PAI-1 5G/5G genotype is an independent risk of intracranial hemorrhage in post-lysis stroke patients.

OBJECTIVE: Thrombolysis by recombinant tissue plasminogen activator (rt-PA) is the main pharmacological therapy in acute ischemic stroke (IS); however, it is only effective in a subset of patients. Here we aimed to investigate the role of plasminogen activator inhibitor-1 (PAI-1), an effective inhibitor of t-PA, and its major polymorphism (PAI-1 4G/5G) in therapy outcome. METHODS: Study population included 131 consecutive IS patients who all underwent thrombolysis. Blood samples were taken on admission, 1 and 24 h after rt-PA infusion. PAI-1 activity and antigen levels were measured from all blood samples and the PAI-1 4G/5G polymorphism was determined. Clinical data including NIHSS were registered on admission and day 1. ASPECTS was assessed using CT images taken before and 24 h after thrombolysis. Intracranial hemorrhage (ICH) was classified according to ECASS II. Long-term outcome was defined 90 days post-event by the modified Rankin Scale (mRS). RESULTS: PAI-1 activity levels dropped transiently after thrombolysis, while PAI-1 antigen levels remained unchanged. PAI-1 4G/5G polymorphism had no effect on PAI-1 levels and did not influence stroke severity. PAI-1 activity/antigen levels as measured on admission were significantly elevated in patients with worse 24 h ASPECTS (<7). Logistic regression analysis including age, sex, NIHSS on admission, BMI, history of arterial hypertension, and hyperlipidemia conferred a significant, independent risk for developing ICH in the presence of 5G/5G genotype (OR:4.75, 95%CI:1.18-19.06). PAI-1 levels and PAI-1 4G/5G polymorphism had no influence on long-term outcomes. INTERPRETATION: PAI-1 5G/5G genotype is associated with a significant risk for developing ICH in post-lysis stroke patients.

Low thrombin generation predicts poor prognosis in ischemic stroke patients after thrombolysis.

Thrombolysis by intravenous recombinant tissue plasminogen activator (rt-PA) is an effective therapy in acute ischemic stroke (AIS). Thrombin generation test (TGT) is a global hemostasis test providing information about the speed and amount of generated thrombin in plasma. Here we aimed to find out whether results of this test before the initiation of thrombolysis might predict outcomes. Study population included 120 consecutive AIS patients, all within 4.5 hours of their symptom onset, who underwent thrombolysis by rt-PA. Blood samples were collected from all patients upon admission and TGT was performed using platelet poor plasma. Clinical data of patients including the NIHSS were registered at admission, day 1 and 7 after therapy. The ASPECT score was assessed using CT images taken before and 24 hours after thrombolysis. Long-term functional outcome was defined 3 months after the event by the modified Rankin Scale. Endogenous Thrombin Potential (ETP) and Peak Thrombin were significantly lower in patients with cardioembolic IS. Symptomatic intracranial hemorrhage (SICH) was found in 6 patients and was significantly associated with low ETP and Peak Thrombin levels. A multiple logistic regression model revealed that an ETP result in the lower quartile is an independent predictor of mortality within the first two weeks (OR: 6.03; 95%CI: 1.2-30.16, p<0.05) and three months after the event (OR: 5.28; 95%CI: 1.27-21.86, p<0.05). Low levels of ETP and Peak Thrombin parameters increase the risk of therapy associated SICH. A low ETP result is an independent predictor of short- and long-term mortality following thrombolysis.

Influence of Hypertension, Alone and in Combination with Other Vascular Risk Factors on Cognition.

Hypertension is one of the most important modifiable risk factors of cardioand cerebrovascular diseases, responsible for the development of severe target organ damages. It has been shown that hypertension is associated with an increased prevalence of cognitive decline. It negatively affects the cognitive battery and accelerates dementia. Beside the known detrimental effects of senile hypertension on cognitive performance in the elderly population, previous studies pointed out that young, hypertensive individuals may also suffer from hypertension related changes in their cognitive capacity. Given the high prevalence of hypertension in a wide range of the age pyramid (young individuals, middle aged adults, elderly people), specific cognitive deficits may be present in a large portion of the population putting a heavy burden on society. Better understanding of the underlying mechanisms of hypertension induced cognitive impairment may contribute to the identification of its initiating pathophysiological factors, and serve an earlier diagnosis, intervention at an early stage and prevention of further deficits. Our aim with the current review was to summarize some of the previous findings regarding altered cognitive performance of individuals with hypertension and of those with the most common co-existing risk factors. Furthermore, efforts to explore effects of various antihypertensive medications on cognition and to survey proposed pathophysiological mechanisms of hypertension induced cognitive changes have been made.