Oxidative stress relates to inflammation and endothelial dysfunction, interacting with conditions such as adiposity, glycemia and smoking. Such oxidative stress, even in young adulthood, may contribute to long term disease risk long before clinical disease. To address these issues, we propose continuation of R01 HL053560, locally called Young Adult Longitudinal Trends in Antioxidants (YALTA). YALTA has been continuously funded since 1995, ancillary to Coronary Artery Risk Development in Young Adults (CARDIA), thus utilizing its infrastructure for cost efficiency and minimal participant burden. CARDIA (n=5115 black and white men and women aged 18-30 in 1985-86) retained 72% of participants at its 7th examination at year 20 and begins year 25 followup in 2010. YALTA's central purpose is to determine oxidative damage and its consequences by seamlessly obtaining additional samples and biochemistries, integrating with the full CARDIA database. YALTA studies oxidation and disease risk (metabolic syndrome, hypertension, dyslipidemia, diabetes, kidney and lung disease, coronary artery calcification, carotid artery wall thickness, and echocardiographic measures). YALTA has assayed over 20 oxidation-related indicators during CARDIA years 0 and 20 and can therefore define the timeframe when these variables become important in disease risk. Our previous measurements have provided a profile of indicators that are associated with elevated oxidative stress and disease risk. We propose to repeat measurement of several informative markers including oxidized LDL, intercellular adhesion molecule-1 (ICAM1), F2-isoprostanes, and HbA1C. In addition, circulating carotenoids and adiponectin will be repeated. Recent technological advances allow introduction of novel indicators, including fluorescent oxidation products, the RNA expression of several oxidant and antioxidant enzymes and a urinary metabolic profile, which will provide information on dietary intakes and flavonoid metabolism. These indicators will provide new information that is critical for our understanding of the evolution of oxidative stress and its interaction with obesity, inflammation, sources of oxidants and dietary intakes in disease risk. We hypothesize that indicators of oxidative damage and poor antioxidant status will be related to low intakes of nutrient-rich diets, physical inactivity, smoking and adiposity. Measurements of oxidant and antioxidant enzyme gene expression will be associated with oxidative stress and its consequences. The measurements of oxidative stress, singly and in combination, will be related to disease risk. The urinary metabolic profile will be related to dietary intakes of nutrient-rich foods and the risk of disease. Several oxidation-related activities are influenced by obesity and these relationships will be identified by the study. YALTA will ultimately be able to relate oxidation-related factors to clinical disease. These studies will aid in the identification of factors which can alter oxidation status and the identification of young adults with a critical need to favorably alter their oxidation status so that they can benefit in the long term from a reduction in oxidative stress.

Public Health Relevance

Atherosclerosis and cardiovascular disease are major public health concerns and remain major causes of death in the United States. A major etiologic factor may be oxidative damage. The YALTA, Young Adult Longitudinal Trends in Antioxidants, study will continue to identify oxidation-related factors in young and middle-aged adults and their association with subclinical and clinical cardiovascular disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL053560-15
Application #
8281454
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Nelson, Cheryl R
Project Start
2000-04-01
Project End
2015-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
15
Fiscal Year
2012
Total Cost
$726,884
Indirect Cost
$205,425
Name
University of Minnesota Twin Cities
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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Barone Gibbs, Bethany; Pettee Gabriel, Kelley; Reis, Jared P et al. (2015) Cross-sectional and longitudinal associations between objectively measured sedentary time and metabolic disease: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Diabetes Care 38:1835-43
Zhu, N; Jacobs, D R; Meyer, K A et al. (2015) Cognitive function in a middle aged cohort is related to higher quality dietary pattern 5 and 25 years earlier: the CARDIA study. J Nutr Health Aging 19:33-8
Wang, Huifen; Jacobs Jr, David R; Gaffo, Angelo L et al. (2015) Serum Urate and Incident Cardiovascular Disease: The Coronary Artery Risk Development in Young Adults (CARDIA) Study. PLoS One 10:e0138067
Carson, April P; Steffes, Michael W; Carr, J Jeffrey et al. (2015) Hemoglobin a1c and the progression of coronary artery calcification among adults without diabetes. Diabetes Care 38:66-71

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