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Effect of Caloric Restriction or Aerobic Exercise Training on Peak Oxygen Consumption and Quality of Life in Obese Older Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial
Open accessAbstract
IMPORTANCE: More than 80% of patients with heart failure with preserved ejection fraction (HFPEF), the most common form of heart failure among older persons, are overweight or obese. Exercise intolerance is the primary symptom of chronic HFPEF and a major determinant of reduced quality of life (QOL). OBJECTIVE: To determine whether caloric restriction (diet) or aerobic exercise training (exercise) improves exercise capacity and QOL in obese older patients with HFPEF. DESIGN, SETTING, AND PARTICIPANTS: Randomized, attention-controlled, 2 × 2 factorial trial conducted from February 2009 through November 2014 in an urban academic medical center. Of 577 initially screened participants, 100 older obese participants (mean [SD]: age, 67 years [5]; body mass index, 39.3 [5.6]) with chronic, stable HFPEF were enrolled (366 excluded by inclusion and exclusion criteria, 31 for other reasons, and 80 declined participation). INTERVENTIONS: Twenty weeks of diet, exercise, or both; attention control consisted of telephone calls every 2 weeks. MAIN OUTCOMES AND MEASURES: Exercise capacity measured as peak oxygen consumption (V̇O2, mL/kg/min; co-primary outcome) and QOL measured by the Minnesota Living with Heart Failure (MLHF) Questionnaire (score range: 0-105, higher scores indicate worse heart failure-related QOL; co-primary outcome). RESULTS: Of the 100 enrolled participants, 26 participants were randomized to exercise; 24 to diet; 25 to exercise + diet; 25 to control. Of these, 92 participants completed the trial. Exercise attendance was 84% (SD, 14%) and diet adherence was 99% (SD, 1%). By main effects analysis, peak V̇O2 was increased significantly by both interventions: exercise, 1.2 mL/kg body mass/min (95% CI, 0.7 to 1.7), P < .001; diet, 1.3 mL/kg body mass/min (95% CI, 0.8 to 1.8), P < .001. The combination of exercise + diet was additive (complementary) for peak V̇O2 (joint effect, 2.5 mL/kg/min). There was no statistically significant change in MLHF total score with exercise and with diet (main effect: exercise, -1 unit [95% CI, -8 to 5], P = .70; diet, -6 units [95% CI, -12 to 1], P = .08). The change in peak V̇O2 was positively correlated with the change in percent lean body mass (r = 0.32; P = .003) and the change in thigh muscle:intermuscular fat ratio (r = 0.27; P = .02). There were no study-related serious adverse events. Body weight decreased by 7% (7 kg [SD, 1]) in the diet group, 3% (4 kg [SD, 1]) in the exercise group, 10% (11 kg [SD, 1] in the exercise + diet group, and 1% (1 kg [SD, 1]) in the control group. CONCLUSIONS AND RELEVANCE: Among obese older patients with clinically stable HFPEF, caloric restriction or aerobic exercise training increased peak V̇O2, and the effects may be additive. Neither intervention had a significant effect on quality of life as measured by the MLHF Questionnaire. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00959660.
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“The study concluded that secondary outcomes (improved metabolic measures) could be generalized to the senior population (age ≥ 65 years), with evidence that weight loss intervention for older adults is effective in improving health outcomes [9,10].”
From Clinical and Economic Impact of a Digital, Remotely-Delivered Intensive Behavioral Counseling Program on Medicare Beneficiaries at Risk for Diabetes and Cardiovascular Disease (2016) · cites this paper as [10]
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“A randomized trial of caloric restriction in patients with heart failure with preserved ejection fraction and obesity showed reductions in symptoms and improvements in exercise function and quality of life. 30”
From Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity (2023) · cites this paper as [30]
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“previous data suggesting that health status and exercise function improve with lifestyle modification-mediated weight loss in patients with heart failure with preserved ejection fraction and obesity, 30”
From Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity (2023) · cites this paper as [30]
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“Evidence in the past several years shows relatively rapid and sizeable improvements in major heart failure symptoms with drug-induced and lifestyle-induced weight loss among people with heart failure with preserved ejection fraction.110,111”
From Definition and diagnostic criteria of clinical obesity (2025) · cites this paper as [111]
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“In ten trials, a weight-reducing diet alone resulted in the desired weight loss, which consisted of fat mass as well as lean mass (290)(291)(292)(294)(295)(296)(297)(298)(299).”
