Peripheral Effects of Exercise on Cardiovascular Health (STRRIDE I)

To investigate the separate effects of the amount of exercise and exercise intensity on cardiovascular risk factors in overweight men and women with mild to moderate dyslipidemia.

BACKGROUND:

Substantial evidence supports a favorable relationships 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 exposures required to achieve health benefits in humans are poorly defined and the mechanisms through which these beneficial adaptations occur are poorly understood. The 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 in humans.

DESIGN NARRATIVE:

In this clinical trial, Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE I), subjects were randomly assigned to one of three graded exercise training regimens or a sedentary control group and asked to train, after an initial ramp period of up to two months, for six months at a given exercise intensity and dose. Parameters reflecting changes in carbohydrate and lipid metabolism were studied at an integrative physiologic level and with measurable biological endpoints in peripheral skeletal muscle (e.g., capillary surface area). It was proposed that the elucidation of the peripheral mechanisms mediating the favorable responses in carbohydrate and lipid metabolism to chronic physical activity would lead to better understanding of the health benefits conferred by physical activity and cardiovascular fitness in humans and point the way toward better exercise recommendations for clients with significant cardiovascular risk factors. The purpose of this study was to investigate the peripheral biological mechanisms through which chronic physical activity altered carbohydrate metabolism and lipid metabolism, resulting in improvements in these parameters of cardiovascular health and fitness in humans. The driving hypothesis was that health benefits derived from habitual exercise were primarily mediated through adaptations occurring in skeletal muscle, probably related to alterations in exposed capillary surface area in skeletal muscle induced by exercise training. The investigators used graded exercise regimens in moderately obese human subjects with mild to moderate lipid metabolic abnormalities to investigate whether induced alterations in skeletal muscle fiber type, metabolic capacity and capillary surface area accounted for favorable alterations in insulin sensitivity and glucose metabolism, lipoprotein levels and lipid metabolism.

Eligibility Criteria:
Inclusion criteria: age 40 to 65 years, sedentary (exercise less than two times per week), overweight or mildly obese (BMI 25 to 35 kg/m2) with mild to moderate lipid abnormalities (either LDL cholesterol 130 to 190 mg/dl; or HDL cholesterol \< 40 mg/dl for men, or 5 \< 45 mg/dl for women). Women were postmenopausal.

Exclusion criteria: diabetes; hypertension; other metabolic or musculoskeletal diseases; current use of or intent to diet; use of confounding medications; overt presence of coronary heart disease; or unwillingness to be randomized to any group.