By Deborah Borfitz
August 20, 2020 | Heart disease researchers might want to start studying heart disease and stroke separately rather than in tandem, based on the latest findings of scientists at the University of Texas Southwestern (UTSW). Depending on the disease and population, the level of “good” high-density lipoprotein (HDL) cholesterol in the blood sometimes is and sometimes isn’t a good risk predictor, says preventive cardiologist Anand Rohatgi, M.D., an associate professor of internal medicine at UTSW.
Measuring the concentration of HDL particles, a little-used measurement of HDL, is a more reliable predictor of heart disease and stroke than the standard metric of total HDL cholesterol—that is, unless you’re trying to assess the risk of a heart attack in someone who is black. Then, surprisingly, neither method is helpful, Rohatgi continues.
Study results, which recently published in Circulation (DOI: 0.1161/CIRCULATIONAHA.120.045713), have spurred a new round of research at UTSW to try to understand the disparity as well as whether HDL particle levels may be associated with specific subtypes of stroke, he adds. Data on 15,784 people were included in the analysis.
The information was pooled from four large studies—the Dallas Heart Study, Atherosclerosis Risk in Communities study, Multi-Ethnic Study of Atherosclerosis, and the Prevention of Renal and Vascular Endstage Disease study—allowing researchers to look at historically underrepresented populations. Participants were 54% male and 22% black, with an average age of 56 years.
In terms of cholesterol, blacks and whites have some things in common, including the level of “bad” low-density lipoprotein cholesterol as a marker of disease, says Rohatgi. “But it has been well known for a while that anyone of African descent typically has higher HDL cholesterol and lower triglyceride levels… and there are some genetic differences to explain that.”
Diagnostic Conundrum
Several earlier cohort studies found that a higher number of HDL particles has a strong negative relationship with heart attack and stroke, says Rohatgi, but it remains a risk prediction tool used primarily in clinical research. Physicians in the clinic can put in an order for the test from a big commercial lab, such as Quest or LabCorp, but the information wouldn’t be relevant for most people because the thresholds for normal are not well determined.
To date, most of the studies involving HDL particle counts have been association studies that weren’t looking for the cut-off level, Rohatgi says. Without that reference point, doctors can’t know when to advise lifestyle modifications like diet and exercise or to prescribe a statin.
Establishing the meaning of a specific particle count might be useful, based on findings of the recent study showing people with the highest HDL particle count (above 37 mmol/L) had a 37% lower risk of heart attack and a 34% lower risk of stroke than those who had the lowest levels. The association was even stronger in women, at 49% and 46%, respectively.
In comparison, in the overall pool of people as well as in women, the standard HDL-C test could predict heart attack risk but not stroke, says Rohatgi.
As has become widely acknowledged, blacks have not been “as thoroughly investigated” as a primary targeted population in clinical studies, so the finding about the performance disparity of the two types of HDL risk calculators was revelatory, Rohatgi adds. Clinicians need to be working harder and differently to figure out heart disease risk among their black patients.
Rohatgi’s clinical strategy would be to rely more on cardiometabolic factors such as blood sugar level, diabetes risk, body weight and adiposity, and to perhaps “look under the hood” with a coronary calcium test to look for plaque buildup in the arteries, he says.
Starting Point
Addressing the larger problem of healthcare disparities will take a “systems approach,” Rohatgi says, because the cause is multi-factorial—including social determinants of health, access to and delivery of healthcare, the relatively low participation rate of blacks in clinical studies, and poor dissemination of new knowledge that could help disadvantaged groups improve their health status. For doctors in their one-on-one encounters, it requires transparency about the knowns and unknowns so everything possible can be done to preserve and improve patients’ health.
Blacks are at increased risk for a variety of cardiovascular diseases, including high blood pressure, but “a lot of the biology is not really well worked out,” says Rohatgi. Intrinsic differences in their HDL metabolism makes this a particularly good place to start the investigation.
HDL, having a diverse protein cargo, “wears a lot of hats,” Rohatgi says. “Many of its functions may be related to heart disease as well as other things like cancer, eye diseases, and kidney diseases that can also afflict the black population to a higher degree than non-black populations.”