“Good” Cholesterol May Not Be Good for Everyone

Clogged arteries Cardiovascular disease Heart attack

According to a new study, which was supported by the National Institutes of Health (NIH), “good cholesterol” may not be as effective as scientists believed in uniformly predicting cardiovascular disease risk among adults of different racial and ethnic backgrounds.

A study challenges the role of “good” cholesterol in universally predicting heart disease risk.

Lower HDL cholesterol levels were associated with a higher risk of heart attacks in white but not black adults, and higher levels did not protect either group.

One study found that high-density lipoprotein (HDL) cholesterol, often called “good cholesterol,” may not be as effective as scientists believed in uniformly predicting cardiovascular disease risk among adults of different racial and ethnic backgrounds. The study was supported by the National Institutes of Health (NIH).

The research found that while low HDL cholesterol levels predicted increased risk of heart attacks or related deaths for white adults, a long-accepted association, the same was not true for black adults. Furthermore, higher HDL cholesterol levels were not associated with a reduced risk of cardiovascular disease in either group. The study was published on November 21 in the Journal of the American College of Cardiology,

LDL (low-density lipoprotein) cholesterol, sometimes called “bad” cholesterol, makes up most of the cholesterol in your body. High levels of LDL cholesterol increase the risk of heart disease and stroke. HDL (high-density lipoprotein) cholesterol, sometimes called “good” cholesterol, absorbs cholesterol from the blood and carries it back to the liver.

“The goal was to understand this long-established link that labels HDL as the beneficial cholesterol, and whether that is true across ethnicities,” said Nathalie Pamir, Ph.D., lead study author and associate professor of medicine. at the Knight Cardiovascular Institute at Oregon Health and Science University, Portland. “It is well accepted that low HDL cholesterol levels are harmful, regardless of race. Our investigation tested those assumptions.”

To do that, Pamir and his colleagues reviewed data from 23,901 US adults who participated in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. The previous studies that shaped perceptions about “good” cholesterol levels and heart health were conducted in the 1970s through research with a majority of white adult study participants. For the current study, the researchers were able to look at how the cholesterol levels of middle-aged black and white adults without heart disease living across the country overlapped with future cardiovascular events.

Study participants enrolled in REGARDS between 2003 and 2007, and researchers analyzed data collected over a period of 10 to 11 years. The black and white study participants shared similar characteristics, such as age, cholesterol levels and underlying risk factors for heart disease, such as diabetes, high blood pressure or smoking. During this time, 664 black adults and 951 white adults experienced a heart attack or heart attack-related death. Adults with elevated levels of cholesterol and low-density lipoprotein (LDL) triglycerides had a slightly increased risk of cardiovascular disease, consistent with previous research findings.

However, the study was the first to find that lower HDL cholesterol levels only predicted increased risk of cardiovascular disease in white adults. It also builds on findings from other studies showing that high HDL cholesterol levels are not always associated with reduced cardiovascular events. The REGARDS analysis was the largest US study to show this to be true for both black and white adults, suggesting that higher than optimal amounts of “good” cholesterol may not provide cardiovascular benefits for any of the groups.

“What I hope this type of research establishes is the need to revise the cardiovascular disease risk prediction algorithm,” Pamir said. “It could mean that in the future our doctors won’t pat us on the back for having higher HDL cholesterol levels.”

Pamir explained that as researchers study the role of HDL cholesterol in supporting heart health, they are exploring different theories. One is quality over quantity. That is, rather than having more HDL, the quality of HDL’s function (picking up and transporting excess cholesterol out of the body) may be more important in supporting cardiovascular health.

They are also looking microscopically at the properties of HDL cholesterol, including analyzing hundreds of proteins associated with cholesterol transport and how the various associations, based on a protein or groups of proteins, can improve predictions of cardiovascular health.

“HDL cholesterol has long been an enigmatic risk factor for cardiovascular disease,” explained Sean Coady, deputy director of epidemiology in the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute (NHLBI). “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.”

The authors conclude that, in addition to supporting ongoing and future research with diverse populations to explore these connections, the findings suggest that cardiovascular disease risk calculators using HDL cholesterol could lead to inaccurate predictions for black adults.

“When it comes to risk factors for heart disease, you can’t limit it to one race or ethnicity,” Pamir said. “They have to apply to everyone.”

Reference: “Race-Dependent Association of High-Density Lipoprotein Cholesterol Levels With Incident Coronary Artery Disease” by Neil A. Zakai MD, Jessica Minnier PhD, Monika M. Safford MD, Insu Koh PhD, Marguerite R. Irvin PhD , Sergio Fazio MD , PhD, Mary Cushman MD, Virginia J. Howard PhD, and Nathalie Pamir PhD, November 21, 2022, Journal of the American College of Cardiology.
DOI: 10.1016/j.jacc.2022.09.027

The REGARDS study is co-funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging and received additional support from the NHLBI.

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