Juhani Sivenius

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.

ESVS Guidelines. Invasive Treatment for Carotid Stenosis: Indications, Techniques

The European Society for Vascular Surgery brought together a group of experts in the field of carotid artery disease to produce updated guidelines for the invasive treatment of carotid disease. The recommendations were rated according to the level of evidence. Carotid endarterectomy (CEA) is recommended in symptomatic patients with >50% stenosis if the perioperative stroke/death rate is <6% [A], preferably within 2 weeks of the patients last symptoms [A]. CEA is also recommended in asymptomatic men <75 years old with 70-99% stenosis if the perioperative stroke/death risk is <3% [A]. The benefit from CEA in asymptomatic women is significantly less than in men [A]. CEA should therefore be considered only in younger, fit women [A]. Carotid patch angioplasty is preferable to primary closure [A]. Aspirin at a dose of 75-325 mg daily and statins should be given before, during and following CEA. [A] Carotid artery stenting (CAS) should be performed only in high-risk for CEA patients, in high-volume centres with documented low peri-operative stroke and death rates or inside a randomized controlled trial [C]. CAS should be performed under dual antiplatelet treatment with aspirin and clopidogrel [A]. Carotid protection devices are probably of benefit [C].

The significance of intensity of rehabilitation of stroke--a controlled trial.

Of the 373 stroke patients 95 were admitted to the feasibility study of stroke rehabilitation. The patients were divided into two groups, an intensive and a normal treatment group. In this study, the functional recovery of stroke, measured by ADL and motor function was significantly better in the intensive treatment group. There was no difference in institutionalization or incidence of death between the groups. The gain of ADL and motor function was greatest during the first three months after stroke in the intensive treatment group. The conclusion is that intensified physiotherapy seems to improve the functional recovery of stroke patients.

Metabolic Syndrome and the Risk of Stroke in Middle-Aged Men

Background and Purpose— The metabolic syndrome, a clustering of disturbed glucose and insulin metabolism, obesity and abdominal fat distribution, dyslipidemia, and hypertension is associated with cardiovascular diseases. The aim of this study was to examine the relationship of metabolic syndrome, as defined by National Cholesterol Education Program (NCEP) and World Health Organization (WHO) criteria, with the risk for stroke. Methods— Population-based cohort study with an average follow-up of 14.3 years from eastern Finland. A total of 1131 men with no history of cardiovascular disease and diabetes at baseline participated. Sixty-five strokes occurred, of which 47 were ischemic strokes. Results— Men with the metabolic syndrome as defined by the NCEP criteria had a 2.05-fold (95% CI, 1.03 to 4.11; P=0.042) risk for all strokes and 2.41-fold (95% CI, 1.12 to 5.32; P=0.025) risk for ischemic stroke, after adjusting for socioeconomic status, smoking, alcohol, and family history of coronary heart disease. Additional adjustment for ischemic changes during exercise test, serum low-density lipoprotein cholesterol, plasma fibrinogen, energy intake for saturated fats, energy expenditure of leisure time physical activity, and white blood cell count, the results remained significant. The risk ratios among men with metabolic syndrome as defined by the WHO criteria were 1.82 (95% CI, 1.01 to 3.26; P=0.046) for all strokes and 2.16 (95% CI, 1.11 to 4.19; P=0.022) for ischemic stroke. After further adjustment, the respective risks were 2.08 (95% CI, 1.12 to 3.87; P=0.020) and 2.47 (95% CI, 1.21 to 5.07; P=0.013). Conclusion— The risk of any stroke is increased in men with metabolic syndrome, in the absence of stroke, diabetes and cardiovascular disease at baseline. Prevention of the metabolic syndrome presents a great challenge for clinicians with respect to stroke.

Epidemiology of subarachnoid hemorrhage in Finland from 1983 to 1985.

