Risk prediction from low HDL varies by race


November 21, 2022

3 min read

The study authors report no relevant financial disclosures. Ferdinand reports consulting for Boehringer Ingelheim, Eli Lilly, Janssen and Novartis.

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Low HDL was associated with CHD risk among white adults but not Black adults, and high HDL was not protective of risk in either, researchers reported.

CHD risk was similar among Black and white adults with elevated LDL and triglycerides, according to an analysis of the REGARDS study published in the Journal of the American College of Cardiology.

Graphical depiction of data presented in article

Data were derived from Zakai NA, et al. J Am Coll Cardiol. 2022;doi:10.1016/j.jacc.2022.09.027.

“[L]ow HDL-C was associated with increased CHD risk in white but not Black participants, whereas high HDL-C was not associated with CHD risk in either group,” Neil A. Zakai, MD, hematologist at the University of Vermont Medical Center and professor at the Larner College of Medicine at the University of Vermont, and colleagues wrote. “Other lipid parameters, such as LDL-C and triglycerides, did not display race-specific behavior and were comparably associated with CHD risk in Black and white participants. Our race-dependent observations indicate that the underlying biologic mechanism by which HDL-C associates with incident CHD in white and Black participants is different from that of other lipid risk factors.”

Neil A. Zakai

As Healio previously reported, REGARDS was a national population-based cohort study of participants aged 45 years or older in which researchers observed that hypertension awareness, control and treatment were similar in the “stroke belt” (North Carolina, South Carolina, Georgia, Tennessee, Alabama, Mississippi, Arkansas and Louisiana) compared with the rest of the U.S., suggesting that the high incidence of stroke observed there may be due to causes other than hypertension.

Analysis of the REGARDS study

For the present study, researchers used data from REGARDS to determine the impact of race on the association of lipid levels and CHD risk among Black and white individuals.

“The goal was to understand this long-established link that labels HDL as the beneficial cholesterol, and if that’s true for all ethnicities,” Nathalie Pamir, PhD, associate professor of medicine in the Knight Cardiovascular Institute at Oregon Health & Science University in Portland, Oregon, said in a press release. “It’s been well accepted that low HDL cholesterol levels are detrimental, regardless of race. Our research tested those assumptions.”

The analysis included 23,901 CHD-free REGARDS participants (mean age, 64 years; 58% women; 58% white) during a median follow-up of 10 years. During that time, 664 CHD events occurred among Black participants and 951 CHD events occurred among white participants.

LDL and triglyceride levels were associated with increased risk for CHD events among both Black and white participants with no significant interaction by race (P for interaction > .1).

However, researchers observed that low HDL was associated with increased risk for CHD among white participants (HR = 1.22; 95% CI, 1.05-1.43) but not Black participants (HR = 0.94; 95% CI, 0.78-1.14; P for interaction = .08).

In addition, high HDL level was not significantly associated with fewer CHD events among either white (HR = 0.96; 95% CI, 0.79-1.16) or Black participants (HR = 0.91; 95% CI, 0.74-1.12).

“HDL cholesterol has long been an enigmatic risk factor for cardiovascular disease,” Sean Coady, MA, a deputy branch chief of epidemiology in the NHLBI’s division of cardiovascular sciences, said in a 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.”

Race ‘a blunt tool to define ASCVD risk’

Keith C. Ferdinand

In a related editorial, Cardiology Today Editorial Board Member Keith C. Ferdinand, MD, FACC, FAHA, FASPC, FNLA, professor of medicine in the John W. Deming department of medicine at Tulane University School of Medicine, discussed the place for HDL in evaluating CHD risk.

“HDL-C in risk calculations could inaccurately assess and possibly misclassify atherosclerotic CVD risk in Black adults and become a barrier to optimal care. Race, a social construct with limited genetic basis, is a blunt tool to define ASCVD risk,” he wrote. “Although Zakai et al somewhat surprisingly reported that Black and white participants had comparable hypertension rates and diabetes medication use, dyslipidemia is not the primary driver of excess ASCVD in Black adults, in whom highly prevalent and uncontrolled hypertension is the most powerful contributor.”


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