Hemostatic factors, inflammatory markers, and risk of incident venous thromboembolism: The Multi-Ethnic Study of Atherosclerosis

Background Several hemostatic factors and inflammatory markers are associated with the risk of incident venous thromboembolism (VTE), however, most existing data are from case-control studies in Caucasian populations. Objectives We aimed to prospectively confirm previous findings and explore less studied biomarkers in relation to VTE risk in a multi-racial/multi-ethnic cohort. Methods Circulating levels of factor VIII, fibrinogen, D-dimer, plasmin-antiplasmin complex (PAP), C-reactive protein (CRP), and interleukin-6 (IL-6) were measured at baseline (2000-2002) in 6706 participants of the Multi-Ethnic Study of Atherosclerosis. Incident VTE was identified using hospitalization discharge codes from baseline to December 31, 2015. Hazard ratios (HRs) of VTE were estimated in Cox regression models. Results There were 227 events during a median of 14 years of follow-up. Compared with participants in the lowest quartile, the HRs for those above the 95th percentile and p for trend across categories were 3.50 (95% confidence interval [CI] 1.98-6.19; p < .001) for D-dimer, 1.49 (95% CI 0.84-2.63; p = .02) for factor VIII, 1.32 (95% CI 0.76-2.28; p = .99) for fibrinogen, 1.92 (95% CI 1.08-3.42; p = .15) for PAP, 1.68 (95% CI 0.81-3.48; p = .08) for CRP, and 2.55 (95% CI 1.15-5.66; p = .07) for IL-6, after adjustment for demographics and body mass index. For CRP and IL-6, follow-up was restricted to 10 years because of violations of the proportional hazards assumption. No significant interactions by age/ethnicity were observed. Conclusions We demonstrated a fairly novel association between PAP and risk of incident VTE, and contributed further prospective confirmation regarding the associations of D-dimer, factor VIII, and IL-6 with VTE.

Automated summary

The study confirmed associations between various biomarkers (such as D-dimer, factor VIII, and IL-6) and inflammatory markers (such as CRP, fibrinogen, and PAP) with the risk of venous thromboembolism (VTE). A novel association was also found between PAP levels and VTE risk.