Fibrinogen is an Independent Risk Factor for White Matter Hyperintensities in CADASIL but not in Sporadic Cerebral Small Vessel Disease Patients

Abstract

The relationship between fibrinogen and white matter hyperintensities (WMHs) are inconsistent. Whether there are different relationships between WMHs and fibrinogen in disparate subtypes of cerebral small vessel disease (CSVD) remains unknown. Here, we investigated the roles of plasma fibrinogen in sporadic CSVD (sCSVD) and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) patients. We performed a cross-sectional study that included 74 CSVD patients (19 CADASIL and 55 sporadic) and 74 age-and gender-matched healthy controls (HCs). Plasma fibrinogen was determined, and the severity of WMHs in CSVD patients was rated according to Fazekas scales. Univariate analysis and ordinal logistic regression were performed to evaluate the relationship between fibrinogen and the severity of WMHs in CSVD. Both CADASIL and sCSVD patients showed significantly higher plasma fibrinogen levels than HCs. No significant difference in the plasma fibrinogen level was observed between CADASIL and sCSVD. Univariate analysis and ordinal logistic regression indicated that fibrinogen is an independent risk factor for the severity of WMHs in CADASIL patients (odds ratio [OR] =1.064; 95% Confidence interval (CI, 1.004-1.127); p =0.037). However, age (odds ratio [OR] =1.093; 95% CI (1.033-1.156); P = 0.002), but not fibrinogen (odds ratio [OR] =1.004; 95% CI (0.997-1.011); P=0.262), is an independent risk factor for the severity of WMHs in sCSVD patients. Our results suggest that high levels of plasma fibrinogen are associated with the severity of WMHs in CADASIL but not in sCSVD patients, indicating that the role of fibrinogen may be different in disparate subtypes of CSVD. A better understanding of fibrinogen may yield insights into the pathogenesis of CSVD.

Divergent Connectivity Changes in Gray Matter Structural Covariance Networks in Subjective Cognitive Decline, Amnestic Mild Cognitive Impairment, and Alzheimer’s Disease

“…Not only AD but also the other neurodegenerative diseases and cerebral small vessel disease (Zhu et al, 2019) may show cognitive decline at the early stage, such as progressive supranuclear palsy (Yang et al, 2021), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (Guo et al, 2021), and subcortical vascular MCI (Wang et al, 2018). Therefore, a specific biomarker is very important for disease diagnosis, intervention, and therapy.…”

Sex Differences in Hemostatic Factors in Patients With Ischemic Stroke and the Relation With Migraine—A Systematic Review

“…Several hemostatic factors are associated with WMH, showing possible mechanisms of hemostatic factor involvement in pathophysiology of ischemic stroke and migraine besides hypercoagulability. Increased fibrinogen levels have been associated with more severe WMH ( You et al, 2018 ; Guo X. et al, 2021 ), as well as PLA2 ( Zhu et al, 2019 ). Furthermore, increased t-PA activity was associated with progression of WMH in lacunar stroke ( van Overbeek et al, 2016 ).…”

Erythrocytes Are an Independent Protective Factor for Vascular Cognitive Impairment in Patients With Severe White Matter Hyperintensities

“…Therefore, we further conducted multivariable analyses with patients with different severities of WMH and found that hs-CRP may be a common potential marker of different VCI levels in all patients with white matter injury. Inflammation is involved in vascular endothelial injury and nerve fiber demyelination, which is one of the main pathophysiological mechanisms of white matter degeneration (Hilal et al, 2018;Wang T. et al, 2020;Guo et al, 2021;Yang et al, 2021). As a nonspecific inflammatory marker, hs-CRP was significantly associated not only with VCI but also with the severity of white matter degeneration (Hilal et al, 2018;Boots et al, 2020), further confirming the structural basis of the inflammatory response of VCI.…”

“…White matter hyperintensities (WMH), also known as white matter degeneration, are not only a typical imaging feature of CSVD but also an important biomarker of VCI . Our previous study found that fibrinogen was an independent risk factor for WMH in patients with CADASIL, but this correlation was not obvious in patients with sporadic CSVD (Guo et al, 2021). To date, studies examining blood biomarkers of VCI have mainly focused on vascular endothelial dysfunction and have been limited to a certain type of disease, such as CSVD or stroke (Zhu et al, 2019;Wang Y. et al, 2021).…”