Coagulation factor VIII levels and the risk of cardiovascular events: Systematic review and Meta-analysis

Background Numerous epidemiological studies have explored the association between coagulation Factor VIII (FVIII) and cardiovascular event risk; however, the overall results are still inconsistent. Objectives The aim of this systematic review and meta-analysis was to evaluate the relationship between FVIII and the risk of various cardiovascular events. Methods Two independent reviewers screened all available literature to identify studies that met the inclusion criteria. Heterogeneity was evaluated quantitatively via the I² statistic, and corresponding analyses were conducted using random-effects model. Results A total of 22 original studies were included in the quantitative meta-analysis. The meta-analysis results of both case-control and cohort studies showed a positive correlation between FVIII levels and the risk of cardiovascular events (OR = 2.69, 95%CI 2.06–3.49, heterogeneity I ²  = 0%; HR = 1.22, 95%CI 1.14–1.30; heterogeneity I ²  = 64%). In the cohort studies, subgroup analysis revealed a positive correlation between FVIII levels and the risk of myocardial infarction (HR = 1.18, 95% CI 1.06–1.32; heterogeneity I²=55%), ischemic stroke (HR = 1.21, 95%CI 1.11–1.32; heterogeneity I ²  = 11%), heart failure (HR 1.23, 95% CI 1.07–1.42; heterogeneity I²=30%), and composite outcome of cardiovascular disease (HR = 1.39, 95%CI 1.05–1.84; heterogeneity I² = 86%). In the case-control studies, subgroup analysis revealed a positive correlation between FVIII levels and the risk of myocardial infarction (OR = 2.56, 95% CI 1.74–3.77; heterogeneity I² = 0%) and ischemic stroke (OR = 2.80, 95% CI 1.95–4.01; heterogeneity I ²  = 0%). Conclusion The results of this study demonstrate a positive association between elevated FVIII levels and an increased risk of cardiovascular events, particularly myocardial infarction and stroke.