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Abstract   Aims  Heart failure (HF) and atrial fibrillation (AF) frequently coexist and are both associated with increased levels of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). It is known that AF impairs the diagnostic accuracy of NT‐proBNP for HF. The aim of the present study was to compare the diagnostic and predictive accuracy of NT‐proBNP for HF and AF in stable outpatients with cardiovascular risk factors.    Methods and results  Data were obtained from the DIAST‐CHF trial, a prospective cohort study that recruited individuals with cardiovascular risk factors and followed them up for 12 years. Data were validated in three independent population‐based cohorts using the same inclusion/exclusion criteria: LIFE‐Adult ( n  = 2869), SHIP ( n  = 2013), and SHIP‐TREND ( n  = 2408). Serum levels of NT‐proBNP were taken once at baseline. The DIAST‐CHF study enrolled 1727 study participants (47.7% female, mean age 66.9 ± 8.1 years). At baseline, patients without AF or HF ( n  = 1375) had a median NT‐proBNP of 94 pg/mL (interquartile range 51;181). In patients with AF ( n  = 93), NT‐proBNP amounted to 667 (215;1130) pg/mL. It was significantly higher than in the first group ( P  &lt; 0.001) and compared with those with only HF [ n  = 201; 158 (66;363) pg/mL;  P  &lt; 0.001]. The highest levels of NT‐proBNP [868 (213;1397) pg/mL] were measured in patients with concomitant HF and AF ( n  = 58;  P  &lt; 0.001 vs. control and vs. HF,  P  = 1.0 vs. AF). In patients with AF, NT‐proBNP levels did not differ between those with HF and preserved ejection fraction (EF) &gt; 50% [ n  = 38; 603 (175;1070) pg/mL] and those without HF ( P  = 1.0). Receiver‐operating characteristic curves of NT‐proBNP showed a similar area under the curve (AUC) for the detection of AF at baseline (0.84, 95% CI [0.79–0.88]) and for HF with EF &lt; 50% (0.78 [0.72–0.85];  P  = 0.18). The AUC for HF with EF &gt; 50% was significantly lower (0.61 [0.56–0.65]) than for AF ( P  = 0.001). During follow‐up, AF was newly diagnosed in 157 (9.1%) and HF in 141 (9.6%) study participants. NT‐proBNP was a better predictor of incident AF during the first 2 years (AUC: 0.79 [0.75–0.83]) than of newly diagnosed HF (0.59 [0.55–0.63];  P  &lt; 0.001). Data were validated in three independent population‐based cohorts (LIFE‐Adult,  n  = 2869; SHIP,  n  = 2013; and SHIP‐TREND,  n  = 2408).    Conclusions  In stable outpatients, NT‐proBNP is a better marker for prevalent and incident AF than for HF. In AF patients, the diagnostic value of NT‐proBNP for HF with EF &gt; 50% is very limited.

NT‐proBNP as a marker for atrial fibrillation and heart failure in four observational outpatient trials