29; P =0.001). A second analysis using 3192 ancestry informative markers from a genome-wide Affymetrix 6.0 array in ARIC African Americans yielded similar results. Conclusions— European ancestry predicted risk of incident AF. Our study suggests that investigating genetic variants contributing to differential AF risk in individuals of African versus European ancestry will be informative.

Atrial fibrillation (AF) is common among patients with end-stage renal disease, but few data are available on its prevalence among adults with chronic kidney disease (CKD) of lesser severity. methods and results: We evaluated the association of CKD with ECG-detected AF among 26 917 participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a population-based cohort of African-American and white US adults ≥45 years of age. Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease study equation and albuminuria was defined as a urinary albumin to creatinine ratio ≥30 mg/g. Participants were categorized by renal function: no CKD (eGFR ≥60 mL/min/1.73 m(2) without albuminuria, n=21 081), stage 1 to 2 CKD (eGFR ≥60 mL/min/1.73 m(2) with albuminuria n=2938), stage 3 CKD (eGFR 30 to 59 mL/min/1.73 m(2), n=2683) and stage 4 to 5 CKD (eGFR <30 mL/min/1.73 m(2), n=215). The prevalence of AF among participants without CKD, and with stage 1 to 2, stage 3, and stage 4 to 5 CKD was 1.0%, 2.8%, 2.7% and 4.2%, respectively. Compared with participants without CKD, the age-, race-, and sex-adjusted odds ratios for prevalent AF were 2.67 (95% confidence interval, 2.04 to 3.48), 1.68 (95% confidence interval, 1.26 to 2.24) and 3.52 (95% confidence interval, 1.73 to 7.15) among those with stage 1 to 2, stage 3, and stage 4 to 5 CKD. The association between CKD and prevalent AF remained statistically significant after further multivariable adjustment and was consistent across numerous subgroups.Regardless of severity, CKD is associated with an increased prevalence of AF among US adults.

Cigarette smoking increases the risk of coronary heart disease, but whether smoking increases atrial fibrillation (AF) is uncertain.The purpose of this study was to determine the association of cigarette smoking with incident AF in a population-based cohort of blacks and whites.We determined the risk of incident AF through December 2002 in relation to baseline (1987-1989) smoking status and cigarette-years of smoking in over 15,000 participants of the prospective Atherosclerosis Risk in Communities (ARIC) study.Over a mean follow-up of 13.1 years, 876 incident AF events were identified. Compared to never smokers, the multivariable-adjusted hazard ratios (HRs) for AF were 1.32 (95% confidence interval [CI] 1.10-1.57) in former smokers, 2.05 (95% CI 1.71-2.47) in current smokers, and 1.58 (95% CI 1.35-1.85) in ever smokers. In the highest tertile of accumulated smoking amount (>675 cigarette-years), the incidence of AF was 2.10 times greater (95% CI 1.74-2.53) than in those who never smoked. Associations were similar by gender, race, type of event (AF and atrial flutter), and when only AF events identified by study exam ECGs were included. Finally, individuals who quit smoking exhibited a trend indicating a slightly lower risk of developing AF (HR 0.88, 95% CI 0.65-1.17) compared to those who continued to smoke.Smoking was associated with the incidence of AF, with more than a two-fold increased risk of AF attributed to current smoking. In addition, a trend toward a lower incidence of AF appeared among smokers who quit compared to continued smokers.

<h3>Importance</h3> Patients with chronic kidney disease (CKD) are at an increased risk of cardiovascular disease (CVD) compared with the general population. Prior studies have produced contradictory results on the association of dietary sodium intake with risk of CVD, and this relationship has not been investigated in patients with CKD. <h3>Objective</h3> To evaluate the association between urinary sodium excretion and clinical CVD events among patients with CKD. <h3>Design, Setting, and Participants</h3> A prospective cohort study of patients with CKD from 7 locations in the United States enrolled in the Chronic Renal Insufficiency Cohort Study and followed up from May 2003 to March 2013. <h3>Exposures</h3> The cumulative mean of urinary sodium excretion from three 24-hour urinary measurements and calibrated to sex-specific mean 24-hour urinary creatinine excretion. <h3>Main Outcomes and Measures</h3> A composite of CVD events defined as congestive heart failure, stroke, or myocardial infarction. Events were reported every 6 months and confirmed by medical record adjudication. <h3>Results</h3> Among 3757 participants (mean age, 58 years; 45% women), 804 composite CVD events (575 heart failure, 305 myocardial infarction, and 148 stroke) occurred during a median 6.8 years of follow-up. From lowest (&lt;2894 mg/24 hours) to highest (≥4548 mg/24 hours) quartile of calibrated sodium excretion, 174, 159, 198, and 273 composite CVD events occurred, and the cumulative incidence was 18.4%, 16.5%, 20.6%, and 29.8% at median follow-up. In addition, the cumulative incidence of CVD events in the highest quartile of calibrated sodium excretion compared with the lowest was 23.2% vs 13.3% for heart failure, 10.9% vs 7.8% for myocardial infarction, and 6.4% vs 2.7% for stroke at median follow-up. Hazard ratios of the highest quartile compared with the lowest quartile were 1.36 (95% CI, 1.09-1.70;<i>P</i> = .007) for composite CVD events, 1.34 (95% CI, 1.03-1.74;<i>P</i> = .03) for heart failure, and 1.81 (95% CI, 1.08-3.02;<i>P</i> = .02) for stroke after multivariable adjustment. Restricted cubic spline analyses of the association between sodium excretion and composite CVD provided no evidence of a nonlinear association (<i>P</i> = .11) and indicated a significant linear association (<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> Among patients with CKD, higher urinary sodium excretion was associated with increased risk of CVD.

Background— Race and sex differences in silent myocardial infarction (SMI) are not well established. Methods and Results— The analysis included 9498 participants from the Atherosclerosis Risk in Communities (ARIC) study who were free of cardiovascular disease at baseline (visit 1, 1987–1989). Incident SMI was defined as ECG evidence of MI without clinically documented MI (CMI) after the baseline until ARIC visit 4 (1996–1998). Coronary heart disease and all-cause deaths were ascertained starting from ARIC visit 4 until 2010. During a median follow-up of 8.9 years, 317 participants (3.3%) developed SMI and 386 (4.1%) developed CMI. The incidence rates of both SMI and CMI were higher in men (5.08 and 7.96 per 1000-person years, respectively) than in women (2.93 and 2.25 per 1000-person years, respectively; P &lt;0.0001 for both). Blacks had a nonsignificantly higher rate of SMI than whites (4.45 versus 3.69 per 1000-person years; P =0.217), but whites had higher rate of CMI than blacks (5.04 versus 3.24 per 1000-person years; P =0.002). SMI and CMI (compared with no MI) were associated with increased risk of coronary heart disease death (hazard ratio, 3.06 [95% confidence interval, 1.88–4.99] and 4.74 [95% confidence interval, 3.26–6.90], respectively) and all-cause mortality (hazard ratio, 1.34 [95% confidence interval, 1.09–1.65] and 1.55 [95% confidence interval, 1.30–1.85], respectively). However, SMI and CMI were associated with increased mortality among both men and women, with potentially greater increased risk among women (interaction P =0.089 and 0.051, respectively). No significant interactions by race were detected. Conclusions— SMI represents &gt;45% of incident MIs and is associated with poor prognosis. Race and sex differences in the incidence and prognostic significance of SMI exist that may warrant considering SMI in personalized assessments of coronary heart disease risk.

It is unknown whether atrial fibrillation (AF) is associated with an increased risk of sudden cardiac death (SCD) in the general population. This association was examined in 2 population-based cohorts.In the Atherosclerosis Risk in Communities (ARIC) Study, we analyzed data from 15 439 participants (baseline age, 45-64 years; 55.2% women; and 26.6% black) from baseline (1987-1989) through December 31, 2001. In the Cardiovascular Health Study (CHS), we analyzed data from 5479 participants (baseline age, ≥65 years; 58.2% women; and 15.4% black) from baseline (first cohort, 1989-1990; second cohort, 1992-1993) through December 31, 2006. The main outcome was physician-adjudicated SCD, defined as death from a sudden, pulseless condition presumed to be due to a ventricular tachyarrhythmia. The secondary outcome was non-SCD (NSCD), defined as coronary heart disease death not meeting SCD criteria. We used Cox proportional hazards models to assess the association between AF and SCD/NSCD, adjusting for baseline demographic and cardiovascular risk factors.In the ARIC Study, 894 AF, 269 SCD, and 233 NSCD events occurred during follow-up (median, 13.1 years). The crude incidence rates of SCD were 2.89 per 1000 person-years (with AF) and 1.30 per 1000 person-years (without AF). The multivariable hazard ratios (HRs) (95% CIs) of AF for SCD and NSCD were 3.26 (2.17-4.91) and 2.43 (1.60-3.71), respectively. In the CHS, 1458 AF, 292 SCD, and 581 NSCD events occurred during follow-up (median, 13.1 years). The crude incidence rates of SCD were 12.00 per 1000 person-years (with AF) and 3.82 per 1000 person-years (without AF). The multivariable HRs (95% CIs) of AF for SCD and NSCD were 2.14 (1.60-2.87) and 3.10 (2.58-3.72), respectively. The meta-analyzed HRs (95% CIs) of AF for SCD and NSCD were 2.47 (1.95-3.13) and 2.98 (2.52-3.53), respectively.Incident AF is associated with an increased risk of SCD and NSCD in the general population. Additional research to identify predictors of SCD in patients with AF is warranted.

Background: Studies of cardiac disease among adult survivors of childhood cancer have generally relied on self-reported or registry-based data. Objective: To systematically assess cardiac outcomes among survivors of childhood cancer. Design: Cross-sectional study. Setting: St. Jude Children's Research Hospital. Patients: 1853 adult survivors of childhood cancer, aged 18 years or older, who received cancer-related cardiotoxic therapy at least 10 years earlier. Measurements: Baseline history and physical examination, fasting metabolic and lipid panels, echocardiography, electrocardiography, and 6-minute walk test. Results: One half of the survivors (52.3%) were men with a median age of 8 years (range, 0 to 24 years) at cancer diagnosis and 31 years (range, 18 to 60 years) at evaluation. Cardiomyopathy was present in 7.4% survivors (newly identified at the time of evaluation in 4.7%), coronary artery disease in 3.8% (newly identified in 2.2%), valvular regurgitation or stenosis in 28.0% (newly identified in 24.8%), and conduction or rhythm abnormalities in 4.4% (newly identified in 1.4%). Nearly all survivors were asymptomatic. The prevalence of cardiac conditions increased with age at evaluation, ranging from 3% to 24% among survivors aged 30 to 39 years to 10% to 37% among those aged 40 years or older. In multivariable analysis, survivors exposed to anthracycline doses of 250 mg/m2 or more had greater odds of cardiomyopathy (odds ratio, 2.7 [95% CI, 1.1 to 6.9]) than those who were not exposed. Survivors exposed to heart radiation also had increased odds of cardiomyopathy (odds ratio, 1.9 [CI, 1.1 to 3.7]) compared with those who were not exposed. Radiation exposure greater than 1500 cGy with any anthracycline exposure conferred the greatest odds for valve findings. Limitations: Sixty-one percent of survivors exposed to anthracycline chemotherapy or cardiac-directed radiation participated. A comparison group and longitudinal assessments were not available. Conclusion: Cardiovascular screening identified considerable subclinical disease among adult survivors of childhood cancer. Primary Funding Source: National Cancer Institute, American Lebanese Syrian Associated Charities.

Background: Limited information exists on the lifetime risk of atrial fibrillation (AF) in African Americans and by socioeconomic status. Methods: We studied 15 343 participants without AF at baseline from the ARIC (Atherosclerosis Risk in Communities) cohort recruited in 1987 to 1989 from 4 communities in the United States when they were 45 to 64 years of age. Participants have been followed through 2014. Incidence rates of AF were calculated dividing the number of new cases by person-years of follow-up. Lifetime risk of AF was estimated by a modified Kaplan-Meier method considering death as a competing risk. Participants’ family income and education were obtained at baseline. Results: We identified 2760 AF cases during a mean follow-up of 21 years. Lifetime risk of AF was 36% (95% confidence interval, 32%–38%) in white men, 30% (95% confidence interval, 26%–32%) in white women, 21% (95% confidence interval, 13%–24%) in African American men, and 22% (95% confidence interval, 16%–25%) in African American women. Regardless of race and sex, incidence rates of AF decreased from the lowest to the highest categories of income and education. In contrast, lifetime risk of AF increased in individuals with higher income and education in most sex-race groups. Cumulative incidence of AF was lower in those with higher income and education compared with their low socioeconomic status counterparts through earlier life but was reversed after age 80. Conclusions: Lifetime risk of AF in the ARIC cohort was ≈1 in 3 among whites and 1 in 5 among African Americans. Socioeconomic status was inversely associated with cumulative incidence of AF before the last decades of life.

Masked hypertension and elevated nighttime BP are associated with increased risk of hypertensive target organ damage and adverse cardiovascular and renal outcomes in patients with normal kidney function. The significance of masked hypertension for these risks in patients with CKD is less well defined. The objective of this study was to evaluate the association between masked hypertension and kidney function and markers of cardiovascular target organ damage, and to determine whether this relationship was consistent among those with and without elevated nighttime BP.This was a cross-sectional study. We performed 24-hour ambulatory BP in 1492 men and women with CKD enrolled in the Chronic Renal Insufficiency Cohort Study. We categorized participants into controlled BP, white-coat, masked, and sustained hypertension on the basis of clinic and 24-hour ambulatory BP. We obtained echocardiograms and measured pulse wave velocity in 1278 and 1394 participants, respectively.The percentages of participants with controlled BP, white-coat, masked, and sustained hypertension were 49.3%, 4.1%, 27.8%, and 18.8%, respectively. Compared with controlled BP, masked hypertension independently associated with low eGFR (-3.2 ml/min per 1.73 m(2); 95% confidence interval, -5.5 to -0.9), higher proteinuria (+0.9 unit higher in log2 urine protein; 95% confidence interval, 0.7 to 1.1), and higher left ventricular mass index (+2.52 g/m(2.7); 95% confidence interval, 0.9 to 4.1), and pulse wave velocity (+0.92 m/s; 95% confidence interval, 0.5 to 1.3). Participants with masked hypertension had lower eGFR only in the presence of elevated nighttime BP (-3.6 ml/min per 1.73 m(2); 95% confidence interval, -6.1 to -1.1; versus -1.4 ml/min per 1.73 m(2); 95% confidence interval, -6.9 to 4.0, among those with nighttime BP <120/70 mmHg; P value for interaction with nighttime systolic BP 0.002).Masked hypertension is common in patients with CKD and associated with lower eGFR, proteinuria, and cardiovascular target organ damage. In patients with CKD, ambulatory BP characterizes the relationship between BP and target organ damage better than BP measured in the clinic alone.

Background A growing body of evidence suggests that atrial fibrillation ( AF ) is associated with myocardial infarction ( MI ). However, incidence and management of MI in AF is still undefined. Methods and Results We searched MEDLINE via PubMed and Cochrane database between 1965 and 2015. All observational clinical studies and interventional trials reporting 1‐year incidence of MI in AF were included. We also discussed pathophysiological mechanisms, predictors, and therapeutic approaches to reduce the risk of MI in AF . Twenty‐one observational studies and 10 clinical trials were included. The annual rate of MI in observational studies including AF patients ranged from 0.4% to 2.5%. Higher rates of MI were reported in AF patients with stable coronary artery disease (11.5%/year), vascular disease (4.47%/year), heart failure (2.9%/year), and in those undergoing coronary artery interventions (6.3%/year). However, lower annual rates have been described in AF patients from Eastern countries (0.2–0.3%/year), and in those enrolled in clinical trials (from 0.4 to 1.3%/year). Conclusions AF patients had a significant residual risk of MI despite anticoagulant treatment. Coexistence of atherosclerotic risk factors and platelet activation account for the increased risk of MI in AF . Identification of high‐risk AF patients is a needed first step to develop cost‐effective approaches for prevention. A new score, the 2 MACE score, has been recently developed to stratify MI risk in AF , and may help not only in allocating resources to high‐risk groups, but also in design of studies examining novel therapies for prevention of MI in AF .

