Association of fibrinogen αE, fibrinogen γ', and sialylated fibrinogen with development of ischemic stroke in patients with recently diagnosed type 2 diabetes

Background: Stroke is a major cause of death globally, especially in type 2 diabetes (T2D) patients. Fibrinogen is known to predict stroke risk, but fibrinogen is a highly variable protein and we hypothesized that fibrinogen variants can improve stroke prediction. Objectives: We aimed to investigate the association of total fibrinogen and fibrinogen variants with risk of ischemic stroke in T2D patients. 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). We measured total fibrinogen, absolute, and relative levels of 3 fibrinogen variants (fibrinogen alpha E, fibrinogen gamma ', and sialylated fibrinogen) and compared levels between cases and controls. We used logistic regression to determine the association with stroke risk. Results: Total fibrinogen and absolute levels of fibrinogen alpha E, fibrinogen gamma ', and sialylated fibrinogen were higher in stroke cases than controls. Absolute levels of fibrinogen positively associated with risk of stroke for total fibrinogen (highest vs lowest tertile; adjusted odds ratio (OR), 1.9 [95% CI, 0.9-4.2]), fibrinogen gamma ' (OR, 1.8 [0.8-3.8]), and sialylated fibrinogen (OR, 2.5 [1.1-5.8]). Relative levels of fibrinogen variants did not convincingly associate with stroke risk. Conclusion: Patients with T2D who developed stroke had increased levels of total fibrinogen, fibrinogen alpha E, fibrinogen gamma ', and sialylated fibrinogen compared with T2D sialylated fibrinogen prospectively associated with a 2-fold increased risk of ischemic stroke.