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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL049910-09
Application #
6637470
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Sorlie, Paul
Project Start
1994-01-01
Project End
2006-02-28
Budget Start
2003-03-01
Budget End
2006-02-28
Support Year
9
Fiscal Year
2003
Total Cost
$797,521
Indirect Cost
Name
University of Southern California
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Shufelt, Chrisandra; Elboudwarej, Omeed; Johnson, B Delia et al. (2016) Carotid artery distensibility and hormone therapy and menopause: the Los Angeles Atherosclerosis Study. Menopause 23:150-7
Johnson, B Delia; Dwyer, Kathleen M; Stanczyk, Frank Z et al. (2010) The relationship of menopausal status and rapid menopausal transition with carotid intima-media thickness progression in women: a report from the Los Angeles Atherosclerosis Study. J Clin Endocrinol Metab 95:4432-40
Fan, Amy Z; Dwyer, James H (2007) Sex differences in the relation of HDL cholesterol to progression of carotid intima-media thickness: the Los Angeles Atherosclerosis Study. Atherosclerosis 195:e191-6
Fan, Amy Z (2006) Metabolic syndrome and progression of atherosclerosis among middle-aged US adults. J Atheroscler Thromb 13:46-54
Fan, Amy Z; Paul-Labrador, Maura; Merz, C Noel Bairey et al. (2006) Smoking status and common carotid artery intima-medial thickness among middle-aged men and women based on ultrasound measurement: a cohort study. BMC Cardiovasc Disord 6:42
Dwyer, James H; Allayee, Hooman; Dwyer, Kathleen M et al. (2004) Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis. N Engl J Med 350:29-37
Dwyer, James H; Paul-Labrador, Maura J; Fan, Jing et al. (2004) Progression of carotid intima-media thickness and plasma antioxidants: the Los Angeles Atherosclerosis Study. Arterioscler Thromb Vasc Biol 24:313-9
Nordstrom, Cheryl K; Dwyer, Kathleen M; Merz, C Noel Bairey et al. (2003) Leisure time physical activity and early atherosclerosis: the Los Angeles Atherosclerosis Study. Am J Med 115:19-25
Reed, D; Dwyer, K M; Dwyer, J H (2003) Abdominal obesity and carotid artery wall thickness. The Los Angeles Atherosclerosis Study. Int J Obes Relat Metab Disord 27:1546-51
Wu, Huiyun; Dwyer, Kathleen M; Fan, Zhihong et al. (2003) Dietary fiber and progression of atherosclerosis: the Los Angeles Atherosclerosis Study. Am J Clin Nutr 78:1085-91

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