Sandeep R Das

Author(s): Writing Group Members; Mozaffarian, Dariush; Benjamin, Emelia J; Go, Alan S; Arnett, Donna K; Blaha, Michael J; Cushman, Mary; Das, Sandeep R; de Ferranti, Sarah; Despres, Jean-Pierre; Fullerton, Heather J; Howard, Virginia J; Huffman, Mark D; Isasi, Carmen R; Jimenez, Monik C; Judd, Suzanne E; Kissela, Brett M; Lichtman, Judith H; Lisabeth, Lynda D; Liu, Simin; Mackey, Rachel H; Magid, David J; McGuire, Darren K; Mohler, Emile R; Moy, Claudia S; Muntner, Paul; Mussolino, Michael E; Nasir, Khurram; Neumar, Robert W; Nichol, Graham; Palaniappan, Latha; Pandey, Dilip K; Reeves, Mathew J; Rodriguez, Carlos J; Rosamond, Wayne; Sorlie, Paul D; Stein, Joel; Towfighi, Amytis; Turan, Tanya N; Virani, Salim S; Woo, Daniel; Yeh, Robert W; Turner, Melanie B; American Heart Association Statistics Committee; Stroke Statistics Subcommittee

HomeCirculationVol. 133, No. 4Executive Summary: Heart Disease and Stroke Statistics—2016 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—2016 UpdateA Report From the American Heart Association Dariush Mozaffarian, MD, DrPH, FAHA, Emelia J. Benjamin, MD, ScM, FAHA, Alan S. Go, MD, Donna K. Arnett, PhD, MSPH, FAHA, Michael J. Blaha, MD, MPH, Mary Cushman, MD, MSc, FAHA, Sandeep R. Das, MD, MPH, Sarah de Ferranti, MD, MPH, Jean-Pierre Després, PhD, FAHA, Heather J. Fullerton, MD, MAS, Virginia J. Howard, PhD, FAHA, Mark D. Huffman, MD, MPH, FAHA, Carmen R. Isasi, MD, PhD, Monik C. Jiménez, ScD, Suzanne E. Judd, PhD, Brett M. Kissela, MD, MS, FAHA, Judith H. Lichtman, PhD, MPH, Lynda D. Lisabeth, PhD, MPH, FAHA, Simin Liu, MD, ScD, FAHA, Rachel H. Mackey, PhD, MPH, FAHA, David J. Magid, MD, MPH, Darren K. McGuire, MD, MHSc, FAHA, Emile R. MohlerIII, MD, FAHA, Claudia S. Moy, PhD, MPH, Paul Muntner, PhD, Michael E. Mussolino, PhD, FAHA, Khurram Nasir, MD, MPH, Robert W. Neumar, MD, PhD, Graham Nichol, MD, MPH, FAHA, Latha Palaniappan, MD, MS, FAHA, Dilip K. Pandey, MD, PhD, FAHA, Mathew J. Reeves, PhD, FAHA, Carlos J. Rodriguez, MD, MPH, FAHA, Wayne Rosamond, PhD, FAHA, Paul D. Sorlie, PhD, Joel Stein, MD, Amytis Towfighi, MD, Tanya N. Turan, MD, MSCR, FAHA, Salim S. Virani, MD, PhD, Daniel Woo, MD, MS, FAHA, Robert W. Yeh, MD, MSc, FAHA and Melanie B. Turner, MPHon behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Dariush MozaffarianDariush Mozaffarian Search for more papers by this author , Emelia J. BenjaminEmelia J. Benjamin Search for more papers by this author , Alan S. GoAlan S. Go Search for more papers by this author , Donna K. ArnettDonna K. Arnett Search for more papers by this author , Michael J. BlahaMichael J. Blaha Search for more papers by this author , Mary CushmanMary Cushman Search for more papers by this author , Sandeep R. DasSandeep R. Das Search for more papers by this author , Sarah de FerrantiSarah de Ferranti Search for more papers by this author , Jean-Pierre DesprésJean-Pierre Després Search for more papers by this author , Heather J. FullertonHeather J. Fullerton Search for more papers by this author , Virginia J. HowardVirginia J. Howard Search for more papers by this author , Mark D. HuffmanMark D. Huffman Search for more papers by this author , Carmen R. IsasiCarmen R. Isasi Search for more papers by this author , Monik C. JiménezMonik C. Jiménez Search for more papers by this author , Suzanne E. JuddSuzanne E. Judd Search for more papers by this author , Brett M. KisselaBrett M. Kissela 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 , Simin LiuSimin Liu Search for more papers by this author , Rachel H. MackeyRachel H. Mackey Search for more papers by this author , David J. MagidDavid J. Magid Search for more papers by this author , Darren K. McGuireDarren K. McGuire Search for more papers by this author , Emile R. MohlerIIIEmile R. MohlerIII Search for more papers by this author , Claudia S. MoyClaudia S. Moy Search for more papers by this author , Paul MuntnerPaul Muntner Search for more papers by this author , Michael E. MussolinoMichael E. Mussolino Search for more papers by this author , Khurram NasirKhurram Nasir Search for more papers by this author , Robert W. NeumarRobert W. Neumar Search for more papers by this author , Graham NicholGraham Nichol Search for more papers by this author , Latha PalaniappanLatha Palaniappan Search for more papers by this author , Dilip K. PandeyDilip K. Pandey Search for more papers by this author , Mathew J. ReevesMathew J. Reeves Search for more papers by this author , Carlos J. RodriguezCarlos J. Rodriguez Search for more papers by this author , Wayne RosamondWayne Rosamond Search for more papers by this author , Paul D. SorliePaul D. Sorlie Search for more papers by this author , Joel SteinJoel Stein Search for more papers by this author , Amytis TowfighiAmytis Towfighi 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 , Daniel WooDaniel Woo Search for more papers by this author , Robert W. YehRobert W. Yeh 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 published26 Jan 2016https://doi.org/10.1161/CIR.0000000000000366Circulation. 2016;133:447–454Table of Contents*Summary e391. About These Statistics e462. Cardiovascular Health e49Health Behaviors3. Smoking/Tobacco Use e684. Physical Inactivity e785. Nutrition e896. Overweight and Obesity e110Health Factors and Other Risk Factors7. Family History and Genetics e1218. High Blood Cholesterol and Other Lipids e1279. High Blood Pressure e13510. Diabetes Mellitus e14811. Metabolic Syndrome e16212. Chronic Kidney Disease e178Cardiovascular Conditions/Diseases13. Total Cardiovascular Diseases e18414. Stroke (Cerebrovascular Disease) e20415. Congenital Cardiovascular Defects and Kawasaki Disease e23516. Disorders of Heart Rhythm e24717. Sudden Cardiac Arrest e26818. Subclinical Atherosclerosis e27919. Coronary Heart Disease, Acute Coronary Syndrome, and Angina Pectoris e29220. Cardiomyopathy and Heart Failure e30721. Valvular, Venous, and Aortic Diseases e31622. Peripheral Artery Disease e324Outcomes23. Quality of Care e33024. Medical Procedures e34425. Economic Cost of Cardiovascular Disease e349Supplemental Materials26. At-a-Glance Summary Tables e35427. Glossary e358SummaryEach 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 related to heart disease, stroke, and other cardiovascular and metabolic diseases and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, healthcare administrators, researchers, and others seeking the best available data on these conditions. Together, cardiovascular disease (CVD) and stroke produce immense health and economic burdens in the United States and globally. The Statistical Update brings together in a single document up-to-date information on the core health behaviors (including diet, physical activity [PA], smoking, and energy balance) and health factors (including blood pressure, cholesterol, and glucose) that define cardiovascular health; a range of major clinical disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, and peripheral arterial disease); and the associated outcomes (including quality of care, procedures, and economic costs). Since 2006, the annual versions of the Statistical Update have been cited >28 000 times in the literature. In 2014 alone, the various Statistical Updates were cited >5000 times.Each annual version of the Statistical Update undergoes major revisions to include the newest nationally representative data, add additional relevant published scientific findings, remove older information, add new sections or chapters, and increase the number of ways to access and use the assembled information. This year-long process, which begins as soon as the previous Statistical Update is published, is performed by the AHA Statistics Committee faculty volunteers and staff. For example, this year’s edition includes new data on the monitoring and benefits of cardiovascular health in the population, new metrics to assess and monitor healthy diets, additional information in many chapters on the global CVD and stroke burden, new information on stroke in young adults, a new focus on underserved and minority populations, and further evidence-based approaches to changing behaviors, implementation strategies, and implications of the AHA’s 2020 Impact Goals. Below are a few highlights from this year’s Update.Current Status of Cardiovascular Health in the United States (Chapter 2)The concept of cardiovascular health represents a heightened focus for the AHA, with 3 central and novel emphases:—An expanded focus on not only CVD prevention but also promotion of positive cardiovascular health, in addition to the treatment of established CVD—The prioritization of both health behaviors (healthy diet pattern, appropriate energy balance, PA, and nonsmoking) and health factors (optimal blood lipids, blood pressure, glucose levels) throughout the lifespan as primary goals unto themselves—Population-level health promotion strategies to shift the majority of the public toward greater cardiovascular health, in addition to targeting those individuals at greatest CVD risk, because CVD occurs at all risk levels across the population and because healthy lifestyles are uncommon throughout the US populationAmong children, the prevalence of ideal levels of cardiovascular health behaviors and factors currently varies from <1% for the healthy diet pattern to >80% for the smoking, blood pressure, and fasting glucose metrics.Among US adults, the prevalence of ideal levels of cardiovascular health behaviors and factors currently varies from about 1.5% for the healthy diet pattern to up to 78% for the smoking metric (never having smoked or being a former smoker who has quit for >12 months).Fewer children over time are meeting the ideal body mass index metric, whereas more are meeting the ideal smoking and total cholesterol metrics. Other metrics do not show consistent trends over time in children.More adults over time are meeting the smoking metric, whereas fewer are meeting the body mass index and glucose metrics. Trends for other metrics are not evident over time in adults.Effective Approaches to Improve Cardiovascular Health (Chapter 2)The current evidence supports a range of complementary strategies to improve cardiovascular health, including the following:—Individual-focused approaches, which target lifestyle and treatments at the individual level—Healthcare systems approaches, which encourage, facilitate, and reward efforts by providers and patients to improve health behaviors and health factors—Population approaches, which target lifestyle and treatments in schools or workplaces, local communities, and states, as well as throughout the nationSuch approaches can focus on both (1) improving cardiovascular health among those who currently have less than optimal levels and (2) preserving cardiovascular health among those who currently have ideal levels (in particular, children, adolescents, and young adults) as they age.The metrics with the greatest potential for improvement are health behaviors, including diet quality, PA, and body weight. However, each of the cardiovascular health metrics can be improved and deserves major focus.Health Behaviors (Chapters 3 to 6)Based on comparable risk assessment methods, poor lifestyle behaviors and lifestyle-related risk factors are the foremost causes of death and disability in the United States and in the world.Smoking/Tobacco Use (Chapter 3)Although tobacco use has declined substantially in the United States, it remains the second-leading cause of total deaths and disability. The percentage of adults who reported current cigarette use declined from 24.1% in 1998 to 16.9% in 2014; among high school students, the decline was from 36.4% in 1997 to 5.6% in 2013. Still, almost one third of coronary heart disease deaths are attributable to smoking and exposure to secondhand smoke.Declines in tobacco usage in the United States may be threatened by the >450 e-cigarette products that were available in 2014. To date, the risks and benefits of e-tobacco products remain controversial but are an area of intense investigation by scientists, as well as scrutiny by the US Food and Drug Administration. Public health experts are concerned that although e-cigarettes are thought to have a lower risk of harmful effects than conventional cigarettes, they may be a gateway to smoking traditional cigarettes or may promote relapse among former smokers, which could erode gains in the public’s awareness of the harms of tobacco products.Cigarette smoking is associated with 9% of annual aggregated healthcare spending in the United States. Annual smoking-attributable economic costs in the United States, including direct medical costs and lost productivity, are estimated to exceed $289 billion.Physical Inactivity (Chapter 4)In 2013, 15.2% of adolescents reported being inactive during the prior week, and inactivity was more likely to be reported by girls (19.2%) than boys (11.2%). Inactivity was more commonly reported by black (27.3%) and Hispanic (20.3%) girls than their white counterparts (16.1%); similarly, black (15.2%) and Hispanic (12.1%) boys reported more inactivity than white boys (9.2%).According to 2014 National Health Interview Survey data, only half of American adults met the current aerobic PA guidelines (≥150 minutes of moderate PA or 75 minutes of vigorous PA or an equivalent combination each week). Women (47.0%) were less likely to meet the guidelines than men (53.2%), and non-Hispanic blacks (43.5%) and Hispanics (41.3%) were less likely to meet them than non-Hispanic whites (53.5%).Unfortunately, the proportion of individuals meeting PA recommendations is likely to be lower than indicated by self-report data. Studies examining actual (with accelerometers, pedometers, etc) versus self-reported PA indicate that both men and women overestimate their PA substantially (by 44% and 138% for men and women, respectively).Nutrition (Chapter 5)The leading risk factor for death and disability in the United States is suboptimal diet quality, which in 2010 led to 678 000 annual deaths attributable to all causes. Major contributors were insufficient intakes of fruits, nuts/seeds, whole grains, vegetables, and seafood, as well as excess intakes of sodium. In the United States, an estimated 58 000 annual CVD deaths in 2010 were attributable to sodium intake >2.0 g/d, representing 1 in 16 (6.3%) of all CVD deaths and 1 in 8 (13.1%) CVD deaths before age 70 years. Globally, an estimated 1.65 million annual CVD deaths were attributable to sodium intake >2.0 g/d, representing nearly 1 in 10 (9.5%) of all CVD deaths.Between 2003 and 2012, certain aspects of diet quality improved in the United States, including increases in whole grains and reductions in sugar-sweetened beverages. The prevalence of both children and adults meeting the dietary goals improved between 2003 to 2004 and 2011 to 2012. The prevalence of ideal levels of diet (healthy diet score >80) increased from 0.2% to 0.6% in children and from 0.7% to 1.5% in adults. During this period, the proportion of youths aged 5 to 19 years with poor scores on the dietary metric for cardiovascular health decreased steadily from 69.2% to 54.6%, whereas for adults, the decrease was from 50.3% to 41.0%.Although healthier diets cost modestly more than unhealthful diets, comparing extremes of unhealthful versus healthful food-based diet patterns, the more healthful patterns cost on average ≈$1.50 per day more. Similarly priced options are also common; in a comparison of 20 fruits and vegetables versus 20 common snack foods such as cookies, chips, pastries, and crackers, the average price per portion of fruits and vegetables was 31 cents, with an average of 57 calories per portion, versus 33 cents and 183 calories per portion for snack foods.Obesity (Chapter 6)Although the overall prevalence of obesity in US youth did not change between 2003 to 2004 and 2011 to 2012, the prevalence decreased among those aged 2 to 5 years. Obesity decreased among those of higher socioeconomic status but increased among those of lower socioeconomic status. In addition, the overall prevalence of severe obesity in US youth continued to increase, especially among adolescent boys.Overweight and obesity predispose individuals to most major risk factors, including physical inactivity, hypertension, hyperlipidemia, and diabetes mellitus.Excess body weight is among the leading causes of death and disability in the United States and globally, with burdens expected to increase in coming years.Among overweight and obese individuals, existing cardiometabolic risk factors should be monitored and treated intensively with diet quality, PA, and pharmacological or other treatments as necessary. Each of these interventions provides benefits independent of weight loss and maintenance.Estimated mean annual per capita healthcare expenses attributable to obesity are $1160 for men and $1525 for women.Health Factors (Chapters 7 to 12)The prevalence and control of cardiovascular health factors remains a major issue for many Americans.Family History and Genetics (Chapter 7)Familial aggregation of CVD is related to clustering of specific lifestyle and other risk factors, each of which has environmental and genetic contributors. Patients with a family history of coronary artery disease have a higher prevalence of traditional CVD risk factors, underscoring opportunities for prevention.The risk of most CVD conditions is higher in the presence of a family history, including CVD (45% higher odds with sibling history), stroke (50% higher odds with history in a first-degree relative), atrial fibrillation (AF; 80% higher odds with parental history), heart failure (70% higher odds with parental history), and peripheral arterial disease (80% higher odds with family history). This excess risk reflects genetic, epigenetic, and shared behavioral and environmental risk factors.High Blood Cholesterol and Other Lipids (Chapter 8)75.7% of children and 46.6% of adults have ideal cholesterol levels (untreated total cholesterol <170 mg/dL for children and <200 mg/dL for adults). Prevalence of ideal levels has improved over the past decade in children but remained the same in adults.According to 2009 to 2012 data, >100 million US adults ≥20 years of age have total cholesterol levels ≥200 mg/dL; almost 31 million have levels ≥240 mg/dL.During 2003 to 2012, the percentage of adults aged ≥40 years who had used a cholesterol-lowering medication in the past 30 days increased from 20% to 28%.High Blood Pressure (Chapter 9)Based on 2009 to 2012 data, 32.6% of US adults ≥20 years of age have hypertension, which represents ≈80.0 million US adults. African American adults have among the highest prevalence of hypertension in the world. Among non-Hispanic black men and women, the age-adjusted prevalence of hypertension was 44.9% and 46.1%, respectively.National Health and Nutrition Examination Survey (NHANES) data from 2009 to 2012 revealed that among US adults with hypertension, 54.1% were controlled, 76.5% were currently treated, 82.7% were aware they had hypertension, and 17.3% were undiagnosed.From 2003 to 2013, the death rate attributable to high blood pressure increased 8.2%, and the actual number of deaths rose 34.7% (National Heart, Lung, and Blood Institute tabulation). During this 10-year period, the corresponding values were a 14.4% and 30.9% increase in non-Hispanic whites; a 1.7% and 75.5% increase in Hispanics; and a 9.1% decrease and 18.4% increase in non-Hispanic blacks.Diabetes Mellitus (Chapter 10)Diabetes mellitus affects 1 in 10 US adults, with 90% to 95% of cases being type 2 diabetes mellitus. Diabetes mellitus disproportionately affects racial/ethnic minorities. Type 2 diabetes mellitus is increasingly common in children and adolescents; the disease historically was diagnosed primarily in adults ≥40 years of age. The prevalence of type 2 diabetes mellitus in children/adolescents has increased by 30.5% between 2001 and 2009, and it now constitutes ≈50% of all childhood diabetes mellitus.Diabetes mellitus is associated with reduced longevity; men and women with diabetes mellitus live an average of 7.5 and 8.2 years less, respectively, than their counterparts without diabetes mellitus.Metabolic Syndrome (Chapter 11)From 1999 to 2010, the age-adjusted national prevalence of metabolic syndrome in the United States peaked (in 2001–2002) and began to fall. This is attributable to decreases in the age-adjusted prevalence among women and no change in men. In addition, there has been variation in the trends over time for each individual component of the metabolic syndrome. Generally, the national prevalences of hypertriglyceridemia and elevated blood pressure have decreased, whereas hyperglycemia and elevated waist circumference have increased. However, these trends also vary significantly by sex and race/ethnicity.Perhaps most importantly with respect to meeting the 2020 goals, the prevalence of metabolic syndrome increases with greater cumulative life-course exposure to sedentary behavior and physical inactivity; screen time, including television viewing; fast food intake; short sleep duration; and intake of sugar-sweetened beverages. Each of these risk factors is reversible with lifestyle change.Cardiovascular Conditions/Diseases (Chapters 13 to 22)Rates of death attributable to CVD have declined in the United States, but the burden remains high.Total Cardiovascular Diseases (Chapter 13)The 2013 overall rate of death attributable to CVD was 222.9 per 100 000 Americans. The death rates were 269.8 for males and 184.8 for females. The rates were 270.6 for non-Hispanic white males, 356.7 for non-Hispanic black males, 197.4 for Hispanic males, 183.8 for non-Hispanic white females, 246.6 for non-Hispanic black females, and 136.4 for Hispanic females.From 2003 to 2013, death rates attributable to CVD declined 28.8%. In the same 10-year period, the actual number of CVD deaths per year declined by 11.7%. Yet in 2013, CVD still accounted for 30.8% (800 937) of all 2 596 993 deaths, or ≈1 of every 3 deaths in the United States.On the basis of 2013 death rate data, >2200 Americans die of CVD each day, an average of 1 death every 40 seconds. Approximately 155 000 Americans who died of CVD in 2013 were <65 years of age. In 2013, 35% of deaths attributable to CVD occurred before the age of 75 years, which is younger than the current average life expectancy of 78.8 years.For the first time since 1983, more males (402 851) died of CVD than females (398 086).Stroke (Chapter 14)In 2013, stroke fell from the fourth to the fifth leading cause of death in the United States, behind diseases of the heart, cancer, chronic lower respiratory diseases, and unintentional injury.From 2003 to 2013, the relative rate of stroke death fell by 33.7% and the actual number of stroke deaths declined by 18.2%. Yet each year, ≈795 000 people continue to experience a new or recurrent stroke (ischemic or hemorrhagic). Approximately 610 000 of these are first events and 185 000 are recurrent stroke events. In 2013, stroke caused ≈1 of every 20 deaths in the United States. On average, every 40 seconds, someone in the United States has a stroke, and someone dies of one approximately every 4 minutes.The decline in stroke mortality over the past decades, a major improvement in population health observed for both sexes and all race and age groups, has resulted from reduced stroke incidence and lower case fatality rates. The significant improvements in stroke outcomes are concurrent with cardiovascular risk factor control interventions. The hypertension control efforts initiated in the 1970s appear to have had the most substantial influence on the accelerated decline in stroke mortality, with lower blood pressure distributions in the population. Control of diabetes mellitus and high cholesterol and smoking cessation programs, particularly in combination with hypertension treatment, also appear to have contributed to the decline in stroke mortality.Approximately 10% of all strokes occur in people 18 to 50 years of age. Between 1995 and 2008, National Health Interview Survey data reveal that hospitalizations for ischemic stroke increased among adolescents and young adults (aged 5–44 years), whereas subarachnoid hemorrhage hospitalizations decreased during that same time period.Stroke death rates declined more among people aged ≥65 years (−54.1%; from 534.1 to 245.2 per 100 000) than among those aged 45 to 64 years (−53.6%; from 43.5 to 20.2 per 100 000) or those aged 18 to 44 years (−45.9%; from 3.7 to 2.0 per 100 000).Atrial Fibrillation (Chapter 16)Multiple lines of evidence have increased awareness of the burden of unrecognized AF. In individuals without a history of AF with recent pacemaker or defibrillator implantation, subclinical atrial tachyarrhythmias were detected in 10.1% of patients. Subclinical atrial tachyarrhythmias were associated with a 5.6-fold higher risk of clinical AF and ≈13% of ischemic strokes or embolism. A recent systematic review suggested that one needs to screen 170 community-based individuals at least 65 years of age to detect 1 case of AF.In the Framingham Heart Study, there have been striking temporal trends in the epidemiology of AF documented over 50 years. The age-adjusted incidence and prevalence of AF in the white participants increased ≈4-fold, yet the multivariable adjusted hazard of stroke (74%) and death (25%) associated with AF declined over the same time period. Less is known about the epidemiology of AF over time in ethnic/racial minorities.Secondary analyses of observational and randomized data generally support benefits of risk factor modification for primary prevention of AF. There is also growing evidence supporting the value of risk factor reduction, particularly weight management and exercise, in secondary prevention of AF recurrences and symptoms.Sudden Cardiac Arrest (Chapter 17)Each year ≈359 800 people experienced emergency medical services–assessed out-of-hospital cardiac arrests in the United States. Survival to hospital discharge after nontraumatic emergency medical services–treated cardiac arrest with any first recorded rhythm was 10.6% for patients of any age. Of the ≈20 150 bystander-witnessed out-of-hospital cardiac arrests in 2011, 31.4% of victims survived to hospital discharge.Each year, ≈209 000 people are treated for in-hospital cardiac arrest.Subclinical Atherosclerosis (Chapter 18) and Coronary Heart Disease (Chapter 19)CAC was noted as highly predictive of CHD event risk across all age groups, suggesting that once CAC is known, chronological age has less importance. Compared with a CAC score of 0, CAC >100 imparted an increased multivariable-adjusted CHD event risk in younger individuals (45-54 years old) with an HR of 12.4. The respective risk was similar even in the very elderly (75-84 years of age) with an HR of 12.1.Coronary heart disease alone caused ≈1 of every 7 deaths in the United States in 2013. In 2013, 370 213 Americans died of coronary heart disease. Each year, an estimated ≈660 000 Americans have a new coronary attack (defined as first hospitalized myocardial infarction or coronary heart disease death) and ≈305 000 have a recurrent attack. It is estimated that an additional 160 000 silent myocardial infarctions occur each year. Approximately every 34 seconds, 1 American has a coronary event, and approximately every 1 minute 24 seconds, an American will die of one.Heart Failure (Chapter 20)In 2013, 1 in 9 death certificates (284 388 deaths) in the United States mentioned heart failure. Heart failure was the underlying cause in 58 309 of those deaths. The number of any-mention deaths attributable to heart failure was approximately as high in 1995 (287 000) as it was in 2013 (284 000). Additionally, hospital discharges for heart failure remained stable from 2000 to 2010, with first-listed discharges of 1 008 000 and 1 023 000, respectively.Mortality declines in heart failure have been documented, likely related to evidence-based approaches to treat heart failure risk factors and to implementation of angiotensin-converting enzyme inhibitors, β-blockers, coronary revascularization, implantable cardioverter-defibrillators, and cardiac resynchronization therapeutic strategies.Valvular, Venous, and Aortic Diseases (Chapter 21) and Peripheral Artery Disease (Chapter 22)Data suggest that the prevalence of any valve disease is 2.5%, with no difference between men and women.In 2013, 50 222 deaths were related to valvular HD. Of those, 67.5% were due to aortic valve disorders.PAD affects ≈8.5 million Americans aged ≥40 years and is associated with significant morbidity and mortality.In 2013, PAD any-mention mortality was 61 097. PAD was the underlying cause in 13 639 of those deaths.The risk factors for PAD are similar but not identical to those for CHD. DM and cigarette smoking are stronger risk factors for PAD than for CHD. Most studies suggest that the prevalence of PAD is similar in men and women. Metabolic syndrome in older persons (driven most prominently by the HBP component) and elevated inflammation markers are also risk factors.Cardiovascular Quality of Care, Procedure Utilization, and Costs (Chapters 23 to 25)The Statistical Update provides critical data in several sections on the magnitude of healthcare delivery and costs, as well as the quality of healthcare delivery, r

