• HDL-C Level as Predictor of CHD May Be Associated with Race – US Study

    Low-density lipoprotein cholesterol (LDL-C) and triglycerides were modest risk factors for coronary heart disease (CHD) in Black and white adults, while low high-density lipoprotein cholesterol (HDL-C) predicted CHD risk in white but not Black adults, a new study suggests.

    Other important findings of the REasons for Geographic and Racial Differences in Stroke (REGARDS) study were that high HDL-C was not predictive of CHD for either group. Thus, calculating CHD risk from HDL-C could provide inaccurate risk assessment for Black adults.

    These findings were reported by Neil A. Zakai, MD, of the Larner College of Medicine at the University of Vermont, and colleagues in a review published Monday online and in the Nov. 29 issue of the Journal of the American College of Cardiology.

    Potential Race-Related Predictors of CHD

    CHD proves fatal in more Black Americans than white Americans every year, despite Black Americans having a lower risk of developing CHD. CHD clinical risk factors—such as dyslipidemia, hypertension and physical inactivity—may have race-specific associations with CHD in Black Americans. Plasma lipids are known risk factors for CHD, and some of these may have race-specific associations.

    Many risk-assessment models were developed using white, European participants, leaving greater potential for Black adults to be misclassified. Because the association between HDL-C concentration and CHD risk was confirmed in cohorts mostly absent of diversity, the REGARDS study sought to determine whether lipid parameters were risk factors for CHD in both white and Black Americans.

    Over 5 years, 30,239 participants were recruited for the REGARDS study. To meet study criteria, participants had to be ≥45 years old and from the U.S. Of the final selection of participants (n=23,901; 57.8% white, 42.2% Black; 58.4% women, 51.6% men; mean age = 64 ± 9 years) 21% were CHD-free. 21% of participants were from the “stroke buckle” (defined as the coastal plain of Georgia, North Carolina and South Carolina), 35% from the “stroke belt” (defined as a swath of Southern states from North Carolina and Tennessee to Arkansas and Louisiana) and 44% from elsewhere in the U.S. If participants were a race other than Black or white, had undergone cancer treatment in the last year, had chronic medical conditions or were unable to communicate in English, they were excluded from the study.

    Baseline CHD was determined by participant-reported history or electrocardiographic changes at the baseline visit. Over the median 10 years of follow-up, CHD events occurred in 664 Black adults and 951 white adults. LDL-C and triglycerides were predictive of increased risk for CHD in both races, with no significant interaction by race (P [interaction by race] > 0.10).

    Low HDL-C was associated with increased CHD risk in white (hazard ratio [HR] = 1.22; 95% confidence interval [CI] = 1.05-1.43) adults, but not in Black (HR = 0.94; 95% CI = 0.78-1.14) adults (P [interaction by race] = 0.08). High HDL-C was not associated with fewer CHD events in either race (Black adults: HR = 0.91, 95% CI = 0.74-1.12; white adults: HR = 0.96, 95% CI = 0.79-1.16).

    The investigators concluded that both Black and white participants had increased CHD risk associated with LDL-C and triglycerides. However, low HDL-C was only associated with increased CHD risk in white participants. High HDL-C was not a predictor of CHD for either group.

    The authors noted that the Framingham Heart Study—in the 1970s, with 100% white American participants—provides the most recent guidelines on how to assess for CHD, and this should be recalibrated to assess all populations. The authors also state that caution must be taken when understanding the causes of these findings, and the observational design of this study is a limitation to what can be inferred about CHD.

    Equity in Healthcare—Enhanced or Reduced?

    In an editorial commenting on the REGARDS study, Keith C. Ferdinand, MD, of the Tulane University School of Medicine, New Orleans, discussed how inequity has plagued the healthcare system in the number of morbidities and reduced life expectancies it has caused in non-Hispanic Black adults compared to non-Hispanic white adults.

    “Unfortunately, time does not equal progress,” the editorialist said. “This persistent White-Black mortality gap widened with the overall COVID-19 reductions in U.S. life expectancy, disproportionately affecting Black and Hispanic populations.”

    Ferdinand went on to evaluate the REGARDS study’s purpose and notes that atherosclerotic cardiovascular disease (ASCVD) risk in Black adults may be misclassified using the current classification systems, but states that race—being a social construct—is a very “blunt tool to define ASCVD risk.” While Black and white participants had similar hypertension rates, ASCVD in Black adults is not often predicted by dyslipidemia, but rather uncontrolled hypertension.

    Some of the many societal factors (or “social determinants of health” [SDOH]) that contribute to the U.S. White-Black death gap: inability to consistently access healthy foods, inadequate health care, disadvantaged economic status, systemic racism and many more. The SDOH is tied to undertreating high LDL-C, thus promoting mistrust and lack of confidence in healthcare providers, he wrote.

    Ferdinand stated that patients of sub-Saharan African and South Asian descent may show higher levels of lipoprotein(a) (Lp[a]) than white and East Asian patients, but Lp(a) is not routinely calculated in the U.S., going against the European Atherosclerosis Society recommendation that Lp(a) be measured in adults at least once to help implement lifestyle risk-factor management.

    The editorial writer recommended that clinicians use both statin and non-statin therapies for patients who demonstrate the need for both, and that lifestyle changes need to be the foundation of prevention.

    Ferdinand concluded, “…Redefining the role of HDL-C to predict ASCVD risk in Black adults would be welcomed. Nevertheless, these unacceptable, persistent inequities are affected mainly by the SDOH, adverse lifestyles, and structural inequalities, more than due to biological differences.” The editorialist said that future studies should find interventions to eliminate disparities, and clinicians should give patients the best quality care regardless of race, gender, sex, location or socioeconomic status.


    Zakai NA, Minnier J, Safford MM, et al. Race-Dependent Association of High-Density Lipoprotein Cholesterol Levels With Incident Coronary Artery Disease. J Am Coll Cardiol. 2022;22:2104–2115.

    Ferdinand KC. HDL-C in Black Adults for ASCVD Risk Calculation: Benefit or Barrier to Achieving Health Equity? J Am Coll Cardiol. 2022;22:2116–2118.

    Image Credit: peopleimages.com – stock.adobe.com

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