Public Release: 

Genetic risk linked to clinical benefit of statin therapy

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

Brigham and Women's Hospital

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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This work was supported by a grant from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) - R01 HL098082. Full funding information, including all author disclosures, can be found in the full text of the article.

Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in Massachusetts and employs nearly 15,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Brigham Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, more than 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $650 million in funding. For the last 25 years, BWH ranked second in research funding from the National Institutes of Health (NIH) among independent hospitals. BWH continually pushes the boundaries of medicine, including building on its legacy in transplantation by performing a partial face transplant in 2009 and the nation's first full face transplant in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative. For more information, resources and to follow us on social media, please visit BWH's online newsroom.

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