Assessment of a multi-marker risk score for predicting cause-specific mortality at three years in older patients with heart failure and reduced ejection fraction

BACKGROUND: Due to increasing co-morbidity associated with aging, heart failure (HF) has become more prevalent and heterogeneous in older individuals, and non-cardiovascular (CV) mortality has increased. Previously, we defined a multi-marker modality that included cystatin C (CysC), troponin T (TnT), and age. Here, we validated this multi-marker risk score by evaluating its predictions of all-cause mortality and CV mortality in an independent population of older individuals with HF and reduced ejection fraction (HFrEF). METHODS: This prospective cohort study included 124 patients, median age 73 years, that had HFrEF. We determined all-cause mortality and CV mortality at a 3-year follow-up. We compared the risk score to the N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) for predicting all-cause mortality and CV mortality. RESULTS: High risk scores were associated with both all-cause mortality (HR 4.2, 95% CI 2.2-8.1, p < 0.001) and CV mortality (HR 3.6, 95% CI 1.7-8.0, p = 0.0015). Receiver operating characteristics showed similar efficacy for the risk score and NT-proBNP in predicting all-cause mortality (HR 0.74, 95% CI 0.65-0.81 vs. HR 0.74, 95% CI 0.65-0.81, p = 0.99) and CV mortality (HR 0.68, 95% CI 0.59-0.76 vs. HR 0.67, 95% CI 0.58-0.75, p = 0.95). When the risk score was added to the NT-proBNP, the continuous net reclassification improvement was 56% for predicting all-cause mortality (95% CI 18-95%, p = 0.004) and 45% for predicting CV mortality (95% CI 2-89%, p = 0.040). CONCLUSIONS: In HFrEF, a risk score that included age, TnT, and CysC showed efficacy similar to the NT-proBNP for predicting all-cause mortality and CV mortality in an older population.