Prevention of Cardiovascular Stiffening With Aging and Hypertensive Heart Disease

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.

Inclusion Criteria:

- Presence of left ventricular hypertrophy (by MRI, echocardiography or ECG)

- Normal ejection fraction (>50%)

- Elevated cardiac biomarker (high sensitivity troponin, NT-BNP)

Exclusion Criteria:

- age < 40 or >64

- body mass index>35

- history of heart failure, myocarditis, restrictive cardiomyopathy, severe chronic
obstructive pulmonary disease, unstable coronary artery disease or recent (<12 month)
acute coronary syndrome, cerebrovascular disease as evidenced by prior transient
ischemic attack or stroke and active/recent tobacco use (quit < 5 years).

- chronic orthopedic injury that precludes exercise testing