The major goal of this project is to determine the extent to which changes in plasma levels of specific lipoproteins, lipoprotein subspecies, and apolipoproteins are associated with quantitative changes in coronary atherosclerosis during the course of a controlled three year coronary risk factor intervention program.
A second aim i s to identify those lipoprotein variables that are related at baseline to extent of coronary atherosclerosis before initiation of treatment. Lipoprotein analyses will be carried out in 300 patients admitted to Stanford University Medical Center for management of coronary artery disease (coronary artery bypass surgery, transluminal percutaneous coronary angioplasty, or medical treatment). Initial lipoprotein analyses will be performed three weeks after surgery and after medical stabilization (1-3 weeks) in other patients. Subfractions of plasma very low density, low density, and high density lipoproteins (VLDL, LDL, HDL) will be measured by analytic ultracentrifugation with a computer-based quantitation procedure. LDL and HDL subspecies will also be measured by high-resolution polyacrylamide gradient gel electrophoresis. Apolipoproteins AI, AII and B will be measured by enzyme-linked immunosorption assay. Coronary angiography will be performed and computerized quantitation of non-bypassed or non-dilated coronary artery segments will be carried out as part of an existing protocol at Stanford University before initial treatment and at three years following medical management (all subjects) and intensive multiple risk factor intervention (one-half of the subjects, randomly assigned). The special intervention program at Stanford includes improved nutrition, weight reduction, increased aerobic exercise, stress management, and individualized treatment including elimination of cigarette use, reduction of hypertension, and LDL reduction. Lipoprotein studies will be repeated after one, two and three years of follow-up in all subjects. Analyses of lipid and lipoprotein measurements in relation to changes in coronary atherosclerosis will make it possible to identify those lipoprotein parameters most closely involved in this disease process. The results will also indicate whether detailed measurements of specific lipoprotein subclasses and apolipoproteins are more informative than conventional lipid measurements in predicting the extent of coronary artery disease, and in assessing the effects of strategies directed at its prevention and treatment.
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