Detectable levels of cardiac troponin T (cTnT) are strongly associated with structural heart disease and increased risk of death and adverse cardiovascular events; however, cTnT is rarely detectable in the general population using standard assays.To determine the prevalence and determinants of detectable cTnT in the population using a new highly sensitive assay and to assess whether cTnT levels measured with the new assay associate with pathological cardiac phenotypes and subsequent mortality.Cardiac troponin T levels were measured using both the standard and the highly sensitive assays in 3546 individuals aged 30 to 65 years enrolled between 2000 and 2002 in the Dallas Heart Study, a multiethnic, population-based cohort study. Mortality follow-up was complete through 2007. Participants were placed into 5 categories based on cTnT levels.Magnetic resonance imaging measurements of cardiac structure and function and mortality through a median of 6.4 (interquartile range, 6.0-6.8) years of follow-up.In Dallas County, the prevalence of detectable cTnT (≥0.003 ng/mL) was 25.0% (95% confidence interval [CI], 22.7%-27.4%) with the highly sensitive assay vs 0.7% (95% CI, 0.3%-1.1%) with the standard assay. Prevalence was 37.1% (95% CI, 33.3%-41.0%) in men vs 12.9% (95% CI, 10.6%-15.2%) in women and 14.0% (95% CI, 11.2%-16.9%) in participants younger than 40 years vs 57.6% (95% CI, 47.0%-68.2%) in those 60 years and older. Prevalence of left ventricular hypertrophy increased from 7.5% (95% CI, 6.4%-8.8%) in the lowest cTnT category (<0.003 ng/mL) to 48.1% (95% CI, 36.7%-59.6%) in the highest (≥0.014 ng/mL) (P < .001); prevalence of left ventricular systolic dysfunction and chronic kidney disease also increased across categories (P < .001 for each). During a median follow-up of 6.4 years, there were 151 total deaths, including 62 cardiovascular disease deaths. All-cause mortality increased from 1.9% (95% CI, 1.5%-2.6%) to 28.4% (95% CI, 21.0%-37.8%) across higher cTnT categories (P < .001). After adjustment for traditional risk factors, C-reactive protein level, chronic kidney disease, and N-terminal pro-brain-type natriuretic peptide level, cTnT category remained independently associated with all-cause mortality (adjusted hazard ratio, 2.8 [95% CI, 1.4-5.2] in the highest category). Adding cTnT categories to the fully adjusted mortality model modestly improved model fit (P = .02) and the integrated discrimination index (0.010 [95% CI, 0.002-0.018]; P = .01).In this population-based cohort, cTnT detected with a highly sensitive assay was associated with structural heart disease and subsequent risk for all-cause mortality.

This study sought to determine whether there are race and gender differences in the distribution of C-reactive protein (CRP) levels.Few data are available comparing CRP distributions in different race and gender groups. Recent clinical practice recommendations for CRP testing for cardiovascular risk assessment suggest a uniform threshold to define high relative risk (>3 mg/l).We measured CRP in 2,749 white and black subjects ages 30 to 65 participating in the Dallas Heart Study, a multiethnic, population-based, probability sample, and compared levels of CRP between different race and gender groups.Black subjects had higher CRP levels than white subjects (median, 3.0 vs. 2.3 mg/l; p < 0.001) and women had higher CRP levels than men (median, 3.3 vs. 1.8 mg/l; p < 0.001). The sample-weight adjusted proportion of subjects with CRP levels >3 mg/l was 31%, 40%, 51%, and 58% in white men, black men, white women, and black women, respectively (p < 0.05 for each group vs. white men). After adjustment for traditional cardiovascular risk factors, estrogen and statin use, and body mass index, a CRP level >3 mg/l remained more common in white women (odds ratio [OR] 1.6; 95% confidence interval [CI] 1.1 to 2.5) and black women (OR 1.7; 95% CI 1.2 to 2.6) but not in black men (OR, 1.3; 95% CI, 0.8 to 1.9) when compared with white men.Significant race and gender differences exist in the population distribution of CRP. Further research is needed to determine whether race and gender differences in CRP levels contribute to differences in cardiovascular outcomes, and whether thresholds for cardiovascular risk assessment should be adjusted for different race and gender groups.

The prevalence and determinants of cardiac troponin T (cTnT) elevation in the general population are unknown, and the significance of minimally increased cTnT remains controversial. Our objective was to determine the prevalence and determinants of cTnT elevation in a large, representative sample of the general population.cTnT was measured from stored plasma samples in 3557 subjects of the Dallas Heart Study, a population-based sample. cTnT elevation (> or =0.01 microg/L) was correlated with clinical variables and cardiac MRI findings. The sample weight-adjusted prevalence of cTnT elevation in the general population was 0.7%. In univariable analyses, cTnT elevation was associated with older age, black race, male sex, coronary artery calcium by electron beam CT, a composite marker of congestive heart failure (CHF), left ventricular hypertrophy (LVH), diabetes mellitus (DM), and chronic kidney disease (CKD) (P<0.001 for each). Subjects with minimally increased (0.01 to 0.029 microg/L) and increased (> or =0.03 microg/L) cTnT had a similar prevalence of these characteristics. In multivariable logistic regression analysis, LVH, CHF, DM, and CKD were independently associated with cTnT elevation.In the general population, cTnT elevation is rare in subjects without CHF, LVH, CKD, or DM, suggesting that the upper limit of normal for the immunoassay should be <0.01 microg/L. Even minimally increased cTnT may represent subclinical cardiac injury and have important clinical implications, a hypothesis that should be tested in longitudinal outcome studies.

The association between higher body mass index (BMI) and lower B-type natriuretic peptide (BNP) level is thought to be mediated by expression of the natriuretic peptide clearance receptor (NPR-C) in adipose tissue. To explore this association, we tested 2 hypotheses: (1) that N-terminal (NT)-proBNP, which is not believed to bind NPR-C, would not be associated with BMI and (2) that lower BNP would be more closely associated with fat mass than with lean mass.Measurements of BNP, NT-proBNP, and body composition by direct dual energy x-ray absorptiometry (DEXA) were performed in 2707 subjects from the Dallas Heart Study. The associations between obesity and low BNP (<4 ng/L) or low NT-proBNP (lowest sex-specific quartile) were evaluated with multivariable logistic regression models stratified by sex and adjusted for age, race/ethnicity, hypertension, left ventricular mass, and end-diastolic volume. Higher BMI was independently associated with lower BNP and NT-proBNP (all P<0.001). When BMI was replaced with both DEXA-derived lean and fat mass, greater lean mass, but not fat mass, was associated with low BNP and NT-proBNP levels.In a large, population-based cohort, we confirm the previously described association between higher BMI and lower BNP and demonstrate a similar inverse association between BMI and NT-proBNP. Interestingly, both BNP and NT-proBNP are more closely associated with lean mass than with fat mass. These findings do not support the hypothesis that the lower BNP levels seen in obesity are driven by enhanced BNP clearance mediated via NPR-C.

Objective : Visceral (VAT) and abdominal subcutaneous (SAT) adipose tissues contribute to obesity but may have different metabolic and atherosclerosis risk profiles. We sought to determine the associations of abdominal VAT and SAT mass with markers of cardiac and metabolic risk in a large, multiethnic, population‐based cohort of obese adults. Design and Methods : Among obese participants in the Dallas Heart Study, we examined the cross‐sectional associations of abdominal VAT and SAT mass, assessed by magnetic resonance imaging (MRI) and indexed to body surface area (BSA), with circulating biomarkers of insulin resistance, dyslipidemia, and inflammation ( n = 942); and with aortic plaque and liver fat by MRI and coronary calcium by computed tomography ( n = 1200). Associations of VAT/BSA and SAT/BSA were examined after adjustment for age, sex, race, menopause, and body mass index. Results : In multivariable models, VAT significantly associated with the homeostasis model assessment of insulin resistance (HOMA‐IR), lower adiponectin, smaller LDL and HDL particle size, larger VLDL size, and increased LDL and VLDL particle number ( p &lt; 0.001 for each). VAT also associated with prevalent diabetes, metabolic syndrome, hepatic steatosis, and aortic plaque ( p &lt; 0.001 for each). VAT independently associated with C‐reactive protein but not with any other inflammatory biomarkers tested. In contrast, SAT associated with leptin and inflammatory biomarkers, but not with dyslipidemia or atherosclerosis. Associations between SAT and HOMA‐IR were significant in univariable analyses but attenuated after multivariable adjustment. Conclusion : VAT associated with an adverse metabolic, dyslipidemic, and atherogenic obesity phenotype. In contrast, SAT demonstrated a more benign phenotype, characterized by modest associations with inflammatory biomarkers and leptin, but no independent association with dyslipidemia, insulin resistance, or atherosclerosis in obese individuals. These findings suggest that abdominal fat distribution defines distinct obesity sub‐phenotypes with heterogeneous metabolic and atherosclerosis risk.

Ty J. Gluckman, MD, FACC, Chair Niti R. Aggarwal, MD, FACC Nicole M. Bhave, MD, FACC Gregory J. Dehmer, MD, MACC Olivia N. Gilbert, MD, MSc, FACC Chayakrit Krittanawong, MD Dharam J. Kumbhani, MD, SM, FACC Andrea L. Price, CPHQ, RCIS, AACC Javier A. Sala-Mercado, MD, PhD David E.

James L. Januzzi, Jr, MD, FACC, Chair Tariq Ahmad, MD, MPH, FACC Brendan Everett, MD, FACC William Hucker, MD, PHD Dharam J. Kumbhani, MD, SM, FACC Joseph E. Marine, MD, FACC Pamela B. Morris, MD, FACC Robert N. Piana, MD, FACC Sunil V. Rao, MD, FACC Marielle Scherrer-Crosbie, MD, PhD

Background: Obesity may contribute to adverse outcomes in coronavirus disease 2019 (COVID-19). However, studies of large, broadly generalizable patient populations are lacking, and the effect of body mass index (BMI) on COVID-19 outcomes— particularly in younger adults—remains uncertain. Methods: We analyzed data from patients hospitalized with COVID-19 at 88 US hospitals enrolled in the American Heart Association’s COVID-19 Cardiovascular Disease Registry with data collection through July 22, 2020. BMI was stratified by World Health Organization obesity class, with normal weight prespecified as the reference group. Results: Obesity, and, in particular, class III obesity, was overrepresented in the registry in comparison with the US population, with the largest differences among adults ≤50 years. Among 7606 patients, in-hospital death or mechanical ventilation occurred in 2109 (27.7%), in-hospital death in 1302 (17.1%), and mechanical ventilation in 1602 (21.1%). After multivariable adjustment, classes I to III obesity were associated with higher risks of in-hospital death or mechanical ventilation (odds ratio, 1.28 [95% CI, 1.09–1.51], 1.57 [1.29–1.91], 1.80 [1.47–2.20], respectively), and class III obesity was associated with a higher risk of in-hospital death (hazard ratio, 1.26 [95% CI, 1.00–1.58]). Overweight and class I to III obese individuals were at higher risk for mechanical ventilation (odds ratio, 1.28 [95% CI, 1.09–1.51], 1.54 [1.29–1.84], 1.88 [1.52–2.32], and 2.08 [1.68–2.58], respectively). Significant BMI by age interactions were seen for all primary end points ( P -interaction&lt;0.05 for each), such that the association of BMI with death or mechanical ventilation was strongest in adults ≤50 years, intermediate in adults 51 to 70 years, and weakest in adults &gt;70 years. Severe obesity (BMI ≥40 kg/m 2 ) was associated with an increased risk of in-hospital death only in those ≤50 years (hazard ratio, 1.36 [1.01–1.84]). In adjusted analyses, higher BMI was associated with dialysis initiation and with venous thromboembolism but not with major adverse cardiac events. Conclusions: Obese patients are more likely to be hospitalized with COVID-19, and are at higher risk of in-hospital death or mechanical ventilation, in particular, if young (age ≤50 years). Obese patients are also at higher risk for venous thromboembolism and dialysis. These observations support clear public health messaging and rigorous adherence to COVID-19 prevention strategies in all obese individuals regardless of age.

The aim of this study was to assess the impact of extreme (class III) obesity (body mass index [BMI] ≥40 kg/m2) on care and outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Although its prevalence is increasing rapidly, little is known about the impact of extreme obesity on STEMI presentation, treatments, complication rates, and outcomes. The relationship between BMI and baseline characteristics, treatment patterns, and risk-adjusted in-hospital outcomes was quantified for 50,149 patients with STEMI from the National Cardiovascular Data Registry (NCDR) ACTION Registry–GWTG. The proportions of patients with STEMI by BMI category were as follows: underweight (BMI <18.5 kg/m2) 1.6%, normal weight (18.5 kg/m2 ≤BMI <25 kg/m2) 23.5%, overweight (25 kg/m2 ≤BMI <30 kg/m2) 38.7%, class I obese (30 kg/m2 ≤BMI <35 kg/m2) 22.4%, class II obese (35 kg/m2 ≤BMI <40 kg/m2) 8.7%, and class III obese 5.1%. Extreme obesity was associated with younger age at STEMI presentation (median age 55 years for class III obese vs. 66 years for normal weight); a higher prevalence of diabetes, hypertension, and dyslipidemia; a lower prevalence of smoking; and less extensive coronary artery disease and higher left ventricular ejection fraction. Process-of-care measures were similar across BMI categories, including the extremely obese. Using class I obesity as the referent, risk-adjusted in-hospital mortality rates were significantly higher only for class III obese patients (adjusted odds ratio: 1.64; 95% confidence interval: 1.32 to 2.03). Patients with extreme obesity present with STEMI at younger ages and have less extensive coronary artery disease, better left ventricular systolic function, and similar processes and quality of care. Despite these advantages, extreme obesity remains independently associated with higher in-hospital mortality.

Obesity has been linked to the development of hypertension, but whether total adiposity or site-specific fat accumulation underpins this relationship is unclear. This study sought to determine the relationship between adipose tissue distribution and incident hypertension. Normotensive participants enrolled in the Dallas Heart Study were followed for a median of 7 years for the development of hypertension (systolic blood pressure [SBP] ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or initiation of blood pressure medications). Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) was quantified by magnetic resonance imaging and proton-spectroscopic imaging, and lower body fat (LBF) was imaged by dual-energy x-ray absorptiometry. Multivariable relative risk regression was performed to test the association between individual fat depots and incident hypertension, adjusting for age, sex, race/ethnicity, diabetes, smoking, SBP, and body mass index (BMI). Among 903 participants (median age, 40 years; 57% women; 60% nonwhite; median BMI 27.5 kg/m2), 230 (25%) developed incident hypertension. In multivariable analyses, higher BMI was significantly associated with incident hypertension (relative risk: 1.24; 95% confidence interval: 1.12 to 1.36, per 1-SD increase). However, when VAT, SAT, and LBF were added to the model, only VAT remained independently associated with incident hypertension (relative risk: 1.22; 95% confidence interval: 1.06 to 1.39, per 1-SD increase). Increased visceral adiposity, but not total or subcutaneous adiposity, was robustly associated with incident hypertension. Additional studies will be needed to elucidate the mechanisms behind this association.

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

Multiple epidemiological studies from Europe and Asia have demonstrated increased cardiovascular risks associated with isolated elevation of home blood pressure (BP) or masked hypertension (MH). Previous studies have not addressed cardiovascular outcomes associated with MH and white-coat hypertension (WCH) in the general population in the United States.The goal of this study was to determine hypertensive target organ damage and adverse cardiovascular outcomes associated with WCH (high clinic BP, ≥140/90 mm Hg; normal home BP, <135/85 mm Hg), MH (high home BP, ≥135/85 mm Hg; normal clinic BP, <140/90 mm Hg), and sustained hypertension (high home and clinic BP) in the DHS (Dallas Heart Study), a large, multiethnic, probability-based population cohort.Associations among WCH, MH, sustained hypertension, and aortic pulsed wave velocity by magnetic resonance imaging; urinary albumin-to-creatinine ratio; and cystatin C were evaluated at study baseline. Then, associations between WCH and MH with incident cardiovascular outcomes (coronary heart disease, stroke, atrial fibrillation, heart failure, and cardiovascular death) over a median follow-up period of 9 years were assessed.The study cohort comprised 3,027 subjects (50% African Americans). The sample-weighted prevalence rates of WCH and MH were 3.3% and 17.8%, respectively. Both WCH and MH were independently associated with increased aortic pulsed wave velocity, cystatin C, and urinary albumin-to-creatinine ratio. Both WCH (adjusted hazard ratio: 2.09; 95% confidence interval: 1.05 to 4.15) and MH (adjusted hazard ratio: 2.03; 95% confidence interval: 1.36 to 3.03) were independently associated with higher cardiovascular events compared with the normotensive group, even after adjustment for traditional cardiovascular risk factors.In a multiethnic U.S. population, both WCH and MH were independently associated with increased aortic stiffness, renal injury, and incident cardiovascular events. Because MH is common and associated with an adverse cardiovascular profile, home BP monitoring should be routinely performed among U.S. adults.

The coronavirus disease 2019 (COVID-19) pandemic has exposed longstanding racial and ethnic inequities in health risks and outcomes in the United States. We aimed to identify racial and ethnic differences in presentation and outcomes for patients hospitalized with COVID-19.The American Heart Association COVID-19 Cardiovascular Disease Registry is a retrospective observational registry capturing consecutive patients hospitalized with COVID-19. We present data on the first 7868 patients by race/ethnicity treated at 88 hospitals across the United States between January 17, 2020, and July 22, 2020. The primary outcome was in-hospital mortality. Secondary outcomes included major adverse cardiovascular events (death, myocardial infarction, stroke, heart failure) and COVID-19 cardiorespiratory ordinal severity score (worst to best: death, cardiac arrest, mechanical ventilation with mechanical circulatory support, mechanical ventilation with vasopressors/inotrope support, mechanical ventilation without hemodynamic support, and hospitalization alone. Multivariable logistic regression analyses were performed to assess the relationship between race/ethnicity and each outcome adjusting for differences in sociodemographic, clinical, and presentation features, and accounting for clustering by hospital.Among 7868 patients hospitalized with COVID-19, 33.0% were Hispanic, 25.5% were non-Hispanic Black, 6.3% were Asian, and 35.2% were non-Hispanic White. Hispanic and Black patients were younger than non-Hispanic White and Asian patients and were more likely to be uninsured. Black patients had the highest prevalence of obesity, hypertension, and diabetes. Black patients also had the highest rates of mechanical ventilation (23.2%) and renal replacement therapy (6.6%) but the lowest rates of remdesivir use (6.1%). Overall mortality was 18.4% with 53% of all deaths occurring in Black and Hispanic patients. The adjusted odds ratios for mortality were 0.93 (95% CI, 0.76-1.14) for Black patients, 0.90 (95% CI, 0.73-1.11) for Hispanic patients, and 1.31 (95% CI, 0.96-1.80) for Asian patients compared with non-Hispanic White patients. The median odds ratio across hospitals was 1.99 (95% CI, 1.74-2.48). Results were similar for major adverse cardiovascular events. Asian patients had the highest COVID-19 cardiorespiratory severity at presentation (adjusted odds ratio, 1.48 [95% CI, 1.16-1.90]).Although in-hospital mortality and major adverse cardiovascular events did not differ by race/ethnicity after adjustment, Black and Hispanic patients bore a greater burden of mortality and morbidity because of their disproportionate representation among COVID-19 hospitalizations.

In-hospital mortality rates from COVID-19 are high but appear to be decreasing for selected locations in the United States. It is not known whether this is because of changes in the characteristics of patients being admitted.To describe changing in-hospital mortality rates over time after accounting for individual patient characteristics.This was a retrospective cohort study of 20 736 adults with a diagnosis of COVID-19 who were included in the US American Heart Association COVID-19 Cardiovascular Disease Registry and admitted to 107 acute care hospitals in 31 states from March through November 2020. A multiple mixed-effects logistic regression was then used to estimate the odds of in-hospital death adjusted for patient age, sex, body mass index, and medical history as well as vital signs, use of supplemental oxygen, presence of pulmonary infiltrates at admission, and hospital site.In-hospital death adjusted for exposures for 4 periods in 2020.The registry included 20 736 patients hospitalized with COVID-19 from March through November 2020 (9524 women [45.9%]; mean [SD] age, 61.2 [17.9] years); 3271 patients (15.8%) died in the hospital. Mortality rates were 19.1% in March and April, 11.9% in May and June, 11.0% in July and August, and 10.8% in September through November. Compared with March and April, the adjusted odds ratios for in-hospital death were significantly lower in May and June (odds ratio, 0.66; 95% CI, 0.58-0.76; P < .001), July and August (odds ratio, 0.58; 95% CI, 0.49-0.69; P < .001), and September through November (odds ratio, 0.59; 95% CI, 0.47-0.73).In this cohort study, high rates of in-hospital COVID-19 mortality among registry patients in March and April 2020 decreased by more than one-third by June and remained near that rate through November. This difference in mortality rates between the months of March and April and later months persisted even after adjusting for age, sex, medical history, and COVID-19 disease severity and did not appear to be associated with changes in the characteristics of patients being admitted.

