The Effect of Long Duration Exercise on the Diastolic Function of the Heart

Objectives: Chronic physical inactivity contributes to the deaths of nearly 1 in 10 Americans. In seniors, the single most common life-threatening disease is congestive heart failure and for these patients, abnormalities of diastolic function play a critical role in the pathophysiology of their disease. The primary investigator's previous research has demonstrated that: a) healthy but sedentary aging leads to atrophy and stiffening of the heart with reduced myocardial and chamber compliance; b) in contrast, highly competitive senior athletes had cardiac compliance that was indistinguishable from healthy young individuals suggesting that lifelong exercise training prevented this stiffening; c) even prolonged and intense exercise training started after age 65 failed to reverse age-related cardiac and vascular stiffening; d) cardiac stiffening begins in middle age (45-64) and can be substantially prevented by training 4-5 days/wk. The primary objective of this project, is therefore to identify sedentary individuals aged 45-64, and initiate an exercise program carefully designed to maximize effects on cardiovascular compliance and function. After this aim is accomplished, we will have established a novel, practical exercise training strategy designed to prevent the cardiovascular stiffening with aging, improve the functional capacity in our aging population, and ultimately to prevent Heart failure with preserved Ejection Fraction. Such a determination would have enormous public health significance since this condition is quite difficult to treat once established.

Hypothesis: The investigators hypothesize that exercise training implemented 4-5 times/week for 2 yrs in sedentary middle aged men and women (45-64yr) will improve cardiac and vascular compliance to a degree equivalent to life-long exercisers (and sedentary young). The investigators will perform invasive and non-invasive assessment of cardiovascular structure and function before and after an exercise program involving high intensity aerobic intervals, lower intensity endurance ("base training"), and strength training.

Specific Aim: To test our hypothesis, there will be two groups of previously sedentary subjects, ages 45-64 for 2 years, with the following interventions: 1) subjects undergoing prolonged endurance/interval/strength exercise training; and 2) yoga/balance control.

A comprehensive set of "Baseline Testing" (prior to the two year intervention) and "Follow-up Testing" (after the two year intervention) will take place to assess the effects of the intervention. This testing will include submaximal and maximal exercise testing as well as comprehensive invasive (right heart catheterization) and non-invasive (ultrasound) measures of cardiac mechanics, relaxation and morphology. From these data, the following indices of diastolic and systolic function will be generated: Starling and pressure/volume curves; calculations of left ventricle wall stress and strain; and measurements of flow propagation velocity, ejection fraction and relaxation velocity.

Inclusion criteria

• healthy, sedentary men and women
• ages 45-64
• body mass index <30
• absence of co-morbid conditions including hypertension, diabetes, heart failure, asthma, chronic obstructive pulmonary disease, coronary artery disease as evidenced by angina or prior myocardial infarction or cerebrovascular disease as evidenced by prior transient ischemic attack or stroke

Exclusion criteria

• healthy, active (aerobic exercisers greater than 2 days per week) men and women
• ages less than 45 or over 64
• body mass index >30
• presence of co-morbid conditions including hypertension, diabetes, heart failure, asthma, chronic obstructive pulmonary disease, coronary artery disease as evidenced by angina or prior myocardial infarction or cerebrovascular disease as evidenced by prior transient ischemic attack or stroke
• Patients with chronic orthopedic injury that might make them unable to participate in an exercise testing will also be excluded
• Subjects unable to speak English will not be recruited because of the complex experimental studies and the need for precise communication between the volunteers and the research staff to ensure safety.