Risk Factors for Heart Failure with Preserved or Reduced Ejection Fraction Among Medicare Beneficiaries: Application of Competing Risks Analysis and Gradient Boosted Model

Moa P Lee,1,2 Robert J Glynn,1 Sebastian Schneeweiss,1 Kueiyu Joshua Lin,1,3 Elisabetta Patorno,1 Julie Barberio,1 Raisa Levin,1 Thomas Evers,4 Shirley V Wang,1 Rishi J Desai1 1Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital & Harvard Medical School, Boston, MA, USA; 2Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA; 3Department of Medicine, Massachusetts General Hospital & Harvard Medical School, Boston, MA, USA; 4Bayer AG, Wuppertal, GermanyCorrespondence: Rishi J DesaiDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 1620 Tremont Street, Boston, MA 02120, USATel +1 617-278-0932Fax +1 617-232-8602Email rdesai@bwh.harvard.eduBackground: The differential impact of various demographic characteristics and comorbid conditions on development of heart failure (HF) with preserved (pEF) and reduced ejection fraction (rEF) is not well studied among the elderly.Methods: Using Medicare claims data linked to electronic health records, we conducted an observational cohort study of individuals ≥ 65 years of age without HF. A Cox proportional hazards model accounting for competing risk of HFrEF and HFpEF incidence was constructed. A gradient-boosted model (GBM) assessed the relative influence (RI) of each predictor in the development of HFrEF and HFpEF.Results: Among 138,388 included individuals, 9701 developed HF (incidence rate = 20.9 per 1000 person-years). Males were more likely to develop HFrEF than HFpEF (HR = 2.07, 95% CI: 1.81– 2.37 vs. 1.11, 95% CI: 1.02– 1.20, P for heterogeneity < 0.01). Atrial fibrillation and pulmonary hypertension had stronger associations with the risk of HFpEF (HR = 2.02, 95% CI: 1.80– 2.26 and 1.66, 95% CI: 1.23– 2.22) while cardiomyopathy and myocardial infarction were more strongly associated with HFrEF (HR = 4.37, 95% CI: 3.21– 5.97 and 1.94, 95% CI: 1.23– 3.07). Age was the strongest predictor across all HF subtypes with RI from GBM > 35%. Atrial fibrillation was the most influential comorbidity for the development of HFpEF (RI = 8.4%) while cardiomyopathy was the most influential comorbidity for the development of HFrEF (RI = 20.7%).Conclusion: These findings of heterogeneous relationships between several important risk factors and heart failure types underline the potential differences in the etiology of HFpEF and HFrEF.Keywords: heart failure, epidemiology, risk factors, LVEF, HEpEF, HFrEF, competing risks, GBM