C-reactive protein and atrial fibrillation: Insights from epidemiological and Mendelian randomization studies

Background and aims: This study aimed to investigate the role of C-reactive protein (CRP) in atrial fibrillation (AF) from epidemiological and genetic perspectives. Methods and results: Individual-level data from the Kailuan cohort recruited between 2006 and 2017 were included. Serum CRP levels were measured at baseline and at biennial follow-up visits, and incident AF was ascertained from biennial 12-lead ECG assessment and medical records. Cox proportional hazards models were used to assess the association between baseline CRP levels or cumulative exposure to CRP and incident AF. A meta-analysis including nine prospective cohort studies and our current study was also conducted. Mendelian randomization (MR) analysis was performed to evaluate the aetiological role of CRP in AF. In our observational study (n = 86,424), high baseline CRP levels (>3 mg/L), compared with low CRP (<1 mg/L), were not significantly associated with AF risk (HR: 1.18; 95% CI: 0.99–1.40). High cumulative exposure to CRP (HR: 1.49; 95%CI: 1.01–2.21) was significantly associated with an increased risk of AF. Our meta-analysis suggested a positive association between elevated CRP levels and incident AF (relative risk: 1.27; 95% CI: 1.14–1.42). However, no significant association between genetically determined CRP and AF risk was observed in the MR analysis. Conclusion: Evidence from observational studies suggested that elevated serum CRP levels were positively associated with incident AF, while the causal effects of CRP on AF were not supported by the MR analysis. Clinical trial registration: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR-TNRC-11001489.