Usefulness of N-terminal pro-B-type natriuretic Peptide levels for stroke risk prediction in anticoagulated patients with atrial fibrillation

Abstract

Background and purpose: Oral anticoagulation is highly effective in reducing stroke and mortality in atrial fibrillation (AF). Several risk stratification schemes have been developed using clinical characteristics. Elevated levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) are important markers of increased mortality and morbidity in congestive heart failure and general community population. The aim of our study was to assess the predictive value of NT-proBNP levels in an unselected real-world cohort of anticoagulated patients with AF.

Methods: We studied 1172 patients (49% male; median age, 76 years) with permanent AF who were well stabilized on oral anticoagulation (international normalized ratio, 2.0-3.0). Plasma NT-proBNP levels were quantified at baseline. We recorded thrombotic and vascular events, mortality, and major bleeding. The best cutoff points were assessed by receiver-operating characteristic curves.

Results: Median levels (interquartile range) of NT-proBNP were 610 (318-1037) pg/mL. Median follow-up was 1007 (806-1279) days. On multivariate analysis, high NT-proBNP was significantly associated with the risk of stroke (hazards ratio, 2.71; P=0.001) and composite vascular events (acute coronary syndrome or acute heart failure; hazards ratio, 1.85; P=0.016), as well as a significant association with mortality (adjusted hazards ratio, 1.66; P=0.006). No association with bleeding was found (P=0.637). The integrated discrimination improvement (IDI) analysis demonstrated that NT-proBNP improved the Congestive heart failure, Hypertension, Age≥75 (doubled), Diabetes mellitus, Stroke (doubled)-Vascular disease and Sex category (female); CHA2DS2-VASc score for predicting embolic events (relative IDI, 2.8%; P=0.001) and all-cause death (relative IDI, 1.8%; P=0.001).

Conclusions: In real-world cohort of anticoagulated patients with AF, NT-proBNP provided complementary prognostic information to an established clinical risk score (CHA2DS2-VASc) for the prediction of stroke/systemic embolism. NT-proBNP was also predictive of all-cause mortality, suggesting that this biomarker may potentially be used to refine clinical risk stratification in anticoagulated patients with AF.

Keywords: B-type natriuretic peptide; anticoagulants; atrial fibrillation; stroke.