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April 2016

The Pooled Cohort Risk Equations—Black Risk Matters

Author Affiliations
  • 1Department of Epidemiology, Colorado School of Public Health, Aurora
  • 2Division of Cardiology, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
JAMA Cardiol. 2016;1(1):12-14. doi:10.1001/jamacardio.2015.0323

Dating from the 27th Bethesda Conference1 in 1996, there has been a consensus in the preventive cardiology community that the intensity of preventive interventions should be matched to an individual’s absolute level of risk of development of atherosclerotic cardiovascular disease (ASCVD). This consensus was reflected in the adoption of the Framingham Risk Score (FRS) for estimating the 10-year risk of a hard coronary heart disease (CHD) event by the National Cholesterol Education Program’s 2001 Adult Treatment Panel (ATP III) in their executive summary2 and by the adoption of the Pooled Cohort risk equations (PCEs) for estimating the 10-year risk of a hard ASCVD event3 by the American College of Cardiology and the American Heart Association in their 2013 guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults.4

The ability to estimate risk accurately in African Americans is particularly important because they are a higher-risk population. In comparison with non-Hispanic white populations, African Americans have 2 to 3 times the risk of stroke, 2 times the risk of heart failure (HF), and 1.5 to 2 times the risk of CHD.5 Failure to recognize this high-risk status could lead to missed opportunities for prevention. Hence, black risk matters.

The PCEs, validated by Muntner et al6 in a large contemporary cohort of community-dwelling African Americans and whites in the United States, were adopted by the American College of Cardiology and the American Heart Association in 2013 as an improvement on the older FRS for CHD for several reasons. First, the PCEs included stroke and ASCVD death among the outcomes of interest for prevention, expanding beyond the narrower focus of the FRS on myocardial infarction and CHD death only by including stroke, an outcome of substantial importance to African Americans. Second, by pooling data from multiple community-based cohorts, the PCEs derived risk estimation algorithms specific to African Americans and potentially more applicable to African Americans than the FRS, derived from a white cohort in a single community. Third, and also related to the use of multiple cohorts, the PCEs might be more widely applicable to white populations across the United States. Nevertheless, the PCE algorithms developed for use in African Americans were derived from the experience of a population of just under 4400 African Americans,3 and to date the performance of the PCEs has been examined only once previously in an African American population.6 Hence, the study in this issue of JAMA Cardiology by Fox and colleagues7 represents an important contribution to our understanding of risk prediction in African Americans and the performance of the PCEs, including the potential for improvements in risk estimation in general and for African Americans specifically.

Fox and colleagues7 developed and examined several risk estimation algorithms for all cardiovascular disease (CVD), including HF in the outcome of interest, thereby expanding the outcome beyond the ASCVD outcome of interest for the PCEs. They compared the performance of these models with refitted versions of the PCEs (for ASCVD) and the FRS using the FRS for all CVD,8 not the FRS for CHD adopted by the ATP III. The data came from the Jackson Heart Study, a community-based cohort of more than 5300 African Americans residing in Jackson, Mississippi. Fox and colleagues7 examined the contributions of traditional and newer risk markers to estimation of CVD risk and found that the best prediction model for CVD events incorporated traditional risk factors and 2 subclinical disease measures (ankle-brachial index [ABI] plus echocardiographic left ventricular systolic function and hypertrophy). A model they considered more practical for implementation in primary care settings that included traditional risk factors, B-type natriuretic peptide, and ABI yielded modest improvement over a model with only traditional risk factors, but this model did not substantively outperform the PCEs or the FRS for CVD in the Jackson Heart Study cohort.7 These results are not surprising given previous publications indicating that the FRS for CHD performed well to predict the risk of CHD in African American populations,9,10 yet they add important new information by extending this observation to a more comprehensive CVD outcome.

Several strengths of the study by Fox and colleagues7 should be noted. The study population is a contemporary, community-based cohort that should be free from serious selection bias and contamination from downstream interventions, unlike the experience of trial-based populations or cohorts with extensive imaging of subclinical atherosclerosis. A wide range of exposures were measured using standard methods with attention to quality control. Outcomes were assessed over a sufficiently long period to enable estimation of risk comparable to the 10-year estimates provided by the PCEs and the FRS, and the outcomes were identified using high-quality methods. Appropriate statistical approaches were used, including attention to the different outcomes of interest of the various risk scores. It is important to note that the scope of the outcome of interest in the Jackson Heart Study was CVD, inclusive of HF, and that outcome is similar to the scope of the FRS used for comparison purposes. On the other hand, the scope of interest for the PCEs was ASCVD, an outcome that excludes HF. It is also important to note that HF accounted for more than one-third of the CVD events observed. The public health significance of HF, especially in the African American population, underscores the potential importance of efforts to incorporate HF into the outcome of interest for risk assessment.

