2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk

HomeCirculationVol. 129, No. 25_suppl_22013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk Open AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplementary MaterialsOpen AccessResearch ArticlePDF/EPUB2013 ACC/AHA Guideline on the Assessment of Cardiovascular RiskA Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines David C. GoffJr, MD, PhD, FACP, FAHA, Donald M. Lloyd-Jones, MD, ScM, FACC, FAHA, Glen Bennett, MPH, Sean Coady, MS, Ralph B. D’Agostino, Sr, PhD, FAHA, Raymond Gibbons, MD, FACC, FAHA, Philip Greenland, MD, FACC, FAHA, Daniel T. Lackland, DrPH, FAHA, Daniel Levy, MD, Christopher J. O’Donnell, MD, MPH, Jennifer G. Robinson, MD, MPH, FAHA, J. Sanford Schwartz, MD, Susan T. Shero, MS, RN, Sidney C. SmithJr, MD, FACC, FAHA, Paul Sorlie, PhD, Neil J. Stone, MD, FACC, FAHA and Peter W. F. Wilson, MD, FAHA David C. GoffJrDavid C. GoffJr Search for more papers by this author , Donald M. Lloyd-JonesDonald M. Lloyd-Jones Search for more papers by this author , Glen BennettGlen Bennett *Ex-Officio Members. Search for more papers by this author , Sean CoadySean Coady *Ex-Officio Members. Search for more papers by this author , Ralph B. D’AgostinoRalph B. D’Agostino Search for more papers by this author , Raymond GibbonsRaymond Gibbons Search for more papers by this author , Philip GreenlandPhilip Greenland Search for more papers by this author , Daniel T. LacklandDaniel T. Lackland Search for more papers by this author , Daniel LevyDaniel Levy *Ex-Officio Members. Search for more papers by this author , Christopher J. O’DonnellChristopher J. O’Donnell *Ex-Officio Members. Search for more papers by this author , Jennifer G. RobinsonJennifer G. Robinson Search for more papers by this author , J. Sanford SchwartzJ. Sanford Schwartz Search for more papers by this author , Susan T. SheroSusan T. Shero *Ex-Officio Members. Search for more papers by this author , Sidney C. SmithJrSidney C. SmithJr Search for more papers by this author , Paul SorliePaul Sorlie *Ex-Officio Members. Search for more papers by this author , Neil J. StoneNeil J. Stone Search for more papers by this author and Peter W. F. WilsonPeter W. F. Wilson Search for more papers by this author Originally published12 Nov 2013https://doi.org/10.1161/01.cir.0000437741.48606.98Circulation. 2014;129:S49–S73is corrected byCorrectionOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2013: Previous Version 1 Table of ContentsPreamble and Transition to ACC/AHA Guidelines to Reduce Cardiovascular Risk S501. Introduction S521.1. Organization of the Work Group S521.2. Document Review and Approval S521.3. Charge to the Work Group S531.4. Methodology and Evidence Review S532. Risk Assessment: Recommendations S533. Approach to Risk Assessment S534. Development of New Pooled Cohort ASCVD Risk Equations S554.1. Recommendations for Assessment of 10-Year Risk of a First Hard ASCVD Event S555. Implications for Risk Assessment S556. CQs and Systematic Evidence Review S566.1. Critical Question 1 S566.1.1. Summary of Systematic Reviews and Meta-Analyses for CQ1 S566.1.2. Recommendations for CQ1: Use of Newer Risk Markers After Quantitative Risk Assessment S586.2. Critical Question 2 S586.2.1. Summary of Evidence for CQ2 S596.2.2. Recommendations for CQ2: Long-Term Risk Assessment S597. Implementation Considerations for Risk Assessment S598. Evidence Gaps and Future Research Needs S599. Conclusions S60References S60Appendix 1. Author Relationships With Industry and Other Entities (Relevant) S62Appendix 2. Expert Reviewer Relationships With Industry and Other Entities S65Appendix 3. Abbreviations S65Appendix 4. Evidence Statements for CQ1 S66Appendix 5. Evidence Statements for CQ2 S69Appendix 6. Characteristics of Previously Published Risk Scores and Current Pooled Cohort Equations S70Appendix 7. Development and Steps for Implementation of the ASCVD Pooled Cohort Risk Equations S71Preamble and Transition to ACC/AHA Guidelines to Reduce Cardiovascular RiskThe goals of the American College of Cardiology (ACC) and the American Heart Association (AHA) are to prevent cardiovascular diseases (CVD); improve the management of people who have these diseases through professional education and research; and develop guidelines, standards, and policies that promote optimal patient care and cardiovascular health. Toward these objectives, the ACC and AHA have collaborated with the National Heart, Lung, and Blood Institute (NHLBI) and stakeholder and professional organizations to develop clinical practice guidelines for assessment of cardiovascular risk, lifestyle modifications to reduce cardiovascular risk, management of blood cholesterol in adults, and management of overweight and obesity in adults.In 2008, the NHLBI initiated these guidelines by sponsoring rigorous systematic evidence reviews for each topic by expert panels convened to develop