Reverse Epidemiology in Systolic and Nonsystolic Heart Failure

BACKGROUND: Observational studies indicate that classical cardiovascular risk factors as body mass index, total cholesterol, and systolic blood pressure are associated with improved rather than impaired survival in heart failure ("reverse epidemiology"). We estimated the prognostic role of these risk factors in unselected patients with heart failure. METHODS AND RESULTS: Consecutive subjects with heart failure of any cause and severity were enrolled (n=867), and survivors were followed for a median period of 594 days (25th to 75th percentile, 435 to 840). Mean age was 70+/-13 years, 41% were female, New York Heart Association class distribution I through IV was 15%/29%/41%/15%, and 49% had preserved left ventricular ejection function. At follow-up, 34% of the patients had died. Low levels of any risk factor (ie, body mass index, total cholesterol, and systolic blood pressure in the low tertile) indicated the highest mortality risk. After adjustment for age, sex, New York Heart Association class, and ejection fraction, >/=2 risk factors in the high tertile indicated a relative reduction in mortality risk of 51% (hazard ratio, 0.49; 95% CI, 0.35 to 0.68; P=0.001) compared with subjects with 3 risk factors in the low tertile. Further adjustment for cause of heart failure, relevant comorbidities, medication, and biomarkers attenuated this association only modestly (hazard ratio, 0.63; 95% CI, 0.45 to 0.89; P=0.009). CONCLUSIONS: In patients with heart failure, mortality risk counterintuitively increased on a cumulative scale with lower levels of body mass index, total cholesterol, and systolic blood pressure, irrespective of the type and severity of heart failure. Future studies need to identify whether risk factor control as presently recommended should be advocated in all patients with heart failure.