BACKGROUND:

Advances in molecular genetics, genetic epidemiology, population genetics, and identification of new risk factors and clusters of risk factors for cardiovascular disease made 1991 an opportune time to take advantage of the extensive information about cardiovascular disease, pre-clinical atherosclerosis, and risk factors in individuals who had been examined in ongoing, state-of-the-art epidemiological studies supported by the NHLBI. By recruiting first degree relatives of random samples of such defined populations, FHS obtained information about familial aggregation, genetic and environmental contributions to variance in continuous variables, and the frequency and distribution of elevated levels of risk factors and of selected major genes in the general population.

The FHS was initiated by staff and approved by the Clinical Applications and Prevention Advisory Commitee in May, 1990. The Requests for Proposals were released in July 1991. Contracts were awarded in June, 1992.

DESIGN NARRATIVE:

During Phases I and II from May 1992-May 1996, probands, aged 45-69, were recruited from the Framingham Heart Study, the Utah Family Tree Study and the North Carolina and Minnesota sites of the ARIC Study, along with their relatives, for participation in the Family Heart Study. Two groups of probands were selected, either randomly or by a high family risk of CHD as calculated from data from the parent study. Additional family structure and disease history data were collected on 3,150 probands and 22,909 of their relatives. Clinical examination and follow-up of these random and high CHD risk families were conducted on a total of 1,253 families including 5,975 individuals, of whom 102 families including 265 individuals were African-American. The examinations included information on anthropometry, blood pressure, ECG, carotid ultrasound, pulmonary function, and blood chemistries. Questionnaire data included medical and reproductive histories, diet, physical activity, tobacco and alcohol consumption, education, income and psychosocial factors including hostility, social support and stress. Phases I and II included four field centers, a coordinating center, and a central blood laboratory.

In August 1996, Phase III began when cooperative agreements were awarded to a consortium of seven investigator-initiated grants to conduct molecular genetic and genetic epidemiology studies using data collected during Phases I and II. Phase III ended in July 2001. The objective of Phase III was to perform molecular genetic and genetic epidemiology studies using the extensive data on family and medical histories, risk factors, life style, blood specimens, and banked DNA previously collected by the FHS. Studies included novel molecular genetics of candidate genes and genome-wide searches with anonymous markers for the detection, mapping, and characterization of coronary heart disease and atherosclerosis genes. Genetic epidemiology analyses were conducted that contributed new information on the familial aspects of atherosclerosis and intermediate phenotypes in African Americans. Phase III also included four field centers, a central laboratory, a molecular genetics laboratory, and a coordinating center.

The study was renewed in 2001 as the Family Heart Study - Subclinical Atherosclerosis Network (FHS-SCAN) to complete analyses of genome-wide scan data and to genotype promising markers. The study expects to enroll 401 informative pedigrees (3,027 individuals) previously examined and genotyped by the NHLBI Family Heart Study to quantify coronary and aortic calcium volume in order to identify genes associated with atherosclerosis. In addition, 315 African American sibships (770 individuals) previously examined and comparably genotyped by the Hypertension Epidemiology Network (HyperGEN) will be examined at one study center to address these study questions in this minority population.