Biomedical subjects

J Sivenius

Publications and source records attributed to J Sivenius.

At least 19 recordsLinked to original sources

PubMed2000

Hyperinsulinemia and the risk of cardiovascular death and acute coronary and cerebrovascular events in men: the Kuopio Ischaemic Heart Disease Risk Factor Study.

BACKGROUND: The role of hyperinsulinemia as a cardiovascular risk factor is controversial. We studied whether hyperinsulinemia is independently associated with increased cardiovascular morbidity and mortality. METHODS: Fasting serum insulin level and other cardiovascular risk factors were determined in 1521 men in eastern Finland aged 42 to 60 years with neither cardiovascular disease nor diabetes at baseline. Forty-five cardiovascular deaths, 110 acute coronary events, 48 strokes, and 163 any cardiovascular events occurred during an average follow-up of 9.5 years. A total of 163 cardiovascular events (45 cardiovascular deaths, 110 acute coronary events, and 48 strokes) occurred during an average follow-up of 9.5 years. RESULTS: In Cox regression analysis adjusting for age and examination years, fasting serum insulin level as a continuous variable was directly associated with the risk of cardiovascular death (P = .006), acute coronary events (P = .04), and stroke (P = .02). Men with insulin levels of 52 to 66 pmol/L, 67 to 89 pmol/L, and 90 pmol/L or more (3 highest quartiles) had 1.4-fold (95% confidence interval, 0.5-3.7), 1.4-fold (95% confidence interval, 0.5-3.7), and 2.5-fold (95% confidence interval, 1.0-5.9; P = .05) cardiovascular mortality, respectively, compared with men with insulin levels of less than 52 pmol/L (lowest quartile) (P = .04 for linear trend). Adjustment for serum lipid levels, blood pressure, and obesity reduced the excess cardiovascular mortality in the highest insulin quartile by 7%, 33%, and 67%, respectively. There were no statistically significant differences in the incidence of acute coronary events and stroke between the insulin quartiles. CONCLUSIONS: Hyperinsulinemia had a modest association with increased cardiovascular mortality in middle-aged men. This relationship was largely explained by obesity, hypertension, and dyslipidemia. Hyperinsulinemia had even weaker associations with the risk of acute coronary event and stroke.

Acute Disease↗

PubMed2000

Combined SPECT and diffusion-weighted MRI as a predictor of infarct growth in acute ischemic stroke.

UNLABELLED: In acute ischemic stroke, the infarcted core is surrounded by a zone of tissue that has decreased perfusion. Some of this tissue may be salvaged by prompt, effective treatment. Diffusion-weighted MRI is sensitive in detecting the infarcted tissue, whereas SPECT also detects the hypoperfused tissue around the infarcted core. We studied the potential of combined diffusion-weighted MRI and SPECT to predict infarct growth and clinical outcome in patients not receiving thrombolytic treatment. METHODS: Sixteen patients with acute stroke were examined consecutively with diffusion-weighted MRI and 99mTc-ethyl cysteinate dimer (99mTc-ECD) SPECT within 24 h of the onset of symptoms. Follow-up diffusion-weighted MRI was performed on the second day and after 1 wk. The volumes of infarcted and hypoperfused brain tissue were measured from diffusion-weighted MRI and SPECT, respectively. The volume difference between the hypoperfused and infarcted tissue on the first day was compared with the possible increase in infarct volume during the follow-up. Each patient's neurologic status was assessed with the National Institutes of Health Stroke Scale (NIHSS). RESULTS: The volume of infarcted tissue increased from 48 +/- 54 cm3 (mean +/- SD) on the first day to 88 +/- 93 cm3 on the second day (P = 0.001) and to 110 +/- 121 cm3 at 1 wk (P = 0.001). The volume of hypoperfused tissue on the first day was significantly greater than the infarct volume (102 +/- 135 cm3; P = 0.001). The volume difference between the hypoperfused and infarcted tissue on the first day correlated significantly with the infarct growth between the first day and 1 wk (r = 0.71; P < 0.01). Between the first day and 1 wk, the increase of the infarct volume correlated significantly with the change in the NIHSS (r = 0.54; P < 0.05). CONCLUSION: A large hypoperfusion zone around the infarct core in the acute phase of ischemic stroke predicts the infarct growth during the first week, and this correlates significantly with the change in the neurologic status of the patient. Combined diffusion-weighted MRI and SPECT performed within 24 h after the onset of symptoms can be useful in the evaluation of acute stroke to predict infarct growth.

