"It's been well accepted low HDL cholesterol levels are detrimental, regardless of race. Our research tested those assumptions."
The study adds to evidence it can become abnormal - and lead to blocked blood vessels.
A bloodstream tussle takes place between 'bad' or LDL (low-density lipoprotein) cholesterol which dumps fat in the arteries and 'good' cholesterol which takes it away.
But the evidence is growing that more of the latter is not always better. The latest results may help find new ways to protect the heart.
Eating olive oil, fish and nuts raises levels of HDL cholesterol. It is one of the things doctors test for when predicting your risk of a heart attack.
But repeated trials that raise HDL with drugs have flopped, leading doctors to think something else is going on.
Previous research that shaped perceptions about 'good' cholesterol levels and heart health in the 1970s included mostly white adults.
So Pamir and colleagues looked at how cholesterol levels from heart disease-free white and black middle-aged adults overlapped with future cardiovascular events.
They enrolled between 2003 to 2007 and the researchers analyzed information collected over more than a decade.
Those with increased 'bad' cholesterol and harmful blood fats called triglycerides had modestly increased risks for cardiovascular disease.
But the study was the first to find lower HDL cholesterol levels only predicted increased cardiovascular disease risk for white adults.
It also shed fresh light on other studies showing high 'good' cholesterol levels are not always associated with reduced cardiovascular events.
The analysis was the largest to indicate this was true for both black and white people - suggesting higher than optimal amounts may not provide benefits.
Pamir said: "What I hope this type of research establishes is the need to revisit the risk-predicting algorithm for cardiovascular disease.
"It could mean in the future we don't get a pat on the back by our doctors for having higher HDL cholesterol levels."
As researchers study HDL cholesterol's role in supporting heart health they are exploring different theories, she explained.
One is quality over quantity. That is, instead of having more HDL, the quality of its function in picking up and transporting excess cholesterol may be more important.
They are also taking a microscopic look at its properties, including analyzing hundreds of proteins linked with transporting cholesterol.
Varying associations, based on one or more, may improve cardiovascular health predictions.
"The findings suggest a deeper dive into the epidemiology of lipid metabolism is warranted, especially in terms of how race may modify or mediate these relationships."
Cardiovascular disease is the world's biggest killer, claiming around 18 million lives a year.
Risk calculators using HDL cholesterol could lead to inaccurate predictions for black adults.
Added Pamir: "When it comes to risk factors for heart disease, they cannot be limited to one race or ethnicity. They need to apply to everyone."
Participants shared similar characteristics such as age, cholesterol levels and underlying risk factors for heart disease like diabetes, high blood pressure or smoking.
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