Researchers find link between burden of genetic risk factors and reduction of cardiovascular death and heart attacks with statin therapy

Research has demonstrated that the risk for developing coronary heart disease depends on a host of risk factors that are related both to lifestyle and genetics. In a new study from Brigham and Women's Hospital (BWH), Washington University School of Medicine in St. Louis, and Massachusetts General Hospital (MGH), researchers tested whether a composite of genetic variants could identify the risk of cardiovascular death and heart attacks as well as identify individuals who derived greater clinical benefit from statin therapy.

Researchers found that a genetic risk score identified individuals at increased risk for cardiovascular death or a heart attack, both in individuals with and without known coronary disease, with individuals in the highest genetic risk score group having more than a 70 percent increase in the risk of cardiovascular death or a heart attack compared to the lowest risk group. Moreover, the individuals with the highest burden of genetic risk had the largest benefit with statin therapy in terms of reducing the risk of cardiovascular death or heart attacks, with three times the absolute risk reduction seen in the low risk group. These findings are published in the March 3 issue of The Lancet.

"These findings could play an important role in helping physicians understand which patients will benefit the most from statin therapy," said Jessica L. Mega, MD, MPH, first author of the research paper and a cardiologist and Senior Investigator in the TIMI Study Group at BWH.

"Current clinical guidelines base treatment indications, in part, on the estimated 10-year risk of having an event," added Nathan Stitziel, MD, PhD, co-first author of the report and a cardiologist at Washington University in St. Louis. "It is possible that a genetic score such as this one might help refine these risk estimates in the future."

Researchers examined data from 48,421 individuals who experienced 3,477 cardiac events during the study period, and evaluated the association of a genetic risk score, based on 27 known genetic variants, with a first time or repeat cardiac event. After grouping patients by genetic risk, researchers then evaluated the role of statin therapy in reducing the risk of a cardiac event in each group.

They report that those with the lowest genetic risk score had the lowest risk of a first-time or recurring cardiac event, such as heart attack or stroke. In terms of the benefit of statin therapy, researchers observed an increase in both absolute and relative risk reduction across the low, intermediate and high genetic risk categories.

"Over the last five years, we have identified more than two dozen genetic variants that increase risk for heart attack," said Sekar Kathiresan, MD, director of Preventive Cardiology at MGH and co-senior author of the paper. "We wondered if those at highest genetic risk would enjoy the greatest benefit from statin therapy with respect to preventing a first heart attack. This looks to be the case."

"This knowledge will allow us, as cardiologists, to provide more personalized treatment for our patients," said Marc S. Sabatine, MD, MPH, a cardiologist at BWH, chairman of the TIMI Study Group and co-senior author of the paper.

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Link:
Genetic risk linked to clinical benefit of statin therapy

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