Acute Disease↗

PubMed1999

Antiplatelet treatment does not reduce the severity of subsequent stroke. European Stroke Prevention Study 2 Working Group.

OBJECTIVE: To assess the the effect of antiplatelet therapy on the severity of subsequent stroke in patients with stroke and TIA. BACKGROUND: The Second European Stroke Prevention Study (ESPS2) recruited 6,602 patients in four treatment groups: placebo, 2 x 25 mg acetylsalicylic acid (ASA), 2 x 200 mg dipyridamole (DP), and the combination of 50 mg ASA and 400 mg DP per day. Seventy-six percent of the patients had had a stroke as the qualifying event, whereas 24% had a TIA. All patients were followed at 3-month intervals for 2 years. ESPS2 showed a benefit from antiplatelet treatment compared with placebo and an additional benefit using ASA and DP together compared with either of these antiplatelet agents alone. METHODS: In the ESPS2, the study protocol included assessment of severity of end point stroke with the modified Rankin scale once the stroke had clinically stabilized, and no further impairment was observed. There were 824 new stroke events during follow-up. In 701 of them, the initial Rankin scale was known, and this was also evaluated after each nonfatal recurrent stroke. The difference in Rankin scale between treatment groups was analyzed after recurrent stroke, and the progress in Rankin scale between entry and recurrent stroke was quantified by calculating the number of patients with a change of one or more degrees in the scale. RESULTS: There were no significant differences in these changes in Rankin scale between the treatment groups. The mean time to reach an end point of stroke was longest in patients who used ASA + DP (p = 0.057). However, there was no difference among the treatment groups in the time to death during follow-up. CONCLUSION: This study suggests that antiplatelet therapy does not influence the severity of recurrent stroke as evaluated with the Rankin scale. However, antiplatelet therapy seems to lengthen the time the patient remains free from a recurrent stroke.

Aged↗

PubMed1999

Neuroprotection by the alpha2-adrenoceptor agonist, dexmedetomidine, in rat focal cerebral ischemia.

The present study was undertaken to explore the possible neuroprotective effect of the selective alpha2-adrenoceptor agonist, dexmedetomidine in a rat model of focal cerebral ischemia. The effect of dexmedetomidine (9 microg kg(-1)) on infarct volume was assessed and compared to that of glutamate receptor antagonists cis-4(phosphonomethyl)-2-piperidine carboxylic acid (CGS-19755) (20 mg kg(-1)) or 2,3-dihydro-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) (50 mg kg(-1)). Dexmedetomidine decreased total ischemic volume by 40% in the cortex (P<0.05) compared to NaCl-treated control rats, whereas NBQX reduced the infarct by 73% in the cortex (P<0.001) and by 43% in the striatum (P<0.01). Dexmedetomidine infusion was associated with some minor degree of hyperglycemia and hypotension. Drug-induced kidney changes were only seen in NBQX-treated rats. These results suggest that dexmedetomidine reduced ischemic volume despite causing a minor increase in blood glucose concentrations and hypotension. Its neuroprotective efficacy was better than that produced by CGS-19775, and dexmedetomidine was safer with respect to kidney toxicity when compared to NBQX.

Adrenergic alpha-Agonists↗

PubMed1999

Second European Stroke Prevention Study: antiplatelet therapy is effective regardless of age. ESPS2 Working Group.

BACKGROUND: The Second European Stroke Prevention Study (ESPS2) was a randomized, placebo-controlled trial that investigated the efficacy of low-dose acetylsalicylic acid (ASA) and modified-release dipyridamole (DP), alone or in combination, in the secondary prevention of ischemic stroke. The trial demonstrated that the combination was significantly more effective than either agent used alone. The aim of the present study was to evaluate the influence of age on the efficacy of ASA and DP, alone or in combination, in the secondary prevention of stroke in the ESPS2 population. METHODS AND RESULTS: A total of 6602 patients were recruited to the ESPS2 and there were 4 treatment groups: ASA (25 mg twice daily), DP (200 mg twice daily), ASA and DP in a combined formulation, or placebo. Primary endpoints were stroke, death, and stroke or death together. The endpoints evaluated in the present study were stroke, stroke and/or death, and vascular events. Stroke was the qualifying event in 76% of the patients, while 24% had a transient ischaemic attack. Patients were reviewed at 3-month intervals for 2 years. The study population consisted of 2565 (39%) patients aged less than 65 years, 2240 (34%) patients aged between 65 and 74 years, and 1797 (27%) patients aged 75 years and over. Advancing age was associated with an increased incidence of endpoints in all 4 treatment groups. The combination of ASA and DP significantly reduced the incidence of all endpoints, compared with placebo, in each age group. There was no influence of age on the efficacy of antiplatelet therapy for any of the evaluated endpoints. Relative risk reductions of treatment compared with placebo were 11.1-27.6% in the ASA group, 8.0-18.7% in the DP group, and 20.3-45.2% in patients receiving combination therapy. CONCLUSION: This study clearly demonstrates that combination therapy with DP and ASA is superior to either agent used alone in the secondary prevention of ischemic stroke, irrespective of the age of the patient.

