The cardiovascular (C-V) aging in terms of arterial and cardiac structure/function (CV indices) reflects complex interplay between the intrinsic aging effect, burden of CV risk factors in a genetic background and environmental changes beginning in early life, including in utero. This interplay is governed by gene expression mediated in part by epigenetic mechanisms. This renewal application focuses on these aspects in a community-based, black white cohort entering midlife and followed since childhood in the Bogalusa Heart Study.
The Specific Aims of the proposed research are: 1) to continue characterizing the trajectories of cardio-metabolic risk variables since childhood and the familial longevity trait in relation to the arterial and cardiac structure/function (C-V indices);2) to test the hypothesis tht birth weight affects longitudinal changes of DNA methylation (genome-wide and in candidate genes) during adulthood by race;3) to test the hypothesis that there is a temporal relationship between DNA methylation patterns (global and gene-specific) and C-V risk variables measured over 12-20 years;and 4) to determine effect of global and gene-specific DNA methylation in conjunction with candidate gene variants and birth weight on subclinical C-V indices. The proposed study cohort consists of 800 white and 550 black unrelated adults, aged 29-52 years, who have C-V risk factor variables measured serially 6-15 times from childhood, birth weight, adulthood C-V indices, genotype data (38 candidate genes) and stored blood samples (baseline and follow-up, 12-20 years apart). The C-V indices include left ventricular mass and geometric remodeling, carotid artery wall thickness and compliance;candidate genes include those related to C-V risk, fetal growth and one-carbon metabolism. DNA methylation will be measured for the whole genome and 38 genes using Illumina HumanMethylation450 BeadChip. Multivariable regression analyses will be used to examine the birth weight-methylation, gene-methylation and methylation-outcome associations. Findings from this research will further the understanding of the predisposing factors that influence C-V aging in a biracial population reaching mid-life, which have implications for preventive strategies.

Public Health Relevance

Heart attack determined by genetic and environmental factors represents a major public health burden worldwide;however, the aspect of the gene-environment interaction is largely unknown. Findings from this study will provide a potential explanation for the joint impact of genes, DNA modifications and fetal growth on cardiovascular disease risk and have implications in prevention strategies.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Cardiovascular and Sleep Epidemiology (CASE)
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Rossi, Winifred K
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Tulane University
Public Health & Prev Medicine
Schools of Public Health
New Orleans
United States
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Li, Ying; Zhang, Tao; Han, Tianshu et al. (2018) Impact of cigarette smoking on the relationship between body mass index and insulin: Longitudinal observation from the Bogalusa Heart Study. Diabetes Obes Metab 20:1578-1584
Freedman, David S; Lawman, Hannah G; Galuska, Deborah A et al. (2018) Tracking and Variability in Childhood Levels of BMI: The Bogalusa Heart Study. Obesity (Silver Spring) 26:1197-1202
Zhang, Tao; Li, Shengxu; Bazzano, Lydia et al. (2018) Trajectories of Childhood Blood Pressure and Adult Left Ventricular Hypertrophy: The Bogalusa Heart Study. Hypertension 72:93-101
Yan, Yinkun; Zhang, Tao; Li, Shengxu et al. (2018) Black-White Difference in the Impact of Long-Term Blood Pressure From Childhood on Adult Renal Function: The Bogalusa Heart Study. Am J Hypertens 31:1300-1306
Wang, Yiping; Xiong, Xu; Bazzano, Lydia et al. (2018) Childhood cardiovascular health and subfertility: the Bogalusa Heart Study. Pediatr Res :
Harville, Emily W; Chen, Wei; Guralnik, Jack et al. (2018) Reproductive history and physical functioning in midlife: The Bogalusa Heart Study. Maturitas 109:26-31
Harville, Emily W; Jacobs, Marni; Shu, Tian et al. (2018) Feasibility of Linking Long-Term Cardiovascular Cohort Data to Offspring Birth Records: The Bogalusa Heart Study. Matern Child Health J 22:858-865
Du, Yang; Zhang, Tao; Sun, Dianjianyi et al. (2018) Effect of Serum Adiponectin Levels on the Association Between Childhood Body Mass Index and Adulthood Carotid Intima-Media Thickness. Am J Cardiol 121:579-583
Aslibekyan, S; Do, A N; Xu, H et al. (2017) CPT1A methylation is associated with plasma adiponectin. Nutr Metab Cardiovasc Dis 27:225-233
Shen, Wei; Zhang, Tao; Li, Shengxu et al. (2017) Race and Sex Differences of Long-Term Blood Pressure Profiles From Childhood and Adult Hypertension: The Bogalusa Heart Study. Hypertension 70:66-74

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