Age-adjusted natriuretic peptide thresholds for a diagnosis of heart failure in the community: Diagnostic accuracy study

Background: European Society of Cardiology (ESC) chronic heart failure (HF) guidelines recommend a single N-terminal pro-B-type natriuretic peptide (NT-proBNP) threshold of ≥125 pg/mL for specialist referral in symptomatic patients; however, natriuretic peptide levels increase with age. Objectives: We aimed to assess NT-proBNP test performance at age-adjusted thresholds recently proposed by the ESC Heart Failure Association (HFA). Methods: Diagnostic accuracy study using linked primary and secondary care data (2004–2018) in England. NT-proBNP test performance at ESC HFA age-adjusted rule-in thresholds (≥125 pg/mL, ≥250 pg/mL and ≥500 pg/mL for <50 years, 50–74 years and ≥75 years, respectively) and a high-risk threshold (≥2000 pg/mL) was assessed overall, by sex and body mass index (BMI) with ESC's suggested threshold reductions for obesity. Results: Of 155 347 patients with NT-proBNP tests performed, 14 585 (9.4%) were diagnosed with HF. Current ESC single threshold of ≥125 pg/mL had sensitivity 94.6% [95% confidence interval (CI) 94.2–95.0] and specificity 50.0% (49.7–50.3). Age-adjusted thresholds had reduced sensitivity (83.5%, 88.5%, 84.4%) but increased specificity (77.6%, 67.8%, 63.5%) across the respective age groups. The high-risk threshold had sensitivity 38.9% (38.1–39.7) and specificity 96.1% (96.0–96.2). A high BMI was associated with lower sensitivity at each age-adjusted threshold, which improved with adjustment by obesity category. Test performance was similar in women and men. Conclusions: At ESC HFA age-adjusted thresholds, the number of referrals required for HF diagnostic assessment are substantially reduced, but with some (likely lower risk) cases initially being undetected. Lower thresholds for patients with obesity are needed to avoid missing HF cases, but there is no need for adjustment by sex.