<h3>Importance</h3> Race-specific and sex-specific stroke risk varies across the lifespan, yet few reports describe sex differences in stroke risk separately in black individuals and white individuals. <h3>Objective</h3> To examine incidence and risk factors for ischemic stroke by sex for black and white individuals. <h3>Design, Setting, and Participants</h3> This prospective cohort study included participants 45 years and older who were stroke-free from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, enrolled from the continental United States 2003 through 2007 with follow-up through October 2016. Data were analyzed from March 2018 to September 2018. <h3>Exposures</h3> Sex and race. <h3>Main Outcomes and Measures</h3> Physician-adjudicated incident ischemic stroke, self-reported race/ethnicity, and measured and self-reported risk factors. <h3>Results</h3> A total of 25 789 participants (14 170 women [54.9%]; 10 301 black individuals [39.9%]) were included. Over 222 120 person-years of follow-up, 939 ischemic strokes occurred: 159 (16.9%) in black men, 326 in white men (34.7%), 217 in black women (23.1%), and 237 in white women (25.2%). Between 45 and 64 years of age, white women had 32% lower stroke risk than white men (incidence rate ratio [IRR], 0.68 [95% CI, 0.49-0.94]), and black women had a 28% lower risk than black men (IRR, 0.72 [95% CI, 0.52-0.99]). Lower stroke risk in women than men persisted at age 65 through 74 years in white individuals (IRR, 0.71 [95% CI, 0.55-0.94]) but not in black individuals (IRR, 0.94 [95% CI, 0.68-1.30]); however, the race-sex interaction was not significant. At 75 years and older, there was no sex difference in stroke risk for either race. For white individuals, associations of systolic blood pressure (women: hazard ratio [HR], 1.13 [95% CI, 1.05-1.22]; men: 1.04 [95% CI, 0.97-1.11];<i>P</i> = .099), diabetes (women: HR, 1.84 [95% CI, 1.35-2.52]; men: 1.13 [95% CI, 0.86-1.49];<i>P</i> = .02), and heart disease (women: HR, 1.76 [95% CI, 1.30-2.39]; men, 1.26 [95% CI, 0.99-1.60];<i>P</i> = .09) with stroke risk were larger for women than men, while antihypertensive medication use had a smaller association in women than men (women: HR, 1.17 [95% CI, 0.89-1.54]; men: 1.61 [95% CI, 1.29-2.03];<i>P</i> = .08). In black individuals, there was no evidence of a sex difference for any risk factors. <h3>Conclusions and Relevance</h3> For both races, at age 45 through 64 years, women were at lower stroke risk than men, and there was no sex difference at 75 years or older; however, the sex difference pattern may differ by race from age 65 through 74 years. The association of risk factors on stroke risk differed by race-sex groups. While the need for primordial prevention, optimal management, and control of risk factors is universal across all age, racial/ethnic, and sex groups, some demographic subgroups may require earlier and more aggressive strategies.

Background: Atrial myopathy—characterized by changes in left atrial function and size—may precede and promote atrial fibrillation (AF) and cardiac thromboembolism. In people without prior AF or stroke, whether analysis of left atrial function and size can improve ischemic stroke prediction is unknown. Objective: To evaluate the association of echocardiographic left atrial function (reservoir, conduit, and contractile strain) and left atrial size (left atrial volume index) with ischemic stroke and determine whether these measures can improve the stroke prediction achieved by CHA2DS2-VASc score variables. Design: Prospective cohort study. Setting: ARIC (Atherosclerosis Risk in Communities) study. Participants: 4917 ARIC participants without prevalent stroke or AF. Measurements: Ischemic stroke events (2011 to 2019) were adjudicated by physicians. Left atrial strain was measured using speckle-tracking echocardiography. Results: Over 5 years, the cumulative incidences of ischemic stroke in the lowest quintiles of left atrial reservoir, conduit, and contractile strain were 2.99% (95% CI, 1.89% to 4.09%), 3.18% (CI, 2.14% to 4.22%), and 2.15% (CI, 1.09% to 3.21%), respectively, and that of severe left atrial enlargement was 1.99% (CI, 0.23% to 3.75%). On the basis of the Akaike information criterion, left atrial reservoir strain plus CHA2DS2-VASc variables was the best predictive model. With the addition of left atrial reservoir strain to CHA2DS2-VASc variables, 11.6% of the 112 participants with stroke after 5 years were reclassified to higher risk categories and 1.8% to lower risk categories. Among the 4805 participants who did not develop stroke, 12.2% were reclassified to lower and 12.7% to higher risk categories. Decision curve analysis showed a predicted net benefit of 1.34 per 1000 people at a 5-year risk threshold of 5%. Limitation: Underascertainment of subclinical AF. Conclusion: In people without prior AF or stroke, when added to CHA2DS2-VASc variables, left atrial reservoir strain improves stroke prediction and yields a predicted net benefit, as shown by decision curve analysis. Primary Funding Source: National Heart, Lung, and Blood Institute of the National Institutes of Health.

Importance Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation. Objective To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy. Design, Setting, and Participants Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 μV × ms in electrocardiogram lead V 1 , serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m 2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium. Interventions Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508). Main Outcomes and Measures The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage. Results With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52]). Conclusions and Relevance In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin. Trial Registration ClinicalTrials.gov Identifier: NCT03192215

Type 2 diabetes has been inconsistently associated with the risk of atrial fibrillation (AF) in previous studies that have frequently been beset by methodological challenges.Prospective cohort study.The Atherosclerosis Risk in Communities (ARIC) study.Detailed medical histories were obtained from 13 025 participants. Individuals were categorised as having no diabetes, pre-diabetes or diabetes based on the 2010 American Diabetes Association criteria at study baseline (1990-2).Diagnoses of incident AF were obtained to the end of 2007. Associations between type 2 diabetes and markers of glucose homeostasis and the incidence of AF were estimated using Cox proportional hazards models after adjusting for possible confounders.Type 2 diabetes was associated with a significant increase in the risk of AF (HR 1.35, 95% CI 1.14 to 1.60) after adjustment for confounders. There was no indication that individuals with pre-diabetes or those with undiagnosed diabetes were at increased risk of AF compared with those without diabetes. A positive linear association was observed between HbA1c and the risk of AF in those with and without diabetes (HR 1.13, 95% CI 1.07 to 1.20) and HR 1.05, 95% CI 0.96 to 1.15 per 1% point increase, respectively). There was no association between fasting glucose or insulin in those without diabetes, but a significant association with fasting glucose was found in those with the condition. The results were similar in white subjects and African-Americans.Diabetes, HbA1c level and poor glycaemic control are independently associated with an increased risk of AF, but the underlying mechanisms governing the relationship are unknown and warrant further investigation.

Black/white disparities in stroke incidence are well documented, but few studies have assessed the contributions to the disparity. Here we assess the contribution of "traditional" risk factors.A total of 25 714 black and white men and women, aged≥45 years and stroke-free at baseline, were followed for an average of 4.4 years to detect stroke. Mediation analysis using proportional hazards analysis assessed the contribution of traditional risk factors to racial disparities.At age 45 years, incident stroke risk was 2.90 (95% CI: 1.72-4.89) times more likely in blacks than in whites and 1.66 (95% CI: 1.34-2.07) times at age 65 years. Adjustment for risk factors attenuated these excesses by 40% and 45%, respectively, resulting in relative risks of 2.14 (95% CI: 1.25-3.67) and 1.35 (95% CI: 1.08-1.71). Approximately one half of this mediation is attributable to systolic blood pressure. Further adjustment for socioeconomic factors resulted in total mediation of 47% and 53% to relative risks of 2.01 (95% CI: 1.16-3.47) and 1.30 (1.03-1.65), respectively.Between ages 45 to 65 years, approximately half of the racial disparity in stroke risk is attributable to traditional risk factors (primarily systolic blood pressure) and socioeconomic factors, suggesting a critical need to understand the disparity in the development of these traditional risk factors. Because half of the excess stroke risk in blacks is not attributable to traditional risk factors and socioeconomic factors, differential impact of risk factors, residual confounding, or nontraditional risk factors may also play a role.

The metabolic syndrome (MetSyn) has been implicated in the development of atrial fibrillation (AF); however, knowledge of this association among blacks is limited. We determined the risk of incident AF through December 2005 in relation to baseline (1987-1989) MetSyn status in 15,094 participants of the Atherosclerosis Risk in Communities study. Over a mean follow-up of 15.4 years, 1,238 incident AF events were identified. The hazard ratio (HR) for AF among individuals with, compared to those without, the MetSyn was 1.67 (95% CI 1.49-1.87), and associations did not differ by race (P for interaction = .73). The population attributable risk of AF from the MetSyn was 22%. The multivariable-adjusted HRs (95% CI) for each MetSyn component were 1.95 (1.72-2.21) (elevated blood pressure), 1.40 (1.23-1.59) (elevated waist circumference), 1.20 (1.06-1.37) (low high-density lipoprotein cholesterol), 1.16 (1.03-1.31) (impaired fasting glucose), and 0.95 (0.84-1.09) (elevated triglycerides). A monotonically increasing risk of AF with increasing number of MetSyn components was observed, with an HR of 4.40 (95% CI 3.25-5.94) for those with all 5 MetSyn components compared to those with 0 components. In this large cohort, the MetSyn and most of its components were associated with a higher risk of AF in both blacks and whites. Given the high prevalence of the MetSyn, strategies to prevent its development or to control individual components may reduce the burden of AF.

Spatial QRS/T angle and spatial T-wave axis were shown to be strong independent predictors of incident coronary heart disease (CHD) and total mortality, but they are not routinely available. We evaluated whether frontal plane QRS/T angle, easily obtained as the difference between frontal plane axes of QRS and T, provides a suitable substitute for spatial QRS/T angle as a risk predictor. Our study consisted of 13,973 participants from the ARIC Study. Outcome variables were incident CHD and total mortality during a median follow-up of 14 years. Electrocardiographic variables were categorized as abnormal (>/=95th percentile), borderline (>/=75th and <95th percentile), and normal (<75th percentile) separately for men and women. Cox regression was used to assess the effect of electrocardiographic variables on risk of each outcome. The normal category was considered the reference cell. With adjustment for demographic and clinical characteristics, both QRS/T angles were approximately equally strong predictors of total mortality with >50% increased risk. Spatial QRS/T angle was a stronger predictor of incident CHD in women, with a 114% increased risk, but it was not significantly associated with risk of incident CHD in men. Similarly, frontal plane QRS/T angle was statistically significant for only women with a 74% increased risk of incident CHD. In conclusion, frontal plane QRS/T angle as an easily derived risk measure is a suitable clinical substitute for spatial QRS/T angle for risk prediction.

Background and Purpose— Warfarin reduces stroke risk by approximately 60% in patients with atrial fibrillation (AF). Differences in awareness and treatment of AF may contribute to racial and geographic disparities in stroke mortality. The objective was to examine predictors of awareness of the diagnosis of AF and treatment with warfarin. Methods— RE asons for G eographic a nd R acial D ifferences in S troke (REGARDS) is a national, population-based, longitudinal study of 30 239 blacks and whites ≥45 years old with oversampling from blacks and the southeastern stroke belt states. Participants were enrolled January 2003 to October 2007. Data were collected using telephone interview, in-home evaluation, and self-administered questionnaires. The main variable of awareness of AF was defined by a positive answer to “Has a doctor or other health professional ever told you that you had atrial fibrillation?” and whether there was evidence of treatment on the basis of an in-home medications inventory. Results— From baseline electrocardiograms, 432 individuals (88 black and 344 white) had AF. Of these, 88% (360 of 409) had at least 1 additional CHADS 2 stroke risk factor and 60% (258 of 432) were aware of their AF. The odds of blacks being aware of their AF were one third that of whites (OR=0.32; 95% CI: 0.20 to 0.52). Among those aware, the odds of blacks being treated with warfarin were only one fourth as great as whites (OR=0.28; 0.13 to 0.60). Conclusion— Blacks were less likely than whites to be aware of having AF or to be treated with warfarin. Potential reasons for the racial disparity in warfarin treatment warrant further investigation.

•Intensive glycemic control did not alter the rate of incident AF. •The investigators describe a number of predictors of AF in patients with diabetes. •Incident AF is associated with adverse outcomes in patients with diabetes. Atrial fibrillation (AF) is prevalent in patients with type 2 diabetes mellitus (DM) and is associated with markers of poor glycemic control; however, the impact of glycemic control on incident AF and outcomes is unknown. The aims of this study were to prospectively evaluate if intensive glycemic control in patients with DM affects incident AF and to evaluate morbidity and mortality in patients with DM and incident AF. A total of 10,082 patients with DM from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) cohort were studied in a randomized, double-blind fashion. Participants were randomized to an intensive therapeutic strategy targeting a glycated hemoglobin level of <6.0% or a standard strategy targeting a glycated hemoglobin level of 7.0% to 7.9%. Incident AF occurred in 159 patients (1.58%) over the follow-up period, at a rate of 5.9 per 1,000 patient-years in the intensive-therapy group and a rate of 6.37 per 1,000 patient-years in the standard-therapy group (p = 0.52). In a multivariate model, predictors of incident AF were age, weight, diastolic blood pressure, heart rate, and heart failure history. Patients with DM and new-onset AF had a hazard ratio of 2.65 for all-cause mortality (95% confidence interval 1.8 to 3.86, p <0.0001), a hazard ratio of 2.1 for myocardial infarction (95% confidence interval 1.33 to 3.31, p = 0.0015), and a hazard ratio of 3.80 for the development of heart failure (95% confidence interval 2.48 to 5.84, p <0.0001). In conclusion, intensive glycemic control did not affect the rate of new-onset AF. Patients with DM and incident AF had an increased risk for morbidity and mortality compared with those without AF. Atrial fibrillation (AF) is prevalent in patients with type 2 diabetes mellitus (DM) and is associated with markers of poor glycemic control; however, the impact of glycemic control on incident AF and outcomes is unknown. The aims of this study were to prospectively evaluate if intensive glycemic control in patients with DM affects incident AF and to evaluate morbidity and mortality in patients with DM and incident AF. A total of 10,082 patients with DM from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) cohort were studied in a randomized, double-blind fashion. Participants were randomized to an intensive therapeutic strategy targeting a glycated hemoglobin level of <6.0% or a standard strategy targeting a glycated hemoglobin level of 7.0% to 7.9%. Incident AF occurred in 159 patients (1.58%) over the follow-up period, at a rate of 5.9 per 1,000 patient-years in the intensive-therapy group and a rate of 6.37 per 1,000 patient-years in the standard-therapy group (p = 0.52). In a multivariate model, predictors of incident AF were age, weight, diastolic blood pressure, heart rate, and heart failure history. Patients with DM and new-onset AF had a hazard ratio of 2.65 for all-cause mortality (95% confidence interval 1.8 to 3.86, p <0.0001), a hazard ratio of 2.1 for myocardial infarction (95% confidence interval 1.33 to 3.31, p = 0.0015), and a hazard ratio of 3.80 for the development of heart failure (95% confidence interval 2.48 to 5.84, p <0.0001). In conclusion, intensive glycemic control did not affect the rate of new-onset AF. Patients with DM and incident AF had an increased risk for morbidity and mortality compared with those without AF.

Emerging data suggest that left atrial disease may cause ischemic stroke in the absence of atrial fibrillation or flutter (AF). If true, this condition may provide a cause for many strokes currently classified as cryptogenic.Among 6741 participants in the Multi-Ethnic Study of Atherosclerosis who were free of clinically apparent cerebrovascular or cardiovascular disease (including AF) at baseline, we examined the association between markers of left atrial abnormality on a standard 12-lead ECG-specifically P-wave area, duration, and terminal force in lead V1-and the subsequent risk of ischemic stroke while accounting for incident AF.During a median follow-up of 8.5 years, 121 participants (1.8%) had a stroke and 541 participants (8.0%) were diagnosed with AF. In Cox proportional hazards models adjusting for potential baseline confounders, P-wave terminal force in lead V1 was more strongly associated with incident stroke (hazard ratio per 1 SD increase, 1.21; 95% confidence interval, 1.02-1.44) than with incident AF (hazard ratio per 1 SD, 1.11; 95% confidence interval, 1.03-1.21). The association between P-wave terminal force in lead V1 and stroke was robust in numerous sensitivity analyses accounting for AF, including analyses that excluded those with any incident AF or modeled any incident AF as having been present from baseline.We found an association between baseline P-wave morphology and incident stroke even after accounting for AF. This association may reflect an atrial cardiopathy that leads to stroke in the absence of AF.

