Carotid plaque and intima-media thickness and the incidence of ischemic events in patients with atherosclerotic vascular disease.

We aimed to evaluate whether carotid intima-media thickness (CIMT) or the presence of plaque can confer additional predictive value of future cardiovascular (CV) ischemic events in patients with pre-existing atherosclerotic vascular disease. We identified 2317 patients enrolled in the REduction of Atherothrombosis for Continued Health (REACH) registry who had atherosclerotic vascular disease and baseline CIMT measurements. The entire range of CIMT was divided into quartiles and the fourth quartile (≥ 1.5 mm) was defined as carotid plaque. Mean ± standard deviation baseline CIMT was 1.31 ± 0.65 mm. Associated CV ischemic events and vascular-related hospitalizations were evaluated over a 2-year follow-up. There was a positive increase in adjusted hazard ratios (HRs) for all-cause mortality (p = 0.04 for trend) and the quadruple endpoint (CV death, myocardial infarction (MI), stroke, hospitalization for CV events) with increasing quartiles of CIMT (p = 0.0008 for trend), which was mainly driven by the fourth quartile (carotid plaque). HRs for all-cause mortality, CV death, CV death/MI/stroke and the quadruple endpoint comparing the highest (carotid plaque) with the lowest CIMT quartile were 2.09 (95% CI, 1.07-4.10; p = 0.03); 2.49 (1.10-5.67; p = 0.03); 1.71 (1.10-2.67; p = 0.02); and 1.73 (1.31-2.27; p = 0.0001). In conclusion, our analyses suggest that the presence of carotid plaque, rather than the thickness of intima-media, appears to be associated with increased risk of CV morbidity and mortality, but confirmation of these findings in other population and prospective studies is required.

Aggressive therapy with intravenous abciximab and intra-arterial rtPA and additional PTA/stenting improves clinical outcome in acute vertebrobasilar occlusion: combined local fibrinolysis and intravenous abciximab in acute vertebrobasilar stroke treatment (FAST): results of a multicenter study.

BACKGROUND AND PURPOSE: A combined therapy of local recombinant tissue plasminogen activator (rtPA) fibrinolysis and intravenous Abciximab platelet inhibition with additional percutaneous transluminal angioplasty (PTA)/stenting may improve recanalization and neurological outcome in patients with acute vertebrobasilar occlusion. METHODS: Combined FAST therapy consisted on intravenous bolus of Abciximab (0.25 mg/kg) followed by a 12-hour infusion therapy (0.125 microg/kg per minute) and low-dose intra-arterial rtPA (median dosage: 20 mg, FAST cohort: N=47). The results were compared with a retrospective cohort, treated by intraarterial rtPA monotherapy (median dosage: 40 mg, rtPA cohort, N=41). Additional PTA/stenting was performed in case of severe residual stenosis. Recanalization success was classified according to the Trials in Myocardial Infarction (TIMI) criteria: TIMI0/1, failed recanalization; TIMI2/3, successful recanalization. Bleeding complications were evaluated according to severe extracerebral hemorrhage (ECH), asymptomatic intracerebral hemorrhage (AIH), and symptomatic intracerebral hemorrhage (SIH). RESULTS: Overall bleeding rate was higher under the combined therapy, but the SIH rate did not differ (FAST versus rtPA: ECH, 3% versus 0%; AIH, 32% versus 22%; SIH 13% versus 12%). Additional PTA/stenting was performed in 14 (FAST) versus 5 (rtPA) patients. TIMI2/3 recanalization rate was similar (FAST, 72%; rtPA, 68%), but TIMI3 rate was remarkably higher under combined therapy (FAST, 45%; rtPA, N=22%). Neurologic outcome appeared better under combined therapy (FAST versus rtPA: favorable outcome rate: 34% versus 17%) with a significantly lower mortality rate (FAST versus rtPA: 38% versus 68%; P=0.006). These results were consistent for embolic and atherothrombotic occlusions. CONCLUSIONS: Combined therapy of intravenous Abciximab and half dose intra-arterial rtPA with additional PTA/stenting appears to improve neurologic outcome in acute vertebrobasilar occlusion despite an increase of overall bleeding complications.

Predictors of in-hospital mortality in patients with acute ischemic stroke treated with thrombolytic therapy.

