Abstract and Introduction
Abstract
Aims: While atrial fibrillation (AF) is suggested to induce a prothrombotic state, increasing thrombotic risk, it is also hypothesized that coagulation underlies AF onset. However, conclusive evidence is lacking. With this systematic review and meta-analysis, we aimed to summarize and combine the evidence on the associations between coagulation factors with AF in both longitudinal and cross-sectional studies.
Methods and Results: We systematically searched for longitudinal cohort and cross-sectional studies investigating AF and thrombosis. For longitudinal studies, pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. For cross-sectional studies, we determined pooled standardized mean differences (SMDs) and 95% CIs. A total of 17 longitudinal and 44 cross-sectional studies were included. In longitudinal studies, we found significant associations between fibrinogen (HR 1.05, 95% CI 1.00–1.10), 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) and AF incidence. In cross-sectional studies, we found significantly increased levels of fibrinogen (SMD 0.47, 95% CI 0.20–0,74), von Willebrand factor (SMD 0.96, 95% CI 0.28–1.66), P-selectin (SMD 0.31, 95% CI 0.08–0.54), ß-thromboglobulin (SMD 0.82, 95% CI 0.61–1.04), Platelet Factor 4 (SMD 0.42, 95% CI 0.12–0.7), PAI-1 (1.73, 95% CI 0.26–3.19), and D-dimer (SMD 1.74, 95% CI 0.36–3.11) in AF patients, as opposed to controls.
Conclusion: These findings suggest that higher levels of coagulation factors are associated with prevalent and incident AF. These associations are most pronounced with prevalent AF in cross-sectional studies. Limited evidence from longitudinal studies suggests a prothrombotic state underlying AF development.
Introduction
With a lifetime risk of over 22% in men and women at the age of 55, atrial fibrillation (AF) is a highly prevalent disease, expected to increase rapidly considering the ageing of the population.[1,2] This is especially relevant since AF patients are at an increased risk to develop stroke and heart failure, and have an increased risk of hospitalization and death.[3–6] Several risk factors for AF onset are already identified, including older age, male sex, and obesity.[7] While atrial remodelling is generally considered to be the underlying cause of AF, the exact pathways causing atrial remodelling are still largely unknown.[7–11] Previous studies suggest that a prothrombotic state is associated with prevalent AF, eventually leading to thrombotic events.[8] On the other hand, it is also suggested that coagulation underlies AF onset.[12–14] A possible mechanism underlying this association is immunothrombosis, as coagulation may increase local inflammation, stimulating atrial remodelling, and eventually AF development.[15–17] However, studies investigating the relation of coagulation with incidence AF are scarce and contradicting. Additionally, studies looking into the association of coagulation and AF presence investigate a limited amount of biomarkers, and these studies generally have small sample sizes. More conclusive evidence is warranted on the association of coagulation and AF, to improve knowledge on AF risk, AF prevention, and AF management.
We aimed to investigate the role of various markers of coagulation in the development and presence of AF. For this, we performed a systematic review and meta-analysis, summarizing and pooling all available evidence from both longitudinal and cross-sectional studies.
Europace. 2023;25(1):28-39. © 2023 Oxford University Press
Copyright 2007 European Heart Rhythm Association of the European Society of Cardiology (ESC). Published by Oxford University Press. All rights reserved.