Introduction Recent research into the development and progression of coronary artery disease (CAD) links oxidative stress with its pathological features; however, specifics regarding the impact of oxidative stress on CAD, compared to more traditional risk factors, remain unclear. The oxidative stress hypothesis proposes that the oxidation of lipids, in the context of vascular endothelial cell dysfunction, promotes macrophage foam cell formation and the progression of CAD lesions. Measurable genetic and biochemical variations in pro-oxidant and antioxidant enzymes have been studied for relationships with CAD; however, little is known about the relative role oxidative stress plays in the development of CAD, or its end point.
Objectives This study will evaluate and compare multiple genetic and biochemical biomarkers of oxidative stress to determine their relative and additive abilities to predict all-cause and cardiovascular-related mortality in a population with cardiovascular disease.
Methodology Biochemical analysis of stored plasma from an angiography cohort of 1,117 subjects, with a mean follow-up of 8.5 years, will include the following measures of oxidative stress: total antioxidant potential, oxidized low-density lipoprotein, 8-iso-prostaglandin F2α, myeloperoxidase, nitrotyrosine, and paraoxonase. DNA analysis of 894 Caucasian subjects to measure selected polymorphisms and haplotypes of the following genes: myeloperoxidase; NADPH oxidase p22 phox subunit; heme oxygenase 1; and 5-lipoxygenase activating protein. Statistical analysis of results from biochemical and genetic studies, and comparison with semi-quantitatively assessed angiography results, and mortality data from Vital Statistics Canada.
Preliminary Results Two hundred twenty of the patients in this cohort have since died, including 103 cases of CAD-related death. Assays for total antioxidant potential, myeloperoxidase, 8-iso-prostaglandin F2α, oxLDL, and nitrotyrosine have been performed to address the stability and suitability of measuring oxidative stress biomarkers in frozen/thawed plasma samples stored for a mean duration of 8.5 years.
Impact This study will provide novel insight into how biomarkers of oxidative stress correlate with CAD patient mortality. Determining the degree of association between genetic polymorphisms, intermediate phenotypes, and patient mortalities will be a valuable product of this immense study of oxidative stress.
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