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: 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 three fibrinogen variants (fibrinogen α_E, fibrinogen γ´, 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 α_E, fibrinogen γ´, and sialylated fibrinogen were higher in stroke cases than controls. Absolute levels of fibrinogen positively associated with risk of stroke, both for total fibrinogen (highest vs lowest tertile; adjusted odds ratio (OR) 1.9 (95% CI 0.9-4.2)), fibrinogen γ´ (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 α_E, fibrinogen γ´, and sialylated fibrinogen compared with T2D controls. Total fibrinogen and absolute, but not relative, levels of fibrinogen γ´ and sialylated fibrinogen prospectively associated with a 2-fold increased risk of ischemic stroke.