Researchers Hope to Identify Heart Disease Genes

Thousands of Milwaukee-area volunteers are being screened for participation in a major study now underway to identify genes linked to heart disease and the heart's ability to protect itself from damage by growing new blood vessels.

With the help of many local hospitals, physicians and nurses, the Family Heart Health Study being conducted by the Medical College of Wisconsin will evaluate more than 800 subjects who agree to take part out of about 3,000 heart patients screened. A primary focus of the research is to identify genetic susceptibility to heart disease in African Americans, who have historically been under-represented in genetic testing for heart disease.

"The short-term goal is to identify what the specific genetic determinants are for the development of coronary disease," said David D. Gutterman, MD, Northwestern Mutual Professor of Cardiology at the Medical College and principal investigator for the study. "Clearly, a fair amount of coronary disease is driven by environmental and lifestyle factors, but there's a significant genetic component that we've known about for years. We're trying to identify what genes are involved. Rather than just say 'it's in your genes,' we want to know which ones."

The family study is part of continuing research funded by a $6 million grant from the National Institutes of Health. Caucasian subjects are being recruited in equal numbers locally. Data from them and from large-scale research in Germany is being used to compare their genetic heart disease markers and blood vessel growth characteristics to those of African Americans. Heart disease is the leading cause of death for both races.

Recruitment and Education
"A secondary goal is to begin to educate people in the community about heart disease and its importance, especially in the African American population where it's very prevalent," said Dr. Gutterman, "and also to start getting the community more interactive in research projects. We're developing a cohort of subjects so that when we ask the next question we don't have to go through and spend years acquiring another huge set of patients. They're there, and we can go back to them and say 'we've got this other question to ask that might be of benefit to you."

Volunteers with heart disease who have had a heart catheterization and/or angioplasty, and who are willing to give blood samples for genetic testing, are being recruited. Patients do not qualify if they have a recent diagnosis of cancer or are being treated for cancer, if they have chronic kidney failure, or are being treated for severe liver disease. All medical history information and other patient-specific data collected in the study will be kept strictly confidential.

"What we're asking of them is a tube of blood to get the genetic analysis, and a number of questions related to their history and demographics. The questions are mostly related to their medical history, what risk factors for heart disease they have."

Family Traits and "Self-Bypasses"
In a paper published in the journal Nature Genetics (February 2002), Medical College researchers were the first to identify a group of genes that may predispose some people to heart attacks. The Medical College researchers showed that, out of the entire human genome estimated to contain as many as 40,000 genes, they had identified a group of between 100 and 150 genes as likely suspects in predisposition to heart disease.

"Our task now is to explain why heart disease runs in some families and gallops in others," said Dr. Gutterman. Volunteers have the satisfaction of being "part of the answer, part of the solution to solving heart disease," he added. "Our goal is to understand the genetics of the disease that will allow us to develop novel, therapeutic strategies to treat people."

Another goal of the study is to look at why some people are "better" at blood vessel growth than others. Blood vessels are constricted or blocked in ischemic heart disease, which can lead to heart attack. In some people, new blood vessels grow in response to the constriction, thereby alleviating the blockage. The family heart study researchers are also looking for patients who show different degrees of blood vessel growth.

Ulrich Broeckel, PhD, Assistant Professor of Medicine and project leader for the study, has said, "The mechanism leading to development of collateral blood vessels following blockage in a coronary artery shows that some people basically produce their own heart bypasses. We're interested in factors that indicate who will develop the self-bypass and who won't."

Clarence Grim, MD, Medical College Clinical Professor of Medicine, is researching the family heart study with Drs. Gutterman and Broeckel.

Involvement of the Community
Dr. Gutterman noted that community response to the project has been very good, crediting the long and solid history of heart disease research in the Milwaukee area, support of health care providers at all levels, and public outreach and education efforts for the excellent response.

"Clarence Grim and Ulrich Broeckel have been very instrumental in targeting radio, using pamphlets and contacting physicians and hospitals," said Dr. Gutterman, "and as we've got nurses stationed in several hospitals around town, people have recognized that the study is going on and are more amenable to participating in the project. Most of the hospitals in the area have been very forthcoming in letting us come through and recruit subjects.

"Being able to be involved in research is something that the hospitals like, the physicians there enjoy, and it can be a little added bonus for the patients. They find out things about their cholesterol profile and maybe some genetic things they might not otherwise find out."

Part of the Specialized Center of Research on Ischemic Heart Disease in African Americans, directed by Dr. Gutterman, the family heart study is being conducted by the Froedtert & Medical College Cardiovascular Center and the Department of Medicine.

Who is Eligible for the the Family Heart Health Study?
Anyone over the age of 18 years of age who:

1. Is going to get a catherization or
2. Has had a catherization or
3. Has a family member (parent, child, sibling) with history of heart disease evidenced by catheterization

Who is Not Eligible?
Exclusion factors:

1. Recent heart attack (within last 3 months)
2. Receiving treatment for cancer currently or within the last 3 months
3. Receiving treatment for liver disease currently or within the last 3 months
4. Receiving treatment for kidney disease currently or within the last 3 months

If you are interested in taking part in the Family Heart Health Study, call 888-293-1614 for more information.

Dan Ullrich
HealthLink Contributing Writer

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.