Several cardiovascular risk factors have been associated with the risk of atrial fibrillation (AF). Limited and inconsistent evidence exists on the association of blood lipid levels and lipid-lowering medication use with AF risk.We analyzed 13 969 participants (25% African American, 45% men) free of AF at baseline from the Atherosclerosis Risk in Communities study. Fasting high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglycerides, and total cholesterol were measured at baseline (1987-1989) and each of 3 follow-up visits. The incidence of AF was ascertained through 2007. The association of the use of statins and other lipid-lowering medications with AF was estimated in 13 044 Atherosclerosis Risk in Communities participants attending visit 2 (1990-1992), adjusting for covariates from the previous visit. During a median follow-up of 18.7 years, there were 1433 incident AF cases. Multivariable hazard ratios (HRs) and 95% CIs of AF associated with a 1-SD increase in lipid levels were as follows: HDLc, 0.97 (0.91-1.04); LDLc, 0.90 (0.85-0.96); total cholesterol, 0.89 (0.84-0.95); and triglycerides, 1.00 (0.96-1.04). Participants taking lipid-lowering medications had an adjusted HR (95% CI) of AF of 0.96 (0.82-1.13) compared with those not taking medications, whereas those taking statins had an adjusted HR of 0.91 (0.66-1.25) compared with those taking other lipid-lowering medications.Higher levels of LDLc and total cholesterol were associated with a lower incidence of AF. However, HDLc and triglycerides were not independently associated with AF incidence. No association was found between the use of lipid-lowering medications and incident AF.

It is currently unknown whether intensive blood pressure (BP) lowering beyond that recommended would lead to more lowering of the risk of left ventricular hypertrophy (LVH) in patients with hypertension and whether reducing the risk of LVH explains the reported cardiovascular disease (CVD) benefits of intensive BP lowering in this population.This analysis included 8164 participants (mean age, 67.9 years; 35.3% women; 31.2% blacks) with hypertension but no diabetes mellitus from the SPRINT trial (Systolic Blood Pressure Intervention Trial): 4086 randomly assigned to intensive BP lowering (target SBP <120 mm Hg) and 4078 assigned to standard BP lowering (target SBP <140 mm Hg). Progression and regression of LVH as defined by Cornell voltage criteria derived from standard 12-lead ECGs recorded at baseline and biannually were compared between treatment arms during a median follow-up of 3.81 years. The effect of intensive (versus standard) BP lowering on the SPRINT primary CVD outcome (a composite of myocardial infarction, acute coronary syndrome, stroke, heart failure, and CVD death) was compared before and after adjustment for LVH as a time-varying covariate.Among SPRINT participants without baseline LVH (n=7559), intensive (versus standard) BP lowering was associated with a 46% lower risk of developing LVH (hazard ratio=0.54; 95% confidence interval, 0.43-0.68). Similarly, among SPRINT participants with baseline LVH (n=605, 7.4%), those assigned to the intensive (versus standard) BP lowering were 66% more likely to regress/improve their LVH (hazard ratio=1.66; 95% confidence interval, 1.31-2.11). Adjustment for LVH as a time-varying covariate did not substantially attenuate the effect of intensive BP therapy on CVD events (hazard ratio of intensive versus standard BP lowering on CVD, 0.76 [95% confidence interval, 0.64-0.90] and 0.77 [95% confidence interval, 0.65-0.91] before and after adjustment for LVH as a time-varying covariate, respectively).Among patients with hypertension but no diabetes mellitus, intensive BP lowering (target systolic BP <120 mm Hg) compared with standard BP lowering (target systolic BP <140 mm Hg) resulted in lower rates of developing new LVH in those without LVH and higher rates of regression of LVH in those with existing LVH. This favorable effect on LVH did not explain most of the reduction in CVD events associated with intensive BP lowering in the SPRINT trial.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062.

Asymptomatic individuals account for the majority of sudden cardiac deaths (SCDs). Development of effective, low-cost, and noninvasive SCD risk stratification tools is necessary.Participants from the Atherosclerosis Risk in Communities study and Cardiovascular Health Study (n=20 177; age, 59.3±10.1 years; age range, 44-100 years; 56% female; 77% white) were followed up for 14.0 years (median). Five ECG markers of global electric heterogeneity (GEH; sum absolute QRST integral, spatial QRST angle, spatial ventricular gradient [SVG] magnitude, SVG elevation, and SVG azimuth) were measured on standard 12-lead ECGs. Cox proportional hazards and competing risks models evaluated associations between GEH electrocardiographic parameters and SCD. An SCD competing risks score was derived from demographics, comorbidities, and GEH parameters. SCD incidence was 1.86 per 1000 person-years. After multivariable adjustment, baseline GEH parameters and large increases in GEH parameters over time were independently associated with SCD. Final SCD risk scores included age, sex, race, diabetes mellitus, hypertension, coronary heart disease, stroke, and GEH parameters as continuous variables. When GEH parameters were added to clinical/demographic factors, the C statistic increased from 0.777 to 0.790 (P=0.008), the risk score classified 10-year SCD risk as high (>5%) in 7.2% of participants, 10% of SCD victims were appropriately reclassified into a high-risk category, and only 1.4% of SCD victims were inappropriately reclassified from high to intermediate risk. The net reclassification index was 18.3%.Abnormal electrophysiological substrate quantified by GEH parameters is independently associated with SCD in the general population. The addition of GEH parameters to clinical characteristics improves SCD risk prediction.

Electrocardiographic left atrial abnormality has been associated with stroke independently of atrial fibrillation (AF), suggesting that atrial thromboembolism may occur in the absence of AF. If true, we would expect an association with cryptogenic or cardioembolic stroke rather than noncardioembolic stroke.We conducted a case-cohort analysis in the Northern Manhattan Study, a prospective cohort study of stroke risk factors. P-wave terminal force in lead V1 was manually measured from baseline ECGs of participants in sinus rhythm who subsequently had ischemic stroke (n=241) and a randomly selected subcohort without stroke (n=798). Weighted Cox proportional hazard models were used to examine the association between P-wave terminal force in lead V1 and stroke etiologic subtypes while adjusting for baseline demographic characteristics, history of AF, heart failure, diabetes mellitus, hypertension, tobacco use, and lipid levels.Mean P-wave terminal force in lead V1 was 4452 (±3368) μV*ms among stroke cases and 3934 (±2541) μV*ms in the subcohort. P-wave terminal force in lead V1 was associated with ischemic stroke (adjusted hazard ratio per SD, 1.20; 95% confidence interval, 1.03-1.39) and the composite of cryptogenic or cardioembolic stroke (adjusted hazard ratio per SD, 1.31; 95% confidence interval, 1.08-1.58). There was no definite association with noncardioembolic stroke subtypes (adjusted hazard ratio per SD, 1.14; 95% confidence interval, 0.92-1.40). Results were similar after excluding participants with a history of AF at baseline or new AF during follow-up.ECG-defined left atrial abnormality was associated with incident cryptogenic or cardioembolic stroke independently of the presence of AF, suggesting atrial thromboembolism may occur without recognized AF.

The adverse outcomes associated with atrial fibrillation (AF) have been studied in predominantly white cohorts. Racial differences in outcomes associated with AF merit continued investigation.To evaluate the race-specific associations of AF with stroke, heart failure, coronary heart disease (CHD), and all-cause mortality in a community-based cohort.The Atherosclerosis Risk in Communities (ARIC) Study is a prospective, observational cohort. From 1987 through 1989, the ARIC Study enrolled 15 792 men and women and conducted 4 follow-up examinations (2011-2013) with active surveillance for vital status and hospitalizations. Race was determined by self-report and categorized as white, black, or other.Atrial fibrillation (adjudicated using electrocardiograms, hospital discharge codes, and death certificates), stroke, heart failure, CHD, and mortality.After exclusions, 15 080 participants (mean [SD] age, 54.2 [5.8] years; 8290 women [55.5%]; 3831 black individuals [25.4%]) were included in this analysis. During a mean (SD) follow-up of 20.6 (6.2) years, there were 2348 cases of incident AF. The incident rates of AF per 1000 person-years were 8.1 (95% CI, 7.7-8.5) in white individuals and 5.8 (95% CI, 5.2-6.3) in black individuals. The rates of stroke, heart failure, CHD, and mortality were higher in black individuals with AF than white individuals with AF. The association of AF with these outcomes, estimated with rate differences (rate of the end point in those with AF minus the rate in those without AF per 1000 person-years), also differed by race. The rate difference for stroke in individuals with AF was 10.2 (95% CI, 6.6-13.9) in white individuals and 21.4 (95% CI, 10.2-32.6) in black individuals. For heart failure and CHD, the rate differences were 1.5- to 2.0-fold higher in black individuals than white individuals. White individuals with AF had a rate difference of 55.9 (95% CI, 48.1-63.7) for mortality compared with black individuals, who had a rate difference of 106.0 (95% CI, 86.0-125.9).In the prospective ARIC Study, the outcome of AF on the rates of stroke, heart failure, CHD, and mortality was considerably larger in black individuals than white individuals. These results indicate the vulnerability and increased risk in black individuals with AF. Continued investigation of racial differences in AF and its related adverse outcomes are essential to identify and mitigate racial disparities in the treatment of AF.

Cardiac autonomic perturbations frequently antecede onset of paroxysmal atrial fibrillation (AF). Interventions that influence autonomic inputs to myocardium may prevent AF. However, whether low heart rate or heart rate variability (HRV), which are noninvasive measures of cardiac autonomic dysfunction, are associated with AF incidence is unclear.This study sought to study the association between HRV and risk of AF.This study included 11,715 middle-aged adults in the ARIC (Atherosclerosis Risk In Communities) cohort with heart rate and HRV measures obtained from 2-min electrocardiogram recordings performed at baseline (1987 to 1989). These measures included SD of normal-to-normal RR intervals, high-frequency (HF) (0.15 to 0.40 Hz), low-frequency (0.04 to 0.15 Hz), and the low-frequency/HF ratio (denoting a greater sympathetic to parasympathetic dominance). Incident AF cases were ascertained by electrocardiogram at ARIC follow-up visits, hospital discharge diagnosis, or death certificates through 2011.During an average follow-up of 19.4 years, 1,580 or 13.5% of participants developed AF. A baseline heart rate <60 beats/min was associated modestly with an increased risk of AF. Lower overall HRV as well as increased sympathetic/parasympathetic tone were associated independently with a higher risk of AF; the hazard ratio for each 1 SD lower SD of normal-to-normal RR intervals was 1.14 (95% confidence interval: 1.08 to 1.21), for HF was 1.12 (95% confidence interval: 1.06 to 1.17), and for low frequency/HF was 1.08 (95% confidence interval: 1.03 to 1.14).Cardiac autonomic dysfunction denoted by low resting short-term HRV was associated with higher AF incidence. A low heart rate may be associated with higher AF risk. Further studies are needed to determine whether interventions in the general population to restore autonomic balance may prevent AF.

The aim of this study was to assess the relationship between abnormally increased P-wave terminal force in lead V1 , an electrocardiographic (ECG) marker of left atrial abnormality, and incident ischemic stroke subtypes. We hypothesized that associations would be stronger with nonlacunar stroke, given that we expected left atrial abnormality to reflect the risk of thromboembolism rather than in situ cerebral small-vessel occlusion.Our cohort comprised 14,542 participants 45 to 64 years of age prospectively enrolled in the Atherosclerosis Risk in Communities study and free of clinically apparent atrial fibrillation (AF) at baseline. Left atrial abnormality was defined as PTFV1 >4,000μV*ms. Outcomes were adjudicated ischemic stroke, nonlacunar (including cardioembolic) ischemic stroke, and lacunar stroke.During a median follow-up period of 22 years (interquartile range, 19-23 years), 904 participants (6.2%) experienced a definite or probable ischemic stroke. A higher incidence of stroke occurred in those with baseline left atrial abnormality (incidence rate per 1,000 person-years, 6.3; 95% confidence interval [CI]: 5.4-7.4) than in those without (incidence rate per 1,000 person-years, 2.9; 95% CI: 2.7-3.1; p < 0.001). In Cox regression models adjusted for potential confounders and incident AF, left atrial abnormality was associated with incident ischemic stroke (hazard ratio [HR]: 1.33; 95% CI: 1.11-1.59). This association was limited to nonlacunar stroke (HR, 1.49; 95% CI: 1.07-2.07) as opposed to lacunar stroke (HR, 0.89; 95% CI: 0.57-1.40).We found an association between ECG-defined left atrial abnormality and subsequent nonlacunar ischemic stroke. Our findings suggest that an underlying atrial cardiopathy may cause left atrial thromboembolism in the absence of recognized AF.

Although advanced interatrial block (aIAB) is an established electrocardiographic phenotype, its prevalence, incidence, and prognostic significance in the general population are unclear. We examined the prevalence, incidence, and prognostic significance of aIAB in 14,625 (mean age = 54 ± 5.8 years; 26% black; 55% female) participants from the Atherosclerosis Risk in Communities (ARIC) study. aIAB was detected from digital electrocardiograms recorded during 4 study visits (1987 to 1989, 1990 to 1992, 1993 to 1995, and 1996 to 1998). Risk factors for the development of aIAB were examined using multivariable Poisson regression models with robust variance estimates. Cox regression was used to compute hazard ratios and 95% CIs for the association between aIAB, as a time-dependent variable, and atrial fibrillation (AF). AF was ascertained from study electrocardiogram data, hospital discharge records, and death certificates thorough 2010. A total of 69 participants (0.5%) had aIAB at baseline, and 193 (1.3%) developed aIAB during follow-up. The incidence for aIAB was 2.27 (95% CI 1.97 to 2.61) per 1,000 person-years. Risk factors for aIAB development included age, male gender, white race, antihypertensive medication use, low-density lipoprotein cholesterol, body mass index, and systolic blood pressure. In a Cox regression analysis adjusted for sociodemographics, cardiovascular risk factors, and potential confounders, aIAB was associated with an increased risk for AF (hazard ratio 3.09, 95% CI 2.51 to 3.79). In conclusion, aIAB is not uncommon in the general population. Risk factors for developing aIAB are similar to those for AF, and the presence of aIAB is associated with an increased risk for AF. Although advanced interatrial block (aIAB) is an established electrocardiographic phenotype, its prevalence, incidence, and prognostic significance in the general population are unclear. We examined the prevalence, incidence, and prognostic significance of aIAB in 14,625 (mean age = 54 ± 5.8 years; 26% black; 55% female) participants from the Atherosclerosis Risk in Communities (ARIC) study. aIAB was detected from digital electrocardiograms recorded during 4 study visits (1987 to 1989, 1990 to 1992, 1993 to 1995, and 1996 to 1998). Risk factors for the development of aIAB were examined using multivariable Poisson regression models with robust variance estimates. Cox regression was used to compute hazard ratios and 95% CIs for the association between aIAB, as a time-dependent variable, and atrial fibrillation (AF). AF was ascertained from study electrocardiogram data, hospital discharge records, and death certificates thorough 2010. A total of 69 participants (0.5%) had aIAB at baseline, and 193 (1.3%) developed aIAB during follow-up. The incidence for aIAB was 2.27 (95% CI 1.97 to 2.61) per 1,000 person-years. Risk factors for aIAB development included age, male gender, white race, antihypertensive medication use, low-density lipoprotein cholesterol, body mass index, and systolic blood pressure. In a Cox regression analysis adjusted for sociodemographics, cardiovascular risk factors, and potential confounders, aIAB was associated with an increased risk for AF (hazard ratio 3.09, 95% CI 2.51 to 3.79). In conclusion, aIAB is not uncommon in the general population. Risk factors for developing aIAB are similar to those for AF, and the presence of aIAB is associated with an increased risk for AF. Interatrial Block to Guide the Thromboembolic Prevention Strategy: Should It be the Next Step?American Journal of CardiologyVol. 120Issue 3PreviewWe read with great interest the study by O'Neal et al recently published in the American Journal of Cardiology.1 This is the largest epidemiological prospective observational study which explored the arrhythmogenic potential of advanced interatrial block (aIAB). The investigators demonstrated that aIAB was associated with a significantly increased risk for atrial fibrillation (AF) after adjustment for sociodemographics and other cardiovascular risk factors. An additional potential area of exploration in this large patient cohort would be to determine the thromboembolic association of aIAB. Full-Text PDF

