INTIMAL THICKENING & ANTITOXIDANTS IN HISPANICS & ANGLOS

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DESCRIPTION: (Adapted from Investigator's Abstract) Cardiovascular diseases remain the major causes of disability and early death in the U.S., and improved treatment and prevention will stem from knowledge of the etiology of atherosclerosis (Ath). The Los Angeles Atherosclerosis Study (LAAS) is a longitudinal investigation of the etiology of Ath focusing on diet and oxidative mechanisms in a randomly selected cohort of 573 utility workers, with oversampling of Hispanics. Preliminary results include a protective relation between plasma oxygenated carotenoids and 1.3 year change in the intima-media thickness (IMT) of the common carotid arteries, causal interpretation of which is supported by the findings that lutein inhibits monocyte attraction by LDL oxidized in a model of the artery wall, and that lutein supplementation reduced atherosclerosis extent by 86 percent in apo E null mice. Also, higher intake of vitamin C from supplements was significantly associated with increased progression of carotid IMT. In contrast, higher intake of vitamin C from food was associated with reduced progression of carotid IMT, but this protective relation was not significant. The protective relation of HDL-C with IMT was enhanced by higher plasma, beta-cryptoxanthin and by increased plasma level of an enzyme (paraoxonase, PON) that destroys oxidized lipids. This application proposes continued observation of the LAAS cohort with the addition of two ultrasound measures of arterial dysfunction and the investigation of new etiologic factors for Ath suggested by laboratory findings of collaborators. Additional observations will also increase power for detecting relations with IMT. The new risk factors focus on pathways that promote or inhibit LDL damage and inflammatory responses in the artery wall. The new measures of arterial function and dysfunction are (1) endothelial function of the brachial artery (lumen diameter increase in response to hyperemia); and (2) distensibility or stiffness of the common carotid artery. These additional measures, together with those in the original protocol, will allow investigation of relations between longitudinal change in Ath and dietary antioxidants, antioxidant enzymes, and genetic polymorphisms.