New-onset atrial fibrillation (AF) in patients hospitalized with COVID-19 has been reported and associated with poor clinical outcomes. We aimed to understand the incidence of and outcomes associated with new-onset AF in a diverse and representative US cohort of patients hospitalized with COVID-19.We used data from the American Heart Association COVID-19 Cardiovascular Disease Registry. Patients were stratified by the presence versus absence of new-onset AF. The primary and secondary outcomes were in-hospital mortality and major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, stroke, cardiogenic shock, and heart failure). The association of new-onset AF and the primary and secondary outcomes was evaluated using Cox proportional-hazards models for the primary time to event analyses.Of the first 30 999 patients from 120 institutions across the United States hospitalized with COVID-19, 27 851 had no history of AF. One thousand five hundred seventeen (5.4%) developed new-onset AF during their index hospitalization. New-onset AF was associated with higher rates of death (45.2% versus 11.9%) and MACE (23.8% versus 6.5%). The unadjusted hazard ratio for mortality was 1.99 (95% CI, 1.81-2.18) and for MACE was 2.23 (95% CI, 1.98-2.53) for patients with versus without new-onset AF. After adjusting for demographics, clinical comorbidities, and severity of disease, the associations with death (hazard ratio, 1.10 [95% CI, 0.99-1.23]) fully attenuated and MACE (hazard ratio, 1.31 [95% CI, 1.14-1.50]) partially attenuated.New-onset AF was common (5.4%) among patients hospitalized with COVID-19. Almost half of patients with new-onset AF died during their index hospitalization. After multivariable adjustment for comorbidities and disease severity, new-onset AF was not statistically significantly associated with death, suggesting that new-onset AF in these patients may primarily be a marker of other adverse clinical factors rather than an independent driver of mortality. Causality between the MACE composites and AF needs to be further evaluated.

Although gender-specific criteria are common for defining cardiac traits such as left ventricular hypertrophy, left ventricular ejection fraction (LVEF) thresholds widely used in clinical practice have traditionally been the same for women and men, perhaps because it remains uncertain whether there is a systematic difference in LVEF between genders.Using cardiac magnetic resonance imaging in a probability-based sample of Dallas County residents aged 30 to 65 years (1435 women and 1183 men), we compared LVEF in women and men. The association of gender with stroke volume independent of end-diastolic volume (EDV) or other potential confounders was assessed by multivariable analysis. Gender-specific thresholds for a low LVEF were defined at the 2.5th percentile in women and men from a healthy reference subpopulation. The median (25th, 75th percentile) LVEF was higher in women than in men (75% [70%, 79%] in women versus 70% [65%, 75%] in men, P<0.001). Left ventricular EDV and end-systolic volume indexed to body surface area were smaller in women than in men (P<0.001 for both). Gender remained significantly associated with stroke volume, independent of EDV and other potential confounders in multivariable analysis. A low LVEF was defined as below 61% in women and below 55% in men.Women have a higher LVEF than men in the general population, secondary to a higher stroke volume for a given EDV independent of known potential confounders.

We sought to determine if natriuretic peptides are associated with estrogen and androgen status in a population study of young women without known cardiac disease.Circulating concentrations of plasma B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are higher in women than in men, and they may be influenced by estrogens and androgens.Cardiac magnetic resonance imaging, dual energy X-ray absorbtiometry, and measurements of BNP, NT-proBNP, follicle-stimulating hormone (FSH), total testosterone, and sex hormone-binding globulin (SHBG), were performed in 682 women (ages 35 to 49 years) participating in the Dallas Heart Study.In multivariable analyses adjusting for age, race/ethnicity, body mass index (BMI), serum creatinine, left ventricular mass and left ventricular ejection fraction <55%, menopausal status, and FSH were not associated with BNP and NT-proBNP. In contrast, higher SHBG was associated with higher BNP and NT-proBNP, while the free androgen index and calculated free testosterone were inversely associated with BNP and NT-proBNP (p < 0.0001 for each). Addition of SHBG or any measure of free testosterone to the multivariable models modified the effect of BMI and lean mass, such that measures of body composition were no longer significantly associated with BNP or NT-proBNP.Among young women, measures of free testosterone were independently and inversely associated with BNP and NT-proBNP. These results suggest that circulating free testosterone, not estradiol, mediates gender differences in natriuretic peptides. In addition, the association between higher BMI and lean body mass with natriuretic peptides may be mediated by testosterone.

The relation of body fat distribution to left ventricular (LV) structure and function is poorly defined.A total of 2710 participants without heart failure or LV dysfunction in the Dallas Heart Study underwent dual energy x-ray absorptiometry and MRI assessment of fat distribution, LV morphology, and hemodynamics. Cross-sectional associations of fat distribution with LV structure and function were examined after adjustment for age, sex, race, comorbidities, and lean mass. Mean age was 44 years with 55% women; 48% blacks; and 44% obese. After multivariable adjustment, visceral adipose tissue was associated with concentric remodeling characterized by lower LV end-diastolic volume (β=-0.21), higher concentricity (β=0.20), and wall thickness (β=0.09; P<0.0001 for all). In contrast, lower body subcutaneous fat was associated with higher LV end-diastolic volume (β=0.48), reduced concentricity (β=-0.50), and wall thickness (β=-0.28, P<0.0001 for all). Visceral adipose tissue was also associated with lower cardiac output (β=-0.10, P<0.05) and higher systemic vascular resistance (β=0.08, P<0.05), whereas lower body subcutaneous fat associated with higher cardiac output (β=0.20, P<0.0001) and lower systemic vascular resistance (β=-0.18, P<0.0001). Abdominal subcutaneous fat showed weaker associations with concentric remodeling and was not associated with hemodynamics. Among the subset of obese participants, visceral adipose tissue, but not abdominal subcutaneous fat, was significantly associated with concentric remodeling.Visceral adipose tissue, a marker of central adiposity, was independently associated with concentric LV remodeling and adverse hemodynamics. In contrast, lower body subcutaneous fat was associated with eccentric remodeling. The impact of body fat distribution on heart failure risk requires prospective study.

Growth differentiation factor 15 (GDF-15) is produced by cardiomyocytes and atherosclerotic lesions under stress conditions. Although higher circulating GDF-15 concentrations are associated with mortality across a spectrum of cardiovascular conditions, the relationship of GDF-15 with atherosclerosis and mortality in the general population remains undefined.We measured plasma GDF-15 in 3219 participants of the Dallas Heart Study, a population sample of adults ages 30-65 years (55% women, 49% black). GDF-15 was analyzed in prespecified categories (<1200; 1200-1799; and ≥1800 ng/L) and continuously. End points included prevalent coronary artery calcium (CAC>10 Agatston units), increased CAC (CAC≥100 Agatston units) by electron beam computed tomography, and mortality through a median 7.3 years of follow-up (120 deaths, 48 cardiovascular deaths).Increasing GDF-15 associated with older age, black race, hypertension, diabetes, smoking, left ventricular (LV) mass/body surface area, and worse renal function (P<0.0001 for each). In multivariable models adjusted for traditional risk factors, renal function, and LV mass/body surface area, GDF-15≥1800 ng/L was associated with CAC>10 (odds ratio 2.1; 95% CI 1.2-3.7; P=0.01), CAC≥100 (odds ratio 2.6; 95% CI 1.4-4.9; P=0.002), all-cause mortality (hazard ratio 3.5; 95% CI 2.1-5.9, P<0.0001), and cardiovascular mortality (hazard ratio 2.5; 95% CI 1.1-5.8, P=0.03). Adding log GDF-15 to fully adjusted models modestly improved the c statistic (P=0.025), the integrated discrimination index (0.028; P<0.0001) and the category-less net reclassification index (0.42; P=0.002). These findings remained significant with further adjustment for high-sensitivity C-reactive protein, N-terminal pro-B-type natriuretic peptide, and cardiac troponin T.GDF-15 is independently associated with subclinical coronary atherosclerosis and mortality, and its potential role for risk stratification in the general population merits further evaluation.

To the Editor: Adherence to medications is a major challenge clinicians often face in treating hypertension. An increasing number of studies show therapeutic drug monitoring (TDM) is reliable for detecting medication nonadherence in patients who seem to have resistant hypertension (RH) [(1,2)][1

Background: C-reactive protein (CRP) levels are significantly influenced by adiposity and are higher in women compared with men. We postulated that there may be sex differences in the relationship between CRP and body fat. Methods: We measured CRP and body fat parameters in 1166 men and 1413 women ages 30–65 in the population-based Dallas Heart Study. Total fat mass (TFM) was measured using dual-energy x-ray absorptiometry scanning and was subdivided into truncal fat (TrF) and lower body fat (LBF). The TrF/LBF ratio was used to measure fat distribution. Abdominal fat compartments (ip and sc) were measured using magnetic resonance imaging. Log-transformed CRP was used as the outcome variable in sex-combined models with interaction tests. Results: Median body mass index was higher in women than in men (29.9 vs. 28.2 kg/m2), as was TFM (29.7 vs. 20.5 kg) (P < 0.001 each). TFM was linearly associated with log CRP in both sexes, with a steeper slope of association in women (P interaction = 0.003). CRP increased to a greater degree with increasing TrF (P interaction = 0.0004) in women compared with men, even after adjustment for TFM; values were similar across sexes for LBF. Fat distribution (TrF/LBF ratio) was more strongly associated with CRP levels in women vs. men (R2 adjusted for TFM = 0.04 vs. 0.008). Greater increases in CRP were also observed with increasing ip and sc fat in women compared with men. Conclusions: The quantity and distribution of body fat influence CRP to a greater extent in women compared with men. Adiposity as a contributor to subclinical inflammation may be particularly relevant in women. The quantity and distribution of body fat influence C-reactive protein to a greater extent in women compared with men.

Emerging evidence suggests that significant heterogeneity exists in the cardiometabolic risk associated with excess body fat in obese individuals (1). We investigated the associations of novel imaging markers of adiposity, including visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) by magnetic resonance imaging, lower body subcutaneous adipose tissue (LBAT) by dual-energy x-ray absorptiometry, and liver fat by magnetic resonance spectroscopy, with the risk for cardiovascular disease (CVD) events in a multiethnic cohort of obese adults.

The adult mammalian heart is incapable of meaningful regeneration after substantial cardiomyocyte loss, primarily due to the inability of adult cardiomyocytes to divide. Our group recently showed that mitochondria-mediated oxidative DNA damage is an important regulator of postnatal cardiomyocyte cell cycle arrest. However, it is not known whether mechanical load also plays a role in this process. We reasoned that the postnatal physiological increase in mechanical load contributes to the increase in mitochondrial content, with subsequent activation of DNA damage response (DDR) and permanent cell cycle arrest of cardiomyocytes. The purpose of this study was to test the effect of mechanical unloading on mitochondrial mass, DDR, and cardiomyocyte proliferation. We examined the effect of human ventricular unloading after implantation of left ventricular assist devices (LVADs) on mitochondrial content, DDR, and cardiomyocyte proliferation in 10 matched left ventricular samples collected at the time of LVAD implantation (pre-LVAD) and at the time of explantation (post-LVAD). We found that post-LVAD hearts showed up to a 60% decrease in mitochondrial content and up to a 45% decrease in cardiomyocyte size compared with pre-LVAD hearts. Moreover, we quantified cardiomyocyte nuclear foci of phosphorylated ataxia telangiectasia mutated protein, an upstream regulator of the DDR pathway, and we found a significant decrease in the number of nuclear phosphorylated ataxia telangiectasia mutated foci in the post-LVAD hearts. Finally, we examined cardiomyocyte mitosis and cytokinesis and found a statistically significant increase in both phosphorylated histone H3–positive, and Aurora B–positive cardiomyocytes in the post-LVAD hearts. Importantly, these results were driven by statistical significance in hearts exposed to longer durations of mechanical unloading. Prolonged mechanical unloading induces adult human cardiomyocyte proliferation, possibly through prevention of mitochondria-mediated activation of DDR.

The goal of this study was to investigate the association between natriuretic peptides and body fat distribution in a multiethnic cohort. Natriuretic peptides stimulate lipolysis, reduce weight gain, and promote adipocyte browning in animal models, but data are lacking in humans. A total of 2,619 participants without heart failure in the Dallas Heart Study underwent measurements of 1) B-type natriuretic peptide (BNP) and N-terminal pro–B-type natriuretic peptide (NT-proBNP); and 2) body fat distribution by dual energy x-ray absorptiometry and magnetic resonance imaging. Cross-sectional associations of natriuretic peptides with adiposity phenotypes were examined after adjustment for age, sex, race, comorbidities, and body mass index. Median BNP and NT-proBNP levels in the study cohort (mean age 44 years; 56% women, 48% African Americans, 32% obese) were 3.0 and 28.1 pg/ml, respectively. Natriuretic peptide levels above the median were associated with a more favorable body fat profile and less insulin resistance, including lower visceral fat, liver fat, and homeostasis model assessment of insulin resistance index, and increased lower body fat and higher adiponectin (p < 0.05 for each). In multivariable analyses, NT-proBNP remained inversely associated with visceral fat (beta coefficient = −0.08; p < 0.0001) and liver fat (beta coefficient = −0.14; p < 0.0001) and positively associated with lower body fat (beta coefficient = 0.07; p < 0.0001) independent of age, sex, race, and obesity status; findings were similar with BNP. Adjustment for body composition, homeostasis model assessment of insulin resistance index, circulating androgens, and adipocytokines did not attenuate the associations. Higher natriuretic peptide levels were independently associated with a favorable adiposity profile, characterized by decreased visceral and liver fat and increased lower body fat, suggesting a link between the heart and adipose tissue distribution mediated through natriuretic peptides.

Transthoracic echocardiography (TTE) accounts for almost half of all cardiac imaging services and is a widely available and versatile tool. Appropriate use criteria (AUC) for echocardiography were developed to improve patient care and health outcomes. Prior studies have shown that most TTEs are appropriate by AUC. However, the associations among TTE, AUC, and their clinical impact have not been well explored.To describe the proportion of TTEs that affect clinical care in an academic medical center overall and in subgroups defined as appropriate and inappropriate by AUC.Retrospective review of medical records from 535 consecutive TTEs at an academic medical center was performed. The TTEs were classified according to 2011 AUC by 2 cardiologists blinded to clinical impact and were assessed for clinical impact by 2 cardiologists blinded to AUC. Clinical impact was assigned to 1 of the following 3 categories: (1) active change in care, (2) continuation of current care, or (3) no change in care.Five hundred thirty-five patients undergoing TTE.Transthoracic echocardiography. MAIN OUTCOMES AND MEASURES Prevalence of appropriate, inappropriate, and uncertain TTEs and prevalence of clinical impact subcategories.Overall, 31.8% of TTEs resulted in an active change in care; 46.9%, continuation of current care; and 21.3%, no change in care. By 2011 AUC, 91.8% of TTEs were appropriate; 4.3%, inappropriate; and 3.9%, uncertain. We detected no statistically significant difference between appropriate and inappropriate TTEs in the proportion of TTEs that led to active change in care (32.2% vs 21.7%; P= .29).Although 9 in 10 TTEs were appropriate by 2011 AUC, fewer than 1 in 3 TTEs resulted in an active change in care, nearly half resulted in continuation of current care, and slightly more than 1 in 5 resulted in no change in care. The low rate of active change in care (31.8%) among TTEs mostly classified as appropriate (91.8%) highlights the need for a better method to optimize TTE utilization to use limited health care resources efficiently while providing high-quality care.

Medication nonadherence is associated with worse outcomes in patients with atherosclerotic cardiovascular disease (ASCVD), a group who requires long-term therapy for secondary prevention. It is important to understand to what extent drug costs, which are potentially actionable factors, contribute to medication nonadherence.In a nationally representative survey of US adults in the National Health Interview Survey (2013-2017), we identified individuals ≥18 years with a reported history of ASCVD. Participants were considered to have experienced cost-related nonadherence (CRN) if in the preceding 12 months they reported skipping doses to save money, taking less medication to save money, or delaying filling a prescription to save money. We used survey analysis to obtain national estimates.Of the 14 279 surveyed individuals with ASCVD, a weighted 12.6% (or 2.2 million [95% CI, 2.1-2.4]) experienced CRN, including 8.6% or 1.5 million missing doses, 8.8% or 1.6 million taking lower than prescribed doses, and 10.5% or 1.9 million intentionally delaying a medication fill to save costs. Age <65 years, female sex, low family income, lack of health insurance, and high comorbidity burden were independently associated with CRN, with >1 in 5 reporting CRN in these subgroups. Survey respondents with CRN compared with those without CRN had 10.8-fold higher odds of requesting low-cost medications and 8.9-fold higher odds of using alternative, nonprescription, therapies.One in 8 patients with ASCVD reports nonadherence to medications because of cost. The removal of financial barriers to accessing medications, particularly among vulnerable patient groups, may help improve adherence to essential therapy to reduce ASCVD morbidity and mortality.

Low mid-life fitness is associated with higher risk for heart failure (HF). However, it is unclear to what extent this HF risk is modifiable and mediated by the burden of cardiac and noncardiac comorbidities. We studied the effect of cardiac and noncardiac comorbidities on the association of mid-life fitness and fitness change with HF risk.Linking individual subject data from the Cooper Center Longitudinal Study (CCLS) with Medicare claims files, we studied 19,485 subjects (21.2% women) who survived to receive Medicare coverage from 1999 to 2009. Fitness estimated by Balke treadmill time at mean age of 49 years was analyzed as a continuous variable (in metabolic equivalents [METs]) and according to age- and sex-specific quintiles. Associations of mid-life fitness and fitness change with HF hospitalization after age of 65 years were assessed by applying a proportional hazards recurrent events model to the failure time data with each comorbidity entered as time-dependent covariates.After 127,110 person years of Medicare follow-up, we observed 1,038 HF hospitalizations. Higher mid-life fitness was associated with a lower risk for HF hospitalization (hazard ratio [HR] 0.82 [0.76-0.87] per MET) after adjustment for traditional risk factors. This remained unchanged after further adjustment for the burden of Medicare-identified cardiac and noncardiac comorbidities (HR 0.83 [0.78-0.89]). Each 1 MET improvement in mid-life fitness was associated with a 17% lower risk for HF hospitalization in later life (HR 0.83 [0.74-0.93] per MET).Mid-life fitness is an independent and modifiable risk factor for HF hospitalization at a later age.

Objective To determine the association between cardiorespiratory fitness and sedentary behavior, independent of exercise activity. Patients and Methods We included 2223 participants (aged 12-49 years; 1053 females [47%]) without known heart disease who had both cardiovascular fitness testing and at least 1 day of accelerometer data from the National Health and Nutrition Examination Survey 2003-2004. From accelerometer data, we quantified bouts of exercise as mean minutes per day for each participant. Sedentary time was defined as less than 100 counts per minute in mean minutes per day. Cardiorespiratory fitness was derived from a submaximal exercise treadmill test. Multivariable-adjusted linear regression analyses were performed with fitness as the dependent variable. Models were stratified by sex, adjusted for age, body mass index, and wear time, and included sedentary and exercise time. Results An additional hour of daily exercise activity time was associated with a 0.88 (0.37-1.39; P<.001) metabolic equivalent of task (MET) higher fitness for men and a 1.37 (0.43-2.31; P=.004) MET higher fitness for women. An additional hour of sedentary time was associated with a −0.12 (−0.02 to −0.22; P=.03) and a −0.24 (−0.10 to −0.38; P<.001) MET difference in fitness for men and women, respectively. Conclusion After adjustment for exercise activity, sedentary behavior appears to have an inverse association with fitness. These findings suggest that the risk related to sedentary behavior might be mediated, in part, through lower fitness levels.

<h3>Importance</h3> Health insurance is effective in preventing financial hardship from unexpected major health care events. However, it is also essential to assess whether vulnerable patients, particularly those from low-income families, are adequately protected from longitudinal health care costs for common chronic conditions such as atherosclerotic cardiovascular disease (ASCVD). <h3>Objective</h3> To examine the annual burden of total out-of-pocket health expenses among low-income families that included a member with ASCVD. <h3>Design, Setting, and Participants</h3> In this cross-sectional study of the Medical Expenditure Panel Survey from January 2006 through December 2015, all families with 1 or more members with ASCVD were identified. Families were classified as low income if they had an income under 200% of the federal poverty limit. Analyses began December 2017. <h3>Main Outcomes and Measures</h3> Total annual inflation-adjusted out-of-pocket expenses, inclusive of insurance premiums, for all patients with ASCVD. We compared these expenses against annual family incomes. Out-of-pocket expenses of more than 20% and more than 40% of family income defined high and catastrophic financial burden, respectively. <h3>Results</h3> We identified 22 521 adults with ASCVD, represented in 20 600 families in the Medical Expenditure Panel Survey. They correspond to an annual estimated 23 million or 9.9% of US adults with a mean (SE) age of 65 (0.2) years and included 10.9 million women (47.1%). They were represented in 21 million or 15% of US families. Of these, 8.2 million families (39%) were low income. The mean annual family income was $57 143 (95% CI, $55 377-$58 909), and the mean out-of-pocket expense was $4415 (95% CI, $3735-$3976). While financial burden from health expenses decreased throughout the study, even in 2014 and 2015, low-income families had 3-fold higher odds than mid/high–income families of high financial burden (21.4% vs 7.6%; OR, 3.31; 95% CI, 2.55-4.31) and 9-fold higher odds of catastrophic financial burden (9.8% vs 1.2%; OR, 9.35; 95% CI, 5.39-16.20), representing nearly 2 million low-income families nationally. Further, even among the insured, 1.6 million low-income families (21.8%) experienced high financial burden and 721 000 low-income families (9.8%) experienced catastrophic out-of-pocket health care expenses in 2014 and 2015. <h3>Conclusions and Relevance</h3> One in 4 low-income families with a member with ASCVD, including those with insurance coverage, experience a high financial burden, and 1 in 10 experience a catastrophic financial burden due to cumulative out-of-pocket health care expenses. To alleviate economic disparities, policy interventions must extend focus to improving not only access, but also quality of coverage, particularly for low-income families.

Background Nonalcoholic fatty liver disease (NAFLD) and heart failure (HF) are increasing in prevalence. The independent association between NAFLD and downstream risk of HF and HF subtypes (HF with preserved ejection fraction and HF with reduced ejection fraction) is not well established. Methods and Results This was a retrospective, cohort study among Medicare beneficiaries. We selected Medicare beneficiaries without known prior diagnosis of HF. NAFLD was defined using presence of 1 inpatient or 2 outpatient claims using International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD‐9‐CM ), claims codes. Incident HF was defined using at least 1 inpatient or at least 2 outpatient HF claims during the follow‐up period (October 2015–December 2016). Among 870 535 Medicare patients, 3.2% (N=27 919) had a clinical diagnosis of NAFLD. Patients with NAFLD were more commonly women, were less commonly Black patients, and had a higher burden of comorbidities, such as diabetes, obesity, and kidney disease. Over a mean 14.3 months of follow‐up, patients with (versus without) baseline NAFLD had a significantly higher risk of new‐onset HF in unadjusted (6.4% versus 5.0%; P &lt;0.001) and adjusted (adjusted hazard ratio [HR] [95% CI], 1.23 [1.18–1.29]) analyses. Among HF subtypes, the association of NAFLD with downstream risk of HF was stronger for HF with preserved ejection fraction (adjusted HR [95% CI], 1.24 [1.14–1.34]) compared with HF with reduced ejection fraction (adjusted HR [95% CI], 1.09 [0.98–1.2]). Conclusions Patients with NAFLD are at an increased risk of incident HF, with a higher risk of developing HF with preserved ejection fraction versus HF with reduced ejection fraction. The persistence of an increased risk after adjustment for clinical and demographic factors suggests an epidemiological link between NAFLD and HF beyond the basis of shared risk factors that requires further investigation.

