Abstract
AIMS: Inflammation is central in atrial fibrillation (AF) pathophysiology, but the temporal association between inflammatory activity and AF remains uncertain. This study investigated the day-to-day relationship between plasma C-reactive protein (CRP) levels and AF occurrence in continuously monitored individuals. METHODS AND RESULTS: Post hoc analysis of the LOOP study randomizing participants with stroke risk factors to implantable loop recorder (ILR) screening (n = 1501) or usual care. ILR raw data were linked to blood samples collected within 1 day. The outcome was AF episodes lasting ≥60 min. Associations were examined using generalized and linear mixed models and as a self-controlled case series (SCCS). ILR and CRP data were available for 1065 participants combining >1.2 million days of heart rhythm monitoring (including ∼40 000 days with AF) with >7000 CRP measurements. CRP was higher during days with AF (geometric mean 8.37 [7.11-9.86] mg/L) vs. non-AF days (4.02 [3.71-4.35] mg/L). Each doubling of CRP was associated with 36% higher odds of AF (adjusted odds ratio [aOR] 1.36 [1.26-1.47]). Compared with CRP ≤3 mg/L, the odds of AF increased for CRP >10-50 and >50 mg/L (aOR 3.50 [2.18-5.60] and 5.75 [3.48-9.50], respectively). In SCCS analyses, CRP >10 mg/L was associated with higher incidence of AF compared to lower levels (incidence rate ratio 2.41 [1.53-3.80]). CONCLUSION: This exploratory study found a temporal and dose-response relationship between CRP levels and AF occurrence, supporting inflammation as an acute trigger and underscoring the need to evaluate inflammatory markers as potential targets in AF management. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02036450.