Background and History
Heart disease and stroke cluster strongly in families, particularly when the events occur at a young age. Siblings of people with premature coronary disease have an excess risk of having a coronary disease event that is 2-12 times greater than the general population. This well documented fact became the foundation on which the GeneSTAR Study was founded in 1982, under the direction of Dr. Diane Becker while still a doctoral student in the Johns Hopkins Bloomberg School of Public Health. The first study examined the risk perceptions, beliefs, and prevention behaviors of 30-59 year old siblings of people hospitalized under 60 years of age with premature coronary disease. Did siblings perceive their own high relative risk or take any action to ameliorate it? The answer was a resounding “no!” The majority of siblings felt their risk to be the same or even lower than the general population, and most often failed to initiate cardiovascular risk reduction. They would however agree to come in for extensive screening of risk factors.
Screening to determine the true distribution of known and novel risk factors and occult coronary disease, using stress testing and thallium scintigraphy, commenced in 1983, and The Johns Hopkins Sibling and Family Heart Study was born. Joined by Dr. Thomas Pearson, then the new Director of an NHLBI Preventive Cardiology Academic Award in the Division of General Internal Medicine and Dr. Lewis Becker, Director of Nuclear Cardiology, with the assistance of Dr. Pete Kwiterovich, Director of The Johns Hopkins Lipid Research Program and Dr. David M. Levine, then a leading member of the Behavioral Science faculty, the team together began to explore the intersection of their interests in high risk families. Dr. Dan Fintel, at the time a Cardiology Fellow, participated in many of the early clinical encounters and assessments and was nodal in the early exercise imaging work. Our long-term prospective study of risk factors, occult disease, and incident cardiovascular disease in siblings was launched, later extending to offspring and whole pedigrees identified from CAD probands at the time of hospitalization in any of 10 Baltimore Hospitals.
Now followed for cardiovascular and other comorbid incident events from 5-32 years, The Johns Hopkins Sibling and Family Heart Study cohort remains engaged in a series of integrated research studies of cardiovascular disease risk, novel risk interventions, cerebrovascular disease risk, and attendant metabolic and thrombosis phenotypic risk factors. The study has had a long-term interest in African American families and disparities in the cardiovascular disease substrate.
Importantly, GeneSTAR has firmly established in a US population, that family history of coronary disease bears an excess risk of disease far beyond what would be predicted by the Framingham Risk Score (Figure 1 below). Studies continue to look for genetic factors, gene-environment interactions, rare variants, and novel mechanisms.
Observed 10-Year Risk Compared to Predicted in Siblings Based on Baseline Framingham Risk Category
Vaidya D, Yanek LR, Moy TF, Pearson TA, Becker LC, Becker DM. Incidence of coronary artery disease in siblings of patients with premature coronary artery disease: 10 years of follow-up. Am J Cardiol, 2007 Nov 1;100(9):1410-5. PMCID: PMC2128738
GeneSTAR remains under the leadership of its founders and a group of young talented investigators representing many disciplines (see Investigator Tab) and senior advisers.
The dedication of the GeneSTAR families from all over the United States,has been the key to the success of the study yielding a follow-up rate of over 99 percent.
GeneSTAR's Collaborating Founders
Thomas A. Pearson, MD, PhD, MPH
Executive Vice President for Research and Education,
University of Florida Health Science Center
Professor of Epidemiology and Medicine
Colleges of Public Health and Health Professions
College of Medicine, University of Florida
Peter O Kwiterovich, MD (deceased 2014)
Director, Lipid Research Profram
Professor Emeritus, Pediatirics and Medicine
Johns Hopkins University School of Medicine
Dan Fintel, MD
Professor, Medicine (Cardiology)
Northwestern Feinberg School of Medicine
David M. Levine, MD, ScD, MPH
Director, Postdoctoral Training Programs (Medicine)
Professor Medicine, Public Health, Nursing
Johns Hopkins University School of Medicine