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$10 Million NIH Grant to Identify Genes That Might Contribute to Early Atherosclerosis

WINSTON-SALEM, N.C. – Wake Forest University Baptist Medical Center cardiologist David M. Herrington, M.D., M.H.S., is leading a $10 million multicenter study to identify genes that might contribute to early atherosclerosis. Funded by the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH), the study will incorporate research in two NHLBI-funded projects: the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study and the Multi-Ethnic Study of Atherosclerosis (MESA) study.

Atherosclerosis is a multistage process set in motion when cells lining the arteries are damaged as a result of high blood pressure, smoking, toxic substances in the environment, and other agents. Fatty deposits called plaque buildup over time and can entirely shut off blood flow, greatly raising the risk of angina, stroke or heart attack. A slow progressive disease, atherosclerosis may start in childhood.

In the multicenter PDAY study, autopsies were performed on 3,000 young people of both sexes, ages 15 to 34, dying from accidental causes, suicide and homicide. The study, started in 1985 with principal researchers at Louisiana State University Medical Center found that the risk factors for adult coronary artery disease accelerate the production of plaque in the teenage years and their effects are amplified in young adulthood, 20 to 30 years before coronary artery disease becomes apparent. The study concluded that long-range prevention of adult coronary artery disease will require the control of the risk factors early in life.

Liver biopsies obtained in the study and preserved will be used in part 1 of the Herrington study.

“That has produced almost an infinite amount of DNA that now allows us to go back and look at genes that may be related to early atherosclerosis,” said Herrington. “Perhaps the most remarkable thing about this study is the large number of genes that we’re going to look at. We’re actually going to look at 2 million different gene polymorphisms.”

In part 2 of the study, Herrington’s group will take the factors that appear to be associated with atherosclerosis and compare them with effective predictors of heart disease in living participants of the $68 million MESA study. The 10-year multi-center study was funded by the NHLBI in 2000 to find new ways of detecting heart disease before any symptoms occur.

The MESA study will examine 6,500 men and women ages 45 to 84 from various ethnic groups who have no known heart disease. Using non-invasive measures, participants will be screened over the course of the study to determine if certain factors can predict coronary artery disease, stroke or congestive heart failure. Wake Forest Baptist is one of the study sites.

According to Herrington, his five-year study may help identify people who might benefit from more aggressive methods of preventing atherosclerosis.

“If we can identify people in their teens and early adult life—the one’s that have a genetic predisposition to develop atherosclerosis—we can more aggressively manage their risk factors,” said Herrington. “We also hope the study will give us some new and novel insights about what actually causes atherosclerosis, including the discovery of new genes and new pathways that could provide pharmacologic interventions and strategies that may be more effective in preventing the development of heart disease.”

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Media Contacts: Jim Steele, jsteele@wfubmc.edu, Shannon Koontz, shkoontz@wfubmc.edu, or Karen Richardson, krchrdsn@wfubmc.edu, at (336) 716-4587.

Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university’s School of Medicine. The system comprises 1,187 acute care, psychiatric, rehabilitation and long-term care beds and is consistently ranked as one of “America’s Best Hospitals” by U.S. News & World Report.


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