Obesity and reduced physical activity have adverse vascular effects that lead to increases in blood pressure and arterial stiffness and a premature aging of the cardiovascular system. This leads eventually to chronic hypertension, heart failure and cardiovascular mortality. The metabolic effects of sodium are enhanced with obesity and thus sodium consumption likely modulates many of the vascular effects of obesity. W e hypothesize that in young adults, the vascular effects of obesity are reversible with weight reduction and increases in activity. We further hypothesize that sodium intake plays a. role in the extent to which arterial stiffness can be reduced. We propose to test these hypotheses in a clinical trial of 300 adults aged 20 to 45 who are moderately overweight (BMI 25-35). All participants will receive a dietary and activity intervention with a goal of achieving a 10% weight loss and an increase in weekly activity level of 150-200 minutes. Participants will be randomized to either a low sodium or a control sodium intake. The effect of the intervention on the cardiovascular system will be evaluated through measurement of Pulse Wave Velocity (PWV), endothelial function and common carotid will thickness and diameter. The primary trial endpoint will be aortic PWV, because this measure reflects both structural and functional vascular changes that are expected to occur with the intervention. The proposed interventions are expected to influence the vasculature through numerous mechanisms including altering adipocytokine production, insulin resistance, sympathetic activity, the RAAS, inflammation, and glucose and lipid metabolism. Measures of each of these processes have been incorporated and each will be repeated over time to provide a dynamic picture of the effects of the intervention on the vasculature. We will store samples of plasma, serum, urine and DNA to allow further testing through alternate funding mechanisms. The results of this trial will provide valuable information on the best intervention to preserve vascular health. A more thorough understanding of the mechanism linking obesity, sodium consumption and vascular health can be used to formulate targeted therapies for obesity-related vascular damage.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL077525-03
Application #
7446579
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Loria, Catherine
Project Start
2006-07-01
Project End
2011-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
3
Fiscal Year
2008
Total Cost
$697,950
Indirect Cost
Name
University of Pittsburgh
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Lee, Jane J; Woodard, Genevieve A; Gianaros, Peter J et al. (2015) Ectopic adiposity is associated with autonomic risk factors and subclinical cardiovascular disease in young adults. Obesity (Silver Spring) 23:2030-6
Niemczyk, Nancy Anderson; Catov, Janet M; Barinas-Mitchell, Emma et al. (2015) Nulliparity is associated with less healthy markers of subclinical cardiovascular disease in young women with overweight and obesity. Obesity (Silver Spring) 23:1085-91
Cooper, Jennifer N; Evans, Rhobert W; Mori Brooks, Maria et al. (2014) Associations between arterial stiffness and platelet activation in normotensive overweight and obese young adults. Clin Exp Hypertens 36:115-22
Hawkins, Marquis; Gabriel, Kelley P; Cooper, Jennifer et al. (2014) The impact of change in physical activity on change in arterial stiffness in overweight or obese sedentary young adults. Vasc Med 19:257-263
Cooper, Jennifer N; Fried, Linda; Tepper, Ping et al. (2013) Changes in serum aldosterone are associated with changes in obesity-related factors in normotensive overweight and obese young adults. Hypertens Res 36:895-901
Smith, H A; Storti, K L; Arena, V C et al. (2013) Associations between accelerometer-derived physical activity and regional adiposity in young men and women. Obesity (Silver Spring) 21:1299-305
Hughes, Timothy M; Althouse, Andrew D; Niemczyk, Nancy A et al. (2012) Effects of weight loss and insulin reduction on arterial stiffness in the SAVE trial. Cardiovasc Diabetol 11:114
Cooper, Jennifer N; Tepper, Ping; Barinas-Mitchell, Emma et al. (2012) Serum aldosterone is associated with inflammation and aortic stiffness in normotensive overweight and obese young adults. Clin Exp Hypertens 34:63-70
Cooper, Jennifer N; Buchanich, Jeanine M; Youk, Ada et al. (2012) Reductions in arterial stiffness with weight loss in overweight and obese young adults: potential mechanisms. Atherosclerosis 223:485-90
Njoroge, Jennifer N; El Khoudary, Samar R; Fried, Linda F et al. (2011) High urinary sodium is associated with increased carotid intima-media thickness in normotensive overweight and obese adults. Am J Hypertens 24:70-6