"Good" cholesterol not always protective for heart: study

Having high levels of high density lipoprotein (HDL), also called "good" cholesterol, is believed to reduce our heart disease risk, but a new study found an exception to the generally accepted medical maxim.

The study, led by researchers at the University of Pennsylvania and published Thursday in the U.S. journal Science, showed that a rare genetic cause of increased HDL may actually be a "bad" thing.

"Our results indicate that some causes of raised HDL actually increase risk for heart disease," said senior author Daniel Rader, chair of the department of genetics at the University of Pennsylvania.

"This is the first demonstration of a genetic mutation that raises HDL but increases risk of heart disease."

Rader and his colleagues compared lipid-modifying genes of 328 people with markedly elevated HDL to a control group with lower HDL and identified one noteworthy individual who carried two copies of a gene variant.

Normally, HDL is involved in moving cholesterol from peripheral tissues to the liver, where the cholesterol is metabolized and excreted.

A rare mutation in a gene called SCARB1, however, prevents HDL from doing its job, therefore resulting in a buildup of HDL in the blood, the researchers said.

This increase in HDL levels "does not reflect an increase in clearing of cholesterol from the peripheral tissue," explained Michael Holmes, who was not involved in the study, at the University of Oxford.

"This results in reduced clearance of peripheral cholesterol through reverse cholesterol transport, increased furring of arteries (atherosclerosis) and an increase in risk of coronary heart disease," Holmes said in a statement.

The researchers also searched for this genetic mutation using Global Lipid Genetics Consortium data from more than 300,000 individuals.

The SCARB1 variant was found to be rare in the population, but carriers had significantly higher HDL levels.

Notably, people who carry one copy of the SCARB1 variant have a higher risk of coronary heart disease compared with non-carriers.

Rader suggested that a therapeutic approach to increase the expression or activity of SCARB1 could be a new way to reduce the risk of heart disease even though it would reduce HDL blood levels.

"The work demonstrates that the protective effects of HDL are more dependent upon how it functions than merely how much of it is present," Rader concluded. "We still have a lot to learn about the relationship between HDL function and heart disease risk."

Previous research also raised the possibility that HDL might not be quite as protective against heart disease as generally believed by cardiologists, especially after several clinical trials of drugs that raised HDL levels showed little or no effect. Endit