Although an age-related decline in aerobic capacity is well documented, the impact of physical activity, body fat, and genetic variation on the rate of change is not well understood. In addition, little is known about how rate of change in aerobic capacity during early and middle adulthood affects the development of cardiovascular disease risk factors or the incidence of subclinical and clinical cardiovascular disease (CVD) related end-points. We propose to address these issues by conducting an ancillary study in conjunction with the Year 20 CARDIA (Coronary Artery Risk Development in Young Adults) examination, which is scheduled to take place beginning in June, 2005. We anticipate that approximately 3,650 (75%) of the surviving members of the initial cohort of African American and white men and women will return for the Year 20 exam, at which point they will be 38-50 years old. The overall goal of the proposed ancillary study is to understand the complex, longitudinal relations between physical fitness, physical activity, body mass and composition and fat distribution, and genetic factors and their independent or interactive effects on the development of obesity, the metabolic syndrome, and sub-clinical CVD. To accomplish this goal, we propose to measure, on all Year 20 CARDIA participants: [unreadable] Aerobic capacity, by means of a symptom-limited graded exercise treadmill test, using the same protocol as that used in CARDIA at the Year 0 and Year 7 exams; [unreadable] Body composition and fat distribution, using a whole body dual energy x-ray absorptiometery (DEXA) scan; [unreadable] Physical activity, using 7 days of accelerometer recordings; and [unreadable] D NA sequence variants in selected candidate genes associated with cardiorespiratory fitness, components of the metabolic syndrome, and response to regular exercise, using stored DNA. Data from this ancillary study will be combined with core CARDIA examination data to address the following aims: [unreadable] E xamination of the contribution of body mass and composition, fat distribution, objectively measured physical activity and specific genetic polymorphisms to the variance in Year 20 aerobic capacity and in age-related decline in aerobic capacity over a 20-year time period from young adulthood to mid-life, stratifying by race and gender. [unreadable] Longitudinal examination of the effect of aerobic capacity on changes in cardiovascular disease risk factors and on the incidence of CVD-related endpoints (e.g. hypertension, metabolic syndrome, subclinical disease [e.g. coronary artery calcium]). Data from this study should provide information that will help us more deeply understand the interrelationships of cardiorespiratory fitness, body composition, and CVD-related risk factors and endpoints, and may provide the basis for I more extensive evidence-based recommendations on the role of fitness in cardiovascular health. PERFORMANCESITE(S) (organization, city, state) Kaiser Foundation Research Institute, Division of Research, Oakland, CA University of Alabama, Birmingham, AL Northwestern University, Chicago, IL University of Texas, Houston Health Sciences, Houston, TX University of Minnesota, Minneapolis, MN KEY PERSONNEL. See instructions.Use continuation pages as needed to provide the required informationintheformat shown below. Start with Principal Investigator. List all other key personnel in alphabetical order, last name first. Name Organization Role on Project Sidney, Stephen, MD Division of Research Principal Investigator Boerwinkle, Eric, PhD University of Texas, Genetics Center Co-Investigator Carnethon, Mercedes, PhD Northwestern University, Field Center Co-Investigator Jacobs, David R., Jr, PhD University of Minnesota, Field Center Co-Investigator Lewis, Cora, MD, MSPH University of Alabama, Field Center Co-lnvestigator Quesenberry, Charles, Jr., PhD Division of Research Biostatistician Sternfeld, Barbara, PhD Division of Research Co-Investigator Williams, O. Dale, MPH, PhD University of Alabama, Coordinating Center Co-Investigator Disclo-[unreadable].r#- P#_rmi___[unreadable]ion _t_t#_m__nt_ Annlic._hlp. tn _BIR/RTTR Only Rp._ in.qtruc.ti(_n_ [_ Ye_ F"-I No [unreadable] PHS 398 (Rev. 05/01) Page 2__ Form Page 2. Principal Investigator/Program Director (Last, first, middle): Sidney, Stephen, MD RESEARCH GRANT TABLE OF CONTENTS Pa_Numbem Face Page .................................................................................................................................................. 1 Description,