About one half of patients with heart failure (HF) have preserved ejection fraction (HFPEF) rather than reduced ejection fraction (HFREF). The differences in risk factors predisposing to the 2 subtypes of HF are poorly understood. We sought to identify clinical predictors of new-onset HF and to explore differences in HFPEF versus HFREF.

We studied new-onset HF cases between 1981 and 2008 in Framingham Heart Study participants, classified into HFPEF and HFREF (ejection fraction >45% versus ≤45%). We used Cox multivariable regression to examine predictors of 8-year risk of incident HF and competing-risks analysis to identify predictors that differed between HFPEF and HFREF. Among 6340 participants (60±12 years) with 97 808 person-years of follow-up, 512 developed incident HF. Of 457 participants with left ventricular ejection fraction evaluation at the time of HF diagnosis, 196 (43%) were classified as HFPEF and 261 (56%) as HFREF. Fourteen predictors of overall HF were identified. Older age, diabetes mellitus, and a history of valvular disease predicted both types of HF (P≤0.0025 for all). Higher body mass index, smoking, and atrial fibrillation predicted HFPEF only, whereas male sex, higher total cholesterol, higher heart rate, hypertension, cardiovascular disease, left ventricular hypertrophy, and left bundle-branch block predicted risk of HFREF.

Although multiple risk factors preceded overall HF, distinct clusters of risk factors determine risk for new-onset HFPEF versus HFREF. This knowledge may enable the design of clinical trials of targeted prevention and the introduction of therapeutic strategies for prevention of HF and its 2 major subtypes.