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Gene Variants Can Predict Threat of Heart Disease

WEDNESDAY March 19, 2008 -- A combination of cholesterol-associated gene variants can increase a person's risk for heart attack, stroke or sudden cardiac death, Massachusetts General Hospital researchers report.

It may someday be possible to test for these gene variants in order to identify patients who may require more intense monitoring and might benefit from earlier use of cholesterol-lowering medications and other measures to reduce their increased risk for cardiovascular events, the researchers said.

"We feel that our data provides two insights," study lead author Dr. Sekar Kathiresan, director of preventive cardiology at MGH, said in a prepared statement. "First, we provide a foundation for the possibility that a panel of gene variants will eventually be useful in preventive cardiac care. Second, we show that the combination of multiple variants related to cholesterol importantly contribute to the genetic risk for heart attack."

In analysis of data from 5,414 Swedish adults, Kathiresan and colleagues focused on a combination of 9 single-nucleotide polymorphisms (SNPs) previously associated with cholesterol levels. The researchers also looked at the participants' high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels, and their subsequent medical histories.

The participants were given a genotype score, ranged from 0 to 18, based on how many copies of the unfavorable SNPs they had. Those with higher genotype scores had higher LDL (bad) cholesterol and lower HDL (good) cholesterol levels. Those with genotype scores of 11 or higher had a 63 percent greater risk of a cardiovascular event than those with score of nine or lower.

In the overall study population, testing for the panel of nine SNPs was no better than standard risk factors for predicting risk of cardiac events. However, among those classified at intermediate risk by standard measures, the results of testing for the panel of nine SNPs significantly improved the ability to identify people with truly elevated or reduced cardiac event risk levels, the researchers said.

The study appears in the March 20 issue of the New England Journal of Medicine.

"A current clinical dilemma is how early to start patients on cholesterol-lowering medications like statins that can reduce the risk of heart attack," Kathiresan said. "Our data suggest those individuals classified as higher risk based on a genetic test may deserve more intense pharmacological and lifestyle treatments."

However, before this approach can actually be used to help patients, he added, "we need to discover all the risk-related variants -- and there will probably be 50 to 100 -- and then conduct clinical studies confirming that this information can reliably guide patient care."

More information

The U.S. Centers for Disease Control and Prevention has more about heart disease risk factors.

Posted: March 2008


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