critical questions (CQs), interpret the evidence, and craft recommendations. In response to the 2011 report from the Institute of Medicine on the development of trustworthy clinical guidelines,1 the NHLBI Advisory Council recommended that the NHLBI focus specifically on reviewing the highest-quality evidence and partner with other organizations to develop recommendations.2,3 Accordingly, in June 2013 the NHLBI initiated collaboration with the ACC and AHA to work with other organizations to complete and publish the 4 guidelines noted above and make them available to the widest possible constituency. Recognizing that the Expert Work Group/Work Groups did not consider evidence beyond 2011 (except as specified in the methodology), the ACC, AHA, and collaborating societies plan to begin updating these guidelines starting in 2014.The joint ACC/AHA Task Force on Practice Guidelines (Task Force) appointed a subcommittee to shepherd this transition, communicate the rationale and expectations to the writing panels and partnering organizations, and expeditiously publish the documents. The ACC/AHA and partner organizations recruited a limited number of expert reviewers for fiduciary examination of content, recognizing that each document had undergone extensive peer review by representatives of the NHLBI Advisory Council, key federal agencies, and scientific experts. Each writing panel responded to comments from these reviewers. Clarifications were incorporated where appropriate, but there were no substantive changes because the bulk of the content was undisputed.Although the Task Force led the final development of these prevention guidelines, they differ from other ACC/AHA guidelines. First, as opposed to an extensive compendium of clinical information, these documents are significantly more limited in scope and focus on selected CQs on each topic, based on the highest-quality evidence available. Recommendations were derived from randomized trials, meta-analyses, and observational studies evaluated for quality and were not formulated when sufficient evidence was not available. Second, the text accompanying each recommendation is succinct, summarizing the evidence for each question. The Full Panel/Work Group Reports include more detailed information about the evidence statements that serve as the basis for recommendations. Third, the format of the recommendations differs from other ACC/AHA guidelines. Each recommendation has been mapped from the NHLBI grading format to the ACC/AHA Classification of Recommendation/Level of Evidence (COR/LOE) construct (Table 1) and is expressed in both formats. Because of the inherent differences in grading systems and the clinical questions driving the recommendations, alignment between the NHLBI and ACC/AHA formats is in some cases imperfect. Explanations of these variations are noted in the recommendation tables, where applicable.Table 1. Applying Classification of Recommendation and Level of EvidenceTable 1. Applying Classification of Recommendation and Level of EvidenceIn consultation with NHLBI, the policies adopted by the writing panels to manage relationships of authors with industry and other entities (RWI) are outlined in the methods section of each panel report. These policies were in effect when this effort began in 2008 and throughout the writing process and voting on recommendations, until the process was transferred to ACC/AHA in 2013. In the interest of transparency, the ACC/AHA requested that panel authors resubmit RWI disclosures as of July 2013. Relationships relevant to this guideline are disclosed in Appendix 1. None of the ACC/AHA expert reviewers had relevant RWI (Appendix 2). See Appendix 3 for a list of abbreviations used in the guideline.Systematic evidence reports and accompanying summary tables were developed by the expert panels and NHLBI. The guideline was reviewed by the ACC/AHA Task Force and approved by the ACC Board of Trustees, and the AHA Science Advisory and Coordinating Committee. In addition, ACC/AHA sought endorsement from other stakeholders, including professional organizations. It is the hope of the writing panels, stakeholders, professional organizations, NHLBI, and Task Force that the guidelines will garner the widest possible readership for the benefit of patients, providers, and the public health.These guidelines are meant to define practices that meet the needs of patients in most circumstances and are not a replacement for clinical judgment. The ultimate decision about care of a particular patient must be made by the healthcare provider and patient in light of the circumstances presented by that patient. As a result, situations might arise in which deviations from these guidelines may be appropriate. These considerations notwithstanding, in caring for most patients, clinicians can employ the recommendations confidently to reduce the risks of atherosclerotic cardiovascular