We propose to investigate the relationships of fatal and nonfatal coronary heart disease (CHD) to lipoprotein subfractions and other risk factors in a prospective epidemiologic study of 1961 men who were employed Lawrence Livermore National Laboratory (LLNL) between 1954 and 1957. Prior to 1985, Dr. John Gofman and colleagues measured their plasma total cholesterol, blood pressure, height, weight, tobacco use and the following lipoprotein mass concentrations determined by analytic ultracentrifugation: high density lipoproteins of lesser density (HDL2), and greater density (HDL3), lipoproteins (VLDL). Dr. Gofman used the same method of analytic ultracentrifugation to measure lipoprotein subfractions in 1954 as the Donner Laboratory currently uses for epidemiologic and metabolic research. After 10 years of follow- up, Dr. Gofman reported that high concentrations of LDL, IDL, and smaller VLDL of flotation rate Sf 20-100 and low concentrations of HDL2 and HDL3 predicted increased CHD risk. The discovery of computer files containing the baseline lipoprotein subfraction and other risk factor data provides a unique opportunity to examine the relationship of lipoprotein subfraction concentrations to CHD in a prospective epidemiologic study, at minimal cost. We propose to determine the vital status and history of CHD in this cohort through state and national mortality surveillance systems, public records, medical reports at LLNL, hospital records, autopsy reports, and telephone interviews with cohort members. All medical documents will be examined by a physician and endpoints assigned according to international diagnostic criteria. These data will be used to extend Dr. Gofman's initial study from 10 to 30 years of follow-up. These additional years are expected to produce 405 new cases of fatal and nonfatal CHD (from 38 reported by Gofman in 1966 to an expected 443 cases by 1986). Survival analysis will be used to assess the independent contributions of specific lipoprotein subclasses to CHD while controlling for other risk fators, and to allow for censoring at different times during the follow-up period. Among the issues to be examined are: 1) Do HDL2 and HDL3 show different relationships to CHD?; 2) Are relationships of lipoprotein subfractions to CHD independent of other established risk factors?; 3) Do measurement of lipoprotein subfraction concentrations offer significant improvement over total cholesterol in predicting a person's CHD risk? Except for Dr. Gofman's earlier work, there are no prospective epidemiologic studies that examine the relationship of mass of HDL2, HDL3, LDL, IDL, and VLDL subfractions to CHD. Information will be collected for the continued follow-up of the cohort as a resource for future epidemiologic studies.
