HDL Cholesterol Not as "Good" As Once Believed, New Study Shows

Nathalie Pamir, PhD

New research suggests that “good” cholesterol may not be as useful of a biomarker for determining for predicting coronary heart disease as once purported.

An analysis leveraging patient data from the REGARDS cohort, results of the study, which assessed risk of coronary heart disease based on plasma lipid profiles, suggest LDL-C and triglycerides modestly predicted coronary heart disease risk in adults, regardless of race, but low HDL-C was associated with an increased risk in White but not Black adults and high HDL-C was not protective in either group.

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

Since being established in the 1970s, HDL-C has gained a reputation as the “good” cholesterol, with research indicating an inverse and linear association with coronary heart disease. However, more recent data has indicated this association may not be as evident among cohorts that are not mostly composed of White Europeans. With this in mind, Pamir and a team of colleagues embarked on the current research endeavor to better understand why risk equations leveraging HDL-C underperform in Black individuals compared to their White counterparts.

To do so, the current study was designed as an analysis of patient data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Launched in 2003, REGARDS was created as a collaborative effort from the National Institutes of Health and the University of Alabama at Birmingham to understand factors leading to increased rates of cardiovascular and cerebrovascular disease among Black patients compared to their White counterparts.

From 2003-2007, 30,239 Black and White adults aged 45 years or older were recruited into the cohort. Of these, 23,901 were free from coronary heart disease at baseline. This cohort had a mean age of 64±9 years, 57.8% were White, and 58.4% were women. During a median of 10 years of follow-up, 664 and 951 coronary heart disease events occurred among Black and White adults, respectively. For the purpose of analysis, race-specific hazard of plasma lipid levels with incident coronary heart disease, which was assessed using Cox regression models adjusted for clinical and behavioral risk factors.

Upon analysis, results indicated LDL-C and triglycerides were associated with an increased risk of coronary heart disease in both races (P >.10). Further analysis demonstrated low HDL-C was associated with increased coronary heart disease risk in White (HR, 1.22 [95% CI, 1.05-1.43]) but not in Black (HR, 0.94 [95% CI, 0.78-1.14]) adults (P interaction by race=.08); high HDL-C was not associated with decreased CHD events in either race (HR, 0.96 [95% CI, 0.79-1.16] for White participants and HR, 0.91 [95% CI, 0.74-1.12] for Black adults).

“HDL cholesterol has long been an enigmatic risk factor for cardiovascular disease,” explained Sean Coady, a deputy branch chief of epidemiology within the NIH’s National Heart, Lung, and Blood Institute’s Division of Cardiovascular Sciences, in the aforementioned statement. “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.”

This study, “Race-Dependent Association of High-Density Lipoprotein Cholesterol Levels With Incident Coronary Artery Disease,” was published in the Journal of the American College of Cardiology.