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

Therapeutic approaches that lower circulating low-density lipoprotein (LDL)-cholesterol significantly reduced the burden of cardiovascular disease over the last decades. However, the persistent rise in the obesity epidemic is beginning to reverse this decline. Alongside obesity, the incidence of nonalcoholic fatty liver disease (NAFLD) has substantially increased in the last three decades. Currently, approximately one third of world population is affected by NAFLD. Notably, the presence of NAFLD and particularly its more severe form, nonalcoholic steatohepatitis (NASH), serves as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD), thus, raising interest in the relationship between these two diseases. Importantly, ASCVD is the major cause of death in patients with NASH independent of traditional risk factors. Nevertheless, the pathophysiology linking NAFLD/NASH with ASCVD remains poorly understood. While dyslipidemia is a common risk factor underlying both diseases, therapies that lower circulating LDL-cholesterol are largely ineffective against NASH. While there are no approved pharmacological therapies for NASH, some of the most advanced drug candidates exacerbate atherogenic dyslipidemia, raising concerns regarding their adverse cardiovascular consequences. In this review, we address current gaps in our understanding of the mechanisms linking NAFLD/NASH and ASCVD, explore strategies to simultaneously model these diseases, evaluate emerging biomarkers that may be useful to diagnose the presence of both diseases, and discuss investigational approaches and ongoing clinical trials that potentially target both diseases.

To characterize the long term risk of death and hospital readmission after an index admission with covid-19 among Medicare fee-for-service beneficiaries, and to compare these outcomes with historical control patients admitted to hospital with influenza.Retrospective cohort study.United States.883 394 Medicare fee-for-service beneficiaries age ≥65 years discharged alive after an index hospital admission with covid-19 between 1 March 2020 and 31 August 2022, compared with 56 409 historical controls discharged alive after a hospital admission with influenza between 1 March 2018 and 31 August 2019. Weighting methods were used to account for differences in observed characteristics.All cause death within 180 days of discharge. Secondary outcomes included first all cause readmission and a composite of death or readmission within 180 days.The covid-19 cohort compared with the influenza cohort was younger (77.9 v 78.9 years, standardized mean difference -0.12) and had a lower proportion of women (51.7% v 57.3%, -0.11). Both groups had a similar proportion of black beneficiaries (10.3% v 8.1%, 0.07) and beneficiaries with dual Medicaid-Medicare eligibility status (20.1% v 19.2%; 0.02). The covid-19 cohort had a lower comorbidity burden, including atrial fibrillation (24.3% v 29.5%, -0.12), heart failure (43.4% v 49.9%, -0.13), and chronic obstructive pulmonary disease (39.2% v 52.9%, -0.27). After weighting, the covid-19 cohort had a higher risk (ie, cumulative incidence) of all cause death at 30 days (10.9% v 3.9%; standardized risk difference 7.0%, 95% confidence interval 6.8% to 7.2%), 90 days (15.5% v 7.1%; 8.4%, 8.2% to 8.7%), and 180 days (19.1% v 10.5%; 8.6%, 8.3% to 8.9%) compared with the influenza cohort. The covid-19 cohort also experienced a higher risk of hospital readmission at 30 days (16.0% v 11.2%; 4.9%, 4.6% to 5.1%) and 90 days (24.1% v 21.3%; 2.8%, 2.5% to 3.2%) but a similar risk at 180 days (30.6% v 30.6%;-0.1%, -0.5% to 0.3%). Over the study period, the 30 day risk of death for patients discharged after a covid-19 admission decreased from 17.9% to 7.2%.Medicare beneficiaries who were discharged alive after a covid-19 hospital admission had a higher post-discharge risk of death compared with historical influenza controls; this difference, however, was concentrated in the early post-discharge period. The risk of death for patients discharged after a covid-19 related hospital admission substantially declined over the course of the pandemic.

Identification of individuals in the community with left ventricular systolic dysfunction (LVSD) or left ventricular hypertrophy (LVH) may allow earlier initiation of disease-modifying treatment. We performed a comprehensive evaluation of the screening performance of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) for LVSD or LVH. In 2,429 subjects without a history of heart failure, myocardial infarction, valvular abnormalities, or a serum creatinine >2.0 mg/dL enrolled in the Dallas Heart Study, measurement of BNP and NT-proBNP and cardiovascular magnetic resonance imaging were performed. B-type natriuretic peptide and NT-proBNP were robustly associated with magnetic resonance imaging–defined LVH and LVSD (ejection fraction <55%) among men and women (P < .0001 for each). In the overall population, neither test discriminated well for LVH or LVSD (area under the receiver operating characteristic curve [AUROC] <0.7). Among women, no differences in AUROC were observed between BNP and NT-proBNP. Among men, AUROCs were similar between BNP and NT-proBNP in the overall population, but among subgroups age 50 or older, or with hypertension, the AUROCs for NT-proBNP (0.73-0.79) were higher than for BNP (0.63-0.69, P < .05 for each comparison). Compared with subjects with isolated BNP elevation (>97.5th percentile), those with isolated NT-proBNP elevation had worse renal function and more LVH and coronary calcium (P < .05 for each). Overall, neither BNP nor NT-proBNP accurately discriminated subjects with LVH or LVSD in this predominately young and healthy population-based cohort. However, among high-risk men, NT-proBNP performed slightly better than BNP and comparably with other routinely used screening tests such as prostate-specific antigen measurement for prostate cancer.

The Morisky Medication Adherence Scale (MMAS-8) is a questionnaire developed for screening of non-adherence in patients with several chronic conditions, including uncomplicated hypertension. However, its accuracy in predicting non-adherence in patients with apparent treatment-resistant hypertension (a-TRH) is not known. Accordingly, we performed a retrospective study in 47 patients with a-TRH who had completed the eight-item MMAS during the initial clinic visit. Non-adherence was defined as presence of undetected serum levels of at least one prescribed antihypertensive drug by therapeutic drug monitoring. We found that 26% of patients were considered to have low adherence score (<6), while the actual prevalence of non-adherence was 51% by therapeutic drug monitoring. Sensitivity of the MMAS-8 was 26% (95% confidence interval, 10.3%-48.4%) with specificity of 75% (95% confidence interval, 53.3%-90.2%). By multivariate analysis, the MMAS-8 score was not an independent predictor of non-adherence, while certain clinical parameters such as heart rate were found to be independent predictors of non-adherence. Our study suggested limited accuracy of the MMAS-8 in detecting medication non-adherence in a-TRH.

The aim of this study is to examine a relationship between neighborhood-level socioeconomic deprivation and weight change in a multi-ethnic cohort from Dallas County, Texas and whether behavioral/psychosocial factors attenuate the relationship. Non-movers (those in the same neighborhood throughout the study period) aged 18–65 (N = 939) in Dallas Heart Study (DHS) underwent weight measurements between 2000 and 2009 (median 7-year follow-up). Geocoded home addresses defined block groups; a neighborhood deprivation index (NDI) was created (higher NDI = greater deprivation). Multi-level modeling determined weight change relative to NDI. Model fit improvement was examined with adding physical activity and neighborhood environment perceptions (higher score = more unfavorable perceptions) as covariates. A significant interaction between residence length and NDI was found (p-interaction = 0.04); results were stratified by median residence length (11 years). Adjusting for age, sex, race/ethnicity, smoking, and education/income, those who lived in neighborhood > 11 years gained 1.0 kg per one-unit increment of NDI (p = 0.03), or 6 kg for those in highest NDI tertile compared with those in the lowest tertile. Physical activity improved model fit; NDI remained associated with weight gain after adjustment for physical activity and neighborhood environment perceptions. There was no significant relationship between NDI and weight change for those in their neighborhood ≤ 11 years. Living in more socioeconomically deprived neighborhoods over a longer time period was associated with weight gain in DHS.

Physical activity (PA) participation differs by ethnicity, but contributing factors and cardiovascular (CV) outcomes related to these disparities are not well understood. We determined whether health beliefs regarding the benefit of PA contribute to ethnic differences in participation and assessed how these differences impact CV mortality.The Dallas Heart Study is a longitudinal study of CV health. We assessed PA participation and health perceptions by questionnaire among 3,018 African American, Hispanic, and white men and women at baseline visit (2000-2002). Participant mortality was obtained through 2008 using the National Death Index.African Americans (odds ratio 0.65, 95% CI 0.53-0.80) and Hispanics (odds ratio 0.34, 95% CI 0.26-0.45) were less likely to be physically active compared with whites even after accounting for income, educational status, age, sex, body mass index, diabetes, hypertension, and hyperlipidemia. Beliefs regarding the benefits of PA did not contribute to this disparity, as >94% of individuals felt PA was effective in preventing a heart attack across ethnicity. Physical activity participation was associated with a lower risk of all-cause mortality (hazard ratio [HR] 0.66, 95% CI 0.46-0.93) and CV disease death (HR 0.56, 95% CI 0.32-0.97) in multivariable adjusted models. Similar results were seen when restricting to African Americans (CV disease death, HR 0.57, 95% CI 0.31-1.05).Ethnic minorities reported less PA participation, and lack of PA was associated with higher CV mortality overall and among African Americans. Health perception regarding the benefits of PA did not contribute to this difference, indicating there are other ethnic-specific factors contributing to physical inactivity that require future study.

This study sought to assess the effect of coronary artery calcium (CAC) on coronary heart disease (CHD) risk prediction in a younger population.CAC measured by computed tomography improves CHD risk classification in older adults, but the effectiveness of CAC in younger populations has not been fully assessed.In the DHS (Dallas Heart Study), a multiethnic probability-based population sample, traditional CHD risk factors and CAC were measured in participants without baseline cardiovascular disease or diabetes. Incident CHD-defined as CHD death, myocardial infarction, or coronary revascularization-was assessed over a median follow-up of 9.2 years. Predicted CHD risk was assessed with a Weibull model inclusive of traditional risk factors before and after the addition of CAC as ln(CAC + 1). Participants were divided into 3 10-year risk categories, <6%, 6% to <20%, and ≥20%, and the net reclassification improvement (NRI) was calculated. We also performed a random-effects meta-analysis of NRI from previous studies inclusive of older individuals.The analysis comprised 2,084 participants; mean age was 44.4 ± 9.0 years. CAC was independently associated with incident CHD (hazard ratio per SD: 1.90, 95% confidence interval [CI] 1.51 to 2.38; p < 0.001). The addition of CAC to the traditional risk factor model resulted in significant improvement in the C-statistic (delta = 0.03; p = 0.003). Among participants with CHD events, the addition of CAC resulted in net correct upward reclassification of 21%, and among those without CHD, a net correct downward reclassification of 0.5% (NRI: 0.216, p = 0.012). Results remained significant when the outcome was restricted to CHD death and myocardial infarction and when individuals with diabetes were included. The NRI observed in this study was similar to the pooled estimate from previous studies (0.200, 95% CI: 0.140 to 0.258) and the addition of our study to the meta-analysis did not result in significant heterogeneity (I(2) = 0%).CAC scoring also improves CHD risk classification in younger adults.

Abstract Objectives: Although psychosocial stress can result in adverse health outcomes, little is known about how perceptions of neighborhood conditions, a measure of environment‐derived stress, may impact obesity. The association between perceptions of neighborhood environment and obesity (defined as body mass index [BMI] ≥ 30 kg/m 2 ) among 5,907 participants in the Dallas Heart Study, a multi‐ethnic, probability‐based sample of Dallas County residents was examined. Design and Methods: Participants were asked to respond to 18 questions about perceptions of their neighborhood. Factor analysis was used to identify three factors associated with neighborhood perceptions: neighborhood violence, physical environment, and social cohesion. Logistic regression analyses were performed to determine the relationship between each factor (higher quintile = more unfavorable perceptions) and the odds of obesity. Results: Decreasing age, income, and education associated with unfavorable overall neighborhood perceptions and unfavorable perceptions about specific neighborhood factors ( P trend &lt;0.05 for all). Increasing BMI was associated with unfavorable perceptions about physical environment ( P trend &lt;0.05) but not violence or social cohesion. After adjustment for race, age, sex, income, education, and length of residence, physical environment perception score in the highest quintile remained associated with a 25% greater odds of obesity (OR 1.25, [95% CI 1.03‐1.50]). Predictors of obesity related to environmental perceptions included heavy traffic (OR 1.39, [1.17‐1.64]), trash/litter in neighborhood (OR 1.27, [1.01‐1.46]), lack of recreational areas (OR 1.21, [1.01‐1.46]), and lack of sidewalks (OR 1.25, [95% CI 1.04‐1.51]). Conclusions: Thus, unfavorable perceptions of environmental physical conditions are related to increased obesity. Efforts to improve the physical characteristics of neighborhoods, or the perceptions of those characteristics, may assist in the prevention of obesity in this community.

Duchenne muscular dystrophy (DMD) is frequently complicated by development of a cardiomyopathy. Despite significant medical advances provided to DMD patients over the past 2 decades, there remains a group of DMD patients who die prematurely. The current study sought to identify a set of prognostic factors that portend a worse outcome among adult DMD patients.A retrospective cohort of 43 consecutive patients was followed in the adult UT Southwestern Neuromuscular Cardiomyopathy Clinic. Clinical data were abstracted from the electronic medical record to generate baseline characteristics. The population was stratified by survival to time of analysis and compared with characteristics associated with death. The DMD population was in the early 20s, with median follow-up times over 2 years. All the patients had developed a cardiomyopathy, with the majority of the patients on angiotensin-converting enzyme inhibitors (86%) and steroids (56%), but few other guideline-directed heart failure medications. Comparison between the nonsurviving and surviving cohorts found several poor prognostic factors, including lower body mass index (17.3 [14.8-19.3] versus 25.8 [20.8-29.1] kg/m2, P<0.01), alanine aminotransferase levels (26 [18-42] versus 53 [37-81] units/L, P=0.001), maximum inspiratory pressures (13 [0-30] versus 33 [25-40] cmH2O, P=0.03), and elevated cardiac biomarkers (N-terminal pro-brain natriuretic peptide: 288 [72-1632] versus 35 [21-135] pg/mL, P=0.03].The findings demonstrate a DMD population with a high burden of cardiomyopathy. The nonsurviving cohort was comparatively underweight, and had worse respiratory profiles and elevated cardiac biomarkers. Collectively, these factors highlight a high-risk cardiovascular population with a worse prognosis.

Abstract Aims To investigate the obesity paradox and association of extreme obesity with long-term outcomes among older ST-segment elevation myocardial infarction (STEMI) patients. Methods and results Nineteen thousand four hundred and ninety-nine patients ≥65 years with STEMI surviving to hospital discharge in NCDR ACTION Registry-GWTG linked to Centers for Medicare and Medicaid Services outcomes between 2007 and 2012 were stratified by body mass index (BMI) (kg/m2) into normal weight (18.5–24.9), overweight (25–29.9), class I (30–34.9), class II (35–39.9), and class III/extreme obese (≥40) categories. Multivariable-adjusted associations were evaluated between BMI categories and mortality by Cox proportional hazards models, and days alive and out of hospital (DAOH) by generalized estimating equations, within 3 years after discharge. Seventy percent of patients were overweight/obese and 3% extremely obese. Normal weight patients were older and more likely to smoke; while extremely obese patients were younger and more likely to be female and black, with lower socioeconomic status and more comorbidity (P ≤ 0.001). A U-shaped association was observed between BMI categories and mortality: patients with class I obesity were at lowest risk, while normal weight [hazard ratio (HR) 1.30, 95% confidence interval (CI) 1.15–1.47] and extremely obese patients (HR 1.33, 95% CI 1.02–1.74) had higher mortality. Normal weight [odds ratio (OR) 0.79, 95% CI 0.68–0.90] and extremely obese (OR 0.73, 95% CI 0.54–0.99) individuals also had lower odds of DAOH. Conclusion Mild obesity is associated with lower long-term risk in older STEMI patients, while normal weight and extreme obesity are associated with worse outcomes. These findings highlight hazards faced by an increasing number of older individuals with normal weight or extreme obesity and cardiovascular disease.

Background To assess the current landscape of the heart failure (HF) epidemic and provide targets for future health policy interventions in Medicare, a contemporary appraisal of its epidemiology across inpatient and outpatient care settings is needed. Methods and Results In a national 5% sample of Medicare beneficiaries from 2002 to 2013, we identified a cohort of 2 331 939 unique fee-for-service Medicare beneficiaries ≥65-years-old followed for all inpatient and outpatient encounters over a 10-year period (2004–2013). Preexisting HF was defined by any HF encounter during the first year, and incident HF with either 1 inpatient or 2 outpatient HF encounters. Mean age of the cohort was 72 years; 57% were women, and 86% and 8% were white and black, respectively. Within this cohort, 518 223 patients had preexisting HF, and 349 826 had a new diagnosis of HF during the study period. During 2004 to 2013, the rates of incident HF declined 32%, from 38.7 per 1000 (2004) to 26.2 per 1000 beneficiaries (2013). In contrast, prevalent (preexisting + incident) HF increased during our study period from 162 per 1000 (2004) to 172 per 1000 beneficiaries (2013) ( P trend &lt;0.001 for both). Finally, the overall 1-year mortality among patients with incident HF is high (24.7%) with a 0.4% absolute decline annually during the study period, with a more pronounced decrease among those diagnosed in an inpatient versus outpatient setting ( P interaction &lt;0.001) Conclusions In recent years, there have been substantial changes in the epidemiology of HF in Medicare beneficiaries, with a decline in incident HF and a decrease in 1-year HF mortality, whereas the overall burden of HF continues to increase.

Current guidelines recommend surgical revascularization (coronary artery bypass graft [CABG]) over percutaneous coronary intervention (PCI) in patients with diabetes mellitus and multivessel coronary artery disease. Few data are available describing revascularization patterns among these patients in the setting of non-ST-segment-elevation myocardial infarction.Using Acute Coronary Treatment and Intervention Outcomes Network Registry-Get with the Guidelines (ACTION Registry-GWTG), we compared the in-hospital use of different revascularization strategies (PCI versus CABG versus no revascularization) in diabetes mellitus patients with non-ST-segment-elevation myocardial infarction who had angiography, demonstrating multivessel coronary artery disease between July 2008 and December 2014. Factors associated with use of CABG versus PCI were identified using logistic multivariable regression analyses. A total of 29 769 patients from 539 hospitals were included in the study, of which 10 852 (36.4%) were treated with CABG, 13 760 (46.2%) were treated with PCI, and 5157 (17.3%) were treated without revascularization. The overall use of revascularization increased over the study period with an increase in the proportion undergoing PCI (45% to 48.9%; Ptrend=0.0002) and no change in the proportion undergoing CABG (36.1% to 34.7%; ptrend=0.88). There was significant variability between participating hospitals in the use of PCI and CABG (range: 22%-100%; 0%-78%, respectively; P value <0.0001 for both). Patient-level, but not hospital-level, characteristics were statistically associated with the use of PCI versus CABG, including anatomic severity of the disease, early treatment of adenosine diphosphate receptor antagonists at presentation, older age, female sex, and history of heart failure.Among patients with diabetes mellitus and multivessel coronary artery disease presenting with non-ST-segment-elevation myocardial infarction, only one third undergo CABG during the index admission. Furthermore, the use of PCI, but not CABG, increased modestly over the past 6 years.

Low cardiorespiratory fitness (CRF) is associated with an increased risk of stroke. However, the extent to which this association is explained by the development of stroke risk factors such as diabetes mellitus, hypertension, and atrial fibrillation is unknown. We evaluated the relationship between midlife CRF and risk of stroke after the age of 65 years, independent of the antecedent risk factor burden.Linking participant data from the Cooper Center Longitudinal Study with Medicare claims files, we studied 19 815 individuals who survived to receive Medicare coverage from 1999 to 2009. CRF estimated at baseline by Balke treadmill time was analyzed as a continuous variable (in metabolic equivalents) and according to age- and sex-specific quintiles (Q1=low CRF). Associations between midlife CRF and stroke hospitalization after the age of 65 years were assessed by applying a proportional hazards recurrent events model to the failure time data with hypertension, diabetes mellitus, and atrial fibrillation as time-dependent covariates.After 129 436 person-years of Medicare follow-up, we observed 808 stroke hospitalizations. After adjustment for baseline risk factors, higher midlife CRF was associated with a lower risk of stroke hospitalization (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.49-0.76; quintiles 4-5 versus 1]. This association remained unchanged after additional adjustment for burden of Medicare-identified stroke risk factors (hypertension, diabetes mellitus, and atrial fibrillation; HR, 0.63; 95% CI, 0.51-0.79; quintiles 4-5 versus 1).There is a strong, inverse association between midlife CRF and stroke risk in later life independent of baseline and antecedent burden of risk factors, such as hypertension, diabetes mellitus, and atrial fibrillation.

Postacute myocardial infarction (AMI) readmissions are common among Medicare beneficiaries (≥65 years) and are associated with significant resource utilization. However, patterns of AMI readmissions for younger age groups in the United States are not known. In the Nationwide Readmissions Database, a nationally representative all-payer database of inpatient hospitalizations, we identified 212,171 index AMI hospitalizations in January to November 2013, weighted to represent 478,247 hospitalizations nationally (mean age 66.9 years, 38% women, 29% low income). This included 26,516 cases in the 18 to 44 age group, 183,703 in the 45 to 64 age group, and 268,027 in the ≥65 age group. The overall 30-day readmission rate was 14.5% and varied across age groups (9.7% [18 to 44], 11.2% [45 to 64], and 17.3% [≥65]). The cumulative cost of 30-day readmissions was $1.1 billion, of which $365 million was spent on those <65 years of age. In multivariable hierarchical models, the risk of readmission was higher in women and in low-income patients, but the effect varied by age (p value for age-gender and age-income interactions <0.05) and was more prominent in the younger age groups. Further, patients in all age groups continue to have a high hospitalization burden beyond the typical 30-day readmission period, with an overall 24% post-AMI 90-day readmission rate. In conclusion, readmissions in young and middle-aged AMI survivors pose a substantial burden on patients and on U.S. health-care resources. Women and low-income patients with AMI, particularly those in younger age groups, are more frequently readmitted, and readmissions continue to burden the health-care system beyond the typical 30-day window. Future investigations would need to be targeted toward a better understanding and improvement of the rehospitalization burden for vulnerable patient groups.

Ticagrelor is a cornerstone of modern antithrombotic therapy alongside aspirin in patients with acute coronary syndrome and after percutaneous coronary intervention. Adverse effects such as bleeding and dyspnea have been associated with premature ticagrelor discontinuation, which may limit any potential advantage of ticagrelor over clopidogrel. The randomized trials of ticagrelor captured adverse events, offering the opportunity to more precisely quantify these effects across studies. Therefore, a meta-analysis of 4 randomized clinical trials of ticagrelor conducted between January 2007 and June 2017 was performed to quantify the incidence and causes of premature ticagrelor discontinuation. Among 66,870 patients followed for a median 18 months, premature ticagrelor discontinuation was seen in 25%; bleeding was the most common cause of discontinuation followed by dyspnea. Versus the comparators, the relative risk of dyspnea-related discontinuation during follow-up was 6.4-fold higher, the relative risk of bleeding was 3.2-fold higher, and the relative risk of discontinuation due to any adverse event was 59% higher for patients receiving ticagrelor. Understanding these potential barriers to adherence to ticagrelor is crucial for informed patient-physician decision making and can inform future efforts to improve ticagrelor adherence. This review discusses the incidence, causes, and biological mechanisms of ticagrelor-related adverse effects and offers strategies to improve adherence to ticagrelor.