The age-standardized incidence of subarachnoid hemorrhage was 33/100,000/yr among Finnish men and 25/100,000/yr among Finnish women. Subarachnoid hemorrhage represented 11% of all strokes detected during 1983-1985 in the community-based stroke register in three areas of Finland. Age-standardized mortality from subarachnoid hemorrhage was 18/100,000/yr among men and 12/100,000/yr among women aged 25-74 years, representing in men 22% and in women 23% of all deaths from stroke in the register. The case-fatality rate of subarachnoid hemorrhage was high: 35% among men and 33% among women within 2 days after the onset of the stroke attack and 48% in men and 46% in women at 1 month. Our findings suggest that the incidence and mortality of subarachnoid hemorrhage in Finland are among the highest worldwide, although differences in criteria, study methods, and classification procedures reduce the comparability of studies from different countries. The occurrence of subarachnoid hemorrhage in our present study is also higher than that previously reported in this country. We believe that this is more likely due to changes in diagnostic classification and improvements in detection of the disease than to a real increase in the morbidity and mortality of subarachnoid hemorrhage.

Transplantation of human embryonic stem cell-derived neural precursor cells and enriched environment after cortical stroke in rats: cell survival and functional recovery

Cortical stem cell transplantation may help replace lost brain cells after stroke and improve the functional outcome. In this study, we transplanted human embryonic stem cell (hESC)‐derived neural precursor cells (hNPCs) or vehicle into the cortex of rats after permanent distal middle cerebral artery occlusion (dMCAO) or sham‐operation, and followed functional recovery in the cylinder and staircase tests. The hNPCs were examined prior to transplantation, and they expressed neuroectodermal markers but not markers for undifferentiated hESCs or non‐neural cells. The rats were housed in either enriched environment or standard cages to examine the effects of additive rehabilitative therapy. In the behavioral tests dMCAO groups showed significant impairments compared with sham group before transplantation. Vehicle groups remained significantly impaired in the cylinder test 1 and 2 months after vehicle injection, whereas hNPC transplanted groups did not differ from the sham group. Rehabilitation or hNPC transplantation had no effect on reaching ability measured in the staircase test, and no differences were found in the cortical infarct volumes. After 2 months we measured cell survival and differentiation in vivo using stereology and confocal microscopy. Housing had no effect on cell survival or differentiation. The majority of the transplanted hNPCs were positive for the neural precursor marker nestin. A portion of transplanted cells expressed neuronal markers 2 months after transplantation, whereas only a few cells co‐localized with astroglial or oligodendrocyte markers. In conclusion, hESC‐derived neural precursor transplants provided some improvement in sensorimotor function after dMCAO, but did not restore more complicated sensorimotor functions.

Stress-Induced Blood Pressure Reactivity and Incident Stroke in Middle-Aged Men

Background and Purpose— Exaggerated blood pressure reactivity to stress is associated with atherosclerosis and hypertension, which are known stroke risk factors, but its relation to stroke is unknown. Previous work also indicates that the association between reactivity and cardiovascular diseases may be influenced by socioeconomic status. Methods— The impact of blood pressure reactivity and socioeconomic status on incident stroke was examined in 2303 men (mean age, 52.8±5.1 years) from a population-based, longitudinal study of risk factors for ischemic heart disease in eastern Finland. Reactivity was calculated as the difference between blood pressure measured during the anticipatory phase of an exercise tolerance test (before exercise) and resting blood pressure, measured 1 week earlier. Mean systolic reactivity was 20 mm Hg (±15.9), and mean diastolic reactivity was 8.6 mm Hg (±8.5). Socioeconomic status was assessed as years of education. One hundred thirteen incident strokes (90 ischemic) occurred in 11.2 (±1.6) years of follow-up. Results— Men with exaggerated systolic reactivity (≥20 mm Hg) had 72% greater risk of any stroke (relative hazard ratio [RH], 1.72; 95% CI, 1.17 to 2.54) and 87% greater risk of ischemic stroke (RH, 1.87; 95% CI, 1.20 to 2.89) relative to less reactive men. Moreover, men who were high reactors and poorly educated were nearly 3 times more likely to suffer a stroke than better educated, less reactive men (RH, 2.90; 95% CI, 1.66 to 5.08). Adjustment for stroke risk factors had little impact on these associations. Diastolic reactivity was unrelated to stroke risk. Conclusions— Excessive sympathetic reactivity to stress may be etiologically important in stroke, especially ischemic strokes, and low socioeconomic status confers added risk.