CONTEXT: Data are limited regarding the risks and benefits of thrombolytic therapy for acute ischemic stroke outside of clinical trials. OBJECTIVE: To investigate predictors of in-hospital mortality in patients with ischemic stroke treated with intravenous tissue plasminogen activator (tPA) within a pooled analysis of large German stroke registers. DESIGN AND SETTING: Prospective, observational cohort study conducted at 225 community and academic hospitals throughout Germany cooperating within the German Stroke Registers Study Group. PATIENTS: A total of 1658 patients with acute ischemic stroke who were admitted to study hospitals between 2000 and 2002 and were treated with tPA. MAIN OUTCOME MEASURE: In-hospital mortality. RESULTS: One hundred sixty-six patients (10%) who received tPA died during hospitalization, with 67.5% of these deaths occurring within 7 days. Factors predicting in-hospital death after tPA use were older age (for each 10-year increment in age, adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3-1.9) and altered level of consciousness (adjusted OR, 3.4; 95% CI, 2.4-4.7). The overall rate of symptomatic intracranial hemorrhage was 7.1% and increased with age. One or more serious complications was observed in 27.2% of all patients and in 83.9% of patients who died after tPA treatment. An inverse relation between the number of patients treated with tPA in the respective hospital and the risk of in-hospital death was observed (adjusted OR, 0.97; 95% CI, 0.96-0.99 for each additional patient treated with tPA per year). CONCLUSION: In patients with ischemic stroke who are treated with tPA, disturbances of consciousness and increasing age are associated with increased in-hospital mortality.

Increased calpain expression following experimental cerebral venous thrombosis in rats.

INTRODUCTION: Calpains are intracellular proteases that are activated by increased intracellular calcium with proteolytic activity mainly against the cytoskeleton. We tested the expression of calpains and their substrates in an animal model of experimental cerebral venous thrombosis. MATERIALS AND METHODS: Cerebral venous thrombosis was induced in seven male rats by rostral and caudal ligation of the superior sagittal sinus and injection of a thrombogenic cephalin suspension. Each animal survived 3 h of thrombosis. Using a polyclonal antibody against the 80 kD subunit of micro-calpain, immunohistochemistry of the region of interest (venous infarction) showed a loss of microtubule-associated protein-2. The micro-calpain-positive cells in the region of interest and normal tissue were measured using a video-imaging microscopy unit with magnification power of 400x. A cell was considered calpain positive when the nucleus and the periplasma were stained by the micro-calpain antibody. RESULTS: The mean infarct size was 13.4+/-3.7% of one whole coronal section. A total of 57+/-14% of the cells were found to be calpain positive in the region of interest, whereas 5+/-2% of all cellular elements in unaffected tissue were calpain positive (p<0.001). CONCLUSIONS: In conclusion, cerebral venous thrombosis causes an increase in calpain expression in affected tissue which is manifested by a loss of microtubule-associated protein-2. This increase might mediate secondary neuronal injury.

Acute basilar artery occlusion treated with combined intravenous Abciximab and intra-arterial tissue plasminogen activator: report of 3 cases.

BACKGROUND: Acute vertebrobasilar occlusion remains a disease with a high mortality even after treatment by local intra-arterial fibrinolysis. Adjunctive treatment with platelet glycoprotein IIb/IIIa receptor inhibitors such as abciximab may facilitate recanalization and improve the neurological outcome. Results after treatment of 3 patients by combined intravenous abciximab and local intra-arterial tissue plasminogen activator (tPA) are reported. CASE DESCRIPTIONS: Treatment was performed within 6 hours of stroke onset. Angiography revealed embolic occlusion of the basilar artery in 2 patients and atherothrombotic occlusion at the vertebrobasilar junction in 1 patient. Therapy consisted of intravenous abciximab bolus administration (0.25 mg/kg) followed by 12-hour infusion therapy (0.125 microg/kg per minute) and local intra-arterial thrombolysis with tPA (10 mg/h). Heparin was only applied for catheter flushing (500 IU/h). The patient with the atherothrombotic occlusion was treated with additional percutaneous transluminal angioplasty and stenting. Complete recanalization of the basilar artery occurred in 2 patients, whose conditions improved clinically to functional independence. In the third patient only partial recanalization was seen, with only slight clinical improvement. This patient died of cardiac failure 2 months later. Besides a subtle subarachnoid hemorrhage (n=1), no intracranial or extracranial bleeding complication was observed. CONCLUSIONS: The combination of glycoprotein IIb/IIIa receptor inhibitor with local intra-arterial tPA might be a promising therapy for patients with acute vertebrobasilar occlusion. Further studies are necessary to define the clinical benefit and the bleeding rate of this new pharmacological approach.