Author + information
- Received April 26, 2019
- Revision received August 19, 2019
- Accepted September 13, 2019
- Published online November 25, 2019.
- Jessica A. Regan, MDa,∗ (, )
- Dalane W. Kitzman, MDb,
- Eric S. Leifer, PhDc,
- William E. Kraus, MDa,f,
- Jerome L. Fleg, MDc,
- Daniel E. Forman, MDd,
- David J. Whellan, MDe,
- Daniel Wojdyla, MSf,
- Kishan Parikh, MDa,f,
- Christopher M. O’Connor, MDg and
- Robert J. Mentz, MDa,f
- aDepartment of Medicine, Duke University School of Medicine, Durham, North Carolina
- bDepartment of Internal Medicine, Section on Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina
- cNational Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
- dDepartment of Medicine, University of Pittsburgh and Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
- eDepartment of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania
- fDuke Clinical Research Institute, Durham, North Carolina
- gInova Heart and Vascular Institute, Falls Church, Virginia
- ↵∗Address for correspondence:
Dr. Jessica A. Regan, Duke University Hospital, 2301 Erwin Road, Box 3951, Durham, North Carolina 27701.
Objectives This study sought to determine whether age modifies the impact of key comorbidities on clinical outcomes for patients with heart failure with reduced ejection fraction (HFrEF).
Background Comorbidities impact outcomes in HFrEF. However, the effect of age on the impact of comorbidities on prognosis is not clearly understood.
Methods Cox proportional hazards models were used assessed interactions between age and comorbidities on the primary composite endpoint (all-cause mortality or hospitalization) and secondary endpoints in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) multicenter trial of 2,331 patients with HFrEF.
Results Age did not significantly modify the effect of any comorbidity on the primary endpoint. However, age significantly modified the effect of body mass index (BMI) on all-cause mortality (interaction p = 0.02). Among patients ≥70 years of age, there was a U-shaped relationship between BMI and 1-year mortality, where BMI of 20 kg/m2 corresponded to 17.6%; a BMI of 30 kg/m2 corresponded to 7.0%; and a BMI of 40 kg/m2 corresponded to 11%. For patients <60 years of age, mortality increased nonsignificantly from 3.2% to 3.7% with increasing BMI. Age also modified the effect of depressive symptoms on all-cause mortality (interaction p = 0.03). Among patients ≥70 years of age, a 1-year mortality rate significantly increased from 7.8% for a Beck Depression Inventory (BDI) score of 5% to 15.6% for BDI of 20. For patients <60 years of age, mortality was nonsignificantly related to BDI. Cumulative comorbidity scores were stronger predictors than age for mortality/hospitalization.
Conclusions In chronic HFrEF, age markedly altered the impact of BMI and depressive symptoms on all-cause mortality, with much higher risk in older patients, but was not as strong a predictor of mortality/hospitalizations as cumulative comorbidity score. (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training [HF-ACTION]; NCT00047437)
The HF-ACTION trial was funded by the National Heart, Lung, and Blood Institute (NHLBI). Additional support was provided by an National Institutes of Health (NIH) grant U01HL064265 from NHLBI. Dr. Kitzman has received research support from NIH grants R01AG18917, R01AG045551, P30-AG21331, and U24-AG059624; and from the Kermit G. Phillips II Endowed Chair; holds stock in Gilead; has received personal fees from Corvia Medical, Relypsa, AbbVie, Akros, St. Luke’s Hospital, Merck, Boehringer Ingelheim, DCRI, and CinRx; and has received grants and personal fees from Novartis, Bayer, and AstraZeneca. Dr. Forman is supported by National Institute on Aging (NIA) grants R01 AG060499-01, R01AG058883, R01AG051376, R01AG053952, P30AG024827, and NIH grant UO1AR071130. Dr. Mentz has received research support from NIH grants U01HL125511-01A1, U10HL110312, and R01AG045551-01A1; support from Akros, Amgen, AstraZeneca, Bayer, GlaxoSmithKline, Gilead, Luitpold/American Regent, Medtronic, Merck, Novartis, Otsuka, and ResMed; has received honoraria from Abbott, Amgen, AstraZeneca, Bayer, Janssen, Luitpold, Pharmaceuticals, Medtronic, Merck, Novartis, and ResMed; and has served on advisory boards for Amgen, AstraZeneca, Luitpold, Merck, Novartis, and Boehringer Ingelheim. The contents of this manuscript are solely the responsibility of the authors and do not necessarily reflect the views of the National Heart, Lung, and Blood Institute, the National Institutes of Health, or the United States Department of Health and Human Services. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Barry Greenberg, MD, served as Guest Editor for this paper.
- Received April 26, 2019.
- Revision received August 19, 2019.
- Accepted September 13, 2019.
- 2019 American College of Cardiology Foundation
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