Incidence and epidemiology of new onset heart failure with preserved vs. reduced ejection fraction in a community-based cohort: 11-year follow-up of PREVEND

Abstract

Differences in clinical characteristics and outcome of patients with established heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) are well established. Data on epidemiology and prediction of new onset HFpEF, compared with HFrEF, have not been described. In 8592 subjects of the Prevention of Renal and Vascular End-stage Disease (PREVEND), a community-based, middle-aged cohort study, we performed cause-specific hazard analyses to study the predictive value of risk factors and established cardiovascular biomarkers on new onset HFrEF vs. HFpEF (left ventricular ejection fraction ≤ 40 and ≥ 50%, respectively). A P-value for competing risk (Pcr) <0.10 between HFrEF and HFpEF was considered statistically significant. All potential new onset heart failure cases were reviewed and adjudicated to HFrEF or HFpEF by an independent committee. During a median follow-up of 11.5 years, 374 (4.4%) subjects were diagnosed with heart failure, of which 125 (34%) with HFpEF and 241 (66%) with HFrEF. The average time to diagnosis of new onset HFrEF was 6.6 ± 3.6 years; it was 8.3 ± 3.3 years for HFpEF (P < 0.001). Male gender was associated with new onset HFrEF, whereas female gender with new onset HFpEF (Pcr < 0.001). Higher age and increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) increased the risk for both HFpEF and HFrEF, although for age this was stronger for HFpEF (Pcr = 0.018), whereas NT-proBNP was stronger associated with risk for HFrEF (Pcr = 0.083). Current smokers, increased highly sensitive troponin T, and previous myocardial infarction conferred a significantly increased risk for HFrEF, but not for HFpEF (Pcr = 0.093, 0.091, and 0.061, respectively). Conversely, a history of atrial fibrillation, increased urinary albumin excretion (UAE), and cystatin C were significantly more associated with the risk for HFpEF, but not for HFrEF (Pcr < 0.001, 0.061, and 0.033, respectively). The presence of obesity at baseline was associated with comparable prognostic information for both HFpEF and HFrEF. Higher age, UAE, cystatin C, and history of atrial fibrillation are strong risk factors for new onset HFpEF. This underscores differential pathophysiological mechanisms for both subtypes of heart failure.