Background and Purpose— Emerging evidence suggests that an underlying atrial cardiopathy may result in thromboembolism before atrial fibrillation (AF) develops. We examined the association between various markers of atrial cardiopathy and the risk of ischemic stroke. Methods— The CHS (Cardiovascular Health Study) prospectively enrolled community-dwelling adults ≥65 years of age. For this study, we excluded participants diagnosed with stroke or AF before baseline. Exposures were several markers of atrial cardiopathy: baseline P-wave terminal force in ECG lead V 1 , left atrial dimension on echocardiogram, and N terminal pro B type natriuretic peptide (NT-proBNP), as well as incident AF. Incident AF was ascertained from 12-lead electrocardiograms at annual study visits for the first decade after study enrollment and from inpatient and outpatient Medicare data throughout follow-up. The primary outcome was incident ischemic stroke. We used Cox proportional hazards models that included all 4 atrial cardiopathy markers along with adjustment for demographic characteristics and established vascular risk factors. Results— Among 3723 participants who were free of stroke and AF at baseline and who had data on all atrial cardiopathy markers, 585 participants (15.7%) experienced an incident ischemic stroke during a median 12.9 years of follow-up. When all atrial cardiopathy markers were combined in 1 Cox model, we found significant associations with stroke for P-wave terminal force in ECG lead V 1 (hazard ratio per 1000 μV*ms 1.04; 95% confidence interval, 1.001–1.08), log-transformed NT-proBNP (hazard ratio per doubling of NT-proBNP, 1.09; 95% confidence interval, 1.03–1.16), and incident AF (hazard ratio, 2.04; 95% confidence interval, 1.67–2.48) but not left atrial dimension (hazard ratio per cm, 0.96; 95% confidence interval, 0.84–1.10). Conclusions— In addition to clinically apparent AF, other evidence of abnormal atrial substrate is associated with subsequent ischemic stroke. This finding is consistent with the hypothesis that thromboembolism from the left atrium may occur in the setting of several different manifestations of atrial disease.

Left ventricular mass is a strong predictor of cardiovascular disease (CVD), and magnetic resonance imaging (MRI) of the heart is a standard of reference for left ventricular mass measurement. Ethnicity is believed to affect electrocardiographic (ECG) performance. We evaluated the diagnostic and prognostic performance of ECG for left ventricular hypertrophy (LVH) as defined by MRI in relationship to ethnicity. Data were analyzed from 4,967 participants (48% men, mean age 62 ± 10 years; 39% white, 13% Chinese, 26% African American, 22% Hispanic) enrolled in the Multi-Ethic Study of Atherosclerosis (MESA) who were followed for a median of 4.8 years for incident CVD. Thirteen traditional ECG-LVH criteria were assessed, and showed overall and ethnicity-specific low sensitivity (10%-26%) and high specificity (88%-99%) in diagnosing MRI-defined LVH. Ten of 13 ECG-LVH criteria showed superior sensitivity and diagnostic performance in African Americans as compared with whites (P = .02-.001). The sum of amplitudes of S wave in V1, S wave in V2, and R wave in V5 (a MESA-specific ECG-LVH criterion) offered higher sensitivity (40.4%) compared with prior ECG-LVH criteria while maintaining good specificity (90%) and diagnostic performance (receiver operating characteristic area = 0.65). In fully adjusted models, only the MESA-specific ECG-LVH criterion, Romhilt-Estes score, Framingham score, Cornell voltage, Cornell duration product, and Framingham-adjusted Cornell voltage predicted increased CVD risk (P < .05). Electrocardiography has low sensitivity but high specificity for detecting MRI-defined LVH. The performance of ECG for LVH detection varies by ethnicity, with African Americans showing higher sensitivity and overall performance compared with other ethnic groups.

The association between physiologic levels of sex hormones and QT-interval duration in humans was evaluated using data from 727 men enrolled in the Third National Health and Nutrition Examination Survey and 2,942 men and 1,885 postmenopausal women enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). Testosterone, estradiol, and sex hormone-binding globulin levels were measured in serum and free testosterone was calculated from those values. QT interval was measured using a standard 12-lead electrocardiogram. In men from the Third National Health and Nutrition Survey, the multivariate adjusted differences in average QT-interval duration comparing the highest quartiles with the lowest quartiles of total testosterone and free testosterone were −8.5 ms (95% confidence interval (CI): −15.5, −1.4) and −8.0 ms (95% CI: −13.2, −2.8), respectively. The corresponding differences were −1.8 ms (95% CI: −3.8, −0.2), and −4.7 ms (95% CI: −6.7, −2.6), respectively, in men from MESA and −0.6 ms (95% CI: −3.0, 1.8) and 0.8 ms (95% CI: −1.6, 3.3), respectively, in postmenopausal women from MESA. Estradiol levels were not associated with QT-interval duration in men, but there was a marginally significant positive association in postmenopausal women. The findings suggest that testosterone levels may explain differences in QT-interval duration between men and women and could be a contributor to population variability in QT-interval duration among men.

Electrocardiographic bundle branch block (BBB) has higher cardiac and all-cause death. However, reports on the association between BBBs and mortality in the general populations are conflicting. The aim of this study was to evaluate the risk for coronary heart disease (CHD) and all-cause death associated with left BBB (LBBB) and right BBB (RBBB) during 14 years of follow-up in 66,450 participants from the Women's Health Initiative (WHI) study. Cox proportional-hazards regression was performed for mortality risk in Women with LBBB (n = 714) and those with RBBB (n = 832). In risk models adjusted for demographic and clinical risk factors in women with cardiovascular disease (CVD), hazard ratios for CHD death were 2.92 (95% confidence interval 2.08 to 4.08, p <0.001) for LBBB and 1.62 (95% confidence interval 1.08 to 2.43, p <0.05) for RBBB, and only LBBB was a significant predictor of all-cause death (hazard ratio 1.43, 95% confidence interval 1.11 to 1.83, p <0.01). In CVD-free women, only LBBB was a significant predictor of CHD death (fully adjusted hazard ratio 2.17, 95% confidence interval 1.37 to 3.43, p <0.01), and neither blocks was predictive of all-cause death. From several repolarization variables that were significant mortality predictors in univariate risk models, after adjustment for other electrocardiographic covariates and risk factors, ST J-point depression in lead aVL ≤−30 μV in women with LBBB was an independent predictor of CHD death, with a more than fivefold increase in risk. None of the repolarization variables were independent predictors in women with RBBB. In conclusion, prevalent LBBB in CVD-free women and LBBB and RBBB in women with CVD were significant predictors of CHD death. In women with LBBB, ST J-point depression in lead aVL was a strong independent predictor of CHD death. Electrocardiographic bundle branch block (BBB) has higher cardiac and all-cause death. However, reports on the association between BBBs and mortality in the general populations are conflicting. The aim of this study was to evaluate the risk for coronary heart disease (CHD) and all-cause death associated with left BBB (LBBB) and right BBB (RBBB) during 14 years of follow-up in 66,450 participants from the Women's Health Initiative (WHI) study. Cox proportional-hazards regression was performed for mortality risk in Women with LBBB (n = 714) and those with RBBB (n = 832). In risk models adjusted for demographic and clinical risk factors in women with cardiovascular disease (CVD), hazard ratios for CHD death were 2.92 (95% confidence interval 2.08 to 4.08, p <0.001) for LBBB and 1.62 (95% confidence interval 1.08 to 2.43, p <0.05) for RBBB, and only LBBB was a significant predictor of all-cause death (hazard ratio 1.43, 95% confidence interval 1.11 to 1.83, p <0.01). In CVD-free women, only LBBB was a significant predictor of CHD death (fully adjusted hazard ratio 2.17, 95% confidence interval 1.37 to 3.43, p <0.01), and neither blocks was predictive of all-cause death. From several repolarization variables that were significant mortality predictors in univariate risk models, after adjustment for other electrocardiographic covariates and risk factors, ST J-point depression in lead aVL ≤−30 μV in women with LBBB was an independent predictor of CHD death, with a more than fivefold increase in risk. None of the repolarization variables were independent predictors in women with RBBB. In conclusion, prevalent LBBB in CVD-free women and LBBB and RBBB in women with CVD were significant predictors of CHD death. In women with LBBB, ST J-point depression in lead aVL was a strong independent predictor of CHD death.

Background Previous studies have reported that atrial fibrillation ( AF ) is associated with cognitive decline and dementia. These studies, however, had limited follow‐up, were based mostly on white and highly selected populations, and did not account for attrition. We evaluated the association of incident AF with 20‐year change in cognitive performance (accounting for attrition) and incident dementia in the ARIC (Atherosclerosis Risk in Communities) Study. Methods and Results We analyzed data from 12 515 participants (mean age, 56.9 [ SD , 5.7] years in 1990–1992; 56% women and 24% black) from 1990 to 1992 through 2011 to 2013. Incident AF was ascertained from study ECG s and hospital discharge codes. Cognitive tests were performed in 1990 to 1992, 1996 to 1998, and 2011 to 2013. Incident dementia was clinician adjudicated. We used generalized estimating equations and Cox proportional hazards models to assess the association of time‐dependent AF with change in Z scores of cognitive tests and incident dementia, respectively. During 20 years, 2106 participants developed AF and 1157 participants developed dementia. After accounting for cardiovascular risk factors, including ischemic stroke, the average decline over 20 years in global cognitive Z score was 0.115 (95% confidence interval, 0.014–0.215) greater in participants with AF than in those without AF . Further adjustment for attrition by multiple imputation by chained equations strengthened the association. In addition, incident AF was associated with an increased risk of dementia (hazard ratio, 1.23; 95% confidence interval, 1.04–1.45), after adjusting for cardiovascular risk factors, including ischemic stroke. Conclusions AF is associated with greater cognitive decline and increased risk of dementia, independent of ischemic stroke. Because cognitive decline is a precursor to dementia, our findings prompt further investigation to identify specific treatments for AF that will delay the trajectory of cognitive decline and, thus, prevent dementia in patients with AF.

Atrial fibrillation (AF) is one of the most common arrhythmias seen in clinical practice. Current evidence suggests that serum uric acid (SUA) could be a marker of oxidative damage, a factor reported as a part of the mechanisms of AF. The purpose of the present study was to evaluate whether SUA predicted AF in the Atherosclerosis Risk In Communities (ARIC) study. The present analysis included 15,382 AF-free black and white men and women, aged 45 to 64 years, from the ARIC study, a population-based prospective cohort in the United States. SUA was determined using the uricase-peroxidase method at baseline. The primary outcome was the incidence of AF, defined as the occurrence of AF detected using hospital discharge codes, scheduled study electrocardiograms, and/or death certificates during the follow-up period (1987 to 2004). We identified 1,085 cases of incident AF. In Cox proportional hazards models adjusted for age, gender, race, center, education, body mass index, serum glucose, systolic and diastolic blood pressure, low-density lipoprotein cholesterol, alcohol use, prevalent coronary heart disease and heart failure, serum creatinine, diuretics, and P-wave duration on the electrocardiogram (as a measure of left atrial size) at baseline, the hazard ratio of AF associated with a SD increment in SUA was 1.16 (95% confidence interval 1.06 to 1.26). The association of SUA with AF risk differed by race and gender (p for interaction <0.01). In conclusion, elevated SUA is associated with a greater risk of AF, particularly among blacks and women. Additional studies should replicate this association and explore potential mechanisms. Atrial fibrillation (AF) is one of the most common arrhythmias seen in clinical practice. Current evidence suggests that serum uric acid (SUA) could be a marker of oxidative damage, a factor reported as a part of the mechanisms of AF. The purpose of the present study was to evaluate whether SUA predicted AF in the Atherosclerosis Risk In Communities (ARIC) study. The present analysis included 15,382 AF-free black and white men and women, aged 45 to 64 years, from the ARIC study, a population-based prospective cohort in the United States. SUA was determined using the uricase-peroxidase method at baseline. The primary outcome was the incidence of AF, defined as the occurrence of AF detected using hospital discharge codes, scheduled study electrocardiograms, and/or death certificates during the follow-up period (1987 to 2004). We identified 1,085 cases of incident AF. In Cox proportional hazards models adjusted for age, gender, race, center, education, body mass index, serum glucose, systolic and diastolic blood pressure, low-density lipoprotein cholesterol, alcohol use, prevalent coronary heart disease and heart failure, serum creatinine, diuretics, and P-wave duration on the electrocardiogram (as a measure of left atrial size) at baseline, the hazard ratio of AF associated with a SD increment in SUA was 1.16 (95% confidence interval 1.06 to 1.26). The association of SUA with AF risk differed by race and gender (p for interaction <0.01). In conclusion, elevated SUA is associated with a greater risk of AF, particularly among blacks and women. Additional studies should replicate this association and explore potential mechanisms.

There is an urgent need to extend sudden cardiac death (SCD) risk stratification beyond the left ventricular ejection fraction (LVEF). We evaluated whether a cumulative electrocardiogram (ECG) risk score would improve identification of individuals at high risk of SCD. In the community-based Oregon Sudden Unexpected Death Study (catchment population ∼1 million), 522 SCD cases with archived 12-lead ECG available (65.3 ± 14.5 years, 66% male) were compared with 736 geographical controls to assess the incremental value of multiple ECG parameters in SCD prediction. Heart rate, LV hypertrophy, QRS transition zone, QRS-T angle, QTc, and Tpeak-to-Tend interval remained significant in the final model, which was externally validated in the Atherosclerosis Risk in Communities (ARIC) Study. Sixteen percent of cases and 3% of controls had ≥4 abnormal ECG markers. After adjusting for clinical factors and LVEF, increasing ECG risk score was associated with progressively greater odds of SCD. Overall, subjects with ≥4 ECG abnormalities had an odds ratio (OR) of 21.2 for SCD [95% confidence interval (CI) 9.4–47.7; P < 0.001]. In the LVEF >35% subgroup, the OR was 26.1 (95% CI 9.9–68.5; P < 0.001). The ECG risk score increased the C-statistic from 0.625 to 0.753 (P < 0.001), with net reclassification improvement of 0.319 (P < 0.001). In the ARIC cohort validation, risk of SCD associated with ≥4 ECG abnormalities remained significant after multivariable adjustment (hazard ratio 4.84; 95% CI 2.34–9.99; P < 0.001; C-statistic improvement 0.759–0.774; P = 0.019). This novel cumulative ECG risk score was independently associated with SCD and was particularly effective for LVEF >35% where risk stratification is currently unavailable. These findings warrant further evaluation in prospective clinical investigations.

Observational studies have identified an association between body mass index (BMI) and incident atrial fibrillation (AF). Inferring causality from observational studies, however, is subject to residual confounding, reverse causation, and bias. The primary objective of this study was to evaluate the causal association between BMI and AF by using genetic predictors of BMI.We identified 51 646 individuals of European ancestry without AF at baseline from 7 prospective population-based cohorts initiated between 1987 and 2002 in the United States, Iceland, and the Netherlands with incident AF ascertained between 1987 and 2012. Cohort-specific mean follow-up ranged from 7.4 to 19.2 years, over which period there was a total of 4178 cases of incident AF. We performed a Mendelian randomization with instrumental variable analysis to estimate a cohort-specific causal hazard ratio for the association between BMI and AF. Two genetic instruments for BMI were used: FTO genotype (rs1558902) and a BMI gene score comprising 39 single-nucleotide polymorphisms identified by genome-wide association studies to be associated with BMI. Cohort-specific estimates were combined by random-effects, inverse variance-weighted meta-analysis.In age- and sex-adjusted meta-analysis, both genetic instruments were significantly associated with BMI (FTO: 0.43 [95% confidence interval, 0.32-0.54] kg/m2 per A-allele, P<0.001; BMI gene score: 1.05 [95% confidence interval, 0.90-1.20] kg/m2 per 1-U increase, P<0.001) and incident AF (FTO, hazard ratio, 1.07 [1.02-1.11] per A-allele, P=0.004; BMI gene score, hazard ratio, 1.11 [1.05-1.18] per 1-U increase, P<0.001). Age- and sex-adjusted instrumental variable estimates for the causal association between BMI and incident AF were hazard ratio, 1.15 (1.04-1.26) per kg/m2, P=0.005 (FTO) and 1.11 (1.05-1.17) per kg/m2, P<0.001 (BMI gene score). Both of these estimates were consistent with the meta-analyzed estimate between observed BMI and AF (age- and sex-adjusted hazard ratio 1.05 [1.04-1.06] per kg/m2, P<0.001). Multivariable adjustment did not significantly change findings.Our data are consistent with a causal relationship between BMI and incident AF. These data support the possibility that public health initiatives targeting primordial prevention of obesity may reduce the incidence of AF.