disease (ASCVD) events.See Tables 2 and 3 for an explanation of the NHLBI recommendation grading methodology.Table 2. NHLBI Grading of the Strength of RecommendationsGradeStrength of Recommendation*AStrong recommendationThere is high certainty based on evidence that the net benefit† is substantial.BModerate recommendationThere is moderate certainty based on evidence that the net benefit is moderate to substantial, or there is high certainty that the net benefit is moderate.CWeak recommendationThere is at least moderate certainty based on evidence that there is a small net benefit.DRecommendation againstThere is at least moderate certainty based on evidence that there is no net benefit or that risks/harms outweigh benefits.EExpert opinion (“There is insufficient evidence or evidence is unclear or conflicting, but this is what the Work Group recommends.”)Net benefit is unclear. Balance of benefits and harms cannot be determined because of no evidence, insufficient evidence, unclear evidence, or conflicting evidence, but the Work Group thought it was important to provide clinical guidance and make a recommendation. Further research is recommended in this area.NNo recommendation for or against (“There is insufficient evidence or evidence is unclear or conflicting.”)Net benefit is unclear. Balance of benefits and harms cannot be determined because of no evidence, insufficient evidence, unclear evidence, or conflicting evidence, and the Work Group thought no recommendation should be made. Further research is recommended in this area.*In most cases, the strength of the recommendation should be closely aligned with the quality of the evidence; however, under some circumstances, there may be valid reasons for making recommendations that are not closely aligned with the quality of the evidence (eg, strong recommendation when the evidence quality is moderate, such as smoking cessation to reduce cardiovascular disease risk or ordering an ECG as part of the initial diagnostic work-up for a patient presenting with possible MI). Those situations should be limited and the rationale explained clearly by the Work Group.†Net benefit is defined as benefits minus risks/harms of the service/intervention.ECG indicates electrocardiogram; MI, myocardial infarction; and NHLBI, National Heart, Lung, and Blood Institute.Table 3. NHLBI Quality Rating of the Strength of EvidenceType of EvidenceQuality Rating*Well-designed, well-executed† RCT that adequately represent populations to which the results are applied and directly assess effects on health outcomes.Meta-analyses of such studies.Highly certain about the estimate of effect.Further research is unlikely to change our confidence in the estimate of effect.HighRCT with minor limitations‡ affecting confidence in, or applicability of, the results.Well-designed, well-executed nonrandomized controlled studies§ and well-designed, well-executed observational studies‖.Meta-analyses of such studies.Moderately certain about the estimate of effect.Further research may have an impact on our confidence in the estimate of effect and may change the estimate.ModerateRCT with major limitations.Nonrandomized controlled studies and observational studies with major limitations affecting confidence in, or applicability of, the results.Uncontrolled clinical observations without an appropriate comparison group (eg, case series, case reports).Physiological studies in humans.Meta-analyses of such studies.Low certainty about the estimate of effect. Further research is likely to have an impact on our confidence in the estimate of effect and is likely to change the estimate.Low*In some cases, other evidence, such as large all-or-none case series (eg, jumping from airplanes or tall structures), can represent high- or moderate-quality evidence. In such cases, the rationale for the evidence rating exception should be explained by the Work Group and clearly justified.†“Well-designed, well-executed” refers to studies that directly address the question; use adequate randomization, blinding, and allocation concealment; are adequately powered; use intention-to-treat analyses; and have high follow-up rates.‡Limitations include concerns with the design and execution of a study that result in decreased confidence in the true estimate of the effect. Examples of such limitations include but are not limited to: inadequate randomization, lack of blinding of study participants or outcome assessors, inadequate power, outcomes of interest that are not prespecified for the primary outcomes, low follow-up rates, and findings based on subgroup analyses. Whether the limitations are considered minor or major is based on the number and severity of flaws in design or execution. Rules for determining whether the limitations are considered minor or major and how they will affect rating of the individual studies will be developed collaboratively with the methodology team.