Reference: J Am Coll Cardiol. 2022 Nov 29;80(22):2104-2115
Practice Point: You might want to stop telling patients that a high HDL level will protect them from heart disease (but exercising still will).
EBM Pearl: Even if “treating the numbers” gets you the results you want, it’s not the same as treating for patient-oriented outcomes. If you conflate these often enough, you’re going to get burned.
“We’ve got to get that HDL up to help prevent a heart attack, sir”. Welp, our thinking (and years of advice) about HDL, the “healthy” cholesterol, might be wrong. A new study challenges assumptions about the relationship of HDL and coronary heart disease (CHD).
Most CHD risk assessment models are based on the Framingham Heart Study (comprised of 100% White American cohorts) and the inverse association between HDL and CHD risk it found. However, in the Dallas Heart Study (48% Black participants), this U-shaped association was seen in White but not in Black participants, and subgroup data from the REGARDS study, a biracial cohort of over 30,000 Black and White adults in the US (42% Black), demonstrated that low HDL was associated with a reduced risk of CHD in Black adults but did not examine the effect of high HDL.
To further assess the impact of race on the association of lipids and incident CHD (non-fatal MI or CHD death), investigators took data from the REGARDS trial, excluded those with pre-existing CHD, and used regression analyses adjusting for (many) baseline clinical and behavioral risk factors to estimate the hazard of lipid levels with incident CHD after about 10 years. Based on this adjusted analysis, they found that 1) low HDL doesn’t correlate with increased risk of CHD in Black adults like it does in White adults, and 2) there was no protective benefit of high HDL for Black (HR: 0.91; 95% CI:0.74-1.12) or White adults (HR: 0.96; 95% CI: 0.79-1.16). LDL and triglycerides displayed a similar linear relationship with CHD in both groups.
There is clearly more to understand about the relationship between HDL and CHD, which likely includes racially-related differences. One way we can understand this relationship (and others) better is through more geographically and racially diverse studies with patient-oriented outcomes. We also need to reconfigure CHD risk algorithms, as the existing models may be misclassifying risk in Black adults and overestimating the benefit of high HDL for both Black and White adults. While we’re at it, we should also reconsider all guidance on all conditions based on data from mostly White populations.
Despite a pendulum that is swinging back towards lipid targets, these data suggest we need to once again focus away from the numbers and towards behaviors, at least until we understand the relationship between HDL and CHD in all populations better. Luckily, our advice to “get that HDL up” was typically followed by a recommendation to increase exercise. So even if the reasons for this advice might be at best incomplete, and at worst, completely wrong, the mechanism by which we were treating the numbers still holds, because there is plenty of evidence that exercise reduces the risk of heart disease.
For more information, see the topic Cardiovascular Disease Major Risk Factors in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Katharine DeGeorge, MD, MS, Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Dan Randall, MD, Deputy Editor at DynaMed; Nicole Jensen, MD, Family Physician at WholeHealth Medical; Vincent Lemaitre, PhD, Senior Medical Writer at DynaMed; and Sarah Hill, MSc, Associate Editor at DynaMed.