HDL isn't clear-cut biomarker, study suggests

A high level of LDL (low-density lipoprotein), also known as "bad cholesterol," has long been linked with a higher risk of heart attack, and lower LDL is used as a marker and target for treatment to reduce the risk of heart attack. On the flip side, a higher level of HDL (high-density lipoprotein) or "good cholesterol" has been linked with lower risk of heart attack. However, a paper in The Lancet looking at gene variants that raise HDL suggests that the links with reduced risk of heart attack aren't quite as clear-cut as we thought--they may be a cause, or they may simply be an effect of other, unknown differences.

The team, from the PROCARDIS Consortium, looked at single nucleotide polymorphisms (SNPs, or changes in a single letter in the genetic code) linked with HDL and LDL cholesterol and found that genetic changes that boost levels of HDL do not necessarily cut the risk of a heart attack. For example, people with a variation in the gene coding for endothelial lipase, which increases HDL levels, had no difference in their risk of heart disease compared with people without the variant.

"It's been assumed that if a patient, or group of patients, did something to cause their HDL levels to go up, then you can safely assume that their risk of heart attack will go down," said senior author Sekar Kathiresan, director of preventive cardiology at Massachusetts General Hospital, associate professor of medicine at Harvard Medical School, and an associate member of the Broad Institute. "This work fundamentally questions that."

Because of this research, and because there are no drugs that specifically raise HDL levels, there are now questions about using HDL as a marker of heart health across the whole population--while it can help estimate people's risk of having a heart attack, working to specifically raise levels of HDL may not have the desired effect. This study also supports the importance of knowing people's genetic traits before developing drugs that target cholesterol, or indeed any disease.

- see the press release
- check out the paper in The Lancet (reg. req.)
- read the comment in The Lancet (reg. req.)