Prevention of Cardiovascular Stiffening With Aging and Hypertensive Heart Disease
Condition: Lv Hypertrophy; Heart Failure, Diastolic; Stiffness, Vascular
MeSH terms: Heart Diseases; Heart Failure, Diastolic; Hypertrophy
Study type: Interventional

Summary: 
      The purpose of this study is to determine whether vigorous exercise training 4-5 days/week
      for one year in sedentary middle aged (ages 40-64) individuals at high risk for future
      development of heart failure will improve cardiac and vascular compliance to a degree
      equivalent to life-long exercisers and the sedentary young. To date, no effective therapy for
      heart failure with preserved ejection fraction (HFpEF) has been found; therefore prevention
      is critical and discovering novel treatment strategies is essential. Exercise training if
      implemented in high risk patients may improve diastolic function and cardiac-vascular
      interactions, preventing further progression to overt heart failure.
    

Detailed description: 
      The global objective of this project is to test novel strategies to prevent diastolic
      dysfunction associated with HFpEF; these include: a) identifying high risk individuals by
      using population derived imaging and blood biomarkers; and b) implementing novel exercise
      training strategies in these middle age individuals, when cardiac plasticity still exists, to
      forestall the development of diastolic abnormalities that progress to HFpEF.

      Prior 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 (40-64) and can be substantially prevented by training 4-5 days/wk. The primary objective
      of this project is therefore to identify high risk sedentary individuals age 40-64, and
      initiate an exercise program carefully designed to maximize effects on cardiovascular
      compliance and function. Findings from this aim would have enormous public health
      significance and establish a novel, practical exercise training strategy designed to reverse
      cardiovascular stiffening.

      Hypothesis:

      Exercise training, when implemented 4-5 times/week over a prolonged period of time in
      sedentary high risk middle aged men and women, age 40-64 will improve cardiac and vascular
      compliance to a degree equivalent to life-long exercisers (and sedentary young);

      Specific Aim:

      To test the hypothesis, two groups of previously sedentary subjects, ages 40-64 at
      particularly high risk for HF will be studied for one year, with the following interventions:
      1) subjects undergoing prolonged endurance/interval/strength exercise training; and 2)
      strength and flexibility /balance control. Subjects will be categorized as high risk and
      enrolled on the basis of elevated serum biomarkers and left ventricular hypertrophy (LVH)
      documented by cardiac MRI. Comprehensive invasive and non-invasive assessment of
      cardiovascular structure and systolic/diastolic function will be performed before and after 1
      year of an exercise intervention involving high intensity aerobic intervals, lower intensity
      endurance training, and strength training, compared with strength and flexibility control.
    

Intervention name(s): High intensity exercise; Yoga
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Subjects will perform high intensity aerobic exercise in addition to moderate intensity sessions 4-5 times per week.; Subjects will perform strength and flexibility exercises.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: LVH; Ventricular Stiffness; Fitness; HFpEF