Background: In response to the public health emergency created by the coronavirus disease 2019 (COVID-19) pandemic, American Heart Association volunteers and staff aimed to rapidly develop and launch a resource for the medical and research community to expedite scientific advancement through shared learning, quality improvement, and research. In &lt;4 weeks after it was first announced on April 3, 2020, AHA’s COVID-19 CVD Registry powered by Get With The Guidelines received its first clinical records. Methods and Results: Participating hospitals are enrolling consecutive hospitalized patients with active COVID-19 disease, regardless of CVD status. This hospital quality improvement program will allow participating hospitals and health systems to evaluate patient-level data including mortality rates, intensive care unit bed days, and ventilator days from individual review of electronic medical records of sequential adult patients with active COVID-19 infection. Participating sites can leverage these data for onsite, rapid quality improvement, and benchmarking versus other institutions. After 9 weeks, &gt;130 sites have enrolled in the program and &gt;4000 records have been abstracted in the national dataset. Additionally, the aggregate dataset will be a valuable data resource for the medical research community. Conclusions: The AHA COVID-19 CVD Registry will support greater understanding of the impact of COVID-19 on cardiovascular disease and will inform best practices for evaluation and management of patients with COVID-19.

<h3>Importance</h3> Heart failure (HF) incidence is declining among Medicare beneficiaries. However, the epidemiological mechanisms underlying this decline are not well understood. <h3>Objective</h3> To evaluate trends in HF incidence across risk factor strata. <h3>Design, Setting, and Participants</h3> Retrospective, national cohort study of 5% of all fee-for-service Medicare beneficiaries with no prior HF followed up from 2011 to 2016. The study examined annual trends in HF incidence among groups with and without primary HF risk factors (hypertension, diabetes, and obesity) and predisposing cardiovascular conditions (acute myocardial infarction [MI] and atrial fibrillation [AF]). <h3>Exposures</h3> The presence of comorbid HF risk factors including hypertension, diabetes, obesity, acute MI, and AF identified by<i>International Classification of Diseases</i>,<i>Ninth Revision</i>,<i>Clinical Modification</i>codes and<i>International Statistical Classification of Diseases</i>,<i>Tenth Revision</i>,<i>Clinical Modification</i>codes. <h3>Main Outcomes and Measures</h3> Incident HF, defined using at least 1 inpatient HF claim or at least 2 outpatient HF claims among those without a previous diagnosis of HF. <h3>Results</h3> Of 1 799 027 unique Medicare beneficiaries at risk for HF (median age, 73 years [interquartile range, 68-79 years]; 56% female [805 060-796 253 participants during the study period]), 249 832 had a new diagnosis of HF. The prevalence of all 5 risk factors increased over time (0.8% mean increase in hypertension per year, 1.9% increase in diabetes, 2.9% increase in obesity, 0.2% increase in acute MI, and 0.4% increase in AF). Heart failure incidence declined from 35.7 cases per 1000 beneficiaries in 2011 to 26.5 cases per 1000 beneficiaries in 2016, consistent across subgroups based on sex and race/ethnicity. A greater decline in HF incidence was observed among patients with prevalent hypertension (relative excess decline, 12%), diabetes (relative excess decline, 3%), and obesity (relative excess decline, 16%) compared with those without corresponding risk factors. In contrast, there was a relative increase in HF incidence among individuals with acute MI (26% vs no acute MI) and AF (22% vs no AF). <h3>Conclusions and Relevance</h3> Findings of this study suggest that the temporal decline in HF incidence among Medicare beneficiaries reflects a decrease in HF incidence among those with primary HF risk factors. The increase in HF incidence among those with acute MI and those with AF highlights potential targets for future HF prevention strategies.

Lower circulating levels of glycine are consistently reported in association with cardiovascular disease (CVD), but the causative role and therapeutic potential of glycine in atherosclerosis, the underlying cause of most CVDs, remain to be established. Here, following the identification of reduced circulating glycine in patients with significant coronary artery disease (sCAD), we investigated a causative role of glycine in atherosclerosis by modulating glycine availability in atheroprone mice. We further evaluated the atheroprotective potential of DT-109, a recently identified glycine-based compound with dual lipid/glucose-lowering properties. Glycine deficiency enhanced, while glycine supplementation attenuated, atherosclerosis development in apolipoprotein E-deficient (Apoe-/-) mice. DT-109 treatment showed the most significant atheroprotective effects and lowered atherosclerosis in the whole aortic tree and aortic sinus concomitant with reduced superoxide. In Apoe-/- mice with established atherosclerosis, DT-109 treatment significantly reduced atherosclerosis and aortic superoxide independent of lipid-lowering effects. Targeted metabolomics and kinetics studies revealed that DT-109 induces glutathione formation in mononuclear cells. In bone marrow-derived macrophages (BMDMs), glycine and DT-109 attenuated superoxide formation induced by glycine deficiency. This was abolished in BMDMs from glutamate-cysteine ligase modifier subunit-deficient (Gclm-/-) mice in which glutathione biosynthesis is impaired. Metabolic flux and carbon tracing experiments revealed that glycine deficiency inhibits glutathione formation in BMDMs while glycine-based treatment induces de novo glutathione biosynthesis. Through a combination of studies in patients with CAD, in vivo studies using atherosclerotic mice and in vitro studies using macrophages, we demonstrated a causative role of glycine in atherosclerosis and identified glycine-based treatment as an approach to mitigate atherosclerosis through antioxidant effects mediated by induction of glutathione biosynthesis.

Background: Impairments in carbohydrate, lipid, and amino acid metabolism drive features of plaque instability. However, where these impairments occur within the atheroma remains largely unknown. Therefore, we sought to characterize the spatial distribution of metabolites within stable and unstable atherosclerosis in both the fibrous cap and necrotic core. Methods: Atherosclerotic tissue specimens from 9 unmatched individuals were scored based on the Stary classification scale and subdivided into stable and unstable atheromas. After performing mass spectrometry imaging on these samples, we identified over 850 metabolite-related peaks. Using MetaboScape, METASPACE, and Human Metabolome Database, we confidently annotated 170 of these metabolites and found over 60 of these were different between stable and unstable atheromas. We then integrated these results with an RNA-sequencing data set comparing stable and unstable human atherosclerosis. Results: Upon integrating our mass spectrometry imaging results with the RNA-sequencing data set, we discovered that pathways related to lipid metabolism and long-chain fatty acids were enriched in stable plaques, whereas reactive oxygen species, aromatic amino acid, and tryptophan metabolism were increased in unstable plaques. In addition, acylcarnitines and acylglycines were increased in stable plaques whereas tryptophan metabolites were enriched in unstable plaques. Evaluating spatial differences in stable plaques revealed lactic acid in the necrotic core, whereas pyruvic acid was elevated in the fibrous cap. In unstable plaques, 5-hydroxyindoleacetic acid was enriched in the fibrous cap. Conclusions: Our work here represents the first step to defining an atlas of metabolic pathways involved in plaque destabilization in human atherosclerosis. We anticipate this will be a valuable resource and open new avenues of research in cardiovascular disease.

ST2, part of the interleukin-1 receptor family, is released from cardiac myocytes under mechanical strain. Soluble ST2 (sST2) concentrations are associated with adverse cardiac events in high-risk cohorts. We evaluated the association of sST2 with all-cause and cardiovascular mortality in a large, low-risk population-based cohort.Plasma sST2 was measured in 3294 subjects from the Dallas Heart Study, a probability-based population cohort. We categorized participants into undetectable (reference group) or quartiles of detectable sST2 concentrations. Associations with all-cause and cardiovascular mortality were assessed over a median 8.3 years of follow-up.sST2 concentrations were not significantly associated with most traditional risk factors, prevalent subclinical cardiovascular disease, or nonfatal cardiac events. However, a higher proportion of African Americans had detectable concentrations of sST2 than non-African Americans (44% vs 21%, respectively, P < 0.0001). In addition, sST2 concentrations were significantly associated with markers of inflammation. Increased sST2 was associated with increased all-cause mortality (Ptrend ≤ 0.0001) and cardiovascular mortality (Ptrend = 0.0004). In fully adjusted models, those in the highest quartile of detectable sST2 were at increased risk for all-cause death compared to those with undetectable sST2 concentrations (adjusted hazard ratio 2.1, 95% CI 1.4-3.2, P = 0.0009).In a low-risk population, sST2 does not associate with traditional cardiovascular risk factors or nonfatal cardiovascular events but is higher in African Americans and is associated with increased all-cause and cardiovascular mortality. Further investigation is needed regarding the role of sST2 in risk prediction, particularly among African Americans.

The natural history of white matter hyperintensity (WMH) progression resulting from normal aging versus comorbid vascular insults remains unclear. Therefore we investigated age-related differences in WMH volumes among a group with comorbid hypertension, abnormal body mass index, and diabetes mellitus to a normal aging group drawn from the same population lacking any of these comorbidities.WMH volumes were acquired using 3T MRI for 2011 Dallas Heart Study participants. The slope of the WMH versus age regression was compared between normal and comorbidity groups<50 and ≥50 years of age where a change in slope was demonstrated.Aging was linearly associated with greater log WMH volume for both normal (P=0.02) and comorbidity (P<0.0001) groups. Beyond 50 years of age, more rapid increases in WMH volumes for age were seen in the group with comorbidities (P<0.0001) but not in the normal group (P=0.173). The between-group difference in slope of expected WMH for age was significantly greater in the comorbidity groups≥50 years of age (P=0.0008) but not <50 years of age (P=0.752).After 50 years of age, but not before, comorbid hypertension, obesity, and diabetes mellitus were associated with significantly larger WMH volumes for age compared with a normal aging group lacking these conditions. These results support the assertion that age-related differences in WMH volumes are significantly increased in the presence of comorbidities, but the effect is only detectable after 50 years of age.

Despite a proposed connection between neighborhood environment and obesity, few longitudinal studies have examined the relationship between change in neighborhood socioeconomic deprivation, as defined by moving between neighborhoods, and change in body weight. The purpose of this study is to examine the longitudinal relationship between moving to more socioeconomically deprived neighborhoods and weight gain as a cardiovascular risk factor.Weight (kilograms) was measured in the Dallas Heart Study (DHS), a multiethnic cohort aged 18-65 years, at baseline (2000-2002) and 7-year follow-up (2007-2009, N=1,835). Data were analyzed in 2013-2014. Geocoded addresses were linked to Dallas County, TX, census block groups. A block group-level neighborhood deprivation index (NDI) was created. Multilevel difference-in-difference models with random effects and a Heckman correction factor (HCF) determined weight change relative to NDI change.Forty-nine percent of the DHS population moved (263 to higher NDI, 586 to lower NDI, 47 within same NDI), with blacks more likely to move than whites or Hispanics (p<0.01), but similar baseline BMI and waist circumference were observed in movers versus non-movers (p>0.05). Adjusting for HCF, sex, race, and time-varying covariates, those who moved to areas of higher NDI gained more weight compared to those remaining in the same or moving to a lower NDI (0.64 kg per 1-unit NDI increase, 95% CI=0.09, 1.19). Impact of NDI change on weight gain increased with time (p=0.03).Moving to more-socioeconomically deprived neighborhoods was associated with weight gain among DHS participants.

Fitness and traditional risk factors have well-known associations with cardiovascular disease (CVD) death in both short-term (10 years) and across the remaining lifespan. However, currently available short-term and long-term risk prediction tools do not incorporate measured fitness.We included 16 533 participants from the Cooper Center Longitudinal Study (CCLS) without prior CVD. Fitness was measured using the Balke protocol. Sex-specific fitness levels were derived from the Balke treadmill times and categorized into low, intermediate, and high fit according to age- and sex-specific treadmill times. Sex-specific 30-year risk estimates for CVD death adjusted for competing risk of non-CVD death were estimated using the cause-specific hazards model and included age, body mass index, systolic blood pressure, fitness, diabetes mellitus, total cholesterol, and smoking. During a median follow-up period of 28 years, there were 1123 CVD deaths. The 30-year risk estimates for CVD mortality derived from the cause-specific hazards model demonstrated overall good calibration (Nam-D'Agostino χ(2) [men, P=0.286; women, P=0.664] and discrimination (c statistic; men, 0.81 [0.80-0.82] and women, 0.86 [0.82-0.91]). Across all risk factor strata, the presence of low fitness was associated with a greater 30-year risk for CVD death.Fitness represents an important additional covariate in 30-year risk prediction functions that may serve as a useful tool in clinical practice.

Identifying high-performing surgical valve centers with the best surgical outcomes is challenging. Hospital surgical volume is a frequently used surrogate for outcomes. However, its ability to distinguish low-performing and high-performing hospitals remains unknown.To examine the association of hospital procedure volume with hospital performance for aortic and mitral valve (MV) surgical procedures.Within an all-payer nationally representative data set of inpatient hospitalizations, this study identified 682 unique hospitals performing surgical aortic valve replacement (SAVR) and MV replacement and repair with or without coronary artery bypass grafting (CABG) between 2007 and 2011. Procedural outcomes were further assessed for a 10-year period (2005-2014) to assess representativeness of study period.In-hospital risk-standardized mortality rate (RSMR) calculated using hierarchical models and an empirical bayesian approach with volume-based shrinkage that allowed for reliability adjustment.At 682 US hospitals, 70 295 SAVR, 19 913 MV replacement, and 17 037 MV repair procedures were performed between 2007 and 2011, with a median annual volume of 43 (interquartile range [IQR], 23-76) SAVR, 13 (IQR, 6-22) MV replacement, and 9 (IQR, 4-19) MV repair procedures. Of 225 SAVR hospitals in the highest-volume tertile, 34.7% and 36.0% were in the highest-RSMR tertile for SAVR + CABG and isolated SAVR procedures, respectively, while 21.5% and 17.5% of the 228 SAVR hospitals in the lowest-volume tertile were in the lowest respective RSMR tertile. Similarly, 36.8% and 43.5% of hospitals in the highest tertile of volume for MV replacement and repair, respectively, were in the corresponding highest-RSMR tertile, and 17.4% and 11.2% of the low-volume hospitals were in the lowest-RSMR tertile for MV replacement and repair, respectively. There was limited correlation between outcomes for SAVR and MV procedures at an institution. If solely volume-based tertiles were used to categorize hospitals for quality, 44.7% of all valve hospitals would be misclassified (as either low performing or high performing) when assessing performance based on tertiles of RSMR.Hospital procedure volume alone frequently misclassifies hospital performance with regard to risk-standardized outcomes after aortic and MV surgical procedures. Valve surgery quality improvement endeavors should focus on a more comprehensive assessment that includes risk-adjusted outcomes rather than hospital volume alone.

Hospitals are subject to federal financial penalties for excessive 30-day hospital readmissions for acute myocardial infarction (AMI). Prospectively identifying patients hospitalized with AMI at high risk for readmission could help prevent 30-day readmissions by enabling targeted interventions. However, the performance of AMI-specific readmission risk prediction models is unknown.We systematically searched the published literature through March 2017 for studies of risk prediction models for 30-day hospital readmission among adults with AMI. We identified 11 studies of 18 unique risk prediction models across diverse settings primarily in the United States, of which 16 models were specific to AMI. The median overall observed all-cause 30-day readmission rate across studies was 16.3% (range, 10.6%-21.0%). Six models were based on administrative data; 4 on electronic health record data; 3 on clinical hospital data; and 5 on cardiac registry data. Models included 7 to 37 predictors, of which demographics, comorbidities, and utilization metrics were the most frequently included domains. Most models, including the Centers for Medicare and Medicaid Services AMI administrative model, had modest discrimination (median C statistic, 0.65; range, 0.53-0.79). Of the 16 reported AMI-specific models, only 8 models were assessed in a validation cohort, limiting generalizability. Observed risk-stratified readmission rates ranged from 3.0% among the lowest-risk individuals to 43.0% among the highest-risk individuals, suggesting good risk stratification across all models.Current AMI-specific readmission risk prediction models have modest predictive ability and uncertain generalizability given methodological limitations. No existing models provide actionable information in real time to enable early identification and risk-stratification of patients with AMI before hospital discharge, a functionality needed to optimize the potential effectiveness of readmission reduction interventions.

Management of heart failure is a major health care challenge. Healthcare providers are expected to use best practices described in clinical practice guidelines, which typically consist of a long series of complex rules. For heart failure management, the relevant guidelines are nearly 80 pages long. Due to their complexity, the guidelines are often difficult to fully comply with, which can result in suboptimal medical practices. In this paper, we describe a heart failure treatment adviser system that automates the entire set of rules in the guidelines for heart failure management. The system is based on answer set programming, a form of declarative programming suited for simulating human-style reasoning. Given a patient's information, the system is able to generate a set of guideline-compliant recommendations. We conducted a pilot study of the system on 21 real and 10 simulated patients with heart failure. The results show that the system can give treatment recommendations compliant with the guidelines. Out of 187 total recommendations made by the system, 176 were agreed upon by the expert cardiologists. Also, the system missed eight valid recommendations. The reason for the missed and discordant recommendations seems to be insufficient information, differing style, experience, and knowledge of experts in decision-making that were not captured in the system at this time. The system can serve as a point-of-care tool for clinics. Also, it can be used as an educational tool for training physicians and an assessment tool to measure the quality metrics of heart failure care of an institution.

Cardiovascular disease is a leading economic and medical burden in the United States (US). As an important risk factor for cardiovascular disease, hypertension represents a critical point of intervention. Less is known about longitudinal effects of neighborhood deprivation on blood pressure outcomes, especially in light of new hypertension guidelines. Longitudinal data from the Dallas Heart Study facilitated multilevel regression analysis of the relationship between neighborhood deprivation, blood pressure change, and incident hypertension over a 9-year period. Factor analysis explored neighborhood perception, which was controlled for in all analyses. Neighborhood deprivation was derived from US Census data and divided into tertiles for analysis. Hypertension status was compared using pre-2017 and 2017 hypertension guidelines. After adjusting for covariates, including moving status and residential self-selection, we observed significant associations between residing in the more deprived neighborhoods and 1) increasing blood pressure over time and 2) incident hypertension. In the fully adjusted model of continuous blood pressure change, significant relationships were seen for both medium (SBP: β = 4.81, SE = 1.39, P = .0005; DBP: β = 2.61, SE = 0.71, P = .0003) and high deprivation (SBP: β = 7.64, SE = 1.55, P < .0001; DBP: β = 4.64, SE = 0.78, P < .0001). In the fully adjusted model of incident hypertension, participants in areas of high deprivation had 1.69 higher odds of developing HTN (OR 1.69; 95% CI 1.02, 2.82), as defined by 2017 hypertension guidelines. Results varied based on definition of hypertension used (pre-2017 vs. 2017 guidelines). These findings highlight the potential impact of adverse neighborhood conditions on cardiometabolic outcomes, such as hypertension.

