The cutoff score of the baseline NIH Stroke Scale (NIHSS) for a favorable chronic outcome was relatively low in patients with PC stroke compared to patients with AC stroke. The NIHSS appears to have limitations with respect to its use when comparing the neurologic severity of PC and AC stroke.

BackgroundAlthough statin therapy is beneficial for the prevention of initial stroke, the benefit for recurrent stroke and its subtypes remains to be determined in Asian, in whom stroke profiles are different from Caucasian. This study examined whether treatment with low-dose pravastatin prevents stroke recurrence in ischemic stroke patients.MethodsThis is a multicenter, randomized, open-label, blinded-endpoint, parallel-group study of patients who experienced non-cardioembolic ischemic stroke. All patients had a total cholesterol level between 4.65 and 6.21 mmol/L at enrollment, without the use of statins. The pravastatin group patients received 10 mg of pravastatin/day; the control group patients received no statins. The primary endpoint was the occurrence of stroke and transient ischemic attack (TIA), with the onset of each stroke subtype set to be one of the secondary endpoints.FindingAlthough 3000 patients were targeted, 1578 patients (491 female, age 66.2 years) were recruited and randomly assigned to pravastatin group or control group. During the follow-up of 4.9 ± 1.4 years, although total stroke and TIA similarly occurred in both groups (2.56 vs. 2.65%/year), onset of atherothrombotic infarction was less frequent in pravastatin group (0.21 vs. 0.64%/year, p = 0.0047, adjusted hazard ratio 0.33 [95%CI 0.15 to 0.74]). No significant intergroup difference was found for the onset of other stroke subtypes, and for the occurrence of adverse events.InterpretationAlthough whether low-dose pravastatin prevents recurrence of total stroke or TIA still needs to be examined in Asian, this study has generated a hypothesis that it may reduce occurrence of stroke due to larger artery atherosclerosis.FundingThis study was initially supported by a grant from the Ministry of Health, Labour and Welfare, Japan. After the governmental support expired, it was conducted in collaboration between Hiroshima University and the Foundation for Biomedical Research and Innovation.

No abstract

Background and Purpose: The influence of stroke subtype on recurrence, and determinants of recurrence-free survival after a first-ever stroke are not fully understood. We aimed to clarify the long-term prognosis by stroke subtypes and to identify determinants for recurrence and death after a first-ever stroke. Methods: We enrolled 1,732 consecutive patients (men/women = 1,134/598, mean age of 65 years) with a first-ever acute stroke who were admitted to our Stroke Care Unit during a period of 20 years. Stroke subtypes were classified as atherothrombotic brain infarction, lacunar infarction, cardioembolic infarction, other type of infarction, and brain hemorrhage. The prognosis was assessed by stroke subtypes. Results: During the hospital stay (mean 61 days), 99 patients died: 73 died directly from stroke. A total of 198 patients had recurrent strokes, and 286 died within 3 years after the index stroke. The overall recurrence rate within the first year was 6.5%, which was different among stroke subtypes. Patients with cardioembolic infarction (9.0%) as well as other type of infarction (9.1%) had more recurrent strokes within the initial year compared with the other subtypes. A history of transient ischemic attack (relative risk = 1.38), atrial fibrillation (1.52), ischemic heart disease (1.40), and disability at discharge (2.64) were independent predictors for the recurrence and death within 3 years after the first-ever stroke. Conclusions: The recurrence rate was different among stroke subtypes within 1 year after the index stroke. Atrial fibrillation, ischemic heart disease, history of transient ischemic attack, and disability at discharge were important determinants for stroke recurrence and death.

Objective-Fluid shear stress induces cyclooxygenase (COX)-2 gene expression in vascular endothelial cells. We investigated the underlying mechanism of this induction. Methods and Results-Exposure of human umbilical vein endothelial cells to laminar shear stress in the physiological range (1 to 30 dyne/cm 2 ) upregulated the expression of COX-2 but not COX-1, a constitutive isozyme of COX. The expression of COX-2 mRNA began to increase within 0.5 hour after the loading of shear stress and reached a maximal level at 4 hours. Roles of the promoter region and the 3Ј-untranslated region in the human COX-2 gene were evaluated by the transient transfection of luciferase reporter vectors into bovine arterial endothelial cells. Shear stress elevated luciferase activity via the region between Ϫ327 and 59 bp. Mutation analysis indicated that cAMP-responsive element (Ϫ59/Ϫ53 bp) was mainly involved in this response. On the other hand, shear stress selectively stabilized COX-2 mRNA. Moreover, shear stress elevated luciferase activity when a 3Ј-untranslated region of COX-2 gene containing 17 copies of the AUUUA mRNA instability motif was inserted into the vector. Key Words: shear stress Ⅲ vascular endothelial cells Ⅲ cyclooxygenase-2 Ⅲ posttranscriptional regulation V ascular endothelial cells are always exposed to a wide variety of biochemical and biomechanical stimuli, including fluid shear stress caused by blood flow. Shear stress modulates several endothelial functions, such as control of vascular tone, maintenance of antithrombotic surfaces, regulation of inflammation, protection against oxidative stresses, and regulation of endothelial cell proliferation and apoptosis. 1 Cyclooxygenase (COX), a rate-limiting enzyme for prostaglandin (PG) biosynthesis, comprises 2 isozymes, COX-1 and COX-2. 2,3 COX-1 is constitutively expressed in most cell species, whereas COX-2 is an inducible enzyme whose expression is regulated differently among cell types. Growing evidence indicates that COX-2 plays a key role in several biological processes, such as inflammation, tumorigenesis, development, and atherogenesis. 4 -9 Laminar shear stress upregulates COX-2 gene expression. 10 COX-2 is involved in lipopolysaccharide-stimulated production of prostacyclin (PGI 2 ) in endothelial cells 11 and is also involved in PGI 2 biosynthesis in healthy humans. 12 Previously, we have reported that shear stress promotes the production of PGD 2 in endothelial cells by stimulating the expression of lipocalintype PGD 2 synthase (L-PGDS), whereas PGI 2 synthase was constitutively expressed but did not respond to shear stress. 13 Therefore, the induction of COX-2 expression by shear stress may be involved in the production of PGI 2 and PGD 2 in endothelial cells. Conclusions-TranscriptionalThree cis-acting elements, namely, the nuclear factor (NF)-B binding site, the NF-interleukin-6 (NF-IL6) binding site, and the cAMP-responsive element (CRE), reside in the region between base pairs Ϫ327 and ϩ59 (Ϫ327/ϩ59) in the human COX-2 gene promoter. Their involveme...