Over the last dozen years or so, research into particles carrying the so-called good cholesterol, known as high-density lipoprotein, or HDL, has presented a much more nuanced and conflicted story about HDL’s effect on cardiovascular disease.
And a new, large study brings new doubts. High HDL cholesterol levels were not associated with protection against heart disease in black or white participants, researchers reported in Journal of the American College of Cardiology.
For low HDL cholesterol, there was a division, with a link to a higher risk of heart disease in white participants but not in black participants.
The study is the first to find a difference in the risk of low HDL cholesterol levels between black and white people. It also adds to the accumulated evidence that high HDL cholesterol isn’t necessarily good for your heart health.
There appear to be other attributes of HDL that can be good. But the researchers also found that HDL’s role in health is complicated and ever-changing, with much to understand.
HDL cholesterol and heart disease
Cholesterol has long been explained as the “good” against the “bad”. A high standard of the guy “good” it has been linked to a lower risk of cardiovascular disease while having many types “bad”carried by low-density lipoprotein particles, or LDL, has been linked to a higher risk.
One of the big ratios to give HDL cholesterol the label of “good” came out of the Framingham Heart Study, a government-led effort launched in 1948 to investigate risk factors for cardiovascular disease.
In 1977, the Framingham researchers reported an inverse relationship between HDL cholesterol and coronary heart disease risk in a group composed of white participants.
But subsequent studies have disproved the premise that high levels are automatically good for heart health. People with a genetic mutation that raises their HDL cholesterol level, for example, have no lower risk of heart attacks than people without the mutation.
And a class of drugs developed to raise HDL cholesterol did a great job boosting the numbers, but it made no difference when it came to cardiovascular risk. However, a person’s HDL cholesterol level is only part of the story.
Commonly reported on blood tests, the level reflects the amount of cholesterol the HDL particles have on board. HDL carries cholesterol from the arteries to the liver to be excreted. This helps prevent cholesterol from building up in the artery walls, which can ultimately impede blood flow.
Recently, HDL research has begun to look beyond its payload of cholesterol.
“The big understanding from the last decade or so is that while it is possible to measure cholesterol, it doesn’t really reflect the actual functions that HDL is performing in the body”says Anand Rohatgi, a cardiologist at the University of Texas Southwestern Medical Center in Dallas.
How well HDL removes cholesterol seems to matter. One measure of this work performance is the ability of HDL to receive cholesterol from a type of cell called a macrophage.
In a U.S. study of nearly 3,000 adults, 49 percent of whom were black, the higher this ability, the lower the incidence of heart attacks or strokes, Rohatgi and colleagues reported in the New England Journal of Medicine in 2014.
Ridding the body of cholesterol is just one of HDL’s many jobs. HDL also has anti-inflammatory and other protective effects that appear to protect against cardiovascular disease. But also these effects they do not always lead to a net good.
Under certain circumstances, HDL can become dysfunctional, such that it reduces its ability to receive cholesterol and contributes to inflammation. The fact that the roles of HDL can change, depending on context, has made studying HDL particles challenging, says Rohatgi.
How well HDL performs is still far from something that can be tested for as part of a regular physical exam. It’s not clear yet “how to do it for the general public”says Nathalie Pamir, a researcher studying cardiology at Oregon Health & Science University in Portland.
The impact of HDL cholesterol on heart health can vary by ethnicity
As researchers work towards a more complete understanding of HDL and how it might best be used as a clinical measure, the view of HDL cholesterol as uniformly “good” it is still vivid. And one’s HDL cholesterol level is still an entry in a widely used calculator which estimates cardiovascular risk.
Pamir and his colleagues wanted to examine what high and low HDL cholesterol levels mean in a contemporary, diverse population.
In the new study, the team analyzed data from the REGARDS study, designed to investigate potential regional and racial differences in death from stroke in the United States. The study included nearly 24,000 participants, 42 percent of whom were black, who didn’t start out with coronary heart disease.
In about 10 years, 664 of 10,095 black participants and 951 of 13,806 white participants have had a heart attack or died from one.
The increase in LDL cholesterol levels “bad” it was linked to a higher risk of coronary heart disease, consistent with past research, the team found. But for HDL cholesterol, high levels weren’t protective for anyone, and low levels were only predictive of higher risk in whites.
This finding suggests that the way HDL cholesterol is used in the cardiovascular disease risk calculator may need to be reviewed, says Pamir.
Rather than just good, HDL cholesterol “it’s complicated”, He says. If a patient has a high level of HDL cholesterol, a doctor “he can say, ‘well, right now we don’t know what that means.'”
Although the study suggests that HDL cholesterol levels impact on the risk of the disease can vary according to ethnicityIt’s important to remember that ethnicity is a social construct, not a biological one, says Clyde Yancy, chief of cardiology at Northwestern University Feinberg School of Medicine in Chicago.
Some of the risk factors for coronary heart disease, including high blood pressure and smoking, “are more prevalent in self-defined black Americans”, he claims. And a community’s access to health care, nutritious food, and education and employment opportunities can influence these risk factors.
“There is something unique about the place and the history of the place that can predispose you to the burden of hypertension, obesity and even diabetes,” says Yancy.
It will take more research to figure out what’s behind the potential race-based difference the study reports, Yancy says, and what it means in terms of HDL cholesterol levels and cardiovascular disease risk.
But the fact remains that high levels of LDL cholesterol, which can build up in the artery wallsare associated with increased risk, he says. “LDL cholesterol appears to be our most relevant barometer”.
Despite all that is known about what affects cardiovascular disease risk, researchers still don’t have the full picture. The number of times cardiologists see heart attacks in patients with normal cholesterol levels and normal blood pressure, Yancy says, suggests that, with current methods, “we are unable to capture the entire risk”.
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