HomeCirculationVol. 138, No. 18Evaluation of a Novel Rule-Out Myocardial Infarction Protocol Incorporating High-Sensitivity Troponin T in a US Hospital Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBEvaluation of a Novel Rule-Out Myocardial Infarction Protocol Incorporating High-Sensitivity Troponin T in a US Hospital Rebecca Vigen, MD, MSCS, Patricia Kutscher, MT, ASCP, Fernabelle Fernandez, MLS, ASCP, Amy Yu, MLS, ASCP, Bryan Bertulfo, MLS, ASCP, Ibrahim A. Hashim, MSc, PhD, Kyle Molberg, MD, Deborah B. Diercks, MD, MPH, Jeffery C. Metzger, MD, MBA, Jose Soto, MD, Dergham Alzubaidy, MD, Lorie Thibodeaux, MHA, Jose A. Joglar, MD, James A. de Lemos, MD and Sandeep R. Das, MD, MPH Rebecca VigenRebecca Vigen Rebecca Vigen, MD, MSCS, 5323 Harry Hines Blvd, Dallas, TX 75390–8830. Email E-mail Address: [email protected] Department of Internal Medicine, Division of Cardiology (R.V., J.A.J., J.A.d.L., S.R.D), University of Texas Southwestern Medical Center, Dallas. Search for more papers by this author , Patricia KutscherPatricia Kutscher Rapid Response Lab (P.K., F.F., A.Y., B.B.), Parkland Health and Hospital System, Dallas, TX. Search for more papers by this author , Fernabelle FernandezFernabelle Fernandez Rapid Response Lab (P.K., F.F., A.Y., B.B.), Parkland Health and Hospital System, Dallas, TX. Search for more papers by this author , Amy YuAmy Yu Rapid Response Lab (P.K., F.F., A.Y., B.B.), Parkland Health and Hospital System, Dallas, TX. Search for more papers by this author , Bryan BertulfoBryan Bertulfo Rapid Response Lab (P.K., F.F., A.Y., B.B.), Parkland Health and Hospital System, Dallas, TX. Search for more papers by this author , Ibrahim A. HashimIbrahim A. Hashim Department of Pathology (I.A.H., K.M.), University of Texas Southwestern Medical Center, Dallas. Search for more papers by this author , Kyle MolbergKyle Molberg Department of Pathology (I.A.H., K.M.), University of Texas Southwestern Medical Center, Dallas. Search for more papers by this author , Deborah B. DiercksDeborah B. Diercks Department of Emergency Medicine (D.B.D., J.C.M.), University of Texas Southwestern Medical Center, Dallas. Search for more papers by this author , Jeffery C. MetzgerJeffery C. Metzger Department of Emergency Medicine (D.B.D., J.C.M.), University of Texas Southwestern Medical Center, Dallas. Search for more papers by this author , Jose SotoJose Soto Department of Internal Medicine, Division of Hospitalist Medicine (J.S., D.A.), University of Texas Southwestern Medical Center, Dallas. Search for more papers by this author , Dergham AlzubaidyDergham Alzubaidy Department of Internal Medicine, Division of Hospitalist Medicine (J.S., D.A.), University of Texas Southwestern Medical Center, Dallas. Search for more papers by this author , Lorie ThibodeauxLorie Thibodeaux Performance Improvement Department, Quality Safety Division (L.T.), Parkland Health and Hospital System, Dallas, TX. Search for more papers by this author , Jose A. JoglarJose A. Joglar Department of Internal Medicine, Division of Cardiology (R.V., J.A.J., J.A.d.L., S.R.D), University of Texas Southwestern Medical Center, Dallas. Search for more papers by this author , James A. de LemosJames A. de Lemos Department of Internal Medicine, Division of Cardiology (R.V., J.A.J., J.A.d.L., S.R.D), University of Texas Southwestern Medical Center, Dallas. Search for more papers by this author and Sandeep R. DasSandeep R. Das Department of Internal Medicine, Division of Cardiology (R.V., J.A.J., J.A.d.L., S.R.D), University of Texas Southwestern Medical Center, Dallas. Parkland Center for Healthcare Innovation and Clinical Outcomes (S.R.D.), Parkland Health and Hospital System, Dallas, TX. Search for more papers by this author Originally published6 Aug 2018https://doi.org/10.1161/CIRCULATIONAHA.118.033861Circulation. 2018;138:2061–2063Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: August 6, 2018: Ahead of Print The US Food and Drug Administration recently approved a high-sensitivity (hs) troponin T (cTnT) assay that has greater sensitivity and precision than the conventional fourth-generation cTnT assay currently in use in the United States.1 Using this assay, European Society of Cardiology (ESC) guidelines endorse a 0/1-hour “rule-out” of myocardial infarction (MI) in low-risk individuals,2 as well as a more traditional 3-hour algorithm.3 However, the safety and effectiveness of rapid MI rule-out algorithms using hs-cTnT in US practice have not been established.A multidisciplinary team at Parkland Health and Hospital System developed a novel hs-cTnT protocol modified from published data.2–4 An important difference from previous protocols was the addition of a 3-hour hs-cTnT measurement for patients classified into the indeterminate zone at 1 hour (Figure [A]). An observational study of unselected patients undergoing MI rule-out was performed to evaluate the safety of the protocol and its potential impact on patient disposition. The proportion of patients who would have been eligible for early rule-out with the new protocol incorporating hs-cTnT was compared with existing practice in which the conventional fourth-generation cTnT assay was tested at baseline and ≥3 hours after presentation. The negative predictive value was calculated to assess safety. Both cTnT and hs-cTnT were measured at 0, 1, and 3 hours after presentation to the Parkland Health and Hospital System emergency department in 536 patients with symptoms warranting MI rule-out (60% chest pain, 16% shortness of breath, 24% other complaints), but no ST elevations on ECG, between August and October of 2017. Individuals were classified into 2 mutually exclusive categories, “ruled out” or “abnormal,” based on hs-cTnT levels and change values (Figure [A]). Individuals were classified as ruled out with the conventional assay if cTnT was <0.01 ng/mL at all time points and abnormal if any value was ≥ 0.01 ng/mL. The final diagnosis was adjudicated by 3 cardiologists based on all available clinical information, including the conventional cTnT assay, using the Third Universal Definition of MI. A second adjudication was performed as a sensitivity analysis using the hs-cTnT assay instead of the conventional assay.2,5 Finally, we compared our new hs-cTnT algorithm with the 0/1 hour ESC algorithm.3 The University of Texas Southwestern institutional review board approved this quality improvement study with a waiver of informed consent.Download figureDownload PowerPointFigure. High-sensitivity (hs) troponin T(cTnT) algorithm and comparisons with conventional cTnT algorithm and European Society of Cardiology (ESC) 0/1 algorithm.A, Parkland Hospital/UT Southwestern protocol for rapid myocardial infarction rule-out using the hs-cTnT assay. B, Proportions of patients ruled out for acute myocardial infarction based on the conventional cTnT algorithm and new hs-cTnT algorithm. C, Comparison of ESC 0/1 algorithm and new hs-cTnT algorithm. NPV indicates negative predictive value; and PPV, positive predictive value.In this cohort (N=536, mean age 55 years, 44% women), the final adjudicated diagnosis was MI in 2.1%, unstable angina in 0.4%, and nonischemic myocardial injury in 17.0%. With the conventional assay, 80.4% of patients ruled out for MI at 3 hours. With the new hs-cTnT protocol, 83.8% ruled out by 3 hours, including 30.0% at baseline, 24.8% at 1 hour, and 28.9% at 3 hours. Compared with 19.6% of patients considered abnormal by the conventional assay, 16.2% of patients were abnormal under the new protocol (P=0.03; McNemar’s test; Figure [B]). The new protocol had a sensitivity and negative predictive value of 100%, specificity of 86%, and positive predictive value of 13% for a final adjudicated diagnosis of MI. After readjudication using hs-cTnT as the gold standard, operating characteristics were identical except for a slightly lower positive predictive value of 12%. Of the patients who ruled out, no recurrent MI events were detected over 30 days of follow-up. When compared with the ESC 0/1 hour algorithm, a higher proportion ruled out with our new algorithm (83.8 versus 55.4%, P<0.0001), resulting from movement of 152/154 patients assigned to observation status with the ESC 0/1 hour algorithm to the rule-out group with the new protocol (Figure [C]).In summary, a new protocol for rapid rule-out of MI using the hs-cTnT assay, applied to a contemporary US emergency department population, ruled out more patients than the existing protocol using the conventional assay, and did so sooner, with more than half of all patients ruled out by 1 hour after presentation. This protocol also appropriately ruled out a much higher proportion than the ESC 0/1 hour algorithm. This early rule-out protocol appears safe, with a sensitivity and negative predictive value of 100%. The positive predictive value of an abnormal hs-cTnT value was notably lower in this population than in prior studies,1 reflecting similar specificity applied to a population with much lower MI prevalence. Thus, clinical judgment remains essential in the interpretation of abnormal troponin values as the hs-cTnT assay becomes adopted in the United States, where troponin is measured more indiscriminately than in many other countries. A subtle but important distinction of our protocol from the ESC 0/1 protocol is the classification of individuals as “abnormal” rather than “rule-in.” We recommend a similar approach in other centers with an anticipated low MI prevalence among those undergoing troponin measurement. This study is limited by its small size and lack of external validation; thus, future studies are needed to externally validate this novel algorithm and determine its resource implications.Sources of FundingDr Vigen was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award UL1TR001105. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.DisclosuresDr Diercks reports consulting income from Roche Diagnostics, and consulting income and research support from Siemens Diagnostics. Dr de Lemos reports grant support from Roche Diagnostics and Abbott Diagnostics and consulting income from Roche Diagnostics, Abbott Diagnostics, Ortho Clinical Diagnostics, and Endpoint Committees for Radiometer and Siemen’s Health Care Diagnostics. Dr Das reports consulting income from Roche Diagnostics. The other authors report no conflicts.Footnoteshttps://www.ahajournals.org/journal/circData sharing: The data and study materials will not be made available to other researchers.Guest Editor for this article was Evangelos Giannitsis, MD.Rebecca Vigen, MD, MSCS, 5323 Harry Hines Blvd, Dallas, TX 75390–8830. Email Rebecca.[email protected]eduReferences1. Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig C, Hartwiger S, Biedert S, Schaub N, Buerge C, Potocki M, Noveanu M, Breidthardt T, Twerenbold R, Winkler K, Bingisser R, Mueller C. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays.N Engl J Med. 2009; 361:858–867. doi: 10.1056/NEJMoa0900428CrossrefMedlineGoogle Scholar2. Reichlin T, Schindler C, Drexler B, Twerenbold R, Reiter M, Zellweger C, Moehring B, Ziller R, Hoeller R, Rubini Gimenez M, Haaf P, Potocki M, Wildi K, Balmelli C, Freese M, Stelzig C, Freidank H, Osswald S, Mueller C. 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Undetectable concentrations of a Food and Drug Administration-approved high-sensitivity cardiac troponin t assay to rule out acute myocardial infarction at emergency department arrival.Acad Emerg Med. 2017; 24:1267–1277. doi: 10.1111/acem.13229CrossrefMedlineGoogle Scholar5. Reichlin T, Twerenbold R, Wildi K, Rubini Gimenez M, Bergsma N, Haaf P, Druey S, Puelacher C, Moehring B, Freese M, Stelzig C, Krivoshei L, Hillinger P, Jäger C, Herrmann T, Kreutzinger P, Radosavac M, Weidmann ZM, Pershyna K, Honegger U, Wagener M, Vuillomenet T, Campodarve I, Bingisser R, Miró Ò, Rentsch K, Bassetti S, Osswald S, Mueller C. Prospective validation of a 1-hour algorithm to rule-out and rule-in acute myocardial infarction using a high-sensitivity cardiac troponin T assay.CMAJ. 2015; 187:E243–E252. doi: 10.1503/cmaj.141349CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited BySandoval Y, Apple F, Mahler S, Body R, Collinson P and Jaffe A (2022) High-Sensitivity Cardiac Troponin and the 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guidelines for the Evaluation and Diagnosis of Acute Chest Pain, Circulation, 146:7, (569-581), Online publication date: 16-Aug-2022.Sandoval Y, Lewis B, Mehta R, Ola O, Knott J, De Michieli L, Akula A, Lobo R, Yang E, Gharacholou S, Dworak M, Crockford E, Rastas N, Grube E, Karturi S, Wohlrab S, Hodge D, Tak T, Cagin C, Gulati R and Jaffe A (2022) Rapid Exclusion of Acute Myocardial Injury and Infarction With a Single High-Sensitivity Cardiac Troponin T in the Emergency Department: A Multicenter United States Evaluation, Circulation, 145:23, (1708-1719), Online publication date: 7-Jun-2022. Chiang C, Chiang C and Ruangsomboon O (2022) Utilizing the European Society of Cardiology 0/3-h algorithm to triage the 0/1-h algorithm observe-zone, European Heart Journal. Acute Cardiovascular Care, 10.1093/ehjacc/zuac025 Thibodeau J, Pham D, Kelly S, Ayers C, Garg S, Grodin J and Drazner M (2022) Subclinical Myocardial Injury and the Phenotype of Clinical Congestion in Patients With Heart Failure and Reduced Left Ventricular Ejection Fraction, Journal of Cardiac Failure, 10.1016/j.cardfail.2021.09.002, 28:3, (422-430), Online publication date: 1-Mar-2022. Harrington J and Felker G (2022) Leveraging Multiple Biomarkers to Assess Risk of Acute Heart Failure: Is More Better?, Journal of Cardiac Failure, 10.1016/j.cardfail.2021.11.015, 28:2, (234-236), Online publication date: 1-Feb-2022. Sarıyer G and Ataman M (2020) The likelihood of requiring a diagnostic test: Classifying emergency department patients with logistic regression, Health Information Management Journal, 10.1177/1833358320908975, 51:1, (13-22), Online publication date: 1-Jan-2022. Kong N, Chua R, Besser S, Heelan L, Nathan S, Spiegel T, van Wijk X and Tabit C (2021) A retrospective analysis of high sensitivity cardiac troponin-T ranges in non-myocardial infarction emergency department visits, BMC Cardiovascular Disorders, 10.1186/s12872-021-02089-0, 21:1, Online publication date: 1-Dec-2021. Sariyer G and Ataman M (2021) How machine learning facilitates decision making in emergency departments: Modelling diagnostic test orders, International Journal of Clinical Practice, 10.1111/ijcp.14980, 75:12, Online publication date: 1-Dec-2021. 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Lopez-Ayala P, Nestelberger T, Boeddinghaus J, Koechlin L, Ratmann P, Strebel I, Gehrke J, Meier S, Walter J, Rubini Gimenez M, Mutschler E, Miró Ò, López-Barbeito B, Martín-Sánchez F, Rodríguez-Adrada E, Keller D, Newby L, Twerenbold R, Giannitsis E, Lindahl B, Mueller C, Zimmermann T, Schoepfer H, Coscia T, Troester V, Reichlin T, Kaeslin M, Christ M, Meier M, Badertscher P, Puelacher C, du Fay de Lavallaz J, Potlukova E, Kawecki D, Geigy N, Rentsch K, Shrestha S, Morawiec B, Munzk P, Breidthardt T, Freese M, Martinez-Nadal G, Fuenzalida C, Calderón S, Rodriguez Adrada E, Ganovská E, Parenica J, von Eckardstein A, Campodarve I, Gea J, Mccord J, Nowak R, Body R, deFilippi C, Christenson R, Panteghini M, Plebani M, Verschuren F, French J, Weiser S and Jernberg T (2021) Novel Criteria for the Observe-Zone of the ESC 0/1h-hs-cTnT Algorithm, Circulation, 144:10, (773-787), Online publication date: 7-Sep-2021. Ganguli I, Cui J, Thakore N, Orav E, Januzzi J, Baugh C, Sequist T and Wasfy J (2021) Downstream Cascades of Care Following High-Sensitivity Troponin Test Implementation, Journal of the American College of Cardiology, 10.1016/j.jacc.2021.04.049, 77:25, (3171-3179), Online publication date: 1-Jun-2021. Westwood M, Ramaekers B, Grimm S, Worthy G, Fayter D, Armstrong N, Buksnys T, Ross J, Joore M and Kleijnen J (2021) High-sensitivity troponin assays for early rule-out of acute myocardial infarction in people with acute chest pain: a systematic review and economic evaluation, Health Technology Assessment, 10.3310/hta25330, 25:33, (1-276) Allen B, Christenson R, Cohen S, Nowak R, Wilkerson R, Mumma B, Madsen T, McCord J, Huis in’t Veld M, Massoomi M, Stopyra J, Montero C, Weaver M, Yang K and Mahler S (2021) Diagnostic Performance of High-Sensitivity Cardiac Troponin T Strategies and Clinical Variables in a Multisite US Cohort, Circulation, 143:17, (1659-1672), Online publication date: 27-Apr-2021. Furmaga J, McDonald S, Hall H, Muthukumar A, Willett K, Basit M and Diercks D (2020) Impact of High‐sensitivity Troponin Testing on Operational Characteristics of an Urban Emergency Department, Academic Emergency Medicine, 10.1111/acem.13956, 28:1, (114-116), Online publication date: 1-Jan-2021. Mumma B, Casey S, Dang R, Polen M, Kaur J, Rodrigo J, Tancredi D, Narverud R, Amsterdam E and Tran N (2020) Diagnostic Reclassification by a High-Sensitivity Cardiac Troponin Assay, Annals of Emergency Medicine, 10.1016/j.annemergmed.2020.06.047, 76:5, (566-579), Online publication date: 1-Nov-2020. Mungai E, Hamilton B and Burns D (2020) Comparison of High-Sensitivity Troponin T Assay to Conventional Troponin T Assay for Rule Out of Acute Coronary Syndrome in the Emergency Department, Advanced Emergency Nursing Journal, 10.1097/TME.0000000000000324, 42:4, (304-314), Online publication date: 1-Oct-2020. Wu A, Kavsak P, Aakre K, Christenson R, Greene D, Apple F, Peacock W, Hollander J, de Lemos J, Morrow D, Januzzi J and Jaffe A (2020) Lot-to-Lot Variation for Commercial High-Sensitivity Cardiac Troponin: Can We Realistically Report Down to the Assay’s Limit of Detection?, Clinical Chemistry, 10.1093/clinchem/hvaa160, 66:9, (1146-1149), Online publication date: 1-Sep-2020. Sandoval Y, Apple F, Saenger A, Collinson P, Wu A and Jaffe A (2020) 99th Percentile Upper-Reference Limit of Cardiac Troponin and the Diagnosis of Acute Myocardial Infarction, Clinical Chemistry, 10.1093/clinchem/hvaa158, 66:9, (1167-1180), Online publication date: 1-Sep-2020. Forman D, de Lemos J, Shaw L, Reuben D, Lyubarova R, Peterson E, Spertus J, Zieman S, Salive M and Rich M (2020) Cardiovascular Biomarkers and Imaging in Older Adults, Journal of the American College of Cardiology, 10.1016/j.jacc.2020.07.055, 76:13, (1577-1594), Online publication date: 1-Sep-2020. Chiang C, Chiang C, Lee G, Gi W, Wu Y, Huang S, Yeo Y, Giannitsis E and Lee C (2020) Safety and efficacy of the European Society of Cardiology 0/1-hour algorithm for diagnosis of myocardial infarction: systematic review and meta-analysis, Heart, 10.1136/heartjnl-2019-316343, 106:13, (985-991), Online publication date: 1-Jul-2020. Nowak R, Christenson R, Jacobsen G, McCord J, Apple F, Singer A, Limkakeng A, Peacock W and deFilippi C (2020) Performance of Novel High-Sensitivity Cardiac Troponin I Assays for 0/1-Hour and 0/2- to 3-Hour Evaluations for Acute Myocardial Infarction: Results From the HIGH-US Study, Annals of Emergency Medicine, 10.1016/j.annemergmed.2019.12.008, 76:1, (1-13), Online publication date: 1-Jul-2020. Kontos M and Turlington J (2020) High-Sensitivity Troponins in Cardiovascular Disease, Current Cardiology Reports, 10.1007/s11886-020-01279-0, 22:5, Online publication date: 1-May-2020. Vigen R, Diercks D, Hashim I, Pandey A, Zhong L, Kutscher P, Fernandez F, Yu A, Bertulfo B, Molberg K, Metzger J, Soto J, Alzubaidy D, Thibodeaux L, Joglar J, Das S and de Lemos J (2020) Association of a Novel Protocol for Rapid Exclusion of Myocardial Infarction With Resource Use in a US Safety Net Hospital, JAMA Network Open, 10.1001/jamanetworkopen.2020.3359, 3:4, (e203359) Gore M and de Lemos J (2020) Clinical Relevance of the 99th Percentile Upper Reference Limit for High-Sensitivity Cardiac Troponin Assays, Clinical Chemistry, 10.1093/clinchem/hvz038, 66:3, (403-405), Online publication date: 1-Mar-2020. Agusala V, Khera R, Cheeran D, Mody P, Reddy P and Link M (2019) Diagnostic and prognostic utility of cardiac troponin in post-cardiac arrest care, Resuscitation, 10.1016/j.resuscitation.2019.06.004, 141, (69-72), Online publication date: 1-Aug-2019. Sandoval Y, Sharain K, Saenger A, Smith S, Apple F and Jaffe A Clinical use of cardiac troponin for acute cardiac care and emerging opportunities in the outpatient setting, Minerva Medica, 10.23736/S0026-4806.18.05874-3, 110:2 McCord J, Newby L and deFilippi C (2019) Response by McCord et al to Letter Regarding Article, “Designing a Better Mousetrap: Reflections on the November 28, 2017, US Food and Drug Administration Meeting on Next-Generation “High-Sensitivity” Cardiac Troponin Assays to Diagnose Myocardial Infarction”, Circulation, 139:4, (564-565), Online publication date: 22-Jan-2019. October 30, 2018Vol 138, Issue 18 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.118.033861PMID: 30372140 Originally publishedAugust 6, 2018 Keywordstroponinspecificitysensitivitymyocardial infarctionPDF download Advertisement SubjectsBiomarkersMyocardial InfarctionQuality and Outcomes

To review the literature systematically to determine whether noninvasive or invasive risk stratification, such as with an electrophysiological study of patients with asymptomatic pre-excitation, reduces the risk of arrhythmic events and improves patient outcomes.PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (all January 1, 1970, through August 31, 2014) were searched for randomized controlled trials and cohort studies examining noninvasive or invasive risk stratification in patients with asymptomatic pre-excitation. Studies were rejected for low-quality design or the lack of an outcome, population, intervention, or comparator of interest or if they were written in a language other than English.Of 778 citations found, 9 studies met all the eligibility criteria and were included in this paper. Of the 9 studies, 1 had a dual design-a randomized controlled trial of ablation versus no ablation in 76 patients and an uncontrolled prospective cohort of 148 additional patients-and 8 were uncontrolled prospective cohort studies (n=1,594). In studies reporting a mean age, the range was 32 to 50 years, and in studies reporting a median age, the range was 19 to 36 years. The majority of patients were male (range, 50% to 74%), and <10% had structural heart disease. In the randomized controlled trial component of the dual-design study, the 5-year Kaplan-Meier estimates of the incidence of arrhythmic events were 7% among patients who underwent ablation and 77% among patients who did not undergo ablation (relative risk reduction: 0.08; 95% confidence interval: 0.02 to 0.33; p<0.001). In the observational cohorts of asymptomatic patients who did not undergo catheter ablation (n=883, with follow-up ranging from 8 to 96 months), regular supraventricular tachycardia or benign atrial fibrillation (shortest RR interval >250 ms) developed in 0% to 16%, malignant atrial fibrillation (shortest RR interval ≤250 ms) in 0% to 9%, and ventricular fibrillation in 0% to 2%, most of whom were children in the last case.The existing evidence suggests risk stratification with an electrophysiological study of patients with asymptomatic pre-excitation may be beneficial, along with consideration of accessory-pathway ablation in those deemed to be at high risk of future arrhythmias. Given the limitations of the existing data, well-designed and well-conducted studies are needed.

<h3>Importance</h3> The association of the Hospital Readmission Reduction Program (HRRP) with reductions in racial disparities in 30-day outcomes for myocardial infarction (MI), is unknown, including whether this varies by HRRP hospital penalty status. <h3>Objective</h3> To assess temporal trends in 30-day readmission and mortality rates among black and nonblack patients discharged after hospitalization for acute MI at low-performing and high-performing hospitals, as defined by readmission penalty status after HRRP implementation. <h3>Design, Setting, and Participants</h3> This observational cohort analysis used data from the multicenter National Cardiovascular Data Registry Chest Pain–MI Registry centers that were subject to the first cycle of HRRP, between January 1, 2008, and November 30, 2016. All patients hospitalized with MI who were included in National Cardiovascular Data Registry Chest Pain–MI Registry were included in the analysis. Data were analyzed from April 2018 to September 2019. <h3>Exposures</h3> Hospital performance category and race (black compared with nonblack patients). Centers were classified as high performing or low performing based on the excess readmission ratio (predicted to expected 30-day risk adjusted readmission rate) for MI during the first HRRP cycle (in October 2012). <h3>Main Outcomes and Measures</h3> Thirty-day all-cause readmission and mortality rates. <h3>Results</h3> Among 753 hospitals that treated 155 397 patients with acute MI (of whom 11 280 [7.3%] were black), 399 hospitals (53.0%) were high performing. Thirty-day readmission rates declined over time in both black and nonblack patients (annualized 30-day readmission rate: 17.9% vs 20.8%). Black (compared with nonblack) race was associated with higher unadjusted odds of 30-day readmission in both low-performing and high-performing centers (odds ratios: before HRRP: low-performing hospitals, 1.14 [95% CI, 1.03-1.26];<i>P</i> = .01; high-performing hospitals, 1.17 [95% CI, 1.04-1.32];<i>P</i> = .01; after HRRP: low-performing hospitals, 1.23 [95% CI, 1.13-1.34];<i>P</i> &lt; .001; high-performing hospitals, 1.25 [95% CI, 1.12-1.39];<i>P</i> &lt; .001). However, these racial differences were not significant after adjustment for patient characteristics. The 30-day mortality rates declined significantly over time in nonblack patients, with stable (nonsignificant) temporal trends among black patients. Adjusted associations between race and 30-day mortality showed that 30-day mortality rates were significantly lower among black (compared with nonblack) patients in the low-performing hospitals (odds ratios: pre-HRRP, 0.79 [95% CI, 0.63-0.97];<i>P</i> = .03; post-HRRP, 0.80 [95% CI, 0.68-0.95];<i>P</i> = .01) but not in high-performing hospitals. Finally, the association between race and 30-day outcomes did not vary after the HRRP period began in either high-performing or low-performing hospitals. <h3>Conclusions and Relevance</h3> In this analysis, 30-day readmission rates among patients with MI declined over time for both black and nonblack patients. Differences in race-specific 30-day readmission rates persisted but appeared to be attributable to patient-level factors. The 30-day mortality rates have declined for nonblack patients and remained stable among black patients. Implementation of the HRRP was not associated with improvement or worsening of racial disparities in readmission and mortality rates.

Fig. 10.2 of the article cited above provides recommendations for the treatment of confirmed hypertension in people with diabetes. Due to a composition error, the initial blood pressure range for the left side of the algorithm was given as ≥140/90 and &amp;lt;160/100 mmHg; the correct initial blood pressure range is ≥130/80 and &amp;lt;160/100 mmHg. The online version of the article (https://doi.org/10.2337/dc23-S010) has been updated to correct the error.

Elevated plasma levels of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-pro-BNP) are seen in the setting of cardiac ischemia and are associated with adverse outcomes in patients with coronary artery disease. The mechanisms leading to natriuretic peptide elevation in patients with coronary artery disease, including the contribution of coronary atherosclerosis itself, have not been fully elucidated. Measurement of NT-pro-BNP, electron beam computed tomography, and cardiac magnetic resonance imaging were performed in 2,445 subjects from the Dallas Heart Study who were free of heart failure and renal insufficiency. Electron beam computed tomography-determined coronary artery calcium scores were categorized as none (<10), mild (> or =10 to <100), moderate (> or =100 to <400), and severe (> or =400). NT-pro-BNP levels increased significantly across increasing coronary artery calcium score categories (p <0.0001 for trend). In multivariate models adjusted for age, gender, race, body mass index, hypertension, history of myocardial infarction, angina, angiotensin-converting enzyme inhibitor use, beta-blocker use, left ventricular (LV) ejection fraction, and LV mass, higher coronary artery calcium scores remained independently associated with higher log NT-pro-BNP levels (p = 0.03). This association persisted in similar models excluding patients with low LV ejection fractions, LV hypertrophy, angina pectoris, and a history of myocardial infarction. In conclusion, these findings support the hypothesis that coronary atherosclerosis may directly influence the activation of the cardiac neurohormonal system.