<h3>Objective:</h3> Given that recent reports have suggested left atrial disease to be an independent risk factor for ischemic stroke, we sought to examine if advanced interatrial block (aIAB) is an independent stroke risk factor. <h3>Methods:</h3> We examined the association between aIAB and incident ischemic stroke in 14,716 participants (mean age 54 ± 5.8 years; 55% female; 26% black) from the Atherosclerosis Risk in Communities Study (ARIC). Cases of aIAB were identified from digital ECGs recorded during the baseline ARIC visit (1987–1989) and the first 3 follow-up study visits (1990–1992, 1993–1995, and 1996–1998). Adjudicated ischemic stroke events were ascertained through December 31, 2010. <h3>Results:</h3> There were 266 (1.8%) participants who had evidence of aIAB. Over a median follow-up of 22 years, 916 (6.2%) ischemic stroke events were detected. The incidence rate (per 1,000 person-years) of ischemic stroke among those with aIAB (incidence rate 8.05, 95% confidence interval [CI] 5.7, 11.4) was more than twice the rate in those without aIAB (incidence rate 3.14, 95% CI 2.94, 3.35). In a multivariable Cox regression analysis adjusted for stroke risk factors and potential confounders, aIAB was associated with an increased risk of ischemic stroke (hazard ratio 1.63, 95% CI 1.13, 2.34). The results were consistent across subgroups of participants stratified by age, sex, and race. <h3>Conclusions:</h3> In the ARIC, aIAB was associated with incident ischemic stroke, which strengthens the hypothesis that left atrial disease should be considered an independent stroke risk factor.

Atrial fibrillation (AF) has a substantial genetic basis. Identification of individuals at greatest AF risk could minimize the incidence of cardioembolic stroke.To determine whether genetic data can stratify risk for development of AF, we examined associations between AF genetic risk scores and incident AF in 5 prospective studies comprising 18 919 individuals of European ancestry. We examined associations between AF genetic risk scores and ischemic stroke in a separate study of 509 ischemic stroke cases (202 cardioembolic [40%]) and 3028 referents. Scores were based on 11 to 719 common variants (≥5%) associated with AF at P values ranging from <1×10-3 to <1×10-8 in a prior independent genetic association study.Incident AF occurred in 1032 individuals (5.5%). AF genetic risk scores were associated with new-onset AF after adjustment for clinical risk factors. The pooled hazard ratio for incident AF for the highest versus lowest quartile of genetic risk scores ranged from 1.28 (719 variants; 95% confidence interval, 1.13-1.46; P=1.5×10-4) to 1.67 (25 variants; 95% confidence interval, 1.47-1.90; P=9.3×10-15). Discrimination of combined clinical and genetic risk scores varied across studies and scores (maximum C statistic, 0.629-0.811; maximum ΔC statistic from clinical score alone, 0.009-0.017). AF genetic risk was associated with stroke in age- and sex-adjusted models. For example, individuals in the highest versus lowest quartile of a 127-variant score had a 2.49-fold increased odds of cardioembolic stroke (95% confidence interval, 1.39-4.58; P=2.7×10-3). The effect persisted after the exclusion of individuals (n=70) with known AF (odds ratio, 2.25; 95% confidence interval, 1.20-4.40; P=0.01).Comprehensive AF genetic risk scores were associated with incident AF beyond associations for clinical AF risk factors but offered small improvements in discrimination. AF genetic risk was also associated with cardioembolic stroke in age- and sex-adjusted analyses. Efforts are warranted to determine whether AF genetic risk may improve identification of subclinical AF or help distinguish between stroke mechanisms.

To describe the incidence of cardiovascular risk factors, or race-related disparities in incidence, across the age spectrum in adults.Longitudinal cohort.National sample.Community-dwelling black and white adults recruited between 2003 and 2007.Incident hypertension, diabetes mellitus, dyslipidemia and atrial fibrillation over 10 years of follow-up in 10,801 adults, stratified according to age (45-54, 55-64, 65-74, ≥75).There was no evidence (P ≥ .68) of an age-related difference in the incidence of hypertension for white men (average incidence 38%), black men (48%), or black women (54%), although for white women incidence increased with age (45-54, 27%; ≥75, 40%). Incidence of diabetes mellitus was lower at older ages for white men (45-54, 15%; ≥75, 8%), black men (45-54, 29%; ≥75, 13%), and white women (45-54, 11%; ≥75, 4%), although there was no evidence (P = .11) of age-related changes for black women (average incidence 21%). For dyslipidemia, incidence for all race-sex groups was approximately 20% for aged 45 to 54 but approximately 30% for aged 54 to 64 and 65 to 74 and approximately 22% for aged 75 and older. Incidence of atrial fibrillation was low at age 45 to 54 (<5%) but for aged 75 and older was approximately 20% for whites and 11% for blacks. The incidence of hypertension, diabetes mellitus, and dyslipidemia was higher in blacks across the age spectrum but lower for atrial fibrillation.Incidence of risk factors remains high in older adults. Blacks have a higher incidence of hypertension, diabetes mellitus, and dyslipidemia after age 45, underscoring the ongoing importance of prevention of all three conditions in mid- to later life.

Obesity is associated with higher risk of atrial fibrillation (AF), but the impact of behavioral weight loss interventions on atrial fibrillation (AF) risk in persons with diabetes is unknown. We addressed this question in the Look AHEAD randomized trial. A total of 5,067 overweight or obese individuals 45 to 76 years old with type 2 diabetes without prevalent AF were randomized to either an intensive lifestyle intervention (ILI) designed to achieve and maintain weight loss through caloric reduction and increased physical activity or a diabetes support and education usual care group. Atrial fibrillation was ascertained from electrocardiograms at study examinations and hospitalization discharge summaries. Multivariable Cox models were used to estimate the intention-to-treat effect of the intervention adjusting for baseline covariates. During a mean follow-up of 9.0 years, 294 incident AF cases were identified. Rates of AF were comparable in the ILI and diabetes support and education groups (6.1 and 6.7 cases per 1,000 person-years, respectively, P = .42). The intervention did not affect AF incidence (multivariable hazard ratio [HR] 0.99, 95% CI 0.77-1.28). Similarly, neither weight loss nor improvement in physical fitness during the first year of the intervention was significantly associated with AF incidence: multivariable hazard ratio (95% CI) comparing top versus bottom quartile was 0.70 (0.41-1.18) for weight loss and 0.88 (0.55-1.43) for physical fitness improvement. In a large randomized trial of overweight and obese individuals with type 2 diabetes, an ILI that induced modest weight loss did not reduce the risk of developing AF.

Elevated levels of circulating liver enzymes have been associated with increased risk of cardiovascular disease. Their possible association with atrial fibrillation (AF) has received little attention.We studied 9333 men and women, aged 53-75 years, free of AF, participating in the Atherosclerosis Risk in Communities Study followed-up from 1996 to 2010. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ glutamyl transpeptidase (GGT) were measured in stored plasma samples. Incident AF was ascertained from hospitalisations and death certificates. Associations between liver enzymes and AF incidence were assessed using multivariable Cox proportional hazards models.During a mean follow-up of 12 years, 1021 incident AF events were identified. Levels of AST, and to a lesser extent ALT, showed a U-shaped association with AF risk, with higher AF risk among individuals in the two extremes of the distribution in minimally adjusted models. The associations were weakened after adjustment for potential confounders. By contrast, GGT, modelled as log base 2, was linearly associated with AF risk after multivariable adjustment: a doubling of GGT levels was associated with a 20% increased risk of AF (95% CI 10% to 30%). Additional adjustment for inflammatory markers did not appreciably affect the results. Associations were not different in men and women, in whites and blacks, among never drinkers of alcohol, and among those without prevalent heart failure.In this community-based prospective study, higher levels of liver enzymes, mainly GGT, were associated with an increased risk of AF. The mechanisms underlying this association deserve further scrutiny.

<h3>Background</h3> Population-based studies have linked measures of sleep disordered breathing to nocturnally occurring atrial fibrillation (AF) episodes. Whether measures of sleep disordered breathing and sleep quality are associated with prevalent AF has not been studied in an unselected population. We investigated the cross-sectional association with prevalent AF of objectively collected prespecified measures of overnight sleep breathing disturbances, sleep stage distributions, arousal and sleep duration. <h3>Methods</h3> AF prevalence, defined by diagnosis codes, study electrocardiography and sleep study were examined among Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent polysomnography in the MESA Sleep Study (n=2048). <h3>Measurements and main results</h3> Higher apnoea hypopnoea index (AHI) was associated with increased odds of AF, although the significance was attenuated after full adjustment for covariates including prevalent cardiovascular disease (OR: 1.22 (0.99 to 1.49) per SD (17/h), p=0.06). Analyses of sleep architecture measures and AF revealed significantly lower odds of AF associated with longer duration of slow wave sleep (OR: 0.66 (0.5 to 0.89) per SD (34 min), p=0.01) which persisted after additionally adjusting for AHI (OR: 0.68 (0.51 to 0.92), p=0.01). Higher sleep efficiency was significantly associated with lower likelihood of AF but the significance was lost when adjusted for AHI. No significant association was present between sleep duration and AF. In a model including AHI and arousal index, the association between AHI and AF was strengthened (AHI: OR 1.49 (1.15 to 1.91) per SD, p=0.002) and a significant inverse association between arousal index and AF was observed (OR 0.65 (0.50 to 0.86) per SD (12/h), p=0.005). <h3>Conclusions</h3> In a study of a large multiethnic population, AF was associated with AHI severity, and was more common in individuals with poor sleep quality as measured by reduced slow wave sleep time, a finding that was independent of AHI.

Background: In people with atrial fibrillation (AF), periods of sinus rhythm present an opportunity to detect prothrombotic atrial remodeling through measurement of P-wave indices (PWIs)—prolonged P-wave duration, abnormal P-wave axis, advanced interatrial block, and abnormal P-wave terminal force in lead V1. We hypothesized that the addition of PWIs to the CHA 2 DS 2 -VASc score would improve its ability to predict AF-related ischemic stroke. Methods: We included 2229 participants from the ARIC study (Atherosclerosis Risk in Communities) and 700 participants from MESA (Multi-Ethnic Study of Atherosclerosis) with incident AF who were not on anticoagulants within 1 year of AF diagnosis. PWIs were obtained from study visit ECGs before development of AF. AF was ascertained using study visit ECGs and hospital records. Ischemic stroke cases were based on physician adjudication of hospital records. We used Cox proportional hazards models to estimate hazard ratios and 95% CIs of PWIs for ischemic stroke. Improvement in 1-year stroke prediction was assessed by C-statistic, categorical net reclassification improvement, and relative integrated discrimination improvement. Results: Abnormal P-wave axis was the only PWI associated with increased ischemic stroke risk (hazard ratio, 1.84; 95% CI, 1.33–2.55) independent of CHA 2 DS 2 -VASc variables, and that resulted in meaningful improvement in stroke prediction. The β estimate was approximately twice that of the CHA 2 DS 2 -VASc variables, and thus abnormal P-wave axis was assigned 2 points to create the P 2 -CHA 2 DS 2 -VASc score. This improved the C-statistic (95% CI) from 0.60 (0.51–0.69) to 0.67 (0.60–0.75) in ARIC and 0.68 (0.52–0.84) to 0.75 (0.60–0.91) in MESA (validation cohort). In ARIC and MESA, the categorical net reclassification improvements (95% CI) were 0.25 (0.13–0.39) and 0.51 (0.18–0.86), respectively, and the relative integrated discrimination improvement (95% CI) were 1.19 (0.96–1.44) and 0.82 (0.36–1.39), respectively. Conclusions: Abnormal P-wave axis—an ECG correlate of left atrial abnormality— improves ischemic stroke prediction in AF. Compared with CHA 2 DS 2 -VASc, the P 2 -CHA 2 DS 2 -VASc is a better prediction tool for AF-related ischemic stroke.

Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.

Atrial fibrillation frequently complicates CKD and is associated with adverse outcomes. Progression to ESRD is a major complication of CKD, but the link with atrial fibrillation has not been fully delineated. In this study, we examined the association of incident atrial fibrillation with the risk of ESRD in patients with CKD.We studied participants in the prospective Chronic Renal Insufficiency Cohort Study without atrial fibrillation at entry. Incident atrial fibrillation was identified by study visit ECGs, self-report, and hospital discharge diagnostic codes, with confirmation by physician adjudication. ESRD through 2012 was ascertained by participant self-report, medical records, and linkage to the US Renal Data System. Data on potential confounders were obtained from self-report, study visits, and laboratory tests. Marginal structural models were used to study the potential association of incident atrial fibrillation with risk of ESRD after adjustment for time-dependent confounding.Among 3091 participants, 172 (5.6%) developed incident atrial fibrillation during follow-up. During mean follow-up of 5.9 years, 43 patients had ESRD that occurred after development of incident atrial fibrillation (11.8/100 person-years) compared with 581 patients without incident atrial fibrillation (3.4/100 person-years). In marginal structural models with inverse probability weighting, incident atrial fibrillation was associated with a substantially higher rate of ESRD (hazard ratio, 3.2; 95% confidence interval, 1.9 to 5.2). This association was consistent across important subgroups by age, sex, race, diabetes status, and baseline eGFR.Incident atrial fibrillation was associated with higher risk of developing ESRD in CKD. Additional study is needed to identify potentially modifiable pathways through which atrial fibrillation was associated with a higher risk of progression to ESRD. More aggressive monitoring and treatment of patients with CKD and atrial fibrillation may improve outcomes in this high-risk population.

Background Heart failure is common in patients with chronic kidney disease. We studied risk factors for incident heart failure among 3557 participants in the CRIC (Chronic Renal Insufficiency Cohort) Study. Methods and Results Kidney function was assessed by estimated glomerular filtration rate ( eGFR ) using serum creatinine, cystatin C, or both, and 24‐hour urine albumin excretion. During an average of 6.3 years of follow‐up, 452 participants developed incident heart failure. After adjustment for age, sex, race, and clinical site, hazard ratio (95% CI ) for heart failure associated with 1 SD lower creatinine‐based eGFR was 1.67 (1.49, 1.89), 1 SD lower cystatin C‐based‐ eGFR was 2.43 (2.10, 2.80), and 1 SD higher log‐albuminuria was 1.65 (1.53, 1.78), all P &lt;0.001. When all 3 kidney function measures were simultaneously included in the model, lower cystatin C‐based eGFR and higher log‐albuminuria remained significantly and directly associated with incidence of heart failure. After adjusting for eGFR , albuminuria, and other traditional cardiovascular risk factors, anemia (1.37, 95% CI 1.09, 1.72, P =0.006), insulin resistance (1.16, 95% CI 1.04, 1.28, P =0.006), hemoglobin A1c (1.27, 95% CI 1.14, 1.41, P &lt;0.001), interleukin‐6 (1.15, 95% CI 1.05, 1.25, P =0.002), and tumor necrosis factor‐α (1.10, 95% CI 1.00, 1.21, P =0.05) were all significantly and directly associated with incidence of heart failure. Conclusions Our study indicates that cystatin C‐based eGFR and albuminuria are better predictors for risk of heart failure compared to creatinine‐based eGFR . Furthermore, anemia, insulin resistance, inflammation, and poor glycemic control are independent risk factors for the development of heart failure among patients with chronic kidney disease.

