April 13, 2007

The MGH studies heart attacks

Coronary heart disease, America's number one killer, is responsible for one out of every five deaths in the country each year. In 2006 alone, more than 865,000 people suffered a heart attack — also known as myocardial infarction, or MI. The most common risk factors associated with coronary heart disease are high cholesterol, hypertension, smoking and diabetes.

According to two MGH researchers, however, a person's genes also may play a role in determining his or her risk for MI. David Altshuler, MD, PhD, of the Department of Molecular Biology, and Sekar Kathiresan, MD, of the MGH Cardiology Division, recently were awarded a $4.3 million grant by the National Heart, Lung, and Blood Institute (NHLBI) for the study, "A Genome-wide Association Study for Early-Onset Myocardial Infarction." In this study, Kathiresan and Altshuler aim to associate cases of early-onset MI — heart attacks in younger patients — with genes that may put the patients at risk. While the average age of a first heart attack is 65.8 for men and 70.4 for women, this study will target 3,000 male and female MI patients aged 50 or 60 years or younger, respectively.

There is evidence to support the idea that inherited genetic variations play a key role in heart attacks, especially in early-onset cases. For example, MI tends to cluster in families even after traditional risk factors are taken into account. Due to recent advances in genetics, now it is possible to search the entire human genome for common variants in DNA that may influence MI risk. Through chip-based genotyping technology, this study will test around one million DNA sequence variants for possible roles in early-onset MI.

Successfully identifying these variants could transform how clinicians understand and treat heart attacks. If the genomic variants are located precisely, scientists could develop new diagnostic tests to allow doctors to identify those most at risk and target their treatments accordingly. Further, knowledge about these genes could allow clinicians to shed light on why heart attacks occur. "This may translate into new biology, new information and new avenues for treatment," says Kathiresan. "We are hopeful that knowledge about these genes will improve our ability to predict, prevent and treat heart attacks."

The project was initiated at the MGH in 1998 by Christopher J. O'Donnell, MD, MPH, an MGH cardiologist and associate director of the Framingham Heart Study. It later was expanded upon by Altshuler and Kathiresan. In 2006, a $300,000 charitable gift from the Fannie E. Rippel Foundation provided the seed funding necessary to secure the NHLBI award. Early results from the project should be available within the next year.