Emerging data suggest that diabetes mellitus is a risk factor for the progression of established heart failure only in those patients with ischemic cardiomyopathy. Whether diabetes mellitus is a risk factor for the progression from asymptomatic left ventricular systolic dysfunction to symptomatic heart failure in patients with left ventricular dysfunction of an ischemic cause is not known.We performed a retrospective analysis of 2821 patients with asymptomatic left ventricular systolic dysfunction from the Studies of Left Ventricular Dysfunction (SOLVD) Prevention trial. We used adjusted survival analysis to examine the effects of ischemic heart disease and diabetes mellitus on 3 prespecified study end points: (1) development of heart failure (HF) symptoms, (2) HF hospitalization, and (3) death or development of symptoms.There is a statistically significant interaction between the cause of left ventricular systolic dysfunction and diabetes mellitus on the risk of development of heart failure symptoms (P = .020). Patients with ischemic cardiomyopathy and diabetes had an increased risk of progression to symptomatic heart failure (HR = 1.56, P < .001), hospitalization for heart failure (HR = 2.16, P < .001), and death or development of symptoms (HR = 1.50, P < .001), compared with patients with ischemic cardiomyopathy without diabetes. In contrast, diabetes was not associated with an increased risk of reaching these end points in patients with nonischemic cardiomyopathy.Diabetes mellitus is a risk factor for the progression from asymptomatic left ventricular systolic dysfunction to symptomatic heart failure, but this risk appears to be confined to those patients with ischemic cardiomyopathy.

Higher C-reactive protein (CRP) levels in women compared with men may reflect sex differences in the relationship between obesity and inflammation. We evaluated how the adipokine leptin influenced these relationships.Dual energy X-ray absorptometry measurements of fat mass and plasma levels of leptin and CRP were measured in 1188 women and 1102 men from the Dallas Heart Study. Analyses were stratified by sex and a leptin/percent fat index was created to evaluate the association between leptin and CRP independent of fat mass. Women had higher body mass index, percent fat mass, and plasma levels of CRP and leptin. CRP levels correlated with leptin levels in both women (Spearman rho=0.48, p<0.0001) and in men (rho=0.27, p<0.0001). In multivariable models adjusting for confounders including total fat mass, leptin/percent fat index remained significantly associated with logCRP in women (p=0.005), but not in men (p=0.95). A significant interaction was observed between sex and leptin levels on CRP (p(interaction)=0.03).Leptin was associated with CRP independent of other measures of obesity in women, but not in men. These findings suggest that sex differences in CRP may reflect sex-related differences in the inflammatory responses to obesity, and may in part, be mediated by leptin.

Context:Previous small case-control studies have suggested an inverse relationship between adiponectin and hepatic steatosis, but whether this finding is independent of insulin sensitivity and other intraabdominal fat depots is unclear.

Therapies targeting high-density lipoprotein cholesterol content (HDL-C) have not improved coronary heart disease (CHD) outcomes. High-density lipoprotein particle concentration (HDL-P) may better predict CHD. However, the impact of race/ethnicity on the relations between HDL-P and subclinical atherosclerosis and incident CHD events has not been described. Participants from the Dallas Heart Study (DHS), a multiethnic, probability-based, population cohort of Dallas County adults, underwent the following baseline measurements: HDL-C, HDL-P by nuclear magnetic resonance imaging, and coronary artery calcium by electron-beam computed tomography. Participants were followed for a median of 9.3 years for incident CHD events (composite of first myocardial infarction, stroke, coronary revascularization, or cardiovascular death). The study comprised 1,977 participants free of CHD (51% women, 46% black). In adjusted models, HDL-C was not associated with prevalent coronary artery calcium (p = 0.13) or incident CHD overall (hazard ratio [HR] per 1 SD 0.89, 95% confidence interval [CI] 0.76 to 1.05). However, HDL-C was inversely associated with incident CHD among nonblack (adjusted HR per 1 SD 0.67, 95% CI 0.46 to 0.97) but not black participants (HR 0.94, 95% CI 0.78 to 1.13, pinteraction = 0.05). Conversely, HDL-P, adjusted for risk factors and HDL-C, was inversely associated with prevalent coronary artery calcium (p = 0.009) and with incident CHD overall (adjusted HR per 1 SD 0.73, 95% CI 0.62 to 0.86), with no interaction by black race/ethnicity (pinteraction = 0.57). In conclusion, in contrast to HDL-C, the inverse relation between HDL-P and incident CHD events is consistent across ethnicities. These findings suggest that HDL-P is superior to HDL-C in predicting prevalent atherosclerosis as well as incident CHD events across a diverse population and should be considered as a therapeutic target. Therapies targeting high-density lipoprotein cholesterol content (HDL-C) have not improved coronary heart disease (CHD) outcomes. High-density lipoprotein particle concentration (HDL-P) may better predict CHD. However, the impact of race/ethnicity on the relations between HDL-P and subclinical atherosclerosis and incident CHD events has not been described. Participants from the Dallas Heart Study (DHS), a multiethnic, probability-based, population cohort of Dallas County adults, underwent the following baseline measurements: HDL-C, HDL-P by nuclear magnetic resonance imaging, and coronary artery calcium by electron-beam computed tomography. Participants were followed for a median of 9.3 years for incident CHD events (composite of first myocardial infarction, stroke, coronary revascularization, or cardiovascular death). The study comprised 1,977 participants free of CHD (51% women, 46% black). In adjusted models, HDL-C was not associated with prevalent coronary artery calcium (p = 0.13) or incident CHD overall (hazard ratio [HR] per 1 SD 0.89, 95% confidence interval [CI] 0.76 to 1.05). However, HDL-C was inversely associated with incident CHD among nonblack (adjusted HR per 1 SD 0.67, 95% CI 0.46 to 0.97) but not black participants (HR 0.94, 95% CI 0.78 to 1.13, pinteraction = 0.05). Conversely, HDL-P, adjusted for risk factors and HDL-C, was inversely associated with prevalent coronary artery calcium (p = 0.009) and with incident CHD overall (adjusted HR per 1 SD 0.73, 95% CI 0.62 to 0.86), with no interaction by black race/ethnicity (pinteraction = 0.57). In conclusion, in contrast to HDL-C, the inverse relation between HDL-P and incident CHD events is consistent across ethnicities. These findings suggest that HDL-P is superior to HDL-C in predicting prevalent atherosclerosis as well as incident CHD events across a diverse population and should be considered as a therapeutic target.

The US Centers for Medicare and Medicaid Services Hospital Readmissions Reduction Program penalizes hospitals with higher-than-expected risk-adjusted 30-day readmission rates (excess readmission ratio [ERR] > 1) after acute myocardial infarction (MI). However, the association of ERR with MI care processes and outcomes are not well established.To evaluate the association between ERR for MI with in-hospital process of care measures and 1-year clinical outcomes.Observational analysis of hospitalized patients with MI from National Cardiovascular Data Registry/Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines centers subject to the first cycle of the Hospital Readmissions Reduction Program between July 1, 2008, and June 30, 2011.The ERR for MI (MI-ERR) in 2011.Adherence to process of care measures during index hospitalization in the overall study population and risk of the composite outcome of mortality or all-cause readmission within 1 year of discharge and its individual components among participants with available Centers for Medicare and Medicaid Services-linked data.The median ages of patients in the MI-ERR greater than 1 and tertiles 1, 2, and 3 of the MI-ERR greater than 1 groups were 64, 63, 64, and 63 years, respectively. Among 380 hospitals that treated a total of 176 644 patients with MI during the study period, 43% had MI-ERR greater than 1. The proportions of patients of black race, those with heart failure signs at admission, and bleeding complications increased with higher MI-ERR. There was no significant association between adherence to MI performance measures and MI-ERR (adjusted odds ratio, 0.94; 95% CI, 0.81-1.08, per 0.1-unit increase in MI-ERR for overall defect-free care). Among the 51 453 patients with 1-year outcomes data available, higher MI-ERR was associated with higher adjusted risk of the composite outcome and all-cause readmission within 1 year of discharge. This association was largely driven by readmissions early after discharge and was not significant in landmark analyses beginning 30 days after discharge. The MI-ERR was not associated with risk for mortality within 1 year of discharge in the overall and 30-day landmark analyses.During the first cycle of the Hospital Readmissions Reduction Program, participating hospitals' risk-adjusted 30-day readmission rates following MI were not associated with in-hospital quality of MI care or clinical outcomes occurring after the first 30 days after discharge.

Objective— To review the literature systematically to determine whether noninvasive or invasive risk stratification, such as with an electrophysiological study of patients with asymptomatic pre-excitation, reduces the risk of arrhythmic events and improves patient outcomes. Methods— PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (all January 1, 1970, through August 31, 2014) were searched for randomized controlled trials and cohort studies examining noninvasive or invasive risk stratification in patients with asymptomatic pre-excitation. Studies were rejected for low-quality design or the lack of an outcome, population, intervention, or comparator of interest or if they were written in a language other than English. Results— Of 778 citations found, 9 studies met all the eligibility criteria and were included in this paper. Of the 9 studies, 1 had a dual design—a randomized controlled trial of ablation versus no ablation in 76 patients and an uncontrolled prospective cohort of 148 additional patients—and 8 were uncontrolled prospective cohort studies (n=1594). In studies reporting a mean age, the range was 32 to 50 years, and in studies reporting a median age, the range was 19 to 36 years. The majority of patients were male (range, 50% to 74%), and &lt;10% had structural heart disease. In the randomized controlled trial component of the dual-design study, the 5-year Kaplan-Meier estimates of the incidence of arrhythmic events were 7% among patients who underwent ablation and 77% among patients who did not undergo ablation (relative risk reduction: 0.08; 95% confidence interval: 0.02 to 0.33; P &lt;0.001). In the observational cohorts of asymptomatic patients who did not undergo catheter ablation (n=883, with follow-up ranging from 8 to 96 months), regular supraventricular tachycardia or benign atrial fibrillation (shortest RR interval &gt;250 ms) developed in 0% to 16%, malignant atrial fibrillation (shortest RR interval ≤250 ms) in 0% to 9%, and ventricular fibrillation in 0% to 2%, most of whom were children in the last case. Conclusions— The existing evidence suggests risk stratification with an electrophysiological study of patients with asymptomatic pre-excitation may be beneficial, along with consideration of accessory-pathway ablation in those deemed to be at high risk of future arrhythmias. Given the limitations of the existing data, well-designed and well-conducted studies are needed.

The relations between renal function and circulating B-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-pro-BNP) in the general population have not been fully elucidated. A total of 2,784 subjects from the Dallas Heart Study, a multiethnic population-based sample of Dallas County, Texas, residents, was studied. Detailed cardiac phenotyping, including magnetic resonance imaging and electron beam computed tomography, as well as measurements of NT-pro-BNP and BNP, were performed. Associations between estimated glomerular filtration rate (eGFR) and both NT-pro-BNP and BNP were evaluated using multivariable statistical analysis techniques. Median eGFR in this young, predominantly healthy population was 97 ml/min/1.73 m2 (interquartile range 84 to 112). Natriuretic peptide levels were not associated with renal function over the normal range of eGFR. Below a threshold eGFR of 90 ml/min/1.73 m2, both NT-pro-BNP and BNP increased in an exponential fashion with decreasing eGFR. These associations remained significant after adjustment for multiple potential confounders (p <0.001 for all). For eGFR <90 ml/min/1.73 m2, the relative increase in NT-pro-BNP was twice as great as that for BNP for a given decrease in eGFR. In conclusion, a threshold effect regarding the association between renal function and natriuretic peptides was shown. With eGFR <90 ml/min/1.73 m2, both NT-pro-BNP and BNP were inversely and independently associated with renal function, with a greater magnitude of association with renal impairment noted for NT-pro-BNP. The relations between renal function and circulating B-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-pro-BNP) in the general population have not been fully elucidated. A total of 2,784 subjects from the Dallas Heart Study, a multiethnic population-based sample of Dallas County, Texas, residents, was studied. Detailed cardiac phenotyping, including magnetic resonance imaging and electron beam computed tomography, as well as measurements of NT-pro-BNP and BNP, were performed. Associations between estimated glomerular filtration rate (eGFR) and both NT-pro-BNP and BNP were evaluated using multivariable statistical analysis techniques. Median eGFR in this young, predominantly healthy population was 97 ml/min/1.73 m2 (interquartile range 84 to 112). Natriuretic peptide levels were not associated with renal function over the normal range of eGFR. Below a threshold eGFR of 90 ml/min/1.73 m2, both NT-pro-BNP and BNP increased in an exponential fashion with decreasing eGFR. These associations remained significant after adjustment for multiple potential confounders (p <0.001 for all). For eGFR <90 ml/min/1.73 m2, the relative increase in NT-pro-BNP was twice as great as that for BNP for a given decrease in eGFR. In conclusion, a threshold effect regarding the association between renal function and natriuretic peptides was shown. With eGFR <90 ml/min/1.73 m2, both NT-pro-BNP and BNP were inversely and independently associated with renal function, with a greater magnitude of association with renal impairment noted for NT-pro-BNP.

<h2>Abstract</h2><h3>Background</h3> Peptidoglycan recognition protein-1 (PGLYRP-1) is part of the innate immune system and binds to peptidoglycan, a component of bacterial cell walls that has been found in human atherosclerotic lesions. Chronic exposure to bacterial antigens may cause or exacerbate the inflammatory response to lipid deposition within arterial walls. We hypothesized that PGLYRP-1 is associated with subclinical atherosclerosis as measured by computed tomography and magnetic resonance imaging. <h3>Methods and results</h3> PGLYRP-1 was measured in 3222 subjects in the Dallas Heart Study, a probability-based population sample age 30–65 including 50% African-Americans and 56% women. Coronary artery calcium (CAC) was measured by electron beam computed tomography (<i>n</i>=2467), abdominal aortic wall thickness (AWT) by magnetic resonance imaging (MRI) (<i>n</i>=2270), and abdominal aortic plaque burden (APB) by MRI (<i>n</i>=2256). In univariable analyses, increasing levels of PGLYRP-1 were associated with all major cardiovascular risk factors, with inflammatory markers such as C-reactive protein, and with CAC, AWT, and APB (<i>p</i><0.0001 for each). In multivariable models adjusted for traditional risk factors, logPGLYRP-1 remained significantly associated with CAC (OR 1.1, 95% CI 1.01–1.3 per S.D.; <i>p</i>=0.04) and AWT (<i>p</i>=0.009) but not APB (<i>p</i>=0.09). Further adjustment for novel biomarkers associated with PGLYRP-1 and atherosclerosis attenuated the association with CAC (<i>p</i>=0.18) but not with AWT (<i>p</i>=0.01) or APB (<i>p</i>=0.037). <h3>Conclusion</h3> In this first reported clinical study of PGLYRP-1 in humans, PGLYRP-1 levels were independently associated with atherosclerosis phenotypes that represent different vascular beds and stages of atherosclerosis.

Objective— Endothelial cell–selective adhesion molecule (ESAM) is a junctional-type cellular adhesion molecule (CAM) that is uniquely expressed in vascular endothelium and activated platelets and mediates neutrophil and monocyte diapedesis across the endothelium. Given its role in endothelial pathobiology, we hypothesized that soluble ESAM (sESAM) would be independently associated with atherosclerosis and vascular stiffness. Methods and Results— We measured sESAM, soluble intercellular adhesion molecule (sICAM)-1, and soluble vascular cell adhesion molecule (sVCAM)-1 in 3222 subjects participating in the Dallas Heart Study, a probability-based population sample. Coronary artery calcium (CAC) was measured by electron beam computed tomography, and abdominal aortic wall thickness (AWT), aortic plaque burden (APB), and aortic compliance (AC) by MRI. Increasing levels of sESAM were associated with all major cardiovascular risk factors as well as with inflammatory markers such as monocyte chemoattractant protein-1, but only weakly correlated with sICAM-1 and sVCAM-1. In multivariate analyses, sESAM was independently associated with prevalent CAC (OR 1.2 per SD increase, 95% CI 1.1 to 1.3; P =0.005), AWT ( P =0.035), and AC ( P =0.006), but not APB ( P =0.15). In contrast, no independent associations were observed between sICAM-1 or sVCAM-1 and any of the atherosclerosis phenotypes. Conclusions— In this first reported clinical study of sESAM in humans, sESAM levels were independently associated with CAC, AWT, and AC, whereas sICAM-1 and sVCAM-1 were not. These findings support a unique role of this cellular adhesion molecule in atherosclerosis and suggest the need for further exploration of sESAM as a predictive biomarker and potential mediator of atherosclerosis.

Specific chemokines contribute to vascular inflammation and may be useful biomarkers to detect atherosclerosis. The chemokines CXCL1 and CCL11 have previously been studied in animal or human models of atherosclerosis, while CXCL2 and CCL23 have not. Among 2,454 subjects enrolled in the Dallas Heart Study, a multi-ethnic population-based sample, we measured plasma CCL11, CCL23, CXCL1, and CXCL2, and associated levels with coronary artery calcium (CAC) by computed tomography, and aortic wall thickness, plaque burden, and compliance by magnetic resonance imaging. Elevated chemokine levels were defined as greater than or equal to the median for CCL11 and CCL23 and greater than or equal to the upper detection limit for CXCL1 and CXCL2. Elevated CCL23 (P < 0.01) and CXCL1 (P = 0.01), but not CCL11 and CXCL2, associated with CAC in univariable analyses. After adjustment for traditional risk factors, elevated CCL23 remained associated with CAC (OR 1.3, 95% CI 1.0-1.7; P = 0.02), while the association with CXCL1 was modestly attenuated (OR 1.4, 95% CI 1.0-2.1; P = 0.06). CCL23 also associated with aortic wall thickness, plaque, and compliance in univariable analyses (P < 0.05 for each), but these associations were attenuated after multivariable adjustment. The novel chemotactic protein, CCL23, which has not been previously studied in atherosclerosis, is independently associated with coronary atherosclerosis, suggesting that this chemokine merits further study in animal and human models.

Background— Accumulated data suggest that low-dose aspirin after myocardial infarction (MI) may offer similar efficacy to higher dose aspirin with reduced risk of bleeding. Few data are available on contemporary aspirin dosing patterns after MI in the United States Methods and Results— Aspirin dosing from 221 199 patients with MI (40.2% ST-segment–elevation MI) from 525 US hospitals enrolled in the National Cardiovascular Data Registry’s (NCDR’s) Acute Coronary Treatment and Intervention Outcomes Network Registry-Get with the Guidelines were described, overall and in clinically relevant subgroups. High-dose aspirin was defined as 325 mg and low dose as 81 mg. Between January 2007 and March 2011, 60.9% of patients with acute MI were discharged on high-dose aspirin, 35.6% on low-dose aspirin, and 3.5% on other doses. High-dose aspirin was prescribed at discharge to 73.0% of patients treated with percutaneous coronary intervention and 44.6% of patients managed medically. Among 9075 patients discharged on aspirin, thienopyridine, and warfarin, 44.0% were prescribed high-dose aspirin. Patients with an in-hospital major bleeding event were also frequently discharged on high-dose aspirin (56.7%). A 25-fold variation in the proportion prescribed high-dose aspirin at discharge was observed across participating centers. Conclusions— Most US patients with MI continue to be discharged on high-dose aspirin. Although aspirin dosing after percutaneous coronary intervention largely reflected prevailing guidelines before 2012, high-dose aspirin was prescribed with similar frequency in medically managed patients and to those in categories expected to be at high risk for bleeding. Wide variability in the proportional use of high-dose aspirin across centers suggests significant influence from local practice habits and uncertainty about appropriate aspirin dosing.

To investigate biotin interference on three cardiac troponin (cTn) assays and demonstrate a method to overcome biotin interference.cTn levels were measured in (1) plasma from healthy volunteers on 10-mg daily biotin supplementation mixed with a plasma with known elevated troponin, (2) plasmas with known elevated cTn after mixing in reagent biotin to simulate supplementation, and (3) biotin-spiked plasma specimens pretreated with streptavidin-agarose beads.Daily biotin ingestion (10 mg) and studies simulating daily biotin use resulted in significant interference in the Gen5 cardiac troponin T (cTnT) assay; the contemporary Gen 4 cTnT and high-sensitivity cardiac troponin I (hs-cTnI) assays were unaffected. The biotin interference threshold was 31, 315, and more than 2,000 ng/mL for Gen5 cTnT, cTnT, and hs-cTnI assays, respectively. Streptavidin pretreatment blocked biotin interference in cTn assays.Biotin interference is possible at plasma concentrations achievable by ingestion of over-the-counter supplements that may lead to delayed or missed diagnosis of myocardial injury with the Gen5 cTnT assay.

Background Emerging evidence links acute kidney injury (AKI) in patients with COVID‐19 with higher mortality and respiratory morbidity, but the relationship of AKI with cardiovascular disease outcomes has not been reported in this population. We sought to evaluate associations between chronic kidney disease (CKD), AKI, and mortality and cardiovascular outcomes in patients hospitalized with COVID‐19. Methods and Results In a large multicenter registry including 8574 patients with COVID‐19 from 88 US hospitals, data were collected on baseline characteristics and serial laboratory data during index hospitalization. Primary exposure variables were CKD (categorized as no CKD, CKD, and end‐stage kidney disease) and AKI (classified into no AKI or stages 1, 2, or 3 using a modification of the Kidney Disease Improving Global Outcomes guideline definition). The primary outcome was all‐cause mortality. The key secondary outcome was major adverse cardiac events, defined as cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, new‐onset nonfatal heart failure, and nonfatal cardiogenic shock. CKD and end‐stage kidney disease were not associated with mortality or major adverse cardiac events after multivariate adjustment. In contrast, AKI was significantly associated with mortality (stage 1 hazard ratio [HR], 1.72 [95% CI, 1.46–2.03]; stage 2 HR, 1.83 [95% CI, 1.52–2.20]; stage 3 HR, 1.69 [95% CI, 1.44–1.98]; versus no AKI) and major adverse cardiac events (stage 1 HR, 2.17 [95% CI, 1.74–2.71]; stage 2 HR, 2.70 [95% CI, 2.07–3.51]; stage 3 HR, 3.06 [95% CI, 2.52–3.72]; versus no AKI). Conclusions This large study demonstrates a significant association between AKI and all‐cause mortality and, for the first time, major adverse cardiovascular events in patients hospitalized with COVID‐19.

Atazanavir (ATV), an HIV protease inhibitor (PI) that may be preferred for the treatment of HIV-infected patients with cardiovascular comorbidities because of its favourable effects on plasma lipids, has been associated with cardiac rhythm disturbances.To quantify the effect of ATV on corrected QT (QTc) and QTc dispersion (QTd), markers of the potential for cardiac dysrhythmia, in patients switching from other PIs to ATV.In this prospective, single-centre, open-label study, 12-lead electrocardiograms were performed for subjects at baseline, 2 h after the first dose of ATV, and 1 month after initiation of ATV.Twenty-one patients (19 received ritonavir-boosted ATV) completed the study. There was a trend towards an increase in the QTc at 2 h after the first dose [mean+/-standard deviation 3.19+/-8.0 ms; 95% confidence interval (CI) -0.47 to 6.85 ms; P=0.084]. There was no difference between QTc values at baseline and at 1 month (-1.5+/-8.75 ms; 95% CI -5.50 to 2.46; P=0.43). There was a nonsignificant decrease in the QTd between baseline and 2 h (-5.1+/-15.19 ms; 95% CI -13.22 to 2.96; P=0.197) and between baseline and 1 month (-0.61+/-15.04 ms; 95% CI -8.1 to 6.87; P=0.865). A significant increase in the PR interval (7.4+/-10.7 ms; 95% CI 2.5 to 12.25 ms; P=0.005) was observed at 1 month.The use of ATV did not result in increases in the QTc interval or QTd. However, PR interval monitoring may be warranted in patients with underlying heart block or those treated with atrioventricular nodal blocking agents.