African Americans are consistently found to have a lower prevalence of clinically detected atrial fibrillation (AF) than whites, despite a higher prevalence of major AF risk factors and higher risk of ischemic stroke. Long-term ambulatory ECG monitors provide the opportunity for unbiased AF detection. We determined differences by race/ethnicity in the prevalence of clinically detected AF and in the proportion with monitor-detected AF.We conducted a cross-sectional analysis in the MESA (Multi-Ethnic Study of Atherosclerosis), a community-based cohort study that enrolled 6814 Americans free of clinically recognized cardiovascular disease in 2000 to 2002. At the 2016 to 2018 examination, 1556 individuals participated in an ancillary study involving ambulatory ECG monitoring and had follow-up for clinically detected AF since cohort entry.Among 1556 participants, 41% were white, 25% African American, 21% Hispanic, and 14% Chinese; 51% were women; and the mean age was 74 years. The prevalence of clinically detected AF after 14.4 years' follow-up was 11.3% in whites, 6.6% in African Americans, 7.8% in Hispanics, and 9.9% in Chinese and was significantly lower in African Americans than in whites, in both unadjusted and risk factor-adjusted analyses (adjusted rate difference, -6.6% [95% CI, -10.1% to -3.1%]; P<0.001). By contrast, in the same individuals, the proportion with monitor-detected AF using a 14-day ambulatory ECG monitor was similar in the 4 race/ethnic groups: 7.1%, 6.4%, 6.9%, and 5.2%, respectively (compared with whites, all P>0.5).The prevalence of clinically detected AF was substantially lower in African American than in white participants, without or with adjustment for AF risk factors. However, unbiased AF detection by ambulatory monitoring in the same individuals revealed little difference in the proportion with AF by race/ethnicity. These findings provide support for the hypothesis of differential detection by race/ethnicity in the clinical recognition of AF, which may have important implications for stroke prevention.

The Diabetes Control and Complications Trial (DCCT) and its observational follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) demonstrated the dominant role of glycemia, second only to age, as a risk factor for a first cardiovascular event in type 1 diabetes (T1D). We now investigate the association between established risk factors and the total cardiovascular disease (CVD) burden, including subsequent (i.e., recurrent) events.CVD events in the 1,441 DCCT/EDIC participants were analyzed separately by type (CVD death, acute myocardial infarction [MI], stroke, silent MI, angina, percutaneous transluminal coronary angioplasty/coronary artery bypass graft [PTCA/CABG], and congestive heart failure [CHF]) or as composite outcomes (CVD or major adverse cardiovascular events [MACE]). Proportional rate models and conditional models assessed associations between risk factors and CVD outcomes.Over a median follow-up of 29 years, 239 participants had 421 CVD events, and 120 individuals had 149 MACE. Age was the strongest risk factor for acute MI, silent MI, stroke, and PTCA/CABG, while glycemia was the strongest risk factor for CVD death, CHF, and angina, second strongest for acute MI and PTCA/CABG, third strongest for stroke, and not associated with silent MI. HbA1c was the strongest modifiable risk factor for a first CVD event (CVD: HR 1.38 [95% CI 1.21, 1.56] per 1% higher HbA1c; MACE: HR 1.54 [1.30, 1.82]) and also for subsequent CVD events (CVD: incidence ratio [IR] 1.28 [95% CI 1.09, 1.51]; MACE: IR 1.89 [1.36, 2.61]).Intensive glycemic management is recommended to lower the risk of initial CVD events in T1D. After a first event, optimal glycemic control may reduce the risk of recurrent CVD events and should be maintained.

It remains uncertain whether intensive control of blood pressure (BP) results in a lower risk of atrial fibrillation (AF) in patients with hypertension. Using data from SPRINT (Systolic Blood Pressure Intervention Trial), which enrolled participants with hypertension at increased risk of cardiovascular disease, we examined whether intensive BP lowering (target systolic BP [SBP] <120 mm Hg), compared with standard BP lowering (target SBP<140 mm Hg), results in a lower risk of AF. This analysis included 8022 participants (4003 randomized to the intensive arm and 4019 to standard BP arm) who were free of AF at the time of enrollment and with available baseline and follow-up electrocardiographic data. AF was ascertained from standard 12-lead electrocardiograms recorded at biannual study examinations and an exit visit. During up to 5.2 years of follow-up and a total of 28 322 person-years, 206 incident AF cases occurred; 88 in the intensive BP-lowering arm and 118 in the standard BP-lowering arm. Intensive BP lowering was associated with a 26% lower risk of developing new AF (hazard ratio, 0.74 [95% CI, 0.56-0.98]; P=0.037). This effect was consistent among prespecified subgroups of SPRINT participants stratified by age, sex, race, SBP tertiles, prior cardiovascular disease, and prior chronic kidney disease when interactions between treatment effect and these subgroups were assessed using Hommel adjusted P values. In conclusion, intensive treatment to a target of SBP <120 mm Hg in patients with hypertension at high risk of cardiovascular disease has the potential to reduce the risk of AF. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

Atrial cardiomyopathy, characterized by abnormalities in atrial structure and function, is associated with increased risk of adverse cardiovascular and neurocognitive outcomes, independent of atrial fibrillation. There exists a critical unmet need for a clinical tool that is cost-effective, easy to use, and that can diagnose atrial cardiomyopathy. P wave parameters (PWPs) reflect underlying atrial structure, size, and electrical activation; alterations in these factors manifest as abnormalities in PWPs that can be readily ascertained from a standard 12-lead ECG and potentially be used to aid clinical decision-making. PWPs include P wave duration, interatrial block, P wave terminal force in V1, P wave axis, P wave voltage, P wave area, and P wave dispersion. PWPs can be combined to yield an index (P wave index), such as the morphology-voltage-P-wave duration ECG risk score. Abnormal PWPs have been shown in population-based cohort studies to be independently associated with higher risks of atrial fibrillation, ischemic stroke, sudden cardiac death, and dementia. Additionally, PWPs, either individually or in combination (as a P wave index), have been reported to enhance prediction of atrial fibrillation or ischemic stroke. To facilitate translation of PWPs to routine clinical practice, additional work is needed to standardize measurement of PWPs (eg, via semiautomated or automated measurement), confirm their reliability and predictive value, leverage novel approaches (eg, wavelet analysis of P waves and machine learning algorithms), and finally, define the risk-benefit ratio of specific interventions in high-risk individuals. Our ultimate goal is to repurpose the ubiquitous 12-lead ECG to advance the study, diagnosis, and treatment of atrial cardiomyopathy, thus overcoming critical challenges in prevention of cardiovascular disease and dementia.

Cardiac conduction disease can lead to syncope, heart failure, and death. The only available therapy is pacemaker implantation, with no established prevention strategies. Research to identify modifiable risk factors has been scant.Data from the Cardiovascular Health Study, a population-based cohort study of adults ≥ 65 years with annual 12-lead electrocardiograms obtained over 10 years, were utilized to examine relationships between baseline characteristics, including lifestyle habits, and conduction disease. Of 5050 participants (mean age 73 ± 6 years; 52% women), prevalent conduction disease included 257 with first-degree atrioventricular block, 99 with left anterior fascicular block, 9 with left posterior fascicular block, 193 with right bundle branch block (BBB), 76 with left BBB, and 102 with intraventricular block at baseline. After multivariable adjustment, older age, male sex, a larger body mass index, hypertension, and coronary heart disease were associated with a higher prevalence of conduction disease, whereas White race and more physical activity were associated with a lower prevalence. Over a median follow-up on 7 (interquartile range 1-9) years, 1036 developed incident conduction disease. Older age, male sex, a larger BMI, and diabetes were each associated with incident conduction disease. Of lifestyle habits, more physical activity (hazard ratio 0.91, 95% confidence interval 0.84-0.98, P = 0.017) was associated with a reduced risk, while smoking and alcohol did not exhibit a significant association.While some difficult to control comorbidities were associated with conduction disease as expected, a readily modifiable lifestyle factor, physical activity, was associated with a lower risk.

The feasibility of conducting a large-scale Polypill clinical trial in developing countries remains unclear. More information is needed regarding the efficacy in reducing the risk factors of cardiovascular disease (CVD), side effects, improvement in adherence and physician/patient "acceptability" of the Polypill.We conducted an open-label, parallel-group, randomized clinical trial involving three sites in Sri Lanka that enrolled a total of 216 patients without established CVD. The trial compared a Polypill (75 mg aspirin, 20 mg simvastatin, 10 mg lisinopril and 12.5 mg hydrochlorothiazide) to Standard Practice. After randomization, patients were followed monthly for three months. Pre-specified primary outcomes included reduction in systolic blood pressure, total cholesterol and estimated 10-year CVD risk. We also evaluated the recruitment process and acceptability of the Polypill by both physicians and patients.Patients were recruited in a six-month period as planned. Two hundred three patients (94.0%) completed the treatment program and returned for their three-month follow-up visits. No safety concerns were reported. These findings suggest a high rate of patient acceptability, a finding that is bolstered by the majority of patients completing the trial (90%) indicating that they would take the Polypill "for life" if proven to be effective in reducing CVD risk. Approximately 86% of the physicians surveyed agreed with and supported use of the Polypill for primary prevention and 93% for secondary prevention of CVD. Both the Polypill and Standard Practice resulted in marked reductions in systolic blood pressure, total cholesterol and 10-year risk of CVD. However, the differences between the treatment groups were not statistically significant.We successfully completed a Polypill feasibility trial in Sri Lanka. We were able to document high acceptability of the Polypill to patients and physicians. We were unable to estimate the risk factor reductions on the Polypill because the control group received similar treatment with individual drugs. The Polypill was however simpler and achieved comparable risk factor reductions, highlighting its potential usefulness in the prevention of CVD.NCT00567307.

The PR interval on the electrocardiogram reflects atrial and atrioventricular nodal conduction time. The PR interval is heritable, provides important information about arrhythmia risk, and has been suggested to differ among human races. Genome-wide association (GWA) studies have identified common genetic determinants of the PR interval in individuals of European and Asian ancestry, but there is a general paucity of GWA studies in individuals of African ancestry. We performed GWA studies in African American individuals from four cohorts (n = 6,247) to identify genetic variants associated with PR interval duration. Genotyping was performed using the Affymetrix 6.0 microarray. Imputation was performed for 2.8 million single nucleotide polymorphisms (SNPs) using combined YRI and CEU HapMap phase II panels. We observed a strong signal (rs3922844) within the gene encoding the cardiac sodium channel (SCN5A) with genome-wide significant association (p<2.5×10−8) in two of the four cohorts and in the meta-analysis. The signal explained 2% of PR interval variability in African Americans (beta = 5.1 msec per minor allele, 95% CI = 4.1–6.1, p = 3×10−23). This SNP was also associated with PR interval (beta = 2.4 msec per minor allele, 95% CI = 1.8–3.0, p = 3×10−16) in individuals of European ancestry (n = 14,042), but with a smaller effect size (p for heterogeneity <0.001) and variability explained (0.5%). Further meta-analysis of the four cohorts identified genome-wide significant associations with SNPs in SCN10A (rs6798015), MEIS1 (rs10865355), and TBX5 (rs7312625) that were highly correlated with SNPs identified in European and Asian GWA studies. African ancestry was associated with increased PR duration (13.3 msec, p = 0.009) in one but not the other three cohorts. Our findings demonstrate the relevance of common variants to African Americans at four loci previously associated with PR interval in European and Asian samples and identify an association signal at one of these loci that is more strongly associated with PR interval in African Americans than in Europeans.

The purpose of this study was to examine the association between prolongation of QT interval corrected for heart rate (QTc) with incident stroke.Unlike cardiovascular morbidity and mortality, little is known about the relationship between QTc and risk of stroke.A total of 27,411 participants age 45 years and older without previous stroke from the REGARDS (REasons for Geographic and Racial Differences in Stroke) study were included in this analysis. QTc was calculated using Framingham formula (QTc(Fram)). Stroke cases were identified and adjudicated during up to 8.2 years of follow-up (median, 5.1 years).The risk of incident stroke in study participants with prolonged QTc(Fram) was almost 3 times the risk in those with normal QTc(Fram) (hazard ratio [HR] [95% confidence interval (CI)]: 2.88 [2.12 to 3.92], p < 0.0001). After adjustment for demographics (age, race, and sex), traditional stroke risk factors (antihypertensive medication use, systolic blood pressure, current smoking, diabetes, left ventricular hypertrophy, atrial fibrillation, and previous cardiovascular disease), warfarin use, aspirin use, QRS duration and use of QTc-prolonging drugs, the risk of stroke remained significantly high (HR [95% CI]: 1.67 [1.16 to 2.41], p = 0.0061) and was consistent across several subgroups of REGARDS study participants. Similar results were obtained when the risk of stroke was estimated per 1-SD increase in QTc(Fram), (HR [95% CI]: 1.12 [1.03 to 1.21], p = 0.0053 in multivariable-adjusted model) and when other QTc correction formulas including those of Hodge, Bazett, and Fridericia were used.QTc prolongation is associated with a significantly increased risk of incident stroke independent of traditional stroke risk factors. Examining the risk of stroke associated with QTc-prolonging drugs may be warranted.

<h3>Background</h3> Abnormal atrial repolarization is important in the development of atrial fibrillation (AF), but no direct measurement is available in clinical medicine. <h3>Objective</h3> To determine whether the QT interval, a marker of ventricular repolarization, could be used to predict incident AF. <h3>Methods</h3> We examined a prolonged QT interval corrected by using the Framingham formula (QT_Fram) as a predictor of incident AF in the Atherosclerosis Risk in Communities (ARIC) study. The Cardiovascular Health Study (CHS) and Health, Aging, and Body Composition (ABC) study were used for validation. Secondary predictors included QT duration as a continuous variable, a short QT interval, and QT intervals corrected by using other formulas. <h3>Results</h3> Among 14,538 ARIC study participants, a prolonged QT_Fram predicted a roughly 2-fold increased risk of AF (hazard ratio [HR] 2.05; 95% confidence interval [CI] 1.42–2.96; <i>P</i> < .001). No substantive attenuation was observed after adjustment for age, race, sex, study center, body mass index, hypertension, diabetes, coronary disease, and heart failure. The findings were validated in Cardiovascular Health Study and Health, Aging, and Body Composition study and were similar across various QT correction methods. Also in the ARIC study, each 10-ms increase in QT_Fram was associated with an increased unadjusted (HR 1.14; 95% CI 1.10–1.17; <i>P</i> < .001) and adjusted (HR 1.11; 95% CI 1.07–1.14; <i>P</i> < .001) risk of AF. Findings regarding a short QT interval were inconsistent across cohorts. <h3>Conclusions</h3> A prolonged QT interval is associated with an increased risk of incident AF.

We report relationships between cardiovascular disease risk factors and myocardial structure, function, and scar in patients with type 1 diabetes mellitus in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.Cardiac magnetic resonance was obtained in 1017 patients with type 1 diabetes mellitus. Gadolinium cardiac magnetic resonance was also obtained in 741 patients. The mean age was 49±7 years; 52% were men; and mean duration of diabetes mellitus was 28±5 years. Associations of cardiovascular disease risk factors with cardiac magnetic resonance parameters were examined with linear and logistic regression models. History of macroalbuminuria was positively associated with left ventricular mass (by 14.8 g), leading to a significantly higher ratio of left ventricular mass to end-diastolic volume (by 8%). Mean hemoglobin A(1c) levels over the preceding 22 years were inversely associated with end-diastolic volume (-3.0 mL per unit mean hemoglobin A(1c) percent) and stroke volume (-2.3 mL per unit mean hemoglobin A(1c) percent) and positively related to the ratio of elevated left ventricular mass to end-diastolic volume (0.02 g/mL per unit). The overall prevalence of myocardial scar was 4.3% by cardiac magnetic resonance and 1.4% by clinical adjudication of myocardial infarction. Both mean hemoglobin A(1c) (odds ratio, 1.5 [95% confidence interval, 1.0-2.2] per unit) and macroalbuminuria (odds ratio, 3.5 [95% confidence interval, 1.2-9.9]) were significantly associated with myocardial scar and traditional cardiovascular disease risk factors.In addition to traditional cardiovascular disease risk factors, elevated mean hemoglobin A(1c) and macroalbuminuria were significantly associated with alterations in left ventricular structure and function. The prevalence of myocardial scar was 4.3% in this subcohort of DCCT/EDIC participants with relatively preserved renal function. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00360893 and NCT00360815.

