Abstract
BACKGROUND: Ischemic stroke occurs when a thrombus blocks a cerebral artery, and an important component is the fibrin clot. Different plasma fibrinogen variants have been associated with stroke risk in type 2 diabetes (T2D). We hypothesized that in vitro fibrin clot characteristics are associated with stroke risk and correlate with fibrinogen variants. OBJECTIVE: To investigate the association of fibrin clot characteristics with risk of ischemic stroke in T2D and the correlation of fibrinogen variants with clot characteristics. METHODS: In a nested case-control study with a median follow-up of 4.1 years, we included 144 T2D patients with ischemic stroke (cases) and 144 matched T2D patients without ischemic stroke (controls). Clot formation (velocity [ V (max) ], maximum absorbance [MA], overall hemostasis potential [OHP]), lysis, and structure (fiber density, diameter) were analyzed by turbidimetry. Clot characteristics were compared between cases and controls using a Mann-Whitney test and associated with stroke risk using conditional logistic regression to determine associations with stroke risk. Spearman's rank correlation was used to determine correlations between clot characteristics and fibrinogen variants (fibrinogen α (E) , fibrinogen γ ', and sialylated fibrinogen). RESULTS: Fibrin fiber density at baseline was significantly lower in future stroke cases (4.2 [3.7-4.7] ×10 (22) Da/cm (3) ) than in controls (4.5 [4.0-4.9] ×10 (22) Da/cm (3) ), p : 0.01. Moreover, patients in the highest versus lowest tertile of fiber density had an adjusted OR for ischemic stroke of 0.7 (95% CI: 0.3-1.5). Patients with higher V (max) , MA, OHP, and fiber diameter all had ischemic stroke ORs around 1.5, yet the limited statistical precision of the estimates hampered firm conclusions. Absolute, but not relative, levels of fibrinogen variants correlated with clot characteristics. CONCLUSION: In our study, turbidimetric fibrin clot characteristics were not convincingly associated with ischemic stroke in T2D. Absolute levels of fibrinogen variants correlated consistently with clot characteristics.