PLASMINOGEN-ACTIVATOR INHIBITOR-1 (PAI-1) 4G 5G PROMOTER POLYMORPHISMAND LEVELS IN SUBJECTS WITH CEREBROVASCULAR-DISEASE/

The exact role of the fibrinolytic system in the pathogenesis of strok e remains to be established. Elevated circulating levels of plasminoge n activator inhibitor-1, the principle inactivator of the fibrinolytic system, have been related to the development of myocardial infarction . There is evidence that a polymorphism in the promoter region of tile PAI-1 gene is associated with circulating PAI-1 levels. We studied a common single nucleotide insertion/deletion (4G/5G) polymorphism by PC R in 558 patients with stroke, the pathological type of which was esta blished by cranial computed tomography, and in 172 controls. 4G/5G gen otype and PAI-1 activity were investigated in relation to 1) stroke ty pe and 2) mortality occurring within four weeks, three months and six months of the stroke. No difference in genotype frequency was observed when all cases of stroke were compared with controls nor between the clinically determined subtypes of cerebral infarction. PAI-1 activity was significantly higher in patients with stroke (n = 245) both at pre sentation (11.6 U/ml) and after three months (11.8 U/ml), in paired sa mples, than in control subjects (8.8 U/ml, p <0.0001). Thirty-seven (6 .2%), 86 (14.5%) and 122 (20.5%) patients had died within one, three a nd six months of admission, respectively. PAI-1 activity was independe ntly associated with all-cause mortality ar one and three months after stroke (p = 0.02 and p = 0.03 respectively), but not after sis months . In this population the 4G/5G promoter polymorphism is not associated with an increased risk of stroke. PAI-1 levels were elevated at the t ime of acute stroke which persisted after three months. PAI-I level bu t not genotype was associated with early mortality following stroke.