Predicting Heart Failure With Preserved Ejection Fraction Among Healthy Middle Aged Adults

Background: Heart failure with preserved ejection fraction (HFpEF) is becoming a major health burden. The purpose of the current analysis was to identify predictors of incident HFpEF among healthy adults. Methods: We evaluated asymptomatic self-referred adults aged 40-79 years who were evaluated annually. All subjects were free of heart failure and diabetes at baseline. The study end-point was the development of HFpEF. All events were adjudicated by the authors. Results: Final study population included 20,618 subjects. The median age was 50 years (Interquartile range [IQR] 44-56) and 71% were men. During a median follow up time of 14 years (IQR 8-18), 144 (0.7%) subjects developed study HFpEF. Univariate Cox regression demonstrated that each 5 kg/m² increase in body mass index (BMI) was associated with a significant 50% increased risk for development of HFpEF (95%CI 1.26-1.77, p<.001) and that each 1mg/dL increase in serum uric acid was associated with a 18% increased risk (95% 1.04-1.34, p=.01) for HFpEF. Multivariable model adjusted for age, gender, fasting glucose, LDL-C, HDL-C, estimated GFR , fitness level, smoking status, treated hypertension, uric acid levels and ischemic heart disease as a time-dependent covariate showed that each 5 kg/m² increase in BMI was associated with 43% increased risk for HFpEF (p<.001) and that each 1 mg/dL increase in serum uric acid was associated with a 33% increased risk (p<.001). Interaction analysis demonstrated no difference between men and women in the relationship between HFpEF development and either BMI or uric acid levels (p for interaction > 0.05 for both) Conclusions: BMI and uric acid levels are both independently associated with increased risk for the development of HFpEF among healthy middle aged adults.