Several issues are worthy of special mention to put the study by Fox and colleagues7 in context. First, the traditional risk factors examined in this study include the estimated glomerular filtration rate (eGFR), a variable not included in the PCEs because eGFR did not contribute important information to risk prediction when examined during the process of developing the PCEs.3 The present findings that the PCEs worked as well as the risk algorithms developed in the Jackson Heart Study cohort support the conclusion that eGFR did not contribute important new information to estimation of risk of ASCVD in this cohort.7 Whether eGFR contributes importantly to estimation of risk of CVD (including HF) in African Americans, or more broadly, deserves further study. In addition, body mass index did not contribute important information to 10-year risk estimation in the Jackson Heart Study. This finding is consistent with both the PCEs and the FRS.

Second, Fox and colleagues7 were able to examine the usefulness of a wide range of newer potential risk markers, including adiponectin, leptin, aldosterone, B-type natriuretic peptide, cortisol, high-sensitivity C-reactive protein, endothelin, homocysteine, glycated hemoglobin, the homeostasis model assessment of insulin resistance, ABI, carotid intimal-medial thickness, and echocardiographic measures of left ventricular function and hypertrophy. The finding that the vast majority of these variables provided no important contribution to risk prediction is consistent with a growing body of evidence underscoring the primacy of the traditional risk factors and the difficulty of improving short-term risk prediction with newer biomarkers, at least when predicting risk in samples where broad ranges of age are represented and age is an adjustment covariate. It is interesting to note that the measures of subclinical disease, specifically ABI and echocardiographic measures, contributed the most new information to risk prediction. This result is consistent with the findings by Yeboah and colleagues11,12 that subclinical disease measures, and especially measurement of coronary artery calcium, can improve risk prediction for ASCVD. Given that HF is included in the CVD outcome in the present study,7 it is not surprising that echocardiographic measures would add value to risk prediction.

Third, Fox and colleagues7 conclude that their findings confirm that the current Framingham Heart Study and PCE risk algorithms work well in African Americans and are not easily improved on and that a unique risk calculator for African Americans may not be necessary. As cochairs of the Risk Assessment Working Group that developed the PCEs, we are gratified that the PCE algorithms were found to work well to predict risk of ASCVD in the Jackson Heart Study cohort. Following the results published by Muntner et al,6 the PCEs have now been found to perform well in 2 community-based cohorts of African Americans. We would note that, unlike the FRS, the PCEs include race-specific risk calculators for African American women and men. This specificity may underlie the validity of these algorithms in this cohort. Given the importance of HF to the overall population and the African American population in particular, further research to develop risk prediction models for total CVD may still be useful aspects of our ongoing efforts to prevent CVD.

Where does this new work leave us regarding risk assessment to guide CVD prevention efforts in 2016? Because African Americans are a high-risk population, the ability to estimate that risk is an important step forward in efforts to prevent ASCVD and eliminate health disparities. Black risk matters. We believe that future research on risk estimation could usefully focus on several issues, including risk estimation in other racial/ethnic groups, prediction of an expanded outcome to include HF, and the role of easily attainable measures of subclinical disease in risk prediction. Given the present results by Fox and colleagues7 and other recent findings, it is also time to focus on improving our understanding of how to present risk and benefit information optimally to assist in shared decision making and to help patients adopt and adhere to preventive therapies. While efforts to improve risk assessment and communication continue, these results reinforce the usefulness of the PCEs and the importance of efforts to implement the current guidelines to prevent ASCVD in African Americans.

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Article Information

Corresponding Author: Donald M. Lloyd-Jones, MD, ScM, Division of Cardiology, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 N Lake Shore Dr, Ste 1400, Chicago, IL 60611 (dlj@northwestern.edu).

Published Online: February 24, 2016. doi:10.1001/jamacardio.2015.0323.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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