Administration, Oral↗

PubMed1999

Anger expression and incident stroke: prospective evidence from the Kuopio ischemic heart disease study.

BACKGROUND AND PURPOSE: High levels of anger are associated with an increased risk of coronary heart disease and hypertension, but little is known about the role of anger in stroke risk. METHODS: Anger expression style and risk of incident stroke were examined in 2074 men (mean age, 53.0+/-5.2 years) from a population-based, longitudinal study of risk factors for ischemic heart disease and related outcomes in eastern Finland. Self-reported style of anger expression was assessed by questionnaire at baseline. Linkage to the FINMONICA stroke and national hospital discharge registers identified 64 first strokes (50 ischemic) through 1996. Average follow-up time was 8.3+/-0.9 (mean+/-SD) years. RESULTS: Men who reported the highest level of expressed anger were at twice the risk of stroke (relative hazard, 2.03; 95% CI, 1.05 to 3.94) of men who reported the lowest level of anger, after adjustments for age, resting blood pressure, smoking, alcohol consumption, body mass index, low-density and high-density lipoprotein cholesterol, fibrinogen, socioeconomic status, history of diabetes, and use of antihypertensive medications. Additional analysis showed that these associations were evident only in men with a history of ischemic heart disease (n=481), among whom high levels of outwardly expressed anger (high anger-out) predicted >6-fold increased risk of stroke after risk factor adjustment (relative hazard, 6.87; 95% CI, 1.50 to 31.4). Suppressed anger (anger-in) and controlled anger (anger-control) were not consistently related to stroke risk. CONCLUSIONS: This is the first population-based study to show a significant relationship between high levels of expressed anger and incident stroke. Additional research is necessary to explore the mechanisms that underlie this association.

Anger↗

PubMed1999

Combined diffusion and perfusion MRI with correlation to single-photon emission CT in acute ischemic stroke. Ischemic penumbra predicts infarct growth.

BACKGROUND AND PURPOSE: More effective imaging methods are needed to overcome the limitations of CT in the investigation of treatments for acute ischemic stroke. Diffusion-weighted MRI (DWI) is sensitive in detecting infarcted brain tissue, whereas perfusion-weighted MRI (PWI) can detect brain perfusion in the same imaging session. Combining these methods may help in identifying the ischemic penumbra, which is an important concept in the hemodynamics of acute stroke. The purpose of this study was to determine whether combined DWI and PWI in acute (<24 hours) ischemic stroke can predict infarct growth and final size. METHODS: Forty-six patients with acute ischemic stroke underwent DWI and PWI on days 1, 2, and 8. No patient received thrombolysis. Twenty-three patients underwent single-photon emission CT in the acute phase. Lesion volumes were measured from DWI, SPECT, and maps of relative cerebral blood flow calculated from PWI. RESULTS: The mean volume of infarcted tissue detected by DWI increased from 46.1 to 75.6 cm(3) between days 1 and 2 (P<0.001; n=46) and to 78.5 cm(3) after 1 week (P<0.001; n=42). The perfusion-diffusion mismatch correlated with infarct growth (r=0. 699, P<0.001). The volume of hypoperfusion on the initial PWI correlated with final infarct size (r=0.827, P<0.001). The hypoperfusion volumes detected by PWI and SPECT correlated significantly (r=0.824, P<0.001). CONCLUSIONS: Combined DWI and PWI can predict infarct enlargement in acute stroke. PWI can detect hypoperfused brain tissue in good agreement with SPECT in acute stroke.

