Importance of HDL Cholesterol Overstated for Black Adults

Longstanding assumptions about HDL cholesterol being predictive of coronary heart disease (CHD) didn't hold up for Black adults, according to an analysis of the large REGARDS cohort.

While high plasma HDL cholesterol levels were not protective for either race, low HDL cholesterol was linked to increased CHD risk in white people (adjusted HR 1.22, 95% CI 1.05-1.43) but not Black people (adjusted HR 0.94, 95% CI 0.78-1.14; P=0.08 for interaction by race) in data accrued over a median 10.7 years of follow-up.

"Other lipid parameters, such as LDL-C [LDL cholesterol] and triglycerides, did not display race-specific behavior and were comparably associated with CHD risk in Black and white participants," according to Nathalie Pamir, PhD, lipid biology researcher at the Knight Cardiovascular Institute at Oregon Health and Science University in Portland, and colleagues.

"Collectively, the results support the presence of racial differences that affect the inverse association of HDL-C [HDL cholesterol] and incident CHD," the investigators reported in the November 29 issue of the Journal of the American College of Cardiology.

HDL cholesterol's seemingly linear relationship with CHD had been established in the old Framingham Heart Study, where all cohorts are 100% white and American, the group noted. They suggested that assumptions involving HDL cholesterol in common heart disease prediction tools -- such as Framingham, PROCAM, Pooled Cohort, and MESA -- could partly explain why these equations tend to underperform in Black adults.

"Although we need to gather further population-based evidence, our data support the notion that the value of high HDL-C in risk prediction algorithms should be demoted," the authors said.

"What I hope this type of research establishes is the need to revisit the risk-predicting algorithm for cardiovascular disease," Pamir said in a press release from the NIH, which funded the study. "It could mean that in the future we don't get a pat on the back by our doctors for having higher HDL cholesterol levels."

Moreover, for primary prevention patients at borderline or intermediate atherosclerotic cardiovascular disease (ASCVD) risk according to the Pooled Cohort Equations, clinicians may consider other risk-enhancing factors, such as lipoprotein(a) and coronary artery calcification, that may indicate a need to initiate or intensify statin therapy.

"[R]eaching health equity is a moral and practical imperative, and redefining the role of HDL-C to predict ASCVD risk in Black adults would be welcomed," commented Keith Ferdinand, MD, a cardiologist at Tulane University School of Medicine in New Orleans.

"Nevertheless, the excess Black cardiovascular morbidity and mortality are a complex 'toxic gumbo' of multiple societal factors, beyond any biologic or genetic underpinnings," Ferdinand emphasized in an accompanying editorial.

He listed several social determinants of health that contribute to racial disparities in the U.S.: disadvantaged economic status, lack of adequate healthcare, lower educational attainment, stress-inducing neighborhoods, substandard housing, limited areas for safe physical activity, inadequate access to healthy foods, and long-standing racism.

"Regardless of the calculated need for pharmacotherapy, therapeutic lifestyle changes are the bedrock of prevention," Ferdinand wrote.

For their study, Pamir and colleagues relied on the prospective REGARDS cohort. Participants were self-reported Black or white individuals across the U.S. Included in the present analysis were the nearly 24,000 participants (57.8% white, 58.4% women, mean age 64 years) free of CHD at baseline when recruited in 2003-2007.

Study authors acknowledged that the observational nature of the study precluded any causal conclusions. They added that the geographic breadth of REGARDS enrollment across the country, while good for generalizability, may have affected the completeness of event (i.e., myocardial infarction or CHD death) ascertainment.

"HDL cholesterol has long been an enigmatic risk factor for cardiovascular disease," maintained statistician Sean Coady, MA, of the National Heart, Lung, and Blood Institute, in the NIH press release. "The findings suggest that a deeper dive into the epidemiology of lipid metabolism is warranted, especially in terms of how race may modify or mediate these relationships."

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