Prognostic implications of factor VIII levels in African Americans: insights from a propensity-matched US-based...

Elevated levels of coagulation factor VIII (FVIII) are more commonly observed in African Americans (AAs) and have been linked to higher risks of thromboembolism and other cardiovascular comorbidities. However, the prognostic implications of elevated FVIII levels in AAs have not been well-studied. We queried the TriNetX (August 2005 to August 2019) to compare AAs with FVIII > 200% to those with 50-200%. A propensity score match (PSM) was used to adjust for potential confounders. Primary outcomes were assessed within five years after the index FVIII and included major adverse cardiovascular events (MACE), while exploratory outcomes included venous thromboembolism (VTE), cerebrovascular events, new-onset heart failure (HF), HF exacerbations, and all-cause mortality. A survival analysis using log-rank tests, Kaplan-Meier curves, and a univariate Cox regression was performed to investigate the association of FVIII with the time to development of each outcome after PSM through the hazard ratio (HR). A multivariate-adjusted analysis was performed before PSM for select outcomes. An E-sensitivity analysis was implemented to assess the association of unmeasured confounders post-PSM. Initially, 11,199 patients were identified from the TriNetX database. After PSM, 3,833 patients with balanced baseline characteristics were included in each cohort. Patients with elevated FVIII had a higher 5-year risk of MACE (HR: 1.14, 95% CI: 1.02-1.27, P = 0.017), VTE (HR: 1.23, 95% CI: 1.11-1.35, P < 0.001), new-onset HF (HR: 1.41, 95% CI: 1.14-1.74, P = 0.001), and mortality (HR: 1.37, 95% CI: 1.20-1.57, P < 0.001). In adjusted models, the association between FVIII and new-onset HF attenuated after accounting for vWF and comorbidities, while the mortality risk remained significant (HR: 1.53, 95% CI: 1.34-1.73, P < 0.001). No significant association was found between FVIII and HF exacerbation. Elevated FVIII levels in AAs are linked to a higher risk of adverse cardiovascular outcomes, including new-onset HF. Future research should explore the dynamic interaction of FVIII with these outcomes, including its potential causal role and its use as a marker for the development of these conditions.