§Nonrandomized controlled studies refer to intervention studies where assignment to intervention and comparison groups is not random (eg, quasi-experimental study design).‖Observational studies include prospective and retrospective cohort, case-control, and cross-sectional studies.NHLBI indicates National Heart, Lung, and Blood Institute; and RCT, randomized controlled trials.1. Introduction1.1. Organization of the Work GroupThe Risk Assessment Work Group (Work Group) was composed of 11 members and 5 ex-officio members, including internists, cardiologists, endocrinologists, and experts in cardiovascular epidemiology, biostatistics, healthcare management and economics, and guideline development.1.2. Document Review and ApprovalA formal peer review process, which included 12 expert reviewers and representatives of federal agencies, was initially completed under the auspices of the NHLBI. This document was also reviewed by 3 expert reviewers nominated by the ACC and the AHA when the management of the guideline transitioned to the ACC/AHA. The ACC and AHA Reviewers’ RWI information is published in this document (Appendix 2).This document was approved for publication by the governing bodies of the ACC and AHA and endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation, American Society for Preventive Cardiology, American Society of Hypertension, Association of Black Cardiologists, National Lipid Association, Preventive Cardiovascular Nurses Association, and WomenHeart: The National Coalition for Women With Heart Disease.1.3. Charge to the Work GroupThe Work Group was 1 of 3 work groups appointed by the NHLBI to develop its own recommendations and provide cross-cutting input to 3 Panels for updating guidelines on blood cholesterol, blood pressure (BP), and overweight/obesity. The Work Group was asked to examine the scientific evidence on risk assessment for initial ASCVD events and to develop an approach for quantitative risk assessment that could be used in practice and used or adapted by the risk factor panels (blood cholesterol, hypertension, and obesity) in their guidelines and algorithms. Specifically, the Work Group was charged with 2 tasks:To develop or recommend an approach to quantitative risk assessment that could be used to guide care; andTo use systematic review methodology to pose and address a small number of questions judged to be critical to refining and adopting risk assessment in clinical practice.1.4. Methodology and Evidence ReviewThis guideline is based on the Full Work Group Report supplement, which is provided as a supplement to the guideline. The Full Work Group Report supplement contains background and additional material related to content, methodology, evidence synthesis, rationale, and references and is supported by the NHLBI Systematic Evidence Review, which can be found at (http://www.nhlbi.nih.gov/guidelines/cvd_adult/risk_assessment/). These documents also describe the process for the development of novel, comprehensive multivariable risk equations for the prediction of 10-year risk of development of ASCVD in non-Hispanic African-American and non-Hispanic white men and women from 40 to 79 years of age. These equations were developed from several long-standing population-based cohort studies funded by the NHLBI. Ten-year risk was defined as the risk of developing a first ASCVD event, defined as nonfatal myocardial infarction or coronary heart disease (CHD) death or fatal or nonfatal stroke, over a 10-year period among people free from ASCVD at the beginning of the period.In addition, through evaluation of evidence developed by systematic reviews of the literature, the Work Group addressed the following 2 CQs:CQ1. “What is the evidence with regard to reclassification or contribution to risk assessment when high-sensitivity C-reactive protein (hs-CRP), apolipoprotein B (ApoB), glomerular filtration rate, microalbuminuria, family history, cardiorespiratory fitness, ankle-brachial index (ABI), carotid intima-media thickness (CIMT), or coronary artery calcium (CAC) score is considered in addition to the variables that are in the traditional risk scores?”CQ2. “Are models constructed to assess the long-term (≥15 years or lifetime) risk of a first cardiovascular disease (CVD) event in adults effective in assessing variation in long-term risk among adults at low and/or intermediate short-term risk, whether analyzed separately or in combination?”The evidence and recommendations in the guideline focus on the large proportion of the adult population without clinical signs or symptoms of ASCVD who merit evaluation for the primary prevention of ASCVD. They do not apply to those with clinically manifest ASCVD, who require secondary prevention approaches, or to highly-selected patient subgroups, such as those with symptoms suggestive of CVD, who require diagnostic strategies rather than risk assessment. Furthermore, these recommendations