Acute Disease↗

PubMed1998

Risk factors and antiplatelet therapy in TIA and stroke patients.

Antiplatelet treatment is well established in the secondary prevention of ischemic cerebrovascular events. The reasons for the occurrence of stroke, even though the patient receives drug treatment, have remained unclear. We performed a subgroup analysis of the European Stroke Prevention Study (ESPS 1) to investigate the efficacy of treatment in patients with different cardiovascular risk factors. The ESPS 1 recruited 1306 patients with TIA, RIND or stroke in one single center of Kuopio in Finland. The patients were treated with aspirin 990 mg/day+dipyridamole 225 mg/day or placebo for 2 years or until an endpoint. The endpoints were stroke or death from any cause. The risk factors for endpoints were analyzed by Cox univariate regression analyses. The effect of a single risk factor on the efficacy of antiplatelet therapy was analyzed by Cox proportional hazards model in subgroups according to the significant risk factors found in the univariate analysis. The efficacy of treatment was statistically significant in all subgroups except diabetics and current smokers for the stroke endpoint. When the combined endpoint of stroke or death was used, the treatment failed also to show statistical significance in patients with coronary heart disease. This lack of efficacy might be due to the small sample size. The efficacy of treatment was significantly better in TIA patients than in stroke patients when analyzed with stroke as an end point. This study provides strong evidence that the effectiveness of antiplatelet treatment in ischemic stroke and TIA patients is independent of most cardiovascular risk factors. Furthermore, all patients with TIA and ischemic stroke should receive secondary prevention regardless of whether or not there are risk factors.

Aspirin↗

PubMed1998

Efficacy of antiplatelet treatment in hypertensive patients with TIA or stroke.

We performed a subgroup analysis of the first European Stroke Prevention Study including 1,306 patients recruited in a single center, Kuopio, Finland, to investigate whether or not antiplatelet therapy is effective in the secondary prevention of stroke in hypertensive patients with transient ischemic attack (TIA) or stroke. The patients were treated with aspirin, 990 mg/day, plus dipyridamole, 225 mg/day, or placebo for 2 years. The patients with high systolic blood pressure (> or = 140 mm Hg; n = 1.105) or high diastolic blood pressure (> or = 85 mm Hg; n = 1,120) at entry, were classified into subgroups by blood pressure level. The effect of treatment was statistically significant in all subgroups with high systolic (end-point reduction, 55.2-68.2%) and diastolic blood pressure (end-point reduction, 47.3-82.1%). Risk reduction was, however, greatest in patients with the highest diastolic blood pressure. One possible explanation is that platelets are more activated in these patients, and this can be effectively prevented by antiplatelet therapy. Further studies are needed to confirm this hypothesis.

Aspirin↗

PubMed1997

Alpha2-adrenoreceptor agonist, dexmedetomidine, alters acute gene expression after global ischemia in gerbils.

The effect of dexmedetomidine, a selective alpha2-adrenoreceptor agonist and neuroprotective agent on the expression of immediate early genes and heat shock protein hsp70, was studied using quantitative in situ hybridization in a global ischemia model. At the dose previously shown to be neuroprotective dexmedetomidine inhibited the expression of c-fos and hsp70 mRNA, did not affect jun-B mRNA, and enhanced the induction of NGFI-A mRNA in the postischemic gerbil hippocampus. The reduced gene expression of c-fos and hsp70 was detected in the CA1 pyramidal cells which are prone to ischemic degeneration, whereas the increased gene expression of NGFI-A was measured from the CA3 and dentate gyrus, areas relatively resistant to ischemia. These alterations in early gene expression possibly reflect the mechanisms mediating the neuroprotective effects of alpha2-adrenoreceptor agonists.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1997

Selegiline treatment after transient global ischemia in gerbils enhances the survival of CA1 pyramidal cells in the hippocampus.

