Plasminogen Activator Inhibitor-1 (PAI-1) Gene Polymorphisms Associated with Cardiovascular Risk Factors Involved in Cerebral Venous Sinus Thrombosis

Abstract

Cerebral venous sinus thrombosis (CVST), accounting for less than 1% of stroke cases, is characterized by various causes, heterogeneous clinical presentation and different outcome. The plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms has been found to be associated with CVST. The aim of this retrospective study was to determine the potential association of PAI-1 675 4G/5G polymorphisms and homocysteine levels with cardiovascular risk factors in a group of young patients with CVST. Eighty patients with CVST and an equal number of age and sex matched controls were enrolled. The protocol included demographic and clinical baseline characteristics, neuroimagistic aspects, genetic testing (PAI-1 675 4G/5G polymorphisms), biochemical evaluation (homocysteine—tHcy, the lipid profile, blood glucose, glycohemoglobin—HbA1c, high-sensitive C-reactive protein—hsCRP) data, therapy and prognosis. The PAI-1 675 4G/5G gene polymorphisms were significantly correlated with increased homocysteine level (tHcy) (p < 0.05), higher total cholesterol (TC) (p < 0.05), low- density lipoprotein cholesterol (LDLc) (p = 0.05) and high- sensitive C- reactive protein (hsCRP) (p < 0.05) in patients with CVST when compared with controls. From the PAI-1 gene polymorphisms, the PAI-1 675 4G/5G genotype presented statistically significant values regarding the comparisons of the blood lipids values between the CVST group and control group. The homocysteine (tHcy) was increased in both groups, patients versus controls, in cases with the homozygous variant 4G/4G but the level was much higher in the group with CVST (50.56 µmol/L vs. 20.22 µmol/L; p = 0.03). The most common clinical presentation was headache (91.25%), followed by seizures (43.75%) and focal motor deficits (37.5%). The superior sagittal sinus (SSS) was the most commonly involved dural sinus (56.25%), followed by the lateral sinus (LS) (28.75%). Intima—media thickness (IMT) values were higher in the patients’ group with CVST (0.95 mm vs. 0.88 mm; p < 0.05). The fatal outcome occurred 2.5% of the time. PAI-1 675 4G/5G gene polymorphisms and higher homocysteine concentrations were found to be significantly associated with CVST in young patients.