This proposed project is aimed at investigating the relationship between oxidative stress and coronary heart disease in a population-based case-control study of incident myocardial infarction. In particular, the applicant proposes to analyze the relationship between myocardial infarction and both direct measurements of plasma lipid peroxidation products and paraoxonse activity. The lipid peroxidation profile proposed identifies the oxidized isomeric species of the major plasma polyunsaturated fatty acids linoleic and arachidonic acid. Paraoxonase is a high density lipoprotein associated acylhydrolase, which has been shown to hydrolyze lipid peroxides. It has been reported that individuals with a low paraoxonase activity are subject to increased risk of coronary heart disease, however, a relationship between plasma lipid peroxides and paraoxonase activity has not been established. The proposed study will be conducted as an ancillary project to an ongoing case-control study. Plasma lipid peroxides and paraoxonase activity will be measured in samples (stored at -196 C) from 300 cases (150 men and 150 women) and 400 controls (200 men and 200 women). The strength of the proposed investigation includes: a) the population-based nature of the study, b) adequate sample size to analyze the data separately for men and women and for whites and African Americans separately, c) use of a direct novel measurement of oxidative stress and antioxidant potentials. In addition, to provide novel and important information on issues related to role of oxidative stress in the etiology of coronary heart disease, the proposed program will allow the applicant to gain important knowledge in epidemiology and clinical research methodology.