Selegiline (L-deprenyl) has shown neuroprotective effects in a variety of degenerative processes. The present experiments were designed to test whether post-ischemia administered selegiline would alleviate delayed neuronal death of the gerbil hippocampal pyramidal cells following transient global ischemia. Common carotid arteries were occluded for 5 min. Saline or selegiline, 0.25 mg/kg s.c., was administered 2 h after the ischemia followed by a daily injection for either 3 or 7 days. After decapitation, the delayed death of the hippocampal CA1 pyramidal cells was assessed using Nissl-stained sections. In situ hybridization was used to reveal the expression of hsp70 mRNA 1, 3 or 7 days after the ischemia. Animals treated with selegiline for 7 days showed significantly lower damage score (scale 0-3: 0, normal; 1, < 10% of the neurons damaged; 2, 10-50% damaged; 3, > 50% damaged) compared to the saline-treated animals 1.73 +/- 0.18 and 2.41 +/- 0.16 (mean +/- S.E.M., P = 0.0133), respectively. A similar trend was found in animals after the 3-day treatment: 1.68 +/- 0.32 vs. 2.06 +/- 0.25 (P > 0.5). The expression of hsp70 mRNA in the CA1 pyramidal cell layer was strong still 3 days after the ischemic insult but vanished by 7 days. Densitometric measurements using 14C-plastic standards showed that the intensity of the CA1a hsp70 signal on the 3rd day correlated negatively to the cell-damage score (r = -0.72, P < 0.001), suggesting that hsp70 does not serve as a quantitative marker for CA1 neuronal injury in this model. Instead, the hsp70 expression was associated with improved neuronal survival lasting often longer in selegiline-treated animals (P > 0.5). The results show that a low dose of selegiline can alleviate the delayed hippocampal neuronal death in gerbils when administered 2 h after an ischemic insult.

Animals↗

PubMed1997

Neuroprotective effects of dexmedetomidine in the gerbil hippocampus after transient global ischemia.

BACKGROUND: Cerebral ischemia induces a massive release of norepinephrine associated with neuronal death in the brain. It has been demonstrated that alpha2-adrenoceptor agonists decrease the release and turnover of noradrenaline, and this might prove advantageous in counteracting the neurodegeneration in ischemic brain. Therefore, in the present study, the authors tested whether dexmedetomidine, a selective alpha2-receptor agonist, has neuroprotective effects in a gerbil transient global ischemia model. METHODS: Ischemia was induced by bilateral carotid occlusion for 5 min in diethylether-anesthetized normothermic gerbils. Dexmedetomidine was administered subcutaneously in four different treatment paradigms (6-8 animals/group): 3 or 30 microg/kg 30 min before and thereafter at 3, 12, 24, and 48 h after the occlusion, or 3 or 30 microg/kg at 3, 12, 24, and 48 h after the occlusion. Control animals were subjected to forebrain ischemia but received only saline injections. One week after occlusion, animals were transcardially perfused for histochemistry. Neuronal death in the CA1 and CA3 regions of the hippocampus and in the hilus of the dentate gyrus was evaluated in silver-stained 60-microm coronal sections. RESULTS: Compared with saline-treated ischemic animals, dexmedetomidine at a dose of 3 microg/kg given before and continued after the induction of ischemia reduced the number of damaged neurons in the CA3 area (2 +/- 3 vs. 17 +/- 20 degenerated neurons/mm2; P < 0.05). Also in the dentate hilus, the number of damaged neurons was reduced by dexmedetomidine (3 microg/kg) given before and continued after ischemia (5 +/- 7 vs. 56 +/- 42 degenerated neurons/mm2; P < 0.01). CONCLUSIONS: The present data demonstrate that dexmedetomidine effectively prevents delayed neuronal death in CA3 area and in the dentate hilus in gerbil hippocampus when the management is started before the onset of ischemia and continued for 48 h after reperfusion. Inhibition of ischemia-induced norepinephrine release may be associated with neuroprotection by dexmedetomidine.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1997

Atrial fibrillation in older stroke patients: association with recurrence and mortality after first ischemic stroke.

