Small Molecules Reveal Big Health Risks

Backed by a new, multimillion-dollar federal grant, scientists from Boston University and the National Heart, Lung, and Blood Institute (NHLBI) are on the hunt for two of America’s biggest killers: heart attack and stroke, the nation’s first and third leading causes of death. The goal is to find new biomarkers — warning signs in the form of proteins, small molecules, or genes that are screened for in blood tests — that could allow doctors to identify earlier the patients at risk and to offer more personalized drug or lifestyle interventions to reduce that risk.

The investigation will involve several research projects, known collectively as the Systems Approach to Biomarker Research in Cardiovascular Disease (SABRe) and funded by $7.6 million from the NHLBI, part of the National Institutes of Health.

While the search for new biomarkers will involve collaborations among scientists from BU, industry, and the NHLBI, it will center on the Framingham Heart Study, a multigenerational epidemiological study begun in 1948 by the NHLBI and run by BU since 1971 under NIH contract. Researchers will analyze blood samples collected between 1998 and 2005 from approximately 7,000 Framingham study participants to determine whether specific proteins or genetic markers are associated with heart disease or metabolic syndrome — a group of risk factors, such as obesity and high blood pressure, that can be a precursor to heart disease, stroke, or diabetes.

“We will look at a number of individuals who have been diagnosed with these conditions and compare their biomarkers with healthy individuals,” says Martin Larson, a College of Arts & Sciences research professor of mathematics and a senior statistician with the Framingham Heart Study. Larson emphasizes that no identifiable patient health records will be shared.

The SABRe initiatives will include RNA profiling of blood samples by scientists at the NHLBI and by Jane Freedman, a cardiologist at Boston Medical Center and a School of Medicine professor, and a five-year Cooperative Research and Development Agreement, which is a written agreement between a private company and a government agency to work together on a project, between BU, NHLBI, and BG Medicine of Waltham, Mass.

Scientists at BG Medicine will scour blood samples for 1,000 biomarkers and combine their findings with imaging studies and other medical tests conducted on the Framingham participants over the years. Researchers from the company, BU, and the NHLBI will conduct a statistical analysis of the data to spot associations between individual biomarkers and disease risk. Like all SABRe studies, the findings will be made freely available to other scientists online.

Currently, clinicians assess their patients’ risk for cardiovascular disease based largely on broad indicators such as blood pressure and cholesterol. The current techniques offer relatively blunt tools for identifying who is likely to experience a heart attack or a stroke, says Daniel Levy, director of the Framingham Heart Study and of the NHLBI Center for Population Studies.

“There are a lot of people who don’t have one particular risk factor that stands out as very elevated,” says Levy, a MED professor of medicine. “They might have marginal rates of various risk factors. And if we had better means of identifying their risk early on, we might be able to design better interventions.”

Indeed, the more biomarkers clinicians can link to disease, Levy says, the more personalized they can be in their determination of a patient’s risk and in their recommendations for changes in diet, exercise, or drug regimens.

Just as the identification of high cholesterol as a biomarker for cardiovascular disease led to cholesterol-lowering drugs, the discovery of new biomarkers could, Levy says, tell us a great deal about approaches to prevention and open the door to new therapies.

“This collaborative research effort will add to our understanding of the complex interactions between certain risk factors and disease,” adds Karen Antman, MED dean and Medical Campus provost. “We are greatly indebted to the thousands of Framingham Heart Study participants who continue to contribute to major scientific advances through exciting research projects like this.”

Chris Berdik can be reached at cberdik@bu.edu.