From ESPEN practical guideline: Clinical nutrition and hydration in geriatrics (2022) · cites this paper as [298]
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“Several studies reported that (modest) weight loss caused by lifestyle interventions in obesity-related HFpEF patients improved exercise capacity but had no effect on cardiac structure or function.”
From The cardioprotective effects of semaglutide exceed those of dietary weight loss in mice with HFpEF (2023) · cites this paper as [54]
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Clinical Implications of Resting Metabolic Rate in Heart Failure With Preserved Ejection Fraction
Ibe, T., Naser, J. A., Harada, T., Tada, A., DOI, S., Reddy, Y. N. V., Melenovský, V., Jensen, M. D., & Borlaug, B. A. (2026) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2026.07.014
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Exercise Training in HFpEF: Functional Improvement Beyond Resting Diastolic Indices
Soh, M.-S. (2026) · International Journal of Heart Failure · doi:10.36628/ijhf.2026.0089
Sex-specific association between obesity and sympathetic nerve activity in HFpEF
Washio, T., Hissen, S. L., Akins, J. D., Takeda, R., D’Souza, A. W., MacNamara, J. P., Sarma, S., Trott, D. W., Lutz, K. C., Hearon, C. M., et al. (2026) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00214.2026
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Established and emerging roles of lysosomal dysfunction in cardiac aging
Santin, Y., Simon, I., Parini, A., Lezoualc’h, F., & Sommariva, E. (2026) · Nature Cardiovascular Research · doi:10.1038/s44161-026-00853-z
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Clinical trials and translational advances targeting cardiac aging
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“A randomized trial by Kitzman et al. showed that among obese older patients with HFpEF, caloric restriction or aerobic exercise increased peak VO2, with possible additive effects [36].”
Heart Failure in Focus: Acute Presentation, Risk Factors and Integration of Artificial Intelligence
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“In CM-HFpEF, aerobic exercise training and weight loss by caloric restriction or intermittent fasting was associated with improvements in exercise capacity [14,17].”
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From adiposity to multisystem morbidity: the case for weight loss as disease modification
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“Randomized bene fi ts of semaglutide in obesity-related HFpEF establish adiposity as a modi fi able clinical pathway in that selected phenotype, but they do not demonstrate that FGF23-Klotho modulation mediates the bene fi t (9 – 13, 23, 48 – 51).”
Transforming heart failure care through AI: Advances and future directions
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Skeletal Muscle Dysfunction in Heart Failure
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Self-citation
Metadata
- Authors
- Kitzman, D. W., Brubaker, P., Morgan, T., Haykowsky, M., Hundley, G., Kraus, W. E., Eggebeen, J., & Nicklas, B. J.
- Affiliations
- Wake Forest University Health Sciences (US)
- Wake Forest University (US)
- The University of Texas at Arlington (US)
- Cardiology Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina
- Duke University (US)
- Emory University (US)
- Corresponding author
- Kitzman, Dalane W.
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2016-01-05
- Volume
- 315
- Issue
- 1
- Pages
- 36
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC4787295
- OpenAlex
- W2231944090
- Cited by
- 921
- References
- 44
- Citations by year
- 2026: 94 · 2025: 117 · 2024: 121 · 2023: 89 · 2022: 92 · 2021: 92 · 2020: 90 · 2019: 69 · 2018: 60 · 2017: 66 · 2016: 29
- FWCI
- 153.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Texas at Arlington
- National Institutes of Health (UL1TR001420, R01AG18915)
- Wake Forest School of Medicine (P30AG021332)
- National Institute on Aging (R01AG020583, R01 AG18915, R01AG018915, R37AG018915, P30AG021332)
- National Heart, Lung, and Blood Institute (R01HL093713)
- National Center for Research Resources (M01RR007122)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- heart failure with preserved ejection fraction, obesity, older adults, caloric restriction, aerobic exercise training, peak oxygen uptake, exercise capacity, quality of life, diet and exercise combination, exercise intolerance, heart failure
- MeSH terms
- Aged, Body Composition, Combined Modality Therapy, Female, Heart Failure, Humans, Male, Middle Aged, Obesity, Oxygen Consumption, Patient Compliance, Quality of Life, Surveys and Questionnaires, Stroke Volume, Weight Loss, Exercise, Body Mass Index, Single-Blind Method, Exercise Tolerance, Caloric Restriction, Physical Conditioning, Human
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