OBJECTIVES: The objective of this study was to determine the association of atrial fibrillation (AF) with stroke recurrence and mortality and with the causes of death in ischemic stroke patients aged 75 years and older. DESIGN: A population-based study. SETTING: The cities of Turku and Kuopio in Finland. PARTICIPANTS: The study cohort consisted of 2635 consecutive patients aged 75 years and older, with a first ischemic stroke, registered in the FINMONICA Stroke Register. MEASUREMENTS: 28-day and 1-year stroke mortality, causes of death, and recurrence of stroke. RESULTS: There were 767 stroke patients with AF (mean age 82.2) and 1868 patients without AF (mean age 81.4). Mortality was higher in the AF group both 28 days (33.9% vs 28.1%, P = .003) and 1 year after the attack (52.7% vs 43.0%, P < .001). The age- and sex-adjusted relative risk of death at 28 days was 1.25 in the AF group (95% confidence interval (CI) 1.04-1.50, P = .018), and at 1 year it was 1.41 (95% CI 1.18-1.67, P < .001). In a Cox proportional hazards model, 1-year mortality risk comparing the AF-group with non-AF group was 1.24 (95% CI 1.10-1.39, P < .001). The strongest risk factor predicting 1-year mortality was recent myocardial infarction (MI) (RR 1.90, 95% CI 1.49-2.42). Myocardial infarction was more often the underlying cause of death in the AF group during the period of 28 days, but not from 28 days up to 1 year. The 1-year recurrence rate among those alive at day 28 was 11.5% in the AF group and 9.4% in the non-AF group (P = .240). CONCLUSION: Recent MI and AF are independent negative prognostic factors in older patients with stroke. Although the relative risk estimates attributable to AF are of the same magnitude in older as in middle-aged stroke patients, the much higher prevalence of AF in the older patients emphasizes its absolute impact on the mortality and recurrence after the first ischemic stroke in the age group 75 years and older. The treatment of coexisting cardiac disease also has the potential to prevent deaths and recurrent stroke events in older persons.

Aged↗

PubMed1997

Trends in case-fatality of stroke in Finland during 1983 to 1992.

BACKGROUND AND PURPOSE: Stroke mortality has been declining in Finland during the past 20 years. It is not known, however, whether this favorable development is attributable to the decline in the incidence or case-fatality of stroke. For this reason we examined the trends in case-fatality of stroke, including trends by subtype of stroke. METHODS: The analyses were carried out using data of the community-based FINMONICA Stroke Register, which was operating in three geographic areas of Finland during 1983 to 1992. All stroke events (n = 11,171) in persons aged 35 to 74 years were included in this register. RESULTS: The 28-day case-fatality of stroke fell yearly by 3.6% (P = .01) in men and by 2.6% (P = .2) in women. At the end of the study period, the average 28-day case-fatality of all strokes was 20% in men and 21% in women. Considerable differences by subtype of stroke were observed. The 28-day case-fatalities at the end of the study period were in men-56% for subarachnoid hemorrhage, 42% for intracerebral hemorrhage, and 14% for cerebral infarction. In women, the corresponding figures were 49%, 49%, and 14%. The 28-day case-fatality of subarachnoid hemorrhage did not change during the study period, but for intracerebral hemorrhage, a significant decline was observed in men and there was a declining trend also in women. The 28-day case-fatality of cerebral infarction declined significantly in both genders. CONCLUSIONS: With the exception of subarachnoid hemorrhage, the 28-day case-fatality of stroke has fallen in Finland. It is likely that this fall has contributed to the decline in stroke mortality.

Adult↗

PubMed1997

Atrial fibrillation and stroke. Mortality and causes of death after the first acute ischemic stroke.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is a risk factor for stroke. This study was undertaken to determine the influence of AF on the mortality of stroke patients and on the causes of death after a stroke event. METHODS: Patients with first ischemic stroke who were .35 to 74 years old and registered in the FINMONICA stroke register during 1982 through 1992 were analyzed (n = 6912). There were 642 patients with AF (9.3%) (mean age, 67 years) and 6270 patients without AF (90.3%) (mean age, 63 years). The association between AF and stroke mortality was investigated by use of logistic regression and Cox proportional hazards models. RESULTS: Mortality was higher in the AF group both at 28 days (19.5% versus 14.4%, P < .001) and 1 year after the attack (30.5% versus 21.8%, P < .001). After adjustment for age and sex, the odds ratio for 28-day case fatality (AF versus non-AF) was 1.27 (95% CI, 1.03 to 1.56; P = .003), and that for 1-year mortality was 1.36 (95% CI, 1.14 to 1.63; P < .001). In the proportional hazards model, AF was a significant independent risk factor for 1-year mortality (hazard ratio, 1.26; 95% CI, 1.09 to 1.46; P = .002). Cardiac causes of death were more common in the AF group at the acute stage. In the course of 1 year, there were no differences in the distributions of causes of death. CONCLUSIONS: Stroke patients with AF are at high risk of death both at the acute phase of stroke and during the subsequent year after the first acute stroke event. Mortality from cardiac diseases prevailed in the AF group during the acute phase of stroke. Careful cardiac evaluation and treatment are essential in patients with AF and stroke.

