Assessment of Inflammatory Biomarkers and Incident Atrial Fibrillation in Older Adults

Background Available evidence supports the importance of inflammation in atrial fibrillation (AF) pathogenesis, yet general anti‐inflammatory therapies have failed to show benefit for prevention of the arrhythmia. Better understanding of the specific inflammatory pathways involved is necessary to advance therapeutics. Methods and Results We evaluated 9 circulating markers of inflammation measured by immunoassays and incidence of AF in a population‐based older cohort. Biomarkers included measures of general inflammation and the NLR (nucleotide‐binding oligomerization domain‐like receptor) family pyrin domain containing 3 inflammasome, TNF‐α (tumor necrosis factor α), monocyte activation markers, and sIL‐2 (soluble interleukin‐2). Among 5726 participants (median age 72 years), 1836 developed AF over median follow‐up of 11.5 years. After adjustment for conventional risk factors, 5 biomarkers were positively associated with incident AF: IL‐6 (interleukin‐6), hazard ratio (HR), 1.14 (95% CI, 1.07–1.21); hs‐CRP (high‐sensitivity C‐reactive protein), HR, 1.05 (95% CI, 1.01–1.09); white blood cell count, HR, 1.18 (95% CI, 1.04–1.35); sTNFR1 (soluble TNF receptor 1), HR, 1.21 (95% CI, 1.05–1.39); and sIL‐2Rα (sIL‐2 receptor α), HR, 1.16 (95% CI, 1.05–1.29) (all per doubling of biomarker). sCD14, sCD163, IL‐18, and IL‐1 receptor antagonist showed no association with AF. Upon concurrent adjustment for all biomarkers, only IL‐6 remained significantly associated with the arrhythmia, HR, 1.17 (95% CI, 1.07–1.26). Conclusions Among older adults, IL‐6, hs‐CRP, white blood cell count, sTNFR1, and sIL‐2Rα were positively associated with incident AF, but only IL‐6 retained significance on concurrent adjustment. These findings newly document associations for sTNFR1 and sIL‐2Rα and lend support to a preeminent role for IL‐6 in development of this arrhythmia. The efficacy of IL‐6 blockade for AF prevention awaits completion of appropriate clinical trials.