Background
This study investigated excess risk in patients with heart failure with reduced left ventricular ejection fraction (HFrEF) with or without elevated levels of NT-proBNP (N-terminal pro-brain natriuretic peptide).

Methods
Patients with HFrEF from the NorthStar cohort (n = 1120) were matched on age, sex, and presence of AF (atrial fibrillation/flutter) to five controls without HFrEF from The Danish National Patient Registries. Patients were compared with controls before and after stratification according to baseline NT-proBNP levels, with cutoffs defined as </≥ 600 pg/ml in patients with sinus rhythm and </≥ 900 pg/ml in patients with AF. The primary composite endpoint was a 7-year risk of cardiovascular death or HF admission.

Results
In the HFrEF cohort, 704 patients had high NT-proBNP (median age, 73; mean left ventricular ejection fraction (LVEF), 33%). 416 patients had low NT-proBNP (median age, 65; LVEF, 30%). Patients from both groups were in NYHA class I-III. The primary endpoint occurred in 531 patients (75.4%) with HFrEF and elevated NT-proBNP, and 748 controls (21.3%) (risk difference, 54.2%; 95% confidence interval (CI) 50.7–57.6%). In comparison, it occurred in 199 patients (47.9%) with HFrEF and without elevated NT-proBNP, and 185 controls (8,9%) (risk difference, 38.9%; 95% CI 34.0–43.9%). Risk differences for all secondary endpoints were significant, except for overall mortality in the low NT-proBNP group (risk difference, 3.8%; 95% CI, −0.4–8.0%).

Conclusion
This study identified a significant excess risk in patients with HFrEF across various endpoints, which persisted after stratification into high and low levels of NT-proBNP.