Acute Disease↗

PubMed1997

Studies on the influence of enriched-environment housing combined with systemic administration of an alpha2-adrenergic antagonist on spatial learning and hyperactivity after global ischemia in rats.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether an enriched housing environment and/or systemic administration of the alpha2-adrenergic receptor antagonist atipamezole facilitate the rate of spatial learning after global ischemia in rats. METHODS: Carotid arteries were closed for 20 minutes after permanent cauterization of vertebral arteries on the previous day. Enriched-environment housing and drug/saline treatment were begun 3 days after ischemia. For rehabilitation, housing in an enriched environment was combined with exploration in a labyrinth. Behavioral tests (the open-arena test and water-maze learning set task) were performed after 1-week periods of drug/saline treatment three times. In addition, the open-arena test was performed to evaluate the baseline level of animals 2 days after the induction of ischemia and at the end of the experiment, when the water-maze task was assessed in another room. RESULTS: Rats housed in an enriched environment after ischemia showed better acquisition of the water-maze learning set task after 1 week of housing. The influence of atipamezole treatment on this parameter did not reach statistical significance. In the open-arena test, ischemic animals were slightly hyperactive; however, this symptom was eliminated by housing in an enriched environment. CONCLUSIONS: The present data suggest that housing in an enriched environment facilitates the rate of spatial learning in rats with global ischemia. Rehabilitation also alleviated the hyperactivity observed in ischemic animals.

Adrenergic alpha-2 Receptor Antagonists↗

PubMed1996

European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke.

In 1988, we undertook a randomized, placebo-controlled, double-blind trial to investigate the safety and efficacy of low-dose acetylsalicylic acid (ASA), modified-release dipyridamole, and the two agents in combination for secondary prevention of ischemic stroke. Patients with prior stroke or transient ischemic attack (TIA) were randomized to treatment with ASA alone (50 mg daily), modified-release dipyridamole alone (400 mg daily), the two agents in a combined formulation, or placebo. Primary endpoints were stroke, death, and stroke or death together. TIA and other vascular events were secondary endpoints. Patients were followed on treatment for two years. Data from 6,602 patients were analysed. Factorial analysis demonstrated a highly significant effect for ASA and for dipyridamole in reducing the risk of stroke (p < or = 0.001) and stroke or death combined (p < 0.01). In pairwise comparisons, stroke risk in comparison to placebo was reduced by 18% with ASA alone (p = 0.013); 16% with dipyridamole alone (p = 0.039); and 37% with combination therapy (p < 0.001). Risk of stroke or death was reduced by 13% with ASA alone (p = 0.016); 15% with dipyridamole alone (p = 0.015); and 24% with the combination (p < 0.001). The treatment had no statistically significant effect on the death rate alone. Factorial analysis also demonstrated a highly significant effect of ASA (p < 0.001) and dipyridamole (p < 0.01) for preventing TIA. The risk reduction for the combination was 36% (p < 0.001) in comparison with placebo. Headache was the most common adverse event, occurring more frequently in dipyridamole-treated patients. All-site bleeding and gastrointestinal bleeding were significantly more common in patients who received ASA in comparison to placebo or dipyridamole. We conclude that (1) ASA 25 mg twice daily and dipyridamole, in a modified-release form, at a dose of 200 mg twice daily have each been shown to be equally effective for the secondary prevention of ischemic stroke and TIA; (2) when co-prescribed the protective effects are additive, the combination being significantly more effective than either agent prescribed singly; (3) low-dose ASA does not eliminate the propensity for induced bleeding.

Adult↗

PubMed1996

Incidence and risk factors of ischaemic and haemorrhagic stroke in Europe. EUROSTROKE: A collaborative study among research centres in Europe: rationale and design.

EUROSTROKE is a collaborative study among ten European research centres to investigate (1) the variation in incidence of fatal and non-fatal ischaemic and haemorrhagic stroke among populations in different European countries; (2) whether the observed differences in stroke incidence across countries can be explained by differences in prevalence of established cardiovascular risk factors; (3) the relative importance of selected dietary factors (potassium intake, smoking, alcohol consumption), haemostatic disturbances (fibrinogen) and co-morbidity (rheumatic heart disease, atrial fibrillation) compared to established risk factors as determinants of the occurrence of ischaemic and haemorrhagic stroke. The EUROSTROKE database is drawn from ten European population-based prospective follow-up studies (cohorts) and is designed as a case-control study nested within these ten ongoing studies.

Aged↗