Double‐Blind Study of Gabapentin in the Treatment of Partial Seizures

Summary: Forty‐three patients completed a double‐blind, placebo‐controlled study of Gabapentin (GBP) as add‐on therapy in partial and secondarily generalized seizures. All patients were followed for an initial 3‐month baseline period, after which they were randomly allocated to receive either a placebo or 900 or 1,200 mg/day GBP for 3 months. A statistically significant difference in seizure frequency from the baseline to the treatment phase was noted between patients receiving placebo and GBP 1,200 mg, in whom seizure frequency decreased 57%. The GBP dosage of 900 mg appeared to be ineffective. A close relationship was observed between the serum GBP concentrations and the GBP dosage based on the seizure frequency. Serum GBP concentrations > 2 μg/ml resulted in a lower frequency of seizures. The adverse effects were minor and consisted mainly of transient drowsiness. GBP appears to be effective in the treatment of partial epileptic seizures in a dosage‐related manner

Seasonal Variation in the Occurrence of Stroke in a Finnish Adult Population: The FINMONICA Stroke Register

BACKGROUND AND PURPOSE Seasonal influence on the incidence of and mortality from cerebrovascular disease has been reported during the last three decades, but generally with some discrepancy in results, particularly regarding stroke subtypes. The aim of this study was to examine seasonal variation in the incidence, mortality, and case-fatality rate of stroke in data from the FINMONICA population-based stroke register. METHODS During 1982 to 1992, 15449 stroke events were registered in the monitored populations aged 25 to 99 years in three geographic areas of Finland: the provinces of Kuopio and North Karelia in eastern Finland and the Turku/Loimaa area in southwestern Finland. We analyzed the seasonal and monthly incidence, mortality, and case-fatality rate of stroke and subtypes of stroke by pooling the data for the three areas and stratifying by sex and age. RESULTS The rate of occurrence of ischemic stroke events was 12% (95% confidence interval [CI], 5% to 20%) greater in men and 11% (95% CI, 4% to 19%) greater in women in winter than in summer. For intracerebral hemorrhage, we observed a 28% (95% CI, 3% to 58%) greater rate of occurrence in men and a 33% (95% CI, 6% to 66%) greater rate of occurrence in women in winter than in summer. The occurrence of subarachnoid hemorrhage did not vary significantly by season. The greater incidence of ischemic strokes in winter was particularly prominent among men aged 25 to 64 years and less prominent in elderly men and in women. The 28-day case-fatality rate of ischemic stroke showed significant seasonal variation only in women (P = .001), with the lowest rate in summer. CONCLUSIONS There is a significantly greater incidence of ischemic strokes and intracerebral hemorrhages during winter in Finland. Further research that also takes meteorologic and sociodemographic factors into account is warranted, since it may help to determine new ways to prevent strokes.

Socioeconomic Status and Ischemic Stroke The FINMONICA Stroke Register

Background and Purpose— It has been shown that low socioeconomic status is associated with death from stroke. More-detailed data have, however, remained scanty. The purpose of the present study was to examine the association of socioeconomic status with ischemic stroke. Besides mortality, we analyzed the incidence, case-fatality ratio, and prognosis of ischemic stroke events. Methods— Our population-based study included 6903 first stroke events registered by the FINMONICA Stroke Register in 3 areas of Finland during 1983 to 1992. Indicators of socioeconomic status, such as taxable income and education, were obtained by record linkage of the stroke register data with files of Statistics Finland. Results— Incidence, case-fatality ratio, and mortality rates for ischemic stroke were all inversely related to income. Furthermore, 28 days after the onset of symptoms, a greater proportion of patients with low income than of those with high income was still in institutionalized care and/or in need of help for their activities of daily living. Population-attributable risk of the incidence of first ischemic stroke due to low socioeconomic status was 36% for both sexes. For the death from first ischemic stroke, it was 56% for both sexes. Conclusions— Persons with low socioeconomic status have considerable excess rates of morbidity and mortality from ischemic stroke in Finland. A reduction in this excess could markedly decrease the burden of ischemic stroke to the society and thus constitute an important public health improvement.