Author + information
- Received March 2, 2018
- Revision received May 15, 2018
- Accepted May 16, 2018
- Published online July 30, 2018.
- Nazir Savji, MDa,∗,
- Wouter C. Meijers, MDb,∗,
- Traci M. Bartz, MSc,∗,
- Vijeta Bhambhani, MS, MPHa,d,∗,
- Mary Cushman, MDe,
- Matthew Nayor, MD, MPHa,
- Jorge R. Kizer, MD, MScf,
- Amy Sarma, MDa,
- Michael J. Blaha, MD, MPHg,
- Ron T. Gansevoort, MD, PhDb,
- Julius M. Gardin, MD, MBAh,
- Hans L. Hillege, MD, PhDb,
- Fei Ji, PhDi,
- Willem J. Kop, PhDj,
- Emily S. Lau, MDa,
- Douglas S. Lee, MD, PhDk,
- Ruslan Sadreyev, PhDi,
- Wiek H. van Gilst, PhDb,
- Thomas J. Wang, MDl,
- Markella V. Zanni, MDm,
- Ramachandran S. Vasan, MDn,o,p,
- Norrina B. Allen, PhDq,
- Bruce M. Psaty, MD, PhDr,s,
- Pim van der Harst, MD, PhDb,
- Daniel Levy, MDn,t,
- Martin Larson, ScDn,u,
- Sanjiv J. Shah, MDv,†,
- Rudolf A. de Boer, MD, PhDb,†,
- John S. Gottdiener, MDw,† and
- Jennifer E. Ho, MDa,d,†∗ ()
- aDivision of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
- bDepartment of Internal Medicine, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands
- cDepartment of Biostatistics, University of Washington, Seattle, Washington
- dCardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts
- eUniversity of Vermont Larner College of Medicine, Burlington, Vermont
- fDepartment of Medicine and Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
- gCiccarone Center for the Prevention of Heart Disease, Johns Hopkins University, Baltimore, Maryland
- hDivision of Cardiology, Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey
- iDepartment of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts
- jCenter of Research on Psychology in Somatic Diseases, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands
- kInstitute for Clinical Evaluative Sciences, Toronto, Canada
- lDivision of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
- mDivision of Neuroendocrinology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
- nFramingham Heart Study, Framingham, Massachusetts
- oCardiovascular Medicine Section, Department of Medicine and Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts
- pDepartment of Epidemiology, Boston University School of Public Health, Boston, Massachusetts
- qDepartment of Epidemiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
- rCardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, Washington
- sKaiser Permanente Washington Health Research Institute, Seattle, Washington
- tCenter for Population Studies of the National Heart, Lung, and Blood Institute, Bethesda, Maryland
- uDepartment of Mathematics and Statistics, Boston University, Boston, Massachusetts
- vDivision of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
- wUniversity of Maryland, Baltimore, Maryland
- ↵∗Address for correspondence:
Dr. Jennifer E. Ho, Cardiology Division, Department of Medicine, Massachusetts General Hospital, 185 Cambridge Street, CPZN #3-192, Boston, Massachusetts 02114.
Objectives This study evaluated the associations of obesity and cardiometabolic traits with incident heart failure with preserved versus reduced ejection fraction (HFpEF vs. HFrEF). Given known sex differences in HF subtype, we examined men and women separately.
Background Recent studies suggest that obesity confers greater risk of HFpEF versus HFrEF. Contributions of associated metabolic traits to HFpEF are less clear.
Methods We studied 22,681 participants from 4 community-based cohorts followed for incident HFpEF versus HFrEF (ejection fraction ≥50% vs. <50%). We evaluated the association of body mass index (BMI) and cardiometabolic traits with incident HF subtype using Cox models.
Results The mean age was 60 ± 13 years, and 53% were women. Over a median follow-up of 12 years, 628 developed incident HFpEF and 835 HFrEF. Greater BMI portended higher risk of HFpEF compared with HFrEF (hazard ratio [HR]: 1.34 per 1-SD increase in BMI; 95% confidence interval [CI]: 1.24 to 1.45 vs. HR: 1.18; 95% CI: 1.10 to 1.27). Similarly, insulin resistance (homeostatic model assessment of insulin resistance) was associated with HFpEF (HR: 1.20 per 1-SD; 95% CI: 1.05 to 1.37), but not HFrEF (HR: 0.99; 95% CI: 0.88 to 1.11; p < 0.05 for difference HFpEF vs. HFrEF). We found that the differential association of BMI with HFpEF versus HFrEF was more pronounced among women (p for difference HFpEF vs. HFrEF = 0.01) when compared with men (p = 0.34).
Conclusions Obesity and related cardiometabolic traits including insulin resistance are more strongly associated with risk of future HFpEF versus HFrEF. The differential risk of HFpEF with obesity seems particularly pronounced among women and may underlie sex differences in HF subtypes.
↵∗ Drs. Savji, Meijers, Bartz, and Bhambhani contributed equally to this work and are joint first authors.
↵† Drs. Shah, de Boer, Gottdiener, and Ho contributed equally to this work and are joint senior authors.
This work was partially supported by the National Heart, Lung, and Blood Institute (NHLBI), including the Framingham Heart Study (contract N01-HC25195 and HHSN268201500001I), the Cardiovascular Health Study (CHS; HHSN268201800001C, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086), and grants U01HL080295 and U01HL130114 from the NHLBI, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by R01AG023629 from the National Institute on Aging. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. MESA and the MESA SHARe project are conducted and supported by the NHLBI in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881, and DK063491. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. The PREVEND (Prevention of Renal and Vascular End-Stage Disease) study has been made possible by grants from the Dutch Kidney Foundation. Dr. de Boer is supported by the Netherlands Heart Foundation (CVON-DOSIS, grant 2014-40) and the Innovational Research Incentives Scheme program of the Netherlands Organization for Scientific Research (NWO VIDI, grant 917.13.350). Dr. Nayor received support from K23-HL138260. Dr. Ho is supported by K23-HL116780, R01-HL134893, R01-HL140224, and a Hassenfeld Research Scholar Award (Massachusetts General Hospital). Dr. Lee is supported by a mid-career award from the Heart and Stroke Foundation of Canada; and is the Ted Rogers Chair in Heart Function Outcomes. Dr. Vasan is supported in part by the Evans Medical Foundation and the Jay and Louis Coffman Endowment, Boston University School of Medicine. Dr. Kizer has stock ownership in Amgen, Gilead Sciences, Johnson & Johnson, and Pfizer. Dr. Psaty serves on a DSMB for a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the NHLBI, the National Institutes of Health, or the U.S. Department of Health and Human Services.
- Received March 2, 2018.
- Revision received May 15, 2018.
- Accepted May 16, 2018.
- 2018 American College of Cardiology Foundation