Table of Contents
$15.5 Million Project Targets
Dangerous Cardiovascular Plaques
Research uses advanced imaging and lab technology plus 17 years of data
Researchers will sift genes, proteins and personal habits that compose the puzzle of vulnerable plaque – subtle fatty buildups in artery walls that can burst without warning – under a $15.5 million National Institutes of Health project that began in July.
Eric Boerwinkle, Ph.D.
The goal is to characterize factors that make plaques unstable and prone to rupture – abruptly blocking arteries and causing heart attacks or strokes, said principal investigator Eric Boerwinkle, Ph.D., director of the Human Genetics Center at The University of Texas School of Public Health at Houston. By pinpointing these factors, researchers expect to produce novel predictors of cardiovascular disease and stroke, new targets for medication, and new ways to prevent stroke and heart attack among those with atherosclerosis.
“We are looking at the predictors of stable vs. unstable plaques and at factors that predict chronic plaque buildup translating into acute coronary syndrome,” Boerwinkle said.
UT Health Science Center at Houston President James T. Willerson, M.D., who has been a pioneer in research on vulnerable plaque, said, “This research support allows us to continue our efforts to detect vulnerable atherosclerotic plaques using gene identification and imaging to be able to identify vulnerable patients. Dr. Boerwinkle will be a great leader for this project, and we are very proud of his leadership role in genetic discovery in our country.”
The four-year project, funded by the National Heart, Lung and Blood Institute, will capitalize on advances in imaging and laboratory technology while tapping 17 years of data on 16,000 people in a longterm study of atherosclerosis.
“The demographic data over 17 years really give this project its power. There’s nothing like it,” said Boerwinkle, who also directs the Center for Human Genetics at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM). The original project, Atherosclerosis Risk in Communities (ARIC), has studied risk factors in the condition, also known as hardening of the arteries, among volunteers in North Carolina, Mississippi, Maryland and Minnesota.
Researchers will be able to combine years of data on cholesterol levels, blood pressure, tobacco use, diet and exercise with state-of-the-art genetic and protein analysis. Then they will analyze all of those factors to determine which played a role in the formation of plaque and the incidence of heart attack and stroke.
Advanced MRI scanning of the carotid arteries of a sample of 2,000 ARIC volunteers will be used to characterize vulnerable plaque, which consists mainly of a fibrous cap that covers a core of fat-filled cells. Boerwinkle said total plaque volume, the thinness of the cap, the amount of fat, or lipids, in the core and the presence of calcium will be measured. A high-fat core with a thin cap is thought to be the worst combination, the most likely to rupture and swiftly block an artery.
“We want to know why some people have thin caps with lots of lipid in their plaque and other have thick caps and small amounts of lipid,” Boerwinkle said.
Vulnerable plaque formation and rupture are intimately tied to the body’s inflammatory response – part of its defense against injury and disease. Research has shown that inflammatory proteins in the bloodstream, such as C - reactive protein, can be a measure of cardiovascular disease risk.
Kenneth Wu, M.D., Ph.D., associate director of the Brown Foundation IMM, and director of Vascular Biology Research Center and of the Division of Hematology at the UT Medical School at Houston, will apply a new process to measure inflammatory markers on the white blood cells rather than in the bloodstream. The process may provide a better picture of the proteins’ connection to plaque formation and disease risk.
Christie Ballantyne, M.D., professor of medicine and director of the Center for Cardiovascular Disease Prevention at Baylor College of Medicine, will lead the team’s study of lipids, such as LDL and HDL cholesterol, crucial to plaque formation.
Bruce Wasserman, M.D., assistant professor of radiology at Johns Hopkins University School of Medicine, leads the MRI portion of the study.
An additional aspect of the study, funded by the National Eye Institute, will examine the small blood vessels in the eye for clues of atherosclerosis and heart attack risk.
Originally, medical research pointed to the gradual buildup of fatty plaque in the coronary arteries as the principal cause of heart attack and stroke. These plaques, strongly associated with high cholesterol, gradually narrowed and closed coronary arteries. However, researchers found that only about 30 percent of heart attacks had their origins in this gradual type of blockage.
Vulnerable plaques are harder to detect and may not narrow the arteries at all before rupturing and blocking the blood vessels.
— Scott Merville, Public Affairs