Effects of Resistance and Aerobic Exercise on Cardiovascular Health

Study Overview
=================
Brief Summary
-----------------
This study will investigate the separate and combined effects of aerobic and resistance training on cardiovascular risk factors in overweight men and women with mild to moderate dyslipidemia.

Detailed Description
-----------------
BACKGROUND: Substantial evidence supports a favorable relationship between cardiovascular fitness, physical activity, and cardiovascular health. In particular, it is well established that increased levels of physical activity result in favorable improvements in lipid and carbohydrate metabolism. There is also evidence that increased physical activity and cardiovascular fitness have beneficial effects on cardiovascular health, independent of the effects on specific cardiovascular risk factors. One hypothesis proposes that the beneficial effects of regular exercise in humans is mediated through peripheral mechanisms, in particular through the chronic adaptations in skeletal muscle to habitual exercise. The exercise exposure required to achieve health benefits is poorly defined and the mechanisms through which these beneficial adaptations occur are poorly understood. This study will investigate the peripheral biological mechanisms through which chronic physical activity alters carbohydrate metabolism and lipid metabolism, resulting in improvements in these parameters of cardiovascular health and fitness. DESIGN NARRATIVE: In Studies of a Targeted Risk Reduction Intervention through Defined Exercise II (STRRIDE II), participants will be randomly assigned to one of four exercise training regimens after a 4-month sedentary control period. After an initial ramp period of up to 2 months, participants will be asked to train for 6 months in a given exercise program. The programs differ either in the dose of aerobic exercise or in the mode (e.g., aerobic exercise, resistance exercise, or a combination). Parameters reflecting changes in carbohydrate and lipid metabolism will be studied at an integrative physiologic level and with measurable biological endpoints in peripheral skeletal muscle (capillary surface area). It is proposed that the elucidation of the peripheral mechanisms mediating the favorable responses in carbohydrate and lipid metabolism to chronic physical activity will lead to better understanding of the health benefits conferred by physical activity and cardiovascular fitness. This may also point the way toward better exercise recommendations for clients with significant cardiovascular risk factors. The purpose of this study is to investigate the peripheral biological mechanisms through which chronic physical activity will alter carbohydrate metabolism and lipid metabolism that results in improvement in parameters of cardiovascular health and fitness. The driving hypothesis is that the health benefits derived from habitual exercise are primarily mediated through adaptations occurring in skeletal muscle. The mechanism of change in skeletal muscle differs by the mode of exercise training. It is hypothesized that the health benefits of aerobic exercise are mediated primarily by qualitative changes in skeletal muscles (alterations in exposed capillary surface area in skeletal muscle induced by exercise training) and that the health benefits of resistance exercise are mediated primarily by quantitative changes in skeletal muscles (alterations in fiber area in skeletal muscle induced by exercise training). The investigators will use combination exercise regimens in moderately obese patients with mild to moderate lipid metabolic abnormalities in order to investigate whether induced alterations in skeletal muscle fiber area, metabolic capacity, and capillary surface area account for favorable alterations in insulin sensitivity, glucose metabolism, lipoprotein levels, and lipid metabolism.

Official Title
-----------------
Peripheral Effects of Exercise on Cardiovascular Health (STRRIDE II)

Conditions
-----------------
Cardiovascular Diseases, Heart Diseases, Obesity, Hyperlipidemia, Insulin Resistance, Metabolic Syndrome X

Intervention / Treatment
-----------------
* Behavioral: Resistance Training
* Behavioral: Aerobic Exercise
* Behavioral: Combo
* Behavioral: Continued Sedentary lifestyle


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Sedentary (exercises fewer than two times per week) Overweight or mildly obese (body mass index [BMI] of 25 to 35 kg/m2) with mild to moderate lipid abnormalities (either LDL cholesterol 130 to 190 mg/dl or HDL cholesterol less than 40 mg/dl for men or 5 less than 45 mg/dl for women) Exclusion Criteria: Diabetes Hypertension Other metabolic or musculoskeletal diseases Current use of or intent to diet Use of confounding medication Overt presence of coronary heart disease Unwilling to be randomized to any group

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Resistance Training<br>8 months of Resistance Exercise Training | Behavioral: Resistance Training<br>* Lifting weights 3 times per week; 8 different exercise each time; for each exercise, do three sets = lifting an appropriate weight between 8-12 for each set; rest 45 seconds (at least) between sets<br>|
| Experimental: Aerobic Exercise<br>8 months of Aerobic Exercise Training | Behavioral: Aerobic Exercise<br>* Exercise at 75% of maximal capacity for approximately 2 hours per week<br>|
| Experimental: Combination RT & AT<br>8 months of Combined Aerobic and Resistance Exercise Training | Behavioral: Combo<br>* Lift weights (as described in RT group) and do aerobic exercise (as described in Aerobic group<br>|
| Experimental: Control<br>Control/sedentary intervention | Behavioral: Continued Sedentary lifestyle<br>* No changes<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Cardiometabolic Risk Factors: lipoproteins; Ectopic Fat (Visceral Fat, Liver fat); body composition (fat mass, lean body mass; and Insulin Sensitivity |  | Month 0, Month 4, Year 1, and Year 1 plus 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolic Syndrome (ATP III defined); Maximal Oxygen consumption; muscle biopsy measures (oxidative enzymes, capillary density, myofiber diameter) |  | 0 mths, 4 mths, 1 year and 1 year and 2 weeks |