Effect of Exercise and Weight Loss on Cardiovascular Health

Current estimates indicate that in excess of 65 percent of adults in the United States are
overweight (BMI >25.0 kg/m2) with at least 30 percent of adults classified as obese (BMI >30
kg/m2). Overweight and obesity have been linked to numerous chronic conditions including
cardiovascular disease. The application of cardiac MRI (CMRI) allows for direct measurement
of the cardiac structure, and left ventricular mass (LVM) assessed by CMRI has been shown to
be predictive of cardiovascular disease. Recent studies have shown that LVM is decreased with
weight loss; however, there is a lack of information on the added benefit of physical
activity to weight loss on these direct measures of cardiovascular structure and function.
Thus, consistent with PA-09-243, this study will examine the effect of two recommended doses
of physical activity combined with a dietary intervention on changes in the proposed outcomes
of cardiovascular disease risk in overweight adults.

The primary aim of this study is to examine the effect of the consensus public health
recommended level of physical activity [moderate physical activity (MOD-PA) = 150 min/wk]
versus a higher dose of physical activity [high physical activity (HIGH-PA) = 250 min/wk] in
the context of a comprehensive behavioral weight loss program that a includes a reduction in
energy intake measures of cardiovascular function using cardiac MRI and biomarkers of
vascular disease risk. Each of these exercise doses will be compared independently to a Diet
Only group intervention on the proposed primary and secondary outcomes, with MOD-PA also
compared to HIGH-PA. This study involves the recruitment of 390 overweight and obese adults
who will be randomly assigned to one of the above conditions (Diet Only, MOD-PA, HIGH-PA) for
a period of 12 months. The primary outcome is LVM measured by cardiac MRI. Secondary outcomes
include additional cardiac MRI measures (aortic pulse wave velocity, end diastolic volume,
aortic distensibility), inflammatory markers (CRP and TNFα) and selected adipocytokines
(adiponectin) as biomarkers of risk related to vascular outcomes, body weight, body
composition, and cardiorespiratory fitness, and traditional CVD risk factors (lipids,
glucose, insulin, blood pressure). Additional secondary analyses will allow for examination
of the effects of physical activity independent of weight change on the primary and secondary
outcomes.

Inclusion Criteria:

- 18-55 years of age.

- Body mass index (BMI) between 25.0 to <40.0 kg/m2.

- Ability to provide informed consent prior to participation in this study.

Exclusion Criteria:

- Females who are currently pregnant or breastfeeding, or reporting that she is planning
a pregnancy within the next 12 months.

- History of bariatric surgery.

- Report current medical condition or treatment for a medical condition that could
affect body weight. These may include the following: cancer (Note: Persons previously
diagnosed with non-melanoma skin cancers, those successfully treated for cancer who
have remained disease-free for five years or more would be eligible for participation
in this study); diabetes mellitus; hyperthyroidism; inadequately controlled
hypothyroidism; chronic renal insufficiency; chronic liver disease; gastrointestinal
disorders including ulcerative colitis, Crohn's disease, or malabsorption syndromes;
etc.

- Current congestive heart failure, angina, uncontrolled arrhythmia, symptoms indicative
of an increased acute risk for a cardiovascular event, prior myocardial infarction,
coronary artery bypass grafting or angioplasty, conditions requiring chronic
anticoagulation (i.e. recent or recurrent DVT).

- Resting systolic blood pressure of >160 mmHg or resting diastolic blood pressure of
>100 mmHg.

- Eating disorders that would contraindicate weight loss or physical activity.

- Alcohol or substance abuse.

- Currently treated for psychological issues (i.e., depression, bipolar disorder, etc),
taking psychotropic medications within the previous 12 months, or hospitalized for
depression within the previous 5 years.

- Report exercise on >3 days per week for >20 minutes per day over the past 3 months.
(NOTE: It is important that individuals are sedentary when entering this study to
allow for maximal effect of the intervention.)

- Report weight loss of >5% or participating in a weight reduction diet in the past 3
months.

- Report plans to relocate to a location not accessible to the study site or having
employment, personal, or travel commitments that prohibit attendance to at least 80
percent of the scheduled intervention sessions and all of the scheduled assessments.