It is proposed to continue studies of oxidative damage and related phenomena in coronary heart disease (CHD) risk in 3650 black and white men and women, ancillary to the NHLBI's CARDIA project. In 2005-2006, 20 years after baseline at ages 18-30, CARDIA will assess the near-middle aged participants for subclinical CHD by measuring coronary artery calcification (CAC) and carotid artery intimal medial thickening, as well as other factors that may affect atherogenesis (body fatness, blood pressure, circulating lipids, C-reactive protein (CRP), glucose, insulin and albuminuria). Recently this ancillary study demonstrated a relationship between elevated levels of circulating F2-isoprostanes (oxidative damage) and CAC that was independent of CRP, yielding the important insight that a systemic increase in oxidative burden in excess of. that formed by atherosclerosis itself is present in early coronary calcification in humans. The proposed renewal of the ancillary study will collect 23 ml blood and 10 ml urine at CARDIA year 20, do biochemistries in these and preexisting samples, and do data analyses. Blood F2-isoprostanes, phospholipase A2, superoxide dismutase, and carotenoids and tocopherols will be remeasured, and oxidized LDL and myeloperoxidase added, permitting study of associations of antioxidant and oxidative damage levels and their changes with existence and development of subclinical macrovascular disease in this still-young group. Study of gamma glutamyl transferase (GGT), the primary function of which is to regenerate glutathione, an intracellular antioxidant will continue. This ancillary study has shown GGT to be strongly predictive of diabetes and hypertension. In this connection, glutathione and glutathione peroxidase will be assessed. Hemoglobin A1 c, an indicator of glycemia that has been associated with oxidative stress, will be added. By measuring several antioxidants and oxidative damage in different compounds, this project will continue to test the association of antioxidants and oxidative damage with early/subclinical CHD and offer new avenues for CHD prevention. ? ?
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