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Dr. Neilson is Assistant Professor, Department of Clinical Medicine, Ross University School of Medicine, Commonwealth of Dominica, West Indies. Dr. Selfridge is Professor and Chair, Department of Clinical Medicine, Ross University School of Medicine, Commonwealth of Dominica, West Indies.
Dr. Neilson and Dr. Selfridge report no financial relationships relevant to this field of study.
SYNOPSIS: In this prospective, randomized, controlled trial, researchers demonstrated improvements in exercise tolerance and diastolic cardiac function in middle-aged, healthy, sedentary men and women performing intensive aerobic exercise over a two-year period.
SOURCE: Howden EJ, Sarma S, Lawley JS, et al. Reversing the cardiac effects of sedentary aging in middle age — a randomized controlled trial: Implications for heart failure prevention. Circulation 2018;137:1549-1560.
Heart failure (HF) is a common, debilitating, and often fatal disease. Heart failure with preserved ejection fraction (HFpEF) makes up about half of heart failure diagnoses and is associated with increasing ventricular stiffness (loss of compliance) and consequent diastolic dysfunction. Further, there is no highly effective pharmacologic treatment for HFpEF.1 Two leading risk factors for the development of HFpEF are aging and sedentary lifestyle, and fitness in middle age is a strong predictor of future heart failure.2 Competitive master athletes (defined as 35 to 100 years of age) maintain ventricular compliance similar to younger individuals. Howden et al previously found that exercise initiated after age 65 years or in patients with already established HFpEF, although associated with increased quality of life and fitness measures, cannot significantly improve ventricular stiffness resulting from sedentary aging.3,4 Thus, they conducted this study to determine if there was a point in the aging process in which exercise could reverse ventricular stiffness with associated implications for reducing the risk of future heart failure.
Capitalizing on accumulated evidence that high-intensity interval training (HIIT) provides significant improvements in cardiovascular fitness over moderate-intensity exercise5,6 and that an inverse dose-response relationship exists between physical activity and risk of heart failure,7 Howden et al demonstrated that performing a highly structured endurance exercise regimen over two years improved cardiac stiffness and cardiorespiratory fitness in sedentary but otherwise healthy, middle-aged individuals (53 ± 5 years).
The study included 53 participants, about half female (n = 33), with a sedentary lifestyle (no prior history of consistent exercise > 30 minutes three times weekly) and no history or evidence of comorbidities including tobacco use, hypertension, obesity, untreated thyroid disease, chronic lung disease, obstructive sleep apnea, or coronary artery disease. Participants were randomized into either an aerobic and resistance endurance training program (ExT) or a flexibility and balance training/yoga control group. All participants had pretest baseline measures of fitness, exercise capacity, and cardiac function, including echocardiography and cardiac catheterization with manipulations of cardiac filling (preload) using lower-body negative pressure techniques and isotonic saline IV fluid loads, to determine myocardial stiffness measures.
Endurance exercise training included an individualized progressive approach based on baseline measures of fitness, beginning with two to three 30-minute sessions per week and progressing over 10 months to five to six hours per week, including two days of HIIT sessions (four four-minute, 95% maximum exercise intervals separated by three-minute active recovery intervals), a recovery day of light aerobic activity after each HIIT day, one long (at least 60 minutes) and one 30-minute sub-maximum effort session. For the final 14 months, HIIT was reduced to one session per week. The control group participated in yoga, balance, and strength training activities three times per week for two years without incorporation of any aerobic exercise and with a caveat to avoid hot yoga classes or prolonged endurance activities.
All participants in both groups met monthly with a physiologist, and exercise was monitored and compliance documented using exercise logs and a heart rate monitor. Overall mean adherence rate to the ExT intervention was a surprising 88% (± 11%). The adherence rate in the control group was not detailed in the report, although five individuals out of 32 withdrew during the study (citing work commitments, prior injury, personal reasons, and health reasons). Fifty-two participants completed the two-year study; one participant withdrew after the pretest studies were completed.
