Treatments to Raise HDL Cholesterol May Not Reduce Heart Attack Risk

Elevated levels of HDL (high-density lipoprotein) cholesterol have long been recognized as a biomarker for reduced risk of heart disease, however data published in a recent paper found that drug treatment to raise levels of HDL cholesterol might not lower an individual’s heart attack risk.

Investigators at Harvard University Medical School (Boston, MA, USA) used a statistical approach based on “Mendelian randomization” to analyze nucleotide polymorphism (SNP) data from more than 170,000 individuals. The SNPs were in genes linked to HDL metabolism. With such a large number of cases, individual variations evened out and any differences could be attributed to the specific SNPs under investigation.

Results published in the May 17, 2012, online edition of the journal the Lancet revealed that individuals carrying a particular variation in the gene for the enzyme endothelial lipase had HDL levels that were elevated by about six mg/dL, or 10% - representing a level of HDL cholesterol that would be expected to decrease heart attack risk by about 13%. However, this population showed no difference in risk of heart disease compared to those without the variant.

“It has 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 Dr. Sekar Kathiresan, associate professor of medicine at Harvard Medical School. “This work fundamentally questions that. We know that HDL is a great biomarker – it is quite useful in identifying individuals at higher risk of having a heart attack in the future. But we have shown that you cannot assume that raising HDL by any mechanism will help patients. Perhaps other mechanisms exist that can lower risk, but we will need to keep searching for them.”

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Harvard University Medical School