The association of coagulation and hemostasis with atrial fibrillation: a systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): - Erasmus MC MRace grant- The Netherlands Organization for the Health Research and Development (ZonMw) Background Atrial fibrillation (AF) is a highly prevalent cardiac tachyarrhythmia. Recent literature suggests that AF induces a prothrombotic state, ultimately leading to thrombotic events. It is also hypothesized that coagulation underlies AF development through coagulation. Purpose We aimed to assess the associations between selected coagulation factors with AF in both longitudinal and cross-sectional studies, to give further insight on the interaction of coagulation and AF. Methods Through a systematic search of large databases, including Embase, Medline ALL, and Web of Science Core Collection, all longitudinal cohort studies and cross-sectional studies published before 25th of May, 2021 were reviewed. For longitudinal studies, pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated through log-transformed HRs and 95% CIs using the generic inverse variance method. For cross-sectional studies the pooled standardized mean differences (SMD) were calculated through inverse variance weighting. Results 16 longitudinal studies and 44 cross-sectional studies were included. In the longitudinal studies, using complex multivariable models, we found significant associations between fibrinogen (HR1.06, 95% CI 1.01-1.12), Plasminogen activator inhibitor 1 (PAI-1) (HR 1.06, 95% CI 1.00-1.12), and D-dimer (HR 1.10, 95% CI 1.02-1.19), with AF incidence. In cross-sectional studies, we found significant differences between AF patients and controls for fibrinogen (SMD 0.47), D-dimer (SMD 1.74), P-selectin (SMD 0.31), von Willebrand factor (SMD 0.96), PAI-1 (SMD 1.73), ß-thromboglobulin (SMD 0.82), and Platelet Factor 4 (SMD 0.42). Conclusions Atrial fibrillation is associated with higher levels of coagulation factors. These associations are most pronounced in cross-sectional analyses, but limited studies are available investigating a prothrombotic state underlying AF initiation. These results further support the hypothesis of "AF begets AF".