TY - JOUR
T1 - Reversing the Cardiac Effects of Sedentary Aging in Middle Age-A Randomized Controlled Trial
T2 - Implications for Heart Failure Prevention
AU - Howden, Erin J.
AU - Sarma, Satyam
AU - Lawley, Justin S.
AU - Opondo, Mildred
AU - Cornwell, William
AU - Stoller, Douglas
AU - Urey, Marcus A.
AU - Adams-Huet, Beverley
AU - Levine, Benjamin D.
N1 - Funding Information:
This study was supported by National Institutes of Health grant AG017479. The Data Safety and Monitoring Board was chaired by Dr Kitzman from Wake Forest University, and included Dr Kraus (Duke University), Dr Friedman (previously from National Institutes of Health), and Dr Zieman (from the National Institutes of Health).
Funding Information:
This study was supported by National Institutes of Health grant AG017479. The Data Safety and Monitoring Board was chaired by Dr Kitzman from Wake Forest University, and included Dr Kraus (Duke University), Dr Friedman (previously from National Institutes of Health), and Dr Zieman (from the National Institutes of Health). Drs Levine and Sarma were also supported in part by the American Heart Association Strategically Focused Research Network (14SFRN20600009-03). Dr Cornwell is supported by an National Institutes of Health/National Heart, Lung, and Blood Institute mentored patient-oriented research career development award (1K23HL132048-01). Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award UL1TR001105 to UT Southwestern Medical Center.
Publisher Copyright:
© 2018 American Heart Association, Inc.
PY - 2018/4/10
Y1 - 2018/4/10
N2 - 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.
AB - 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.
KW - catheterization
KW - diastole
KW - exercise
KW - humans
KW - monitoring, physiological
KW - prevention & control
KW - ventricular function
KW - ventricular remodeling
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U2 - 10.1161/CIRCULATIONAHA.117.030617
DO - 10.1161/CIRCULATIONAHA.117.030617
M3 - Article
C2 - 29311053
AN - SCOPUS:85046862014
SN - 0009-7322
VL - 137
SP - 1549
EP - 1560
JO - Circulation
JF - Circulation
IS - 15
ER -