Atrial fibrillation (AF) is the most common arrhythmia in women. Large studies evaluating key AF risk factors in older women are lacking. We aimed to identify risk factors for AF in postmenopausal women and measure population burden of modifiable risk factors.Prospective observational study.The Women's Health Initiative (WHI) Observational Study.93 676 postmenopausal women were followed for an average of 9.8 years for cardiovascular outcomes. After exclusion of women with prevalent AF or incomplete data, 8252 of the remaining 81 892 women developed incident AF.Incident AF was identified by WHI-ascertained hospitalisation records and diagnosis codes from Medicare claims. Multivariate Cox hazard regression analysis identified independent risk factors for incident AF.Age, hypertension, obesity, diabetes, myocardial infarction and heart failure were independently associated with incident AF. Hypertension and overweight status accounted for 28.3% and 12.1%, respectively, of the population attributable risk. Hispanic and African-American participants had lower rates of incident AF (HR 0.58, 95% CI 0.47 to 0.70 and HR 0.59, 95% CI 0.53 to 0.65, respectively) than Caucasians.Caucasian ethnicity, traditional cardiovascular risk factors and peripheral arterial disease were independently associated with higher rates of incident AF in postmenopausal women. Hypertension and overweight status accounted for a large proportion of population attributable risk. Measuring burden of modifiable AF risk factors in older women may help target interventions.

OBJECTIVE Heart rate–corrected QT (QTc) interval is associated with mortality in the general population, but this association is less clear in individuals with type 2 diabetes. We assessed the association of QTc interval with all-cause and cardiovascular disease (CVD) mortality in the Diabetes Heart Study. RESEARCH DESIGN AND METHODS We studied 1,020 participants with type 2 diabetes (83% European Americans; 55% women; mean age 61.4 years) who were free of atrial fibrillation, major ventricular conduction defects, and antiarrhythmic therapy at baseline. QT duration was automatically calculated from a standard 12-lead electrocardiogram (ECG). Following American Heart Association/American College of Cardiology Foundation recommendations, a linear scale was used to correct the QT for heart rate. Using Cox regression, risk was estimated per 1-SD increase in QTc interval as well as prolonged QTc interval (&amp;gt;450 ms) vs. normal QTc interval for mortality. RESULTS At baseline, the mean (SD) QTc duration was 414.9 ms (18.1), and 3.0% of participants had prolonged QTc. After a median follow-up time of 8.5 years (maximum follow-up time 13.9 years), 204 participants were deceased. In adjusted multivariate models, a 1-SD increase in QTc interval was associated with an 18% higher risk for all-cause mortality (hazard ratio 1.18 [95% CI 1.03–1.36]) and 29% increased risk for CVD mortality (1.29 [1.05–1.59]). Similar results were obtained when QTc interval was used as a categorical variable (prolonged vs. normal) (all-cause mortality 1.73 [0.95–3.15]; CVD mortality 2.86 [1.35–6.08]). CONCLUSIONS Heart rate QTc interval is an independent predictor of all-cause and CVD mortality in this population with type 2 diabetes, suggesting that additional prognostic information may be available from this simple ECG measure.

Background— The genetic background of atrial fibrillation (AF) in whites and African Americans is largely unknown. Genes in cardiovascular pathways have not been systematically investigated. Methods and Results— We examined a panel of approximately 50 000 common single-nucleotide polymorphisms (SNPs) in 2095 cardiovascular candidate genes and AF in 3 cohorts with participants of European (n=18 524; 2260 cases) or African American descent (n=3662; 263 cases) in the National Heart, Lung, and Blood Institute's Candidate Gene Association Resource. Results in whites were followed up in the German Competence Network for AF (n=906, 468 cases). The top result was assessed in relation to incident ischemic stroke in the Cohorts for Heart and Aging Research in Genomic Epidemiology Stroke Consortium (n=19 602 whites, 1544 incident strokes). SNP rs4845625 in the IL6R gene was associated with AF (relative risk [RR] C allele, 0.90; 95% confidence interval [CI], 0.85–0.95; P =0.0005) in whites but did not reach statistical significance in African Americans (RR, 0.86; 95% CI, 0.72–1.03; P =0.09). The results were comparable in the German AF Network replication, (RR, 0.71; 95% CI, 0.57–0.89; P =0.003). No association between rs4845625 and stroke was observed in whites. The known chromosome 4 locus near PITX2 in whites also was associated with AF in African Americans (rs4611994; hazard ratio, 1.40; 95% CI, 1.16–1.69; P =0.0005). Conclusions— In a community-based cohort meta-analysis, we identified genetic association in IL6R with AF in whites. Additionally, we demonstrated that the chromosome 4 locus known from recent genome-wide association studies in whites is associated with AF in African Americans.

&lt;b&gt;&lt;i&gt;Background/Aims:&lt;/i&gt;&lt;/b&gt; Low heart rate variability (HRV) is a risk factor for adverse outcomes in the general population. We aimed to determine the factors associated with HRV and evaluate the association between low HRV and clinical outcomes in patients with chronic kidney disease (CKD). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A 10-second electrocardiogram was obtained at baseline in the Chronic Renal Insufficiency Cohort (CRIC) Study. HRV was measured by the standard deviation of all R-R intervals (SDNN) and the root mean square of successive differences between R-R intervals (RMSSD). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; In 3,245 CRIC participants with available baseline SDNN and RMSSD, lower HRV was associated with older age, lack of exercise, heart failure, elevated phosphorus and hemoglobin A1c, and low estimated glomerular filtration rate. After a median follow-up of 4.2 years, in fully adjusted models, lower HRV was not associated with renal [SDNN: hazard rate, HR = 0.96 (95% confidence interval, CI 0.88-1.05); RMSSD: HR = 0.97 (95% CI 0.88-1.07)] or cardiovascular outcomes [SDNN: HR = 1.02 (95% CI 0.92-1.13); RMSSD: HR = 1.00 (95% CI 0.90-1.10)]. There was a nonlinear relationship between RMSSD and all-cause mortality with increased risk with both low and high RMSSD (p = 0.04). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; In a large cohort of patients with CKD, multiple risk factors for renal and cardiovascular diseases were associated with lower HRV. Lower HRV was not associated with increased risk for renal or cardiovascular outcomes, but both low and high RMSSD were associated with increased risk for all-cause mortality. In conclusion, HRV measured by RMSSD may be a novel and independent risk factor for mortality in CKD patients.

At age 45 years, blacks have a stroke mortality ≈3× greater than their white counterparts, with a declining disparity at older ages. We assess whether this black-white disparity in stroke mortality is attributable to a black-white disparity in stroke incidence versus a disparity in case fatality.We first assess if black-white differences in stroke mortality within 29 681 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort reflect national black-white differences in stroke mortality and then assess the degree to which black-white differences in stroke incidence or 30-day case fatality after stroke contribute to the disparities in stroke mortality.The pattern of stroke mortality within the study mirrors the national pattern, with the black-to-white hazard ratio of ≈4.0 at age 45 years decreasing to ≈1.0 at age 85 years. The pattern of black-to-white disparities in stroke incidence shows a similar pattern but no evidence of a corresponding disparity in stroke case fatality.These findings show that the black-white differences in stroke mortality are largely driven by differences in stroke incidence, with case fatality playing at most a minor role. Therefore, to reduce the black-white disparity in stroke mortality, interventions need to focus on prevention of stroke in blacks.

Metabolic syndrome (MS) and atrial fibrillation (AF) are associated with increased cardiovascular disease morbidity and mortality. This analysis evaluated the association between MS and AF in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. MS was defined using criteria recommended in the joint interim statement from several international societies. AF was defined by electrocardiogram (ECG) and/or self-report and by ECG alone. In patients with 0, 1, 2, 3, 4, and 5 MS components, prevalences of AF by ECG and/or self-report were 5.5%, 7.7%, 8.2%, 9.2%, 9.6%, and 11.5%, respectively (p for trend <0.001). After multivariable adjustment, each MS component except serum triglycerides was significantly associated with AF. The multivariable-adjusted odds ratio for AF, defined by ECG and/or or self-reported history, comparing those with to those without MS was 1.20 (95% confidence interval 1.10 to 1.29). Results were consistent when AF was defined by ECG alone (odds ratio 1.15, 95% confidence interval 0.92 to 1.39). In conclusion, MS is associated with an increased prevalence of AF. Further studies investigating a potential mechanism for this excess risk are warranted. Metabolic syndrome (MS) and atrial fibrillation (AF) are associated with increased cardiovascular disease morbidity and mortality. This analysis evaluated the association between MS and AF in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. MS was defined using criteria recommended in the joint interim statement from several international societies. AF was defined by electrocardiogram (ECG) and/or self-report and by ECG alone. In patients with 0, 1, 2, 3, 4, and 5 MS components, prevalences of AF by ECG and/or self-report were 5.5%, 7.7%, 8.2%, 9.2%, 9.6%, and 11.5%, respectively (p for trend <0.001). After multivariable adjustment, each MS component except serum triglycerides was significantly associated with AF. The multivariable-adjusted odds ratio for AF, defined by ECG and/or or self-reported history, comparing those with to those without MS was 1.20 (95% confidence interval 1.10 to 1.29). Results were consistent when AF was defined by ECG alone (odds ratio 1.15, 95% confidence interval 0.92 to 1.39). In conclusion, MS is associated with an increased prevalence of AF. Further studies investigating a potential mechanism for this excess risk are warranted.

Existing equations for prediction of atrial fibrillation (AF) have been developed and validated in white and African-American populations. Whether these models adequately predict AF in more racially and ethnically diverse populations is unknown.We studied 6663 men and women 45 to 84 years of age without AF at baseline (2000-2002) enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). Of these, 38% were non-Hispanic whites, 28% non-Hispanic African Americans, 22% Hispanics, and 12% Chinese Americans. AF during follow-up was ascertained from hospitalization discharge codes through 2012. Information collected at baseline was used to calculate predicted 5-year risk of AF using the previously published simple CHARGE-AF model, which only includes clinical variables, and a biomarker-enriched CHARGE-AF model, which also considers levels of circulating N-terminal of the prohormone B-type natriuretic peptide and C-reactive protein. For comparison purposes, we also assessed performance of the 10-year Framingham AF model. During a mean follow-up of 10.2 years, 351 cases of AF were identified. The C-statistic of the CHARGE-AF models were 0.779 (95% CI, 0.744-0.814) for the simple model and 0.825 (95% CI, 0.791-0.860) for the biomarker-enriched model. Calibration was adequate in the biomarker-enriched model (χ(2)=7.9; P=0.55), but suboptimal in the simple model (χ(2)=25.6; P=0.002). In contrast, the 10-year Framingham score had a C-statistic (95% CI) of 0.746 (0.720-0.771) and showed poor calibration (χ(2)=57.4; P<0.0001).The CHARGE-AF risk models adequately predicted 5-year AF risk in a large multiethnic cohort. These models could be useful to select high-risk individuals for AF screening programs or for primary prevention trials in diverse populations.

Although silent myocardial infarction (SMI) accounts for about one-half of the total number of myocardial infarctions (MIs), the risk of heart failure (HF) among patients with SMI is not well established.The purpose of this study was to examine the association of SMI and clinically manifested myocardial infarction (CMI) with HF, as compared with patients with no MI.This analysis included 9,243 participants from the ARIC (Atherosclerosis Risk In Communities) study who were free of cardiovascular disease at baseline (ARIC visit 1: 1987 to 1989). SMI was defined as electrocardiographic evidence of MI without CMI after the baseline until ARIC visit 4 (1996 to 1998). HF events were ascertained starting from ARIC visit 4 until 2010 in individuals free of HF before that visit.Between ARIC visits 1 and 4, 305 SMIs and 331 CMIs occurred. After ARIC visit 4 and during a median follow-up of 13.0 years, 976 HF events occurred. The incidence rate of HF was higher in both CMI and SMI participants than in those without MI (incidence rates per 1,000 person-years were 30.4, 16.2, and 7.8, respectively; p < 0.001). In a model adjusted for demographics and HF risk factors, both SMI (hazard ratio [HR]: 1.35; 95% confidence interval [CI]: 1.02 to 1.78) and CMI (HR: 2.85; 95% CI: 2.31 to 3.51) were associated with increased risk of HF compared with no MI. These associations were consistent in subgroups of participants stratified by several HF risk predictors. However, the risk of HF associated with SMI was stronger in those younger than the median age (53 years) (HR: 1.66; 95% CI: 1.00 to 2.75 vs. HR: 1.19; 95% CI: 0.85 to 1.66, respectively; overall interaction p by MI type <0.001).SMI is associated with an increased risk of HF. Future research is needed to examine the cost effectiveness of screening for SMI as part of HF risk assessment, and to identify preventive therapies to improve the risk of HF among patients with SMI.

The objective of this analysis was to determine the natural history and prospective association of cardiovascular risk factors with early repolarization (ER). ER is common and has been suggested to increase risk for cardiovascular mortality in middle-aged adults. Data are sparse regarding the natural history of ER from young adulthood to middle age. We examined 5,069 participants (mean age 25 years at baseline; 40% black) from the CARDIA (Coronary Artery Risk Development in Young Adults) cohort over 20 years. Electrocardiograms were recorded at years 0 (Y0), 7 (Y7), and 20 (Y20) and coded as either definite, probable, possible, or no ER. Logistic regression was used to determine the association of cardiovascular risk factors with the presence of ER cross-sectionally and prospectively. A total of 941 of the 5,069 participants (18.6%) had definite ER at baseline, and only 119 of 2,505 participants (4.8%) at the Y20 examination still demonstrated the presence of ER. Younger age, black race, male sex, longer exercise duration and QRS duration, and lower body mass index (BMI), heart rate, QT index, and Cornell voltage were associated cross-sectionally with the presence of ER. Predictors of maintenance of ER from Y0 to Y20 were black race (odds ratio [OR]: 2.62; 95% CI; 1.61 to 4.25), BMI (OR: 0.62 per 1 SD; 95% CI: 0.40 to 0.94), serum triglyceride levels (OR: 0.66 per 1 SD; 95% CI: 0.45 to 0.98), and QRS duration (OR: 1.68 per 1 SD; 95% CI: 1.37 to 2.06) at baseline. The prevalence of ER was significantly higher than previous estimates among asymptomatic young adults, and the majority of ER regressed by middle age. Black race, lower BMI, lower serum triglyceride levels, and longer QRS duration were independently associated with maintenance of ER over time.

Background: Low serum magnesium (Mg) has been associated with an increased risk of cardiovascular disease (CVD), including ventricular arrhythmias, but the association between serum or dietary Mg and atrial fibrillation (AF) has not been investigated. Methods and Results: A total of 14,290 men and women (75% white; 53% female; mean age, 54 years) free of AF at baseline participating in the Atherosclerosis Risk in Communities study in the United States, were studied. Incident AF cases through 2009 were ascertained from electrocardiograms, hospital discharge codes, and death certificates. Multivariate Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for AF associated with serum and dietary Mg quintiles. Over a median follow-up time of 20.6 years, 1,755 incident AF cases were identified. In multivariate models, lower serum Mg was associated with higher AF risk: compared to individuals in the middle quintile (≥0.80–0.83mmol/L), the HR (95% CI) of AF in quintiles 1, 2, 4, and 5 were 1.34 (1.16–1.54), 0.99 (0.85–1.16), 1.04 (0.90–1.22), and 1.06 (0.91–1.23), respectively. There was no evidence of significant interactions between serum Mg and sex or race. No association between dietary Mg and AF risk was observed. Conclusions: Lower serum Mg was associated with a higher AF risk, and this association was not different between whites and African Americans. Dietary Mg was not associated with AF risk. (Circ J 2013; 77: 323–329)

Several reports have demonstrated that prolongation of the QT interval is associated with sudden cardiac death (SCD). However, it is unknown whether any of the components within the QT interval are responsible for its association with SCD.We examined the association of the individual QT-interval components (R-wave onset to R-peak, R-peak to R-wave end, ST-segment, T-wave onset to T-peak, and T-peak to T-wave end) with SCD in 12 241 participants (54±5.7 years; 26% black; 55% women) from the ARIC study (Atherosclerosis Risk in Communities). The QT interval and its components were measured at baseline (1987-1989) from 12-lead ECGs. SCD cases were adjudicated by a group of physicians through December 31, 2012. During a median follow-up of 23.6 years, a total of 346 cases of SCD were identified. Although prolongation of the QT interval was associated with a 49% increased risk of SCD (hazard ratio, 1.49; 95% confidence interval, 1.01-2.18), only the T-wave onset to T-peak component (per 1-SD increase: hazard ratio, 1.19; 95% confidence interval, 1.06-1.34) was associated with SCD and not any of the other components in separate models. When all of the QT-interval components were included in the same model, T-wave onset to T-peak remained the strongest predictor of SCD (per 1-SD increase: hazard ratio, 1.21; 95% confidence interval, 1.06-1.37).The risk of SCD with the QT interval is driven by prolongation of the T-wave onset to T-peak component. This suggests that shifting the focus from the overall QT interval to its individual components will refine SCD prediction in the community.

