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

Abstract

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). 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. 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). 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.