Reversing the Cardiac Effects of Sedentary Aging in Middle Age—A Randomized Controlled Trial

Erin J. Howden, Satyam Sarma, Justin S. Lawley, Mildred Opondo, William Cornwell, Douglas Stoller, Marcus A. Urey, Beverley Adams-Huet, Benjamin D. Levine

Circulation4/10/2018·DOI·Read paper

Abstract

Background: Poor fitness in middle age is a risk factor for heart failure, particularly heart failure with a preserved ejection fraction. The development of heart failure with a preserved ejection fraction is likely mediated through increased left ventricular (LV) stiffness, a consequence of sedentary aging. In a prospective, parallel group, randomized controlled trial, we examined the effect of 2 years of supervised high-intensity exercise training on LV stiffness. Methods: Sixty-one (48% male) healthy, sedentary, middle-aged participants (53±5 years) were randomly assigned to either 2 years of exercise training (n=34) or attention control (control; n=27). Right heart catheterization and 3-dimensional echocardiography were performed with preload manipulations to define LV end-diastolic pressure-volume relationships and Frank-Starling curves. LV stiffness was calculated by curve fit of the diastolic pressure-volume curve. Maximal oxygen uptake (Vo 2 max) was measured to quantify changes in fitness. Results: Fifty-three participants completed the study. Adherence to prescribed exercise sessions was 88±11%. Vo 2 max increased by 18% (exercise training: pre 29.0±4.8 to post 34.4±6.4; control: pre 29.5±5.3 to post 28.7±5.4, group×time P <0.001) and LV stiffness was reduced (right/downward shift in the end-diastolic pressure-volume relationships; preexercise training stiffness constant 0.072±0.037 to postexercise training 0.051±0.0268, P =0.0018), whereas there was no change in controls (group×time P <0.001; pre stiffness constant 0.0635±0.026 to post 0.062±0.031, P =0.83). Exercise increased LV end-diastolic volume (group×time P <0.001), whereas pulmonary capillary wedge pressure was unchanged, providing greater stroke volume for any given filling pressure (loading×group×time P =0.007). Conclusions: In previously sedentary healthy middle-aged adults, 2 years of exercise training improved maximal oxygen uptake and decreased cardiac stiffness. Regular exercise training may provide protection against the future risk of heart failure with a preserved ejection fraction by preventing the increase in cardiac stiffness attributable to sedentary aging. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02039154.

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