Effects of Atrial Fibrillation Screening According to N-Terminal Pro-B-Type Natriuretic Peptide: a Secondary Analysis of the Randomized LOOP Study

Lucas Yixi Xing, Søren Zöga Diederichsen, Søren Højberg, Derk W Krieger, Claus Graff, Ruth Frikke-Schmidt, Morten S Olesen, Axel Brandes, Lars Køber, Ketil Jørgen Haugan, Jesper Hastrup Svendsen

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Background: Research suggests NT-proBNP (N-terminal pro-B-type natriuretic peptide) to be a strong predictor of incident atrial fibrillation (AF) and stroke. However, its utility in AF screening remains unknown. The aim of this study was to investigate NT-proBNP as a potential marker for screening efficacy with respect to AF yield and stroke prevention. Methods: In the LOOP Study (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals), 6004 AF-naïve individuals at least 70 years old and with additional stroke risk factors were randomized 1:3 to either screening with an implantable loop recorder (ILR) and initiation of anticoagulation upon detection of AF episodes lasting ≥6 minutes or usual care (control). This post hoc analysis included study participants with available NT-proBNP measurement at baseline. Results: A total of 5819 participants (96.9% of the trial population) were included. The mean age was 74.7 years (SD, 4.1 years) and 47.5% were female. The median NT-proBNP level was 15 pmol/L (interquartile range, 9-28 pmol/L) corresponding to 125 pg/mL (interquartile range, 76-233 pg/mL). NT-proBNP above median was associated with an increased risk of AF diagnosis both in the ILR group (hazard ratio, 1.84 [95% CI, 1.51-2.25]) and the control group (hazard ratio, 2.79 [95% CI, 2.30-3.40]). Participants with NT-proBNP above the median were also at higher risk of clinical events compared with those having lower levels (hazard ratio, 1.21 [95% CI, 0.96-1.54] for stroke or systemic embolism [SE], 1.60 [95% CI, 1.32-1.95] for stroke/SE/cardiovascular death, and 1.91 [95% CI, 1.61-2.26] for all-cause death). Compared with usual care, ILR screening was associated with significant reductions in stroke/SE and stroke/SE/cardiovascular death among participants with NT-proBNP above median (hazard ratio, 0.60 [95% CI, 0.40-0.90] and 0.70 [95% CI, 0.53-0.94], respectively) but not among those with lower levels (P interaction=0.029 for stroke/SE and 0.045 for stroke/SE/cardiovascular death). No risk reduction in all-cause death was observed in either NT-proBNP subgroup for ILR versus control (P interaction=0.68). Analyzing NT-proBNP as a continuous variable yielded similar findings. Conclusions: In an older population with additional stroke risk factors, ILR screening for AF was associated with a significant reduction in stroke risk among individuals with higher NT-proBNP levels but not among those with lower levels. These findings should be considered hypothesis generating and warrant further study before clinical implementation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450.

Original languageEnglish
Issue number24
Pages (from-to)1788-1797
Publication statusPublished - 13. Jun 2023


  • atrial fibrillation
  • mass screening
  • natriuretic peptide, brain
  • stroke
  • Embolism/complications
  • Peptide Fragments
  • Humans
  • Male
  • Natriuretic Peptide, Brain
  • Stroke/prevention & control
  • Biomarkers
  • Female
  • Aged
  • Atrial Fibrillation/diagnosis


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