This study sought to examine the association between left ventricular hypertrophy (LVH), defined by cardiac magnetic resonance (CMR) and electrocardiography (ECG), with incident atrial fibrillation (AF).Previous studies of the association between AF and LVH were based primarily on echocardiographic measures of LVH.The MESA (Multi-Ethnic Study of Atherosclerosis) enrolled 4,942 participants free of clinically recognized cardiovascular disease. Incident AF was based on MESA-ascertained hospital-discharge International Classification of Diseases codes and Centers for Medicare and Medicaid Services inpatient hospital claims. CMR-LVH was defined as left ventricular mass ≥95th percentile of the MESA population distribution. Eleven ECG-LVH criteria were assessed. The association of LVH with incident AF was evaluated using multivariable Cox proportional hazards models adjusted for CVD risk factors.During a median follow-up of 6.9 years, 214 incident AF events were documented. Participants with AF were more likely to be older, hypertensive, and overweight. The risk of AF was greater in participants with CMR-derived LVH (hazard ratio [HR]: 2.04, 95% confidence interval [CI]: 1.15 to 3.62). AF was associated with ECG-derived LVH measure of Sokolow-Lyon voltage product after adjusting for CMR-LVH (HR: 1.83, 95% CI: 1.06 to 3.14, p = 0.02). The associations with AF for CMR-LVH and Sokolow-Lyon voltage product were attenuated when adjusted for CMR left atrial volumes.In a multiethnic cohort of participants without clinically detected cardiovascular disease, both CMR and ECG-derived LVH were associated with incident AF. ECG-LVH showed prognostic significance independent of CMR-LVH. The association was attenuated when adjusted for CMR left atrial volumes.

<h3>Objective</h3> Migraine with visual aura is associated with cardioembolic stroke risk. The aim of this study was to test association between migraine with visual aura and atrial fibrillation (AF), in the Atherosclerosis Risk in Communities study. <h3>Methods</h3> In the Atherosclerosis Risk in Communities study, a longitudinal, community-based cohort study, participants were interviewed for migraine history in 1993–1995 and were followed for incident AF through 2013. AF was adjudicated using ECGs, discharge codes, and death certificates. Multivariable Cox proportional hazards models were used to study the relation between migraine and its subtypes with incident AF, compared with controls without headaches. Mediation analysis was conducted to test whether AF was a mediator of migraine with visual aura-associated stroke risk. <h3>Results</h3> Of 11,939 participants assessed for headache and without prior AF or stroke, 426 reported migraines with visual aura, 1,090 migraine without visual aura, 1,018 nonmigraine headache, and 9,405 no headache. Over a 20-year follow-up period, incident AF was noted in 232 (15%) of 1,516 with migraine and 1,623 (17%) of 9,405 without headache. After adjustment for multiple confounders, migraine with visual aura was associated with increased risk of AF compared to no headache (hazard ratio 1.30, 95% confidence interval 1.03–1.62) as well as when compared to migraine without visual aura (hazard ratio 1.39, 95% confidence interval 1.05–1.83). The data suggest that AF may be a potential mediator of migraine with visual aura–stroke risk. <h3>Conclusions</h3> Migraine with aura was associated with increased risk of incident AF. This may potentially lead to ischemic strokes.

Patch electrocardiographic (ECG) monitors permit extended noninvasive ambulatory monitoring. To guide use of these devices, information is needed about their performance. We sought to determine in a large general population sample the acceptability of patch ECG monitors, the yield of arrhythmia detection, and the consistency of findings in participants monitored twice.

Atrial fibrillation (AF) is the most common sustained arrhythmia in patients with chronic kidney disease (CKD). In this study, we examined the association between inflammation and AF in 3,762 adults with CKD, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. AF was determined at baseline by self-report and electrocardiogram (ECG). Plasma concentrations of interleukin(IL)-1, IL-1 Receptor antagonist, IL-6, tumor necrosis factor (TNF)-α, transforming growth factor-β, high sensitivity C-Reactive protein, and fibrinogen, measured at baseline. At baseline, 642 subjects had history of AF, but only 44 had AF in ECG recording. During a mean follow-up of 3.7 years, 108 subjects developed new-onset AF. There was no significant association between inflammatory biomarkers and past history of AF. After adjustment for demographic characteristics, comorbid conditions, laboratory values, echocardiographic variables, and medication use, plasma IL-6 level was significantly associated with presence of AF at baseline (Odds ratio [OR], 1.61; 95% confidence interval [CI], 1.21 to 2.14; P = 0.001) and new-onset AF (OR, 1.25; 95% CI, 1.02 to 1.53; P = 0.03). To summarize, plasma IL-6 level is an independent and consistent predictor of AF in patients with CKD.

Silent myocardial infarction (SMI) accounts for about half of the total number of MIs, and is associated with poor prognosis as is clinically documented MI (CMI). The electrocardiographic (ECG) spatial QRS/T angle has been a strong predictor of cardiovascular outcomes. Whether spatial QRS/T angle also is predictive of SMI, and the easy-to-obtain frontal QRS/T angle will show similar association are currently unknown. We examined the association between the spatial and frontal QRS/T angles, separately, with incident SMI among 9498 participants (mean age 54 years, 57% women, and 20% African-American), who were free of cardiovascular disease at baseline (visit 1, 1987–1989) from the Atherosclerosis Risk in Communities (ARIC) study. Incident SMI was defined as MI occurring after the baseline until visit 4 (1996–1998) without CMI. The frontal plane QRS/T angle was defined as the absolute difference between QRS axis and T axis. Values greater than the sex-specific 95th percentiles of the QRS/T angles were considered wide (abnormal). A total of 317 (3.3%) incident SMIs occurred during a 9-year median follow-up. In a model adjusted for demographics, cardiovascular risk factors and potential confounders, both abnormal frontal (HR 2.28, 95% CI 1.58–3.29) and spatial (HR 2.10, 95% CI 1.44–3.06) QRS/T angles were associated with an over 2-fold increased risk of incident SMI. Similar patterns of associations were observed when the results were stratified by sex. Both frontal and spatial QRS/T angles are predicative of SMI suggesting a potential use for these markers in identifying individuals at risk.

Background The American Heart Association has defined metrics of ideal cardiovascular health known as Life's Simple 7 ( LS 7) to prevent cardiovascular disease. We examined the association between LS 7 and incident atrial fibrillation ( AF ) in a biracial cohort of middle‐ and older‐aged adults without known cardiovascular disease. Methods and Results This analysis included 13 182 ARIC (Atherosclerosis Risk in Communities) study participants (mean baseline age=54±5.7 years; 56% women; 25% black) free of AF and cardiovascular disease. An overall LS 7 score was calculated as the sum of the LS 7 component scores and classified as inadequate (0‐4), average (5‐9), or optimal (10‐14) cardiovascular health. The primary outcome was incident AF , identified primarily by ECG and hospital discharge coding of AF through December 31, 2014. A total of 2266 (17%) incident AF cases were detected over a median follow‐up of 25.1 years. Compared with the inadequate category (n=1057), participants in the average (n=8629) and optimal (n=3496) categories each had a lower risk of developing AF in a multivariable Cox proportional hazards model (hazard ratio 0.59, 95% confidence interval 0.51, 0.67 for average; and hazard ratio 0.38, 95% confidence interval 0.32, 0.44 for optimal). In a similar model, a 1‐point‐higher LS 7 score was associated with a 12% lower risk of incident AF (hazard ratio 0.88, 95% confidence interval 0.86, 0.89). Conclusions A higher LS 7 score is strongly associated with a lower risk of AF in individuals without baseline cardiovascular disease. Determining whether interventions that improve the population's cardiovascular health also reduce AF incidence is needed.

Background Cardiac biomarkers may signal mechanistic pathways involved in heart failure (HF), a leading complication in chronic kidney disease. We tested the associations of NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity troponin T (hsTnT), galectin-3, growth differentiation factor-15 (GDF-15), and soluble ST2 (sST2) with incident HF in chronic kidney disease. Methods and Results We examined adults with chronic kidney disease enrolled in a prospective, multicenter study. All biomarkers were measured at baseline. The primary outcome was incident HF. Secondary outcomes included HF with preserved ejection fraction (EF≥50%) and reduced ejection fraction (EF<50%). Cox models were used to test the association of each cardiac biomarker with HF, adjusting for demographics, kidney function, cardiovascular risk factors, and medication use. Among 3314 participants, all biomarkers, with the exception of galectin-3, were significantly associated with increased risk of incident HF (hazard ratio per SD higher concentration of log-transformed biomarker): NT-proBNP (hazard ratio, 2.07; 95% CI, 1.79-2.39); hsTnT (hazard ratio, 1.38; 95% CI, 1.21-1.56); GDF-15 (hazard ratio, 1.44; 95% CI, 1.26-1.66) and sST2 (hazard ratio, 1.19; 95% CI, 1.05-1.35). Higher NT-proBNP, hsTnT, and GDF-15 were also associated with a greater risk of HF with reduced EF; while higher NT-proBNP GDF-15 and sST2 were associated with HF with preserved EF. Galectin-3 was not associated with either HF with reduced EF or HF with preserved EF. Conclusions In chronic kidney disease, elevations of NT-proBNP, hsTnT, GDF-15, sST2 were associated with incident HF. There was a borderline association of galectin-3 with incident HF. NT-proBNP and hsTnT were more strongly associated with HF with reduced EF, while the associations of the newer biomarkers GDF-15 and sST2 were stronger for HF with preserved EF.

Low heart rate variability (HRV) has been linked to increased total mortality in the general population; however, the relationship between low HRV and sudden cardiac death (SCD) is less well-characterized. The goal of this study was to evaluate the relationship between low HRV and SCD in a community-based cohort. Our cohort consisted of 12,543 participants from the Atherosclerosis Risk in Communities (ARIC) study. HRV measures were derived from 2-minute electrocardiogram recordings obtained during the baseline exam (1987–89). Time domain measurements included the standard deviation of all normal RR intervals (SDNN) and the root mean squared successive difference (r-MSSD). Frequency domain measurements included low frequency power (LF) and high frequency (HF) power. During a median follow-up of 13 years, 215 SCDs were identified from physician adjudication of all coronary heart disease deaths through 2001. In multivariable adjusted Cox proportional hazards models, each standard deviation decrement in SDNN, LF, and HF were associated with 24%, 27% and 16% increase in SCD risk, respectively. Low HRV is independently associated with increased risk of SCD in the general population.

Genome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear. Here, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction. Our approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes.

Background Current literature examining the prospective relationship between depression and other measures of negative affect with atrial fibrillation (AF) are limited. We determined the relationships of depression, anger, anxiety, and chronic stress with incident AF in a multiethnic cohort of middle- and older-aged adults. Methods and Results This analysis included 6644 MESA (Multi-Ethnic Study of Atherosclerosis) study participants who were free of AF at baseline. Depressive symptoms were assessed at baseline and defined as either a 20-item Center for Epidemiologic Studies Depression Scale score ≥16 or use of antidepressant medications. The Spielberger Trait Anger Scale, Spielberger Trait Anxiety Scale, and Chronic Burden Scale were also administered at baseline to assess anger, anxiety, and chronic stress, respectively. The primary outcome was incident AF , identified by follow-up study visit ECGs, hospital discharge diagnoses, or Medicare claims data. A total of 875 (13%) incident AF cases were detected over a median follow-up of nearly 13 years. A Center for Epidemiologic Studies Depression Scale score ≥16 (referent, Center for Epidemiologic Studies Depression Scale score <2) and antidepressant use were associated with a 34% and 36% higher risk of AF , respectively, in separate adjusted Cox proportional hazards analyses (hazard ratio, 1.34; 95% CI 1.04-1.74 for Center for Epidemiologic Studies Depression Scale ≥16; hazard ratio, 1.36; 95% CI , 1.04-1.77 for antidepressant use). No significant associations were observed for anger, anxiety, or chronic stress with development of AF . Conclusions Depressive symptoms are associated with an increased risk of incident AF . Further study into whether improving depressive symptoms reduces AF incidence is important.

Background: The prevalence of subclinical atrial fibrillation (AF) in the elderly general population is unclear. We sought to define the prevalence of subclinical AF in a community-based elderly population and to characterize subclinical AF and the incremental diagnostic yield of 4 versus 2 weeks of continuous ECG monitoring. Methods: We conducted a cross-sectional analysis within the community-based multicenter observational ARIC study (Atherosclerosis Risk in Communities) using visit 6 (2016–2017) data. The 2616 ARIC study participants who wore a leadless, ambulatory ECG monitor (Zio XT Patch) for up to 2 weeks were aged 79±5 years, 42% men, and 26% black. In a subset, 386 participants without clinically recognized AF wore the monitor twice, each time for up to 2 weeks. We characterized the prevalence of subclinical AF (ie, AF detected on the Zio XT Patch without clinically recognized AF) over 2 weeks of monitoring and the diagnostic yield of 4 versus 2 weeks of monitoring. Results: The prevalence of subclinical AF was 2.5%; the prevalence of subclinical AF was 3.3% among white men, 2.5% among white women, 2.1% among black men, and 1.6% among black women. Subclinical AF was mostly intermittent (75%). Among those with intermittent subclinical AF, 91% had AF burden ≤10% during the monitoring period. In a subset of 386 participants without clinical AF, 78% more subclinical AF was detected by 4 weeks versus 2 weeks of ECG monitoring. Conclusions: In our study, the prevalence of subclinical AF was lower than previously reported and monitoring beyond 2 weeks provided substantial incremental diagnostic yield. Future studies should focus on individuals with higher risk to increase diagnostic yield and consider continuous monitoring duration longer than 2 weeks.

We recently described the association between periodontal disease (PD) and stroke risk. The purpose of this study was to test the association between PD, dental care utilization and incident atrial fibrillation (AF), as well as AF as a mediator to PD- stroke association. In dental cohort of the Atherosclerosis Risk in Communities Study (ARIC), participants without prior AF underwent full-mouth periodontal measurements. PD was defined on an ordinal scale as healthy (referent), mild, moderate and severe. In ARIC main cohort, participants were classified as regular or episodic dental care users. These patients were followed for AF, over 17 years. Cox proportional hazards models adjusted for AF risk factors were used to study relationships between PD severity, dental care utilization and AF. Mediation analysis was used to test if AF mediated the PD- stroke association. In dental ARIC cohort, 5,958 were assessed without prior AF, 754 were found to have AF. Severe PD was associated with AF on both univariable (crude HR, 1.54; 95% CI, 1.26-1.87) and multivariable (adjusted HR, 1.31, 95% CI, 1.06-1.62) analyses. Mediation analysis suggested AF mediates the association between PD and stroke. In the main ARIC cohort, 9,666 participants without prior AF were assessed for dental care use, 1558 were found to have AF. Compared with episodic users, regular users had a lower risk for AF on univariable (crude HR, 0.82, 95% CI, 0.74-0.90) and multivariable (adjusted HR, 0.88, 95% CI, 0.78-0.99) analyses. PD is associated with AF. The association may explain the PD-stroke risk. Regular users had a lower risk of incident AF compared with episodic users.