TY - JOUR
T1 - Association of fibrinogen αE, fibrinogen γ', and sialylated fibrinogen with development of ischemic stroke in patients with recently diagnosed type 2 diabetes
AU - Daugaard, Nicoline
AU - Bladbjerg, Else–Marie –M
AU - Lundsgaard Svane, Helene Mathilde
AU - Thomsen, Reimar Wernich
AU - Nielsen, Jens Steen
AU - Palarasah, Yaseelan
AU - de Maat, Moniek P.M.
AU - Münster, Anna–Marie Bloch
N1 - Publisher Copyright:
© 2025 The Author(s)
PY - 2025/7
Y1 - 2025/7
N2 - 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 αE, 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 αE, fibrinogen γ′, 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 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 αE, 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.
AB - 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 αE, 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 αE, fibrinogen γ′, 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 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 αE, 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.
KW - Case-Control studies
KW - diabetes mellitus, type 2
KW - fibrinogen
KW - ischemic stroke
UR - https://www.scopus.com/pages/publications/105004817209
U2 - 10.1016/j.jtha.2025.03.023
DO - 10.1016/j.jtha.2025.03.023
M3 - Journal article
C2 - 40187413
AN - SCOPUS:105004817209
SN - 1538-7933
VL - 23
SP - 2213
EP - 2225
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
IS - 7
ER -