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Cardiovascular Disease: Role of “Good” Cholesterol Is Challenged

HDL cholesterol may not be as useful in predicting cardiovascular disease risk among persons of various races and ethnicities as experts formerly believed.

When it comes to predicting the risk of cardiovascular disease among people of different races and ethnicities, blood HDL cholesterol isn’t as useful as experts used to think it was before, reports a new study.

Cholesterol is a waxy, fat-like organic substance called lipids. The compound is biosynthesized and serves as an essential structural component of animal cell membranes and a precursor molecule for the biosynthesis of steroid hormones and vitamin D.

Cholesterol, in its free OH form and combined with protein, termed lipoprotein, is circulated in our blood. Among the lipoproteins, low-density lipoprotein (LDL) represents are called bad cholesterol, and high-density lipoprotein (HDL) is frequently called “good cholesterol”.

However, recent studies started revealing different stories. The failure of randomized trials designed to increase HDL cholesterol has raised questions about the significance of HDL cholesterol in human health and disease (Keene et al., 2014).

HDL cholesterol may not be as helpful as scientists formerly assumed in predicting cardiovascular disease risk among individuals of different races and ethnicities (Gordon et al., 1977).

New analysis shows that HDL cholesterol levels predicted a higher risk of heart attacks or related fatalities for white individuals but not for Black persons. Higher HDL cholesterol levels did not lessen cardiovascular disease risk for either group.

The study, which was published in the Journal of the American College of Cardiology, found that while low levels of HDL cholesterol have long been linked to a higher risk of heart attacks or related deaths in white adults, this was not the case for Black adults. Also, higher levels of HDL cholesterol were not linked to a lower risk of heart disease in either group (Zakai et al., 2022).

“The goal was to understand this long-established association that designates HDL as the good cholesterol, and if that is true for all ethnicities,” said Nathalie Pamir, Ph.D., the study’s principal author and an associate professor of medicine at Oregon Health & Science University, Portland. Low HDL cholesterol is harmful to all races. We tested these assumptions.”

Pamir and her colleagues investigated data from more than 23,900 volunteers in the Reasons for Geographic and Racial Differences in Stroke Study (REGARDS). In the 1970s, white adult study participants changed their ideas about “excellent” cholesterol levels and heart health. Researchers looked at how cholesterol levels of middle-aged Black and white adults without heart disease correlated with future cardiovascular events.

Researchers analyzed REGARDS data collected during a 10- to 11-year period. Black and white study participants had similar ages, cholesterol levels, and heart disease risk factors such as diabetes, hypertension, and smoking. Six hundred sixty-four black individuals and 951 white people had heart attacks or died from them. According to earlier research, adults with high LDL cholesterol and triglycerides risked cardiovascular disease.

cholesterol cardiovascular risk

The study found that lower HDL cholesterol levels only predicted greater cardiovascular disease risk for white adults. It extends on previous findings that high HDL cholesterol isn’t always linked to fewer cardiovascular events. The REGARDS analysis was the most extensive U.S. study to reveal that greater than ideal concentrations of “good” cholesterol may not give cardiovascular advantages for either group.

Pamir hopes this research indicates the necessity to review the cardiovascular disease risk-predicting methodology. It could mean that doctors no longer praise us for having high HDL cholesterol.

Pamir said researchers are studying numerous possibilities about HDL’s significance in heart health. Quality trumps quantity. Instead of having more HDL, its quality in taking up and moving excess cholesterol may be more significant for cardiovascular health.

They are also studying hundreds of proteins related to transferring cholesterol to see how different relationships may enhance cardiovascular health forecasts.

HDL cholesterol is a perplexing risk factor for cardiovascular disease, says NHLBI’s Sean Coady.

“The findings encourage a deeper dig into lipid metabolism epidemiology, notably how race may affect or mediate these associations.”

In addition to promoting existing and future research with varied populations to explore these linkages, the authors conclude that cardiovascular disease risk calculators utilizing HDL cholesterol could lead to erroneous projections for Black adults.

Pamir noted: heart disease risk factors cannot be restricted to a single race or ethnicity. They must be applied to all.

Related Publication and Further Readings

Gordon, T., W. P. Castelli, et al. (1977). “High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study.” Am J Med 62(5): 707-714.

Keene, D., C. Price, et al. (2014). “Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117,411 patients.” BMJ 349: g4379.

Zakai, N. A., J. Minnier, et al. (2022). “Race-Dependent Association of High-Density Lipoprotein Cholesterol Levels With Incident Coronary Artery Disease.” Journal of the American College of Cardiology 80(22): 2104-2115.

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