The ExT intervention at 10 months resulted in an 18% increase in mean VO2max (95% confidence interval [CI], 15-22%; P < 0.05), with a slight decrease noted in the control group of -1% (95% CI, 4.8-2.7%; P < 0.05). No additional changes were noted in the ensuing 14 months for either group. Left ventricular end-diastolic volume measured by echocardiography (correlating with ventricular compliance) showed a similar pattern of increasing by about 17% in the ExT group and no change in the control group, with maximum effect at 10 months. After two years, pretest procedures were repeated in all participants to assess left ventricular end-diastolic pressure volume and cardiac stiffness models. Participants in the ExT group demonstrated statistically significant (P < 0.05) decreases in mean resting heart rate from 63 bpm (95% CI, 60-67) pre-intervention to 58 bpm (95% CI, 55-61) post-intervention, with no change pre- and post- noted in the controls. Increases in mean stroke volume index for the ExT group also were significant from 42 mL/m2 (95% CI, 39-45) to 45 mL/m2 (95% CI, 42-49) compared to no change in the control group 41 mL/m2 (95% CI, 38-43) to 42 mL/m2 (95% CI, 39-44). Statistically significant changes (P < 0.05) also were noted in end-diastolic volume index and transmural pressures correlating with increased left ventricular compliance and indicating an overall improvement in diastolic function. No statistically significant changes in any of these parameters were noted in the control group, indicating that the control intervention exercise program did not confer the benefits of increased left ventricular compliance that were evident from the HIIT/aerobic/endurance program.
This study is the next step in establishing prescriptive lifestyle changes aimed at preventing or postponing the development of HF. From 2001 to 2014, 6.5 million Americans were diagnosed with HF. With an aging population over the next 10 years, this number is expected to increase to more than 8 million. Overall, one-year mortality in Medicare patients with HF is nearly 30%. Data showed HF was a principal diagnosis in approximately 900,000 hospital discharges, more than 2.3 million physician office visits, and more than 450,000 emergency department visits. In 2012, cost estimates due to HF were more than $30 billion and are expected to rise to nearly $70 billion by 2030.8
We know lifestyle choices, including exercise, are key determinants of cardiovascular health. The American Heart Association (AHA) 2018 update on Heart Disease and Stroke8 indicates the number of adults exercising enough is a mere 21.5%, leading to one of the seven AHA goals for heart health: at least 150 minutes of weekly exercise, including incorporating vigorous exercise activities. Participants in the ExT arm of this study adhered to these recommendations, averaging 150-180 minutes/week with incorporation of HIIT. However, they did so in a highly individualized, structured, progressive, and supervised program, elements that clearly could overcome common barriers to adherence to exercise recommendations for sedentary individuals. Such a program would prove prohibitive to many if it was associated with any cost not covered by insurance.
Additionally, there are important questions to be answered about the general applicability of this study as a preventive recommendation. Although these participants were sedentary, none had comorbidities or major risk factors associated with cardiac disease. The average body mass index of participants was 26 kg/m2, the lower range of “overweight” and not representative of a large subset of sedentary and at-risk Americans. None had used tobacco in the last 10 years. The study was limited to 33 women, one black, and two Hispanic participants. African Americans have the highest risk of HF. Of the nearly 1 million people newly diagnosed with HF each year, half are women.1 This study was insufficiently powered to allow for statistically significant interpretation of results for these important demographic groups. Further studies focused on these groups will be necessary to determine if this exercise intervention is a viable strategy for preventing the devastating effect of HF.
Currently, the exercise volume maintained in the ExT group in this study aligns with current AHA recommendations of about 150 minutes/per week. The study included one HIIT session per week, and although no adverse events due to the ExT program were reported, the participants were carefully selected and closely monitored, unlike most individuals who initiate exercise programs. The volume and intensity of this exercise program could not and should not be initiated by sedentary middle-aged adults without supervision and baseline assessment of cardiac health. Although this study adds much in terms of understanding the physiology of the aging heart and the capacity to reverse age-related changes, we already have substantial evidence that AHA exercise recommendations are associated with reduced overall morbidity and mortality. These recommendations should not change. Additional studies are needed in a wider range of more representative U.S. populations to determine if the authors’ exercise intervention can improve diastolic function due to aging in these groups.
Financial Disclosure: Integrative Medicine Alert’s Executive Editor David Kiefer, MD; Peer Reviewer Suhani Bora, MD; Relias Media Executive Editor Leslie Coplin; Editor Jonathan Springston; and Editorial Group Manager Terrey L. Hatcher report no financial relationships relevant to this field of study.