Aldosterone antagonists (AldA) improve survival after myocardial infarction (MI) in patients with left ventricular systolic dysfunction (ejection fraction [EF] <40%) concomitant with either clinical heart failure (HF) or diabetes mellitus (DM). Although current American College of Cardiology/American Heart Association guidelines provide a class I recommendation for AldA therapy in such patients, how US practice reflects these recommendations is unclear. Using data from the National Cardiovascular Data Registry ACTION Registry-GWTG, we describe contemporary discharge AldA prescription patterns among 202,213 patients discharged after acute MI from 526 US sites participating in ACTION Registry-GWTG between January 2007 and March 2011. Overall, 10.0% of patients were eligible for AldA without documented contraindication, with only 14.5% of eligible patients receiving AldA at discharge. Among the subset of AldA-eligible patients discharged on otherwise optimal medical therapy (68.9%), AldAs were prescribed to 16.1%. Aldosterone antagonist use was higher in patients with EF <40% and clinical HF with or without DM (17.7% and 16.6%, respectively), compared with patients with EF <40% and DM without clinical HF (7.8%, P < .001 for each). Fewer than 2% of participating centers used AldA in ≥50% of eligible patients. Despite clinical outcome evidence and class I guideline recommendations, AldAs are underused in the United States, with only 1 in 7 eligible patients prescribed AldA at discharge after MI. This contrasts with high use of other evidence-based post-MI medications and identifies a specific gap in translation of evidence into clinical practice.

Excess adipose tissue has been implicated in the pathogenesis of insulin resistance and atherosclerosis and is a key risk factor for blood pressure (BP) elevation. However, circulating levels of adiponectin, a protein produced by adipose tissue and widely implicated in the pathogenesis of insulin resistance and atherosclerosis, are inversely proportional to adiposity. The relationship between adiponectin and incident hypertension has not been determined in the general US population.Normotensive participants (n = 1233) enrolled in the Dallas Heart Study, a multiethnic, probability-based population sample of Dallas County adults were followed for median of 7 years. Retroperitoneal, intraperitoneal, visceral, and subcutaneous adipose tissue were measured at baseline by magnetic resonance imaging. Liver fat content was measured by 1 H-magnetic resonance spectroscopy. Relative risk regression was used to determine the association of adiponectin with incident hypertension after adjustment for age, race, sex, BMI, smoking, diabetes, baseline systolic BP, total cholesterol, and regional fat depot.Of the 1233 study participants (median age 40 years, 40% black, and 56% women), 391 (32%) had developed hypertension over a median follow-up of 7 years. Adiponectin levels were associated with reduced risk of incident hypertension (RR 0.81, 95% CI [0.68-0.96]) in the fully adjusted model, which included liver fat. Similar results were observed after adjustment for subcutaneous or visceral fat depots when tested individually or simultaneously in the model.Our study suggested a protective role of adiponectin against incident hypertension independent of body fat distribution.

Previous studies have demonstrated ethnic/racial differences in cardiorespiratory fitness (CRF). However, the relative contributions of body mass index (BMI), lifestyle behaviors, socioeconomic status (SES), cardiovascular (CV) risk factors, and cardiac function to these differences in CRF are unclear. In this study, we included 2,617 Dallas Heart Study participants (58.6% women, 48.6% black; 15.7% Hispanic) without CV disease who underwent estimation of CRF using a submaximal exercise test. We constructed multivariable-adjusted linear regression models to determine the association between race/ethnicity and CRF, which was defined as peak oxygen uptake (ml/kg/min). Black participants had the lowest CRF (blacks: 26.3 ± 10.2; whites: 29.0 ± 9.8; Hispanics: 29.1 ± 10.0 ml/kg/min). In multivariate analysis, both black and Hispanic participants had lower CRF after adjustment for age and gender (blacks: Std β = -0.15; p value ≤0.0001, Hispanics: Std β = -0.05, p value = 0.01; ref group: whites). However, this association was considerably attenuated for black (Std β = -0.04, p value = 0.03) and no longer significant for Hispanic ethnicity (p value = 0.56) after additional adjustment for BMI, lifestyle factors, SES, and CV risk factors. Additional adjustment for stroke volume did not substantially change the association between black race/ethnicity and CRF (Std β = -0.06, p value = 0.01). In conclusion, BMI, lifestyle, SES, and traditional risk factor burden are important determinants of ethnicity-based differences in CRF.

Background Increased blood pressure ( BP ) variability and nondipping status seen on 24‐hour ambulatory BP monitoring are often observed in autonomic failure ( ATF ). Methods and Results We assessed BP variability and nocturnal BP dipping in 273 patients undergoing ambulatory BP monitoring at Southwestern Medical Center between 2010 and 2017. SD , average real variability, and variation independent of mean were calculated from ambulatory BP monitoring. Patients were divided into a discovery cohort (n=201) and a validation cohort (n=72). ATF was confirmed by formal autonomic function test. In the discovery cohort, 24‐hour and nighttime average real variability, SD , and variation independent of mean did not differ significantly between ATF (n=25) and controls (n=176, all P &gt;0.05). However, daytime SD, daytime coefficient of variation, and daytime variation independent of mean of systolic BP ( SBP ) were all significantly higher in patients with ATF than in controls in both discovery and validation cohorts. Nocturnal BP dipping was more blunted in ATF patients than controls in both cohorts (both P &lt;0.01). Using the threshold of 16 mm Hg, daytime SD SBP yielded a sensitivity of 77% and specificity of 82% in detecting ATF in the validation cohort, whereas nondipping status had a sensitivity of 80% and specificity of 44%. The area under the receiver operator characteristic of daytime SD SBP was greater than the area under the receiver operator characteristic of nocturnal SBP dipping (0.79 [0.66‐0.91] versus 0.73 [0.58‐0.87], respectively). Conclusions Daytime SD of SBP is a better screening tool than nondipping status in detecting autonomic dysfunction.

Patients with very severe hypertriglyceridemia (triglyceride levels ≥2000 mg/dL; 22.6 mmol/L) require aggressive treatment. However, little research exists on the underlying etiologies and management of very severe hypertriglyceridemia.We hypothesized (i) very severe hypertriglyceridemia in adults is mostly associated with secondary causes and (ii) most patients with very severe hypertriglyceridemia lack appropriate follow-up and treatment.We queried electronic medical records at Parkland Health and Hospital Systems for lipid measurements in the year 2016 and identified patients with serum triglyceride levels ≥2000 mg/dL (22.6 mmol/L). We extracted data on demographics, underlying causes, lipid-lowering therapy, and follow-up.One hundred sixty-four serum triglyceride measurements were ≥2000 mg/dL (22.6 mmol/L) in 103 unique patients. Of these, 60 patients were admitted to the hospital (39 for acute pancreatitis). Most were Hispanic (79%). The major conditions associated with very severe hypertriglyceridemia included uncontrolled diabetes mellitus (74%), heavy alcohol use (10%), medication use (7%), and hypothyroidism (2%). Two patients were known to have monogenic causes of hypertriglyceridemia. After the index measurement of triglycerides ≥2000 mg/dL (22.6 mmol/L), the use of triglyceride-lowering drugs increased, most prominently the use of fish oil supplements, which increased by 80%. However, in follow-up visits, hypertriglyceridemia was addressed in only 50% of encounters, and serum triglycerides were remeasured in only 18%.In summary, very severe hypertriglyceridemia was quite prevalent (∼0.1% of all lipid measurements) in our large county health care system, especially in Hispanic men. Most cases were related to uncontrolled diabetes mellitus, and follow-up monitoring was inadequate.

The Affordable Care Act expanded Medicaid eligibility allowing low-income individuals greater access to health care. However, the uptake of state Medicaid expansion has been variable. It remains unclear how the Medicaid expansion was associated with the temporal trends in use of evidence-based cardiovascular drugs.We used the publicly available Medicaid Drug Utilization and Current Population Survey to extract filled prescription rates per 1000 Medicaid beneficiaries of statins, antihypertensives, P2Y12 inhibitors, and direct oral anticoagulants. We defined expander states as those who expanded Medicaid on or before January 1, 2014, and nonexpander states as those who had not expanded by December 31, 2018. Difference-in-differences (DID) analyses were performed to compare the association of the Medicaid expansion with per-capita cardiovascular drug prescription rates in expander versus nonexpander states.Between 2011 and 2018, the total number of prescriptions among all Medicaid beneficiaries increased, with gains of 89.7% in statins (11.0 to 20.8 million), 76% in antihypertensives (35.3 to 62.2 million), and 37% in P2Y12 inhibitors (1.7 to 2.3 million). Medicaid expansion was associated with significantly greater increases in quarterly prescriptions (per 1000 Medicaid beneficiaries) of statins (DID estimate [95% CI]: 22.5 [16.5-28.6], P<0.001), antihypertensives (DID estimate [95% CI]: 63.2 [47.3-79.1], P<0.001), and P2Y12 inhibitors (DID estimate [95% CI]: 1.7 [1.2-2.2], P<0.001). Between 2013 and 2018, >75% of the expander states had increases in prescription rates of both statins and antihypertensives. In contrast, 44% of nonexpander states saw declines in statins and antihypertensives. The Medicaid expansion was not associated with higher direct oral anticoagulants prescription rates (DID estimate [95% CI] 0.9 [-0.3 to 2.1], P=0.142).The 2014 Medicaid expansion was associated with a significant increase in per-capita utilization of cardiovascular prescription drugs among Medicaid beneficiaries. These gains in utilization may contribute to long-term cardiovascular benefits to lower-income and previously underinsured populations.

Racial disparities in heart failure hospitalization and mortality are well established; however, the association between different social determinants of health (SDOH) and length of stay (LOS) and the extent to which this association may differ across racial groups is not well established.We utilized data from the Get With The Guidelines-Heart Failure registry to evaluate the association between SDOH, as determined by patients' residential ZIP Code and LOS among patients hospitalized with heart failure. We also assessed the race-specific contribution of the ZIP Code-level SDOH to LOS in patients of Black and non-Black races. Finally, we evaluated SDOH predictors of racial differences in LOS at the hospital level.Among 301 500 patients (20.2% Black race), the median LOS was 4 days. In adjusted analysis accounting for patient-level and hospital-level factors, SDOH parameters of education, income, housing instability, and foreign-born were significantly associated with LOS after adjusting for clinical status and hospital-level factors. SDOH parameters accounted for 25.8% of the total attributable risk for prolonged LOS among Black patients compared with 10.1% in patients of non-Black race. Finally, hospitals with disproportionately longer LOS for Black versus non-Black patients were more likely to care for disadvantaged patients living in ZIP Codes with a higher percentage of foreign-born and non-English speaking areas.ZIP Code-level SDOH markers can identify patients at risk for prolonged LOS, and the effects of SDOH parameters are significantly greater among Black adults with heart failure as compared with non-Black adults.

The COVID-19 pandemic has evolved through multiple phases characterized by new viral variants, vaccine development, and changes in therapies. It is unknown whether rates of cardiovascular disease (CVD) risk factor profiles and complications have changed over time.We analyzed the American Heart Association COVID-19 CVD registry, a national multicenter registry of hospitalized adults with active COVID-19 infection. The time period from April 2020 to December 2021 was divided into 3-month epochs, with March 2020 analyzed separately as a potential outlier. Participating centers varied over the study period. Trends in all-cause in-hospital mortality, CVD risk factors, and in-hospital CVD outcomes, including a composite primary outcome of cardiovascular death, cardiogenic shock, new heart failure, stroke, and myocardial infarction, were evaluated across time epochs. Risk-adjusted analyses were performed using generalized linear mixed-effects models.A total of 46 007 patient admissions from 134 hospitals were included (mean patient age 61.8 years, 53% male, 22% Black race). Patients admitted later in the pandemic were younger, more likely obese, and less likely to have existing CVD (Ptrend ≤0.001 for each). The incidence of the primary outcome increased from 7.0% in March 2020 to 9.8% in October to December 2021 (risk-adjusted Ptrend=0.006). This was driven by an increase in the diagnosis of myocardial infarction and stroke (Ptrend<0.0001 for each). The overall rate of in-hospital mortality was 14.2%, which declined over time (20.8% in March 2020 versus 10.8% in the last epoch; adjusted Ptrend<0.0001). When the analysis was restricted to July 2020 to December 2021, no temporal change in all-cause mortality was seen (adjusted Ptrend=0.63).Despite a shifting risk factor profile toward a younger population with lower rates of established CVD, the incidence of diagnosed cardiovascular complications of COVID increased from the onset of the pandemic through December 2021. All-cause mortality decreased during the initial months of the pandemic and thereafter remained consistently high through December 2021.

BACKGROUND: Apparent resistant hypertension (aRH) carries excess cardiovascular risk beyond nonresistant forms of hypertension; however, our understanding of this at-risk population, as defined by current US practice guidelines, is limited. Accordingly, we sought to evaluate the prevalence, clinical characteristics, and pharmacotherapeutic patterns of patients with aRH using contemporary blood pressure guidance. METHODS: We classified patients at 3 large healthcare systems by hypertensive status using contemporary hypertension guidelines. We subsequently described the demographic and clinical characteristics of patients with aRH and compared these factors among hypertensive patients without aRH and between those with controlled and uncontrolled aRH. RESULTS: A total of 2 420 468 patients were analyzed, of whom 1 343 489 (55.6%) were hypertensive according to contemporary guidelines. Among hypertensive patients, 11 992 (8.5%) met criteria for aRH, with nearly all assessed comorbid conditions, particularly diabetes and heart failure, being more common in those with aRH. When compared with patients with uncontrolled aRH, those with controlled aRH were more frequently prescribed a beta-blocker, diuretic, and nitrate, with the largest standardized difference observed for a mineralocorticoid receptor antagonist (35.4% versus 10.4%, Cohen D 0.62). Consistent findings were noted in sensitivity analyses using the blood pressure threshold of 140/90 mm Hg. CONCLUSIONS: In an analysis of over 2.4 million individuals, a lower prevalence of aRH was observed than previously reported (12%–15%), but with a high burden of comorbidities. Identification of differences in pharmacotherapy between patients with controlled and uncontrolled aRH, particularly lower rates of mineralocorticoid receptor antagonist use, help define potential opportunities to improve care and lower cardiovascular risk.

Timely reperfusion in ST-segment elevation myocardial infarction (STEMI) patients improves clinical outcomes. Implementing strategies to target institutional-specific delays are crucial for improved patient care.Using a novel strategy to analyze specific components of door-to-balloon time (DBT) at our institution, we previously identified several specific interval delays in our prior STEMI protocol. We then implemented 4 strategies to reduce DBT: (1) emergency department physician activation of the STEMI protocol; (2) "single call" broadcast paging of the STEMI team by the page operator; (3) immediate feedback to the emergency and cardiology departments with joint monthly quality improvement meetings; and (4) transfer of the off-hours STEMI patient directly to the laboratory on activation by an in-hospital team. After implementation of the new protocol, we examined each component time interval from the first 59 consecutive STEMI patients treated with the new protocol between March 2007 and June 2008 and compared time intervals with the previous 184 STEMI patients. Compared with the previous 184 STEMI patients, the median DBT of the subsequent 59 STEMI patients significantly improved from 125 to 86 minutes (P<0.0001). This improvement was largely driven by a decrease in the interval from the initial 12-lead ECG to activation of the on-call catheterization team (from 40 to 11 minutes, P<0.0001).After examining specific component delays in our institution's DBT, we were able to successfully use quality improvement strategies to focus on specific sources of delay in our institution. This dramatically improved our median DBT toward the goal of achieving a guideline-recommended <90 minutes for all patients.

Although chronic lung disease (CLD) is common among patients with myocardial infarction (MI), little is known about the influence of CLD on patient management and outcomes following MI. Using the National Cardiovascular Data Registry's ACTION Registry-GWTG, demographics, clinical characteristics, treatments, processes of care, and in-hospital adverse events after acute MI were compared between patients with (n = 22,624) and without (n = 136,266) CLD. Multivariable adjustment was performed to determine the independent association of CLD with treatments and adverse events. CLD (17.0% of non–ST-elevation MI [NSTEMI] and 10.1% of ST-elevation MI [STEMI] patients) was associated with older age, female sex, and a greater burden of comorbidities. Among NSTEMI patients, those with CLD were less likely to undergo cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass graft compared to those without; in contrast, no differences were seen in invasive therapies for STEMI patients with or without CLD. Multivariable-adjusted risk of major bleeding was significantly increased in CLD patients with NSTEMI (13.0% vs 8.1%, ORadj = 1.27, 95% CI = 1.20-1.34, P < .001) and STEMI (16.0% vs 10.5%, ORadj = 1.19, 95% CI = 1.10-1.29, P < .001). In NSTEMI, CLD was associated with a higher risk of inhospital mortality (ORadj = 1.21, 95% CI = 1.11-1.33); in STEMI no association between CLD and mortality was seen (ORadj = 1.05, 95% CI = 0.95-1.17). CLD is common among patients with MI and is independently associated with an increased risk for major bleeding. In NSTEMI, CLD is also associated with receiving less revascularization and with increased in-hospital mortality. Special attention should be given to this high-risk subgroup for the prevention and management of complications after MI.

Sedentary behavior is an adverse health risk factor that is independent of physical activity. The relationship between sedentary behavior, exercise activity and the ankle-brachial index (ABI) is not well understood. We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2003–2004. Accelerometer data were used to quantify exercise and sedentary time for each participant. A low ABI was defined as a value &lt;1.0 (including borderline values). Multi-variable adjusted logistic regression analyses were performed with sedentary and exercise times as independent variables, adjusting for important confounders. There were 1443 asymptomatic participants (mean age 61 years, 49% female, 55% current/prior smokers) with mean daily sedentary and exercise times of 454±144 and 18±20 minutes, respectively. Of the participants, 23% had an ABI &lt;1.0 (8.7% with ABI &lt;0.9). Sedentary time was positively associated with a low ABI (odds ratio [OR] 1.22 per 1 standard deviation [SD], [95% confidence interval (CI), 1.03–1.43]; p=0.02) while exercise time was inversely associated with a low ABI (OR 0.71 per 1 SD, [95% CI, 0.57–0.89]; p=0.003). Sedentary time is associated with low ABI values in the asymptomatic population. This association appears to be independent of exercise time and warrants further investigation.

Readmissions after hospitalization for acute myocardial infarction (AMI) are common. However, the few currently available AMI readmission risk prediction models have poor-to-modest predictive ability and are not readily actionable in real time. We sought to develop an actionable and accurate AMI readmission risk prediction model to identify high-risk patients as early as possible during hospitalization.We used electronic health record data from consecutive AMI hospitalizations from 6 hospitals in north Texas from 2009 to 2010 to derive and validate models predicting all-cause nonelective 30-day readmissions, using stepwise backward selection and 5-fold cross-validation. Of 826 patients hospitalized with AMI, 13% had a 30-day readmission. The first-day AMI model (the AMI "READMITS" score) included 7 predictors: renal function, elevated brain natriuretic peptide, age, diabetes mellitus, nonmale sex, intervention with timely percutaneous coronary intervention, and low systolic blood pressure, had an optimism-corrected C-statistic of 0.73 (95% confidence interval, 0.71-0.74) and was well calibrated. The full-stay AMI model, which included 3 additional predictors (use of intravenous diuretics, anemia on discharge, and discharge to postacute care), had an optimism-corrected C-statistic of 0.75 (95% confidence interval, 0.74-0.76) with minimally improved net reclassification and calibration. Both AMI models outperformed corresponding multicondition readmission models.The parsimonious AMI READMITS score enables early prospective identification of high-risk AMI patients for targeted readmissions reduction interventions within the first 24 hours of hospitalization. A full-stay AMI readmission model only modestly outperformed the AMI READMITS score in terms of discrimination, but surprisingly did not meaningfully improve reclassification.

<h3>Importance</h3> In 2015, the US Food and Drug Administration approved 2 new medications for treatment of heart failure with reduced ejection fraction, sacubitril/valsartan and ivabradine. However, few national data are available examining their contemporary use and associated costs. <h3>Objective</h3> To evaluate national patterns of use of sacubitril/valsartan and ivabradine and associated therapeutic spending in Medicare Part D and Medicaid. <h3>Design, Setting, and Participants</h3> In this US nationwide claims-based study, we analyzed data from the Medicare Part D Prescription Drug Event and Medicaid Utilization and Spending data sets to compare national patterns of use of sacubitril/valsartan and ivabradine between 2016 and 2017. <h3>Main Outcomes and Measures</h3> Changes in total spending, per-beneficiary/claim spending, number of beneficiaries, and number of claims between 2016 and 2017 for sacubitril/valsartan and ivabradine. <h3>Results</h3> The number of Medicare beneficiaries prescribed sacubitril/valsartan increased from 35 423 to 90 606 (156% increase from 2016 to 2017). Medicare beneficiaries prescribed ivabradine increased from 15 856 to 23 213 (46% increase). In 2017, Medicare Part D spent $227 million and $7.3 million on sacubitril/valsartan and ivabradine, respectively. This represented increases of 241% and 59% compared with 2016 spending, respectively. The annual Medicare per-beneficiary spending on sacubitril/valsartan and ivabradine was $2512 and $2400. Parallel trends in use patterns and spending were observed among Medicaid beneficiaries. <h3>Conclusions and Relevance</h3> Although initial experiences suggested slow uptake after regulatory approval, these national data demonstrate an increase in use of sacubitril/valsartan and, to a lesser degree, ivabradine in the United States. Current annual per-beneficiary expenditures remain less than spending thresholds that have been reported to be cost-effective. Ongoing efforts are needed to promote high-value care while improving affordability and access to established and emerging heart failure therapies.

Neighborhood environment perception (NEP) has been associated with health outcomes. However, little is known about how NEP relates to routine healthcare utilization. This study investigated the relationship between NEP and independent subfactors with healthcare utilization behavior, as measured by self-reported (1) usual source of healthcare and (2) time since last routine healthcare check-up. We used cross-sectional data from the Dallas Heart Study, which features a diverse, probability-based sample of Dallas County residents ages 18 to 65. We used logistic regression modeling to examine the association of self-reported NEP and routine healthcare utilization. NEP was assessed via a questionnaire exploring residents' neighborhood perceptions, including violence, the physical environment, and social cohesion. Routine healthcare utilization was assessed via self-reported responses regarding usual source of care and time since last routine healthcare check-up. The analytic sample (N = 1706) was 58% black, 27% white, 15% Hispanic, 42% male, and had a mean age of 51 (SD = 10.3). Analysis of NEP by tertile demonstrated that younger age, lower income, and lower education were associated with unfavorable overall NEP (p trend <0.05 for each). After adjustment for potential confounders, including neighborhood deprivation, health insurance, disease burden and psychosocial factors, we found that individuals with more unfavorable perception of their physical environment were more likely to report lack of a usual source of care (p = 0.013). Individuals with more unfavorable perception of the neighborhood physical environment or greater neighborhood violence reported longer time periods since last routine visit (p = 0.001, p = 0.034 respectively). There was no relationship between perceived social cohesion and healthcare utilization. Using a multi-ethnic cohort, we found that NEP significantly associates with report of a usual source of care and time since last routine check-up. Our findings suggest that public health professionals should prioritize improving NEP since it may act as barrier to routine preventive healthcare and ideal health outcomes.