Nazir Savji1, Wouter C Meijers2, Traci M Bartz3, Vijeta Bhambhani4, Mary Cushman5, Matthew Nayor1, Jorge R Kizer6, Amy Sarma1, Michael J Blaha7, Ron T Gansevoort2, Julius M Gardin8, Hans L Hillege2, Fei Ji9, Willem J Kop10, Emily S Lau1, Douglas S Lee11, Ruslan Sadreyev9, Wiek H van Gilst2, Thomas J Wang12, Markella V Zanni13, Ramachandran S Vasan14, Norrina B Allen15, Bruce M Psaty16, Pim van der Harst2, Daniel Levy17, Martin Larson18, Sanjiv J Shah19, Rudolf A de Boer2, John S Gottdiener20, Jennifer E Ho21. 1. Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. 2. Department of Internal Medicine, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands. 3. Department of Biostatistics, University of Washington, Seattle, Washington. 4. Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts. 5. University of Vermont Larner College of Medicine, Burlington, Vermont. 6. Department of Medicine and Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York. 7. Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins University, Baltimore, Maryland. 8. Division of Cardiology, Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey. 9. Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts. 10. Center of Research on Psychology in Somatic Diseases, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands. 11. Institute for Clinical Evaluative Sciences, Toronto, Canada. 12. Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. 13. Division of Neuroendocrinology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. 14. Framingham Heart Study, Framingham, Massachusetts; Cardiovascular Medicine Section, Department of Medicine and Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts; Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts. 15. Department of Epidemiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. 16. Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, Washington; Kaiser Permanente Washington Health Research Institute, Seattle, Washington. 17. Framingham Heart Study, Framingham, Massachusetts; Center for Population Studies of the National Heart, Lung, and Blood Institute, Bethesda, Maryland. 18. Framingham Heart Study, Framingham, Massachusetts; Department of Mathematics and Statistics, Boston University, Boston, Massachusetts. 19. Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 20. University of Maryland, Baltimore, Maryland. 21. Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: jho1@mgh.harvard.edu.
Abstract
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.
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.
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