The atherosclerotic process begins in childhood. With the exception of those with rare inborn errors of metabolism, atherosclerosis does not reach the clinical horizon until the fifth decade or later, when the best opportunities for prevention and intervention have been lost. The investigators goal is to identify traits, measured in children, that are the most informative discriminators of a family history of coronary artery disease (CAD). This study takes advantage of resources established by the Rochester Family Heart Study (RFHS), an NIH- supported population-based research program that has collected genetic, biochemical and physical examination data on 3938 individuals in 573 three- and-four generation pedigrees ascertained without regard to health status. Clinical endpoint evaluations of CAD have been made on 3829 living and deceased adults in these same 573 pedigrees. The investigators propose to study 800 healthy children from these pedigrees who were 5-20 years of age at entry (i.e., baseline) into the RFHS. Both clinically defined CAD in grandparents and parents and evidence of chronic, asymptomatic CAD (without clinically defined CAD) measured by coronary artery calcification detected by Electron Beam Computed Tomography will be used to classify children with respect to family history of CAD.
Aims 1 and 2 will involve a cross-sectional study to identify which of 26 risk factors of CAD discriminate between healthy children ages (5-10) with and without a strong family history of CAD.
Aims 3 and 4 will determine whether measures of change in the 26 risk factor trait levels over a ten-year period in the same sample (ages 15-30 at follow-up) will improve the ability to discriminate between children with and without a strong family history of CAD.
Aim 5 will investigate whether information about variation in 18 CAD susceptibility genes improves the ability to discriminate between children with and without a strong family history of CAD beyond that provided by the established CAD risk factor levels at baseline and/or by changes in levels over a ten-year period. The traits identified in children that discriminate between those with and without a strong family history of CAD will suggest which biological processes are candidates for modification by diet, drugs, exercise, or other changes in lifestyle.
