BACKGROUND Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. METHODS In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. RESULTS By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P = 0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P = 0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P = 0.003). CONCLUSIONS In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.)

Background and Purpose-Atrial fibrillation (AF) is a major risk factor for ischemic stroke and its prevalence increases steeply with age. Population-based data on its influence on stroke outcome are scarce. Methods-We evaluated the prevalence of AF and its influence on prognosis in patients with a first-ever ischemic stroke from a population-based registry. Results-The presence of AF at stroke onset and during the acute phase was confirmed by a standard electrocardiogram in 869 (24.6%) of 3530 patients with ischemic stroke. With respect to patients without the arrhythmia, those with AF were more frequently women, aged 80 years and older, with coronary heart disease and peripheral arterial disease. The presence of AF was associated with high 30-day (32.5%; 95% CI, 29.3 to 35.6) and 1-year case-fatality rates (49.5%; 95% CI, 46.2 to 52.8), with a higher stroke recurrence rate within the first year of follow-up (6.6% versus 4.4%; Pϭ0.046) and with the worst survival after an average follow-up of 45.2 months (PϽ0.0001). At the multivariate Cox regression analysis, AF was an independent predictor of 30-day and 1-year mortality. Approximately 17% of all deaths were attributable to the presence of AF. Conclusions-We found a high prevalence of AF in patients with a first-ever ischemic stroke, especially among elderly women. The overall contribution of AF to stroke mortality was relevant, suggesting that together with new strategies to prevent the development of the arrhythmia more appropriate treatments are needed, mostly in elderly women.

Background and Purpose-The purpose of this study was to evaluate the incidence and prognosis of intracerebral hemorrhage. Methods-We analyzed data referring to our prospective population-based registry, including patients with a first-ever stroke followed up to 10 years. Results-In a 5-year period, we included 549 patients (247 men and 302 women; mean ageϮSD, 73.6Ϯ12.5 years) with an intracerebral hemorrhage. The crude annual incidence rate was 36.9 per 100 000 (95% CI, 33.8 to 40.0), 32.9 per 100 000 when standardized to the 2006 European population, and 15.9 per 100 000 when standardized to the world population. The case-fatality rate was 34.6% (95% CI, 30.6 to 38.6) at 7 days; it increased to 50.3% (95% CI, 46.1 to 54.5) at 30 days and to 59.0% (95% CI, 54.9 to 63.1) at 1 year. Diabetes mellitus and posterior fossa hemorrhage were associated with an increased risk of 7-and 30-day mortality, whereas older age was associated with an increased risk of 30-day mortality only. At the Kaplan-Meier analysis, the 10-year survival rate was 24.1% (95% CI, 20.1 to 28.1). Conclusions-Intracerebral hemorrhage is characterized by a severe prognosis, mostly in the short term. Because of the high proportion of fatal events that occurs early after the stroke, it is mandatory to identify and apply specific therapeutic strategies for patients with intracerebral hemorrhage.

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Migraine is a predominantly female disorder. Menarche, menstruation, pregnancy, and menopause, and also the use of hormonal contraceptives and hormone replacement treatment may influence migraine occurrence. Migraine usually starts after menarche, occurs more frequently in the days just before or during menstruation, and ameliorates during pregnancy and menopause. Those variations are mediated by fluctuation of estrogen levels through their influence on cellular excitability or cerebral vasculature. Moreover, administration of exogenous hormones may cause worsening of migraine as may expose migrainous women to an increased risk of vascular disease. In fact, migraine with aura represents a risk factor for stroke, cardiac disease, and vascular mortality. Studies have shown that administration of combined oral contraceptives to migraineurs may further increase the risk for ischemic stroke. Consequently, in women suffering from migraine with aura caution should be deserved when prescribing combined oral contraceptives.Electronic supplementary materialThe online version of this article (doi:10.1007/s10194-012-0424-y) contains supplementary material, which is available to authorized users.