were not developed for use in specific subgroups of asymptomatic individuals at unusually high risk, such as those with genetically determined extreme values of traditional risk factors (eg, patients with familial hypercholesterolemia).2. Risk Assessment: RecommendationsSee Table 4 for a summary of the recommendations for risk assessment.Table 4. Summary of Recommendations for Risk AssessmentTable 4. Summary of Recommendations for Risk Assessment3. Approach to Risk AssessmentIn addressing its charge, the Work Group recognized the need for a risk assessment approach that was based on the types of data that primary care providers could easily collect and that could be implemented in routine clinical practice. After deliberation, the Work Group endorsed the existing and widely used paradigm of matching the intensity of preventive efforts with the individual’s absolute risk.23,24 The Work Group acknowledges that none of the risk assessment tools or novel risk markers examined in the present document have been formally evaluated in randomized controlled trials of screening strategies with clinical events as outcomes. Nevertheless, this approach balances an understanding of an individual’s absolute risk of CVD and potential treatment benefits against the potential absolute risks for harm from therapy. With the use of this framework, treatment can be targeted to those most likely to benefit without undue risk of harm, in the context of a “risk discussion.” A risk discussion could include the assessment of the patient’s risk of ASCVD, as well as potential benefits, negative aspects, risks, and patient preferences with regard to initiation of relevant preventive therapies.By its nature, such an approach requires a platform for reliable quantitative estimation of absolute risk based on data from representative population samples. It is important to note that risk estimation is based on group averages, which are then applied to individual patients in practice. This process is admittedly imperfect; no one has 10% or 20% of a heart attack during a 10-year period. Individuals with the same estimated risk will either have or not have the event of interest, and only those patients who are destined to have an event can have their event prevented by therapy. The criticism of the risk-estimation approach to treatment decision making also applies to the alternative, and much less efficient approach, of checking the patient’s characteristics against numerous and complex inclusion and exclusion criteria for a potentially large number of pertinent trials. Only a small fraction of trial participants have events, and only a fraction of these events are prevented by therapy. Using either approach, the clinician must apply the average results obtained from groups of patients to the individual patient in practice.Given the modification and adoption of the Framingham 10-year risk score for CHD risk assessment by the Third Report of the National Cholesterol Education Program Expert Work Group on Diagnosis, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)24 and the uptake of this algorithm by practice sites across the United States, the Work Group began by discussing the value of retaining this algorithm. In collaboration with other NHLBI panels, the Work Group decided not to use this algorithm in its 2013 recommendations because of the algorithm's derivation in an exclusively white sample population and the limited scope of the outcome (in determining CHD alone). Rather, the Work Group derived risk equations from community-based cohorts that are broadly representative of the US population of whites and African Americans, and the Work Group focused on estimation of first hard ASCVD events (defined as first occurrence of nonfatal myocardial infarction, CHD death, or fatal or nonfatal stroke) as the outcome of interest because they were deemed to be of greater relevance to both patients and providers. The focus on hard ASCVD, rather than CHD alone, is also consistent with evidence reviewed in a statement from the AHA and American Stroke Association calling for the inclusion of ischemic stroke in the outcome of interest for CVD risk assessment.25Numerous multivariable risk scores and equations have been derived and published (Appendix 6; for more details, see the Full Work Group Report supplement). As part of its deliberations, the Work Group considered previously published risk scores with validation in NHLBI cohort data as one possible approach. However, several persistent concerns with existing risk equations were identified, including nonrepresentative or historically dated populations, limited ethnic diversity, narrowly defined endpoints, endpoints influenced by provider preferences (eg, elective revascularizations), and endpoints with poor reliability (eg, angina and heart failure). Given the inherent limitations of existing scores, the Work Group judged that a