Risk factors for cerebral ischemic events in patients with atrial fibrillation on warfarin for stroke prevention.

BACKGROUND AND PURPOSES: Patients with atrial fibrillation (AF) on treatment with oral anticoagulants may still suffer ischemic cerebrovascular events. The aim of this study was to evaluate the risk factors for cerebral ischemic events in warfarin-treated AF patients with an International Normalized Ratios (INR) above 1.8 on admission. METHODS: In a case-control study, cases were consecutive patients with AF who were on warfarin and who were admitted to four Italian hospitals after an acute cerebrovascular ischemic event (ischemic stroke or transient ischemic attack) with an INR above 1.8. Controls were selected from a single anticoagulation clinic and were patients with AF on adequate warfarin treatment who did not suffer cerebrovascular events. RESULTS: Cases were identified among 4785 consecutive patients with an ischemic cerebral event. 148 cases (3.1%, 21 with transient ischemic events and 127 with ischemic strokes) had AF and were taking warfarin with an INR above 1.8 on admission. On multivariate analysis, diabetes (OR 3.8; 95% CI 1.09-13.82, p=0.025), hyperlipidemia (OR 4.5; 95% CI 1.11-18.23, p=0.035) and carotid/vertebral atherosclerosis on ultrasound (OR 3.0; 95% CI 1.13-8.41, p=0.028) were independent predictors for ischemic cerebral events. The use of statins was inversely correlated with an ischemic event (OR 0.1; 95% CI 0.06-0.47. p=0.001). CONCLUSIONS: Carotid/vertebral atherosclerosis, diabetes and hyperlipidemia are associated with an increased risk for ischemic events in patients with AF on adequate warfarin treatment. Statins significantly reduce the risk of ischemic events.

Gender differences in patients with acute ischemic stroke.

Stroke has a greater effect on women than men owing to the fact that women have more stroke events and are less likely to recover. Age-specific stroke rates are higher in men; however, because of women's longer life expectancy and the much higher incidence of stroke at older ages, women have more stroke events than men overall. The aims of this prospective study in consecutive patients were to assess whether there are gender differences in stroke risk factors, treatment or outcome. Consecutive patients with ischemic stroke were included in this prospective study at four study centers. Disability was assessed using a modified Rankin Scale score (>or=3 indicating disabling stroke) in both genders at 90 days. Outcomes and risk factors in both genders were compared using the chi(2) test. Multiple logistic regression analysis was used to identify any independent predictors of outcome. A total of 1136 patients were included in this study; of these, 494 (46%) were female. Women were statistically older compared with men: 76.02 (+/- 12.93) and 72.68 (+/- 13.27) median years of age, respectively. At admission, females had higher NIH Stroke Scale scores compared with males (9.4 [+/- 6.94] vs 7.6 [+/- 6.28] for men; p = 0.0018). Furthermore, females tended to have more cardioembolic strokes (153 [30%] vs 147 [23%] for men; p = 0.004). Males had lacunar and atherosclerotic strokes more often (146 [29%] vs 249 [39%] for men; p = 0.002, and 68 [13%] vs 123 [19%] for men; p = 0.01, respectively). The mean modified Rankin Scale score at 3 months was also significantly different between genders, at 2.5 (+/- 2.05) for women and 2.1 (+/- 2.02) for men (p = 0.003). However, at multivariate analysis, female gender was not an indicator for negative outcome. It was concluded that female gender was not an independent factor for negative outcome. In addition, both genders demonstrated different stroke pathophysiologies. These findings should be taken into account when diagnostic workup and treatment are being planned.

Stroke pharmacogenomics.

Circulatory disease accounts for fifteen million deaths each year, of which stroke accounts for four and a half million- with an estimated nine million stroke survivors annually. The overall incidence rate of stroke is 2 to 2.5 per thousand adults with an approximate prevalence of 5 per thousand and an estimated 5-year risk of stroke recurrence of 15 to 40 percent. Conventional risk factors for stroke include: increasing age, hypertension, diabetes mellitus, smoking, increased body mass index, ischