A study questions the role of “good” cholesterol in the universal prediction of heart disease risk.
Lower levels of HDL cholesterol were associated with increased risks of heart attacks in white but not black adults, and higher levels were not protective for either group.
High-density lipoprotein (HDL) cholesterol, often referred to as the “good cholesterol,” may not be as effective as scientists once believed in predicting cardiovascular disease risk in adults, study finds of different racial and ethnic backgrounds. The study was supported by the National Institutes of Health (NIH).
Research found that while low HDL cholesterol levels predicted an increased risk of heart attacks or associated death for white adults — a long-accepted association — the same was not true for black adults. Additionally, higher HDL cholesterol levels were not associated with a reduced risk of cardiovascular disease for 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 your body’s cholesterol. High levels of LDL cholesterol increase your risk of heart disease and stroke. HDL (high density lipoprotein) cholesterol, sometimes called “good” cholesterol, absorbs cholesterol from the blood and brings it back to the liver.
“The goal was to understand this long-established link that qualifies HDL as beneficial cholesterol, and whether this is true for all ethnicities,” said Nathalie Pamir, Ph.D., lead study author and professor. MD from the Knight Cardiovascular Institute at Oregon Health & Science University in Portland. “It is well accepted that low HDL cholesterol levels are detrimental, regardless of race. Our research tested these hypotheses.
To do this, Pamir and his colleagues looked at data from 23,901 American adults who participated in the Reasons for Geographic and Racial Differences in Stroke Study (REGARDS). Earlier 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, researchers were able to examine how the cholesterol levels of middle-aged black and white adults without heart disease who lived across the country overlapped with future cardiovascular events.
Study participants enrolled in REGARDS between 2003 and 2007, and researchers analyzed the information collected over a period of 10 to 11 years. Black and white participants in the study shared similar characteristics, such as age, cholesterol levels and underlying risk factors for heart disease, including diabetes, high blood pressure or smoking. During that time, 664 black adults and 951 white adults suffered a heart attack or heart attack-related death. Adults with increased levels of low-density lipoprotein (LDL) cholesterol and triglycerides had slightly increased risks of cardiovascular disease, consistent with previous research findings.
However, the study was the first to find that lower HDL cholesterol levels only predicted an increased risk of cardiovascular disease in white adults. It also expands on the results of other studies showing that high HDL cholesterol levels are not always associated with a reduction in cardiovascular events. The REGARDS analysis was the largest US study to show this to be true for black and white adults, suggesting that higher than optimal amounts of “good” cholesterol may not provide cardiovascular benefits for either the other group.
“What I hope this type of research establishes is the need to revisit the risk prediction algorithm for cardiovascular disease,” Pamir said. “It could mean that in the future our doctors won’t praise us 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, instead of having more HDL, the quality of HDL function – picking up and transporting excess cholesterol from the body – may be more important in supporting cardiovascular health.
They also examine the properties of HDL cholesterol under the microscope, including analyzing hundreds of proteins associated with cholesterol transport and how various associations, based on one 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, associate chief of epidemiology in the division of cardiovascular sciences at the National Heart, Lung, and Blood Institute (NHLBI). “The results suggest that a deeper dive into the epidemiology of lipid metabolism is warranted, particularly with regard to 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 links, the findings suggest that cardiovascular disease risk calculators using HDL cholesterol may lead to inaccurate predictions for black adults.
“When it comes to risk factors for heart disease, they cannot be restricted to race or ethnicity,” Pamir said. “They must 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.
The REGARDS study is co-funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Aging and has received additional support from the NHLBI.
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