new risk score was needed to address some of the deficiencies of existing scores—for example, the need for a population sample that approaches, to the degree possible, the ideal sample for algorithm development and closely represents the US population.Data are sparse on the use and impact of absolute risk scores in clinical practice in primary-prevention settings.26 Two systematic reviews, based on few studies, support the conclusion that risk assessment, combined with counseling, is associated with favorable but modest changes in patient knowledge and intention to change and in provider prescribing behavior and risk factor control.27,28 No data are available on hard event outcomes. The Work Group specifically calls for research in this area (Section 8).The Work Group notes that the “2009 ACCF/AHA Performance Measures for the Primary Prevention of Cardiovascular Disease in Adults” specifically recommended use of global CVD risk estimation in clinical practice.29 Likewise, the US Preventive Services Task Force recommendations for aspirin,30 the NHLBI Adult Treatment Panel III recommendations,24 and European31 and Canadian32,33 guidelines for primary prevention of CVD, among others, have all recommended the use of absolute risk assessment for decision making about the intensity of lifestyle and pharmacological preventive interventions. Risk scores have been implemented in practice through paper scoring sheets and, increasingly, through Web sites and downloadable applications. The electronic medical record can be adapted to estimate absolute risks automatically by using patient data and published equations, and it is anticipated that risk estimation with this technology will become a mainstream application of the current and future risk algorithms.4. Development of New Pooled Cohort ASCVD Risk EquationsHaving made the decision to develop new equations to estimate the 10-year risk of developing a first ASCVD event, the Work Group used the best available data from community-based cohorts of adults, with adjudicated endpoints for CHD death, nonfatal myocardial infarction, and fatal or nonfatal stroke. Cohorts that included African-American or white participants with at least 12 years of follow-up were included. Data from other racial/ethnic groups were insufficient, precluding their inclusion in the final analyses. The final pooled cohorts included participants from several large, racially and geographically diverse, modern NHLBI-sponsored cohort studies, including the ARIC (Atherosclerosis Risk in Communities) study,8 the Cardiovascular Health Study,5 and the CARDIA (Coronary Artery Risk Development in Young Adults) study,7 combined with applicable data from the Framingham Original and Offspring Study cohorts.4,6The Work Group used state-of-the-art statistical methods to derive and internally validate the Pooled Cohort Equations, which provide sex- and race-specific estimates of the 10-year risk of ASCVD for African-American and white men and women 40 to 79 years of age. The variables that statistically merit inclusion in the risk assessment equations are age, total cholesterol, high-density lipoprotein cholesterol, systolic BP (including treated or untreated status), diabetes mellitus (diabetes), and current smoking status.An expanded description of the derivation and validation of the Pooled Cohort Equations, as well as the means for implementing them in clinical practice, is provided in Appendix 7. Additional details are provided in the Full Work Group Report supplement. A specific clinical vignette is also provided as an example in Appendix 7. In the clinical vignette, the 10-year risk is calculated for a patient 55 years of age who is a nonsmoker without diabetes, and with total cholesterol level of 213 mg/dL, high-density lipoprotein cholesterol level of 50 mg/dL, and untreated systolic BP of 120 mm Hg. With these values used in the Pooled Cohort Equations, the predicted 10-year ASCVD risks are 2.1% for white women, 3.0% for African-American women, 5.3% for white men, and 6.1% for African-American men.Numerous other potential risk markers were considered for inclusion in the Pooled Cohort Equations: for many, no additional utility was demonstrated when they were included; for others, data are insufficient at the present time to determine their additional value. The equations were also assessed in external validation studies with data from other available cohorts. Other than the Framingham CHD risk score (and its derivative ATP III risk assessment profile) and the European SCORE (System for Cardiac Operative Risk Evaluation) algorithm for CVD death, these equations have been subjected to more rigorous validation than other currently available equations, and they are the only risk assessment equations that include significant numbers of African Americans and that focus on estimation of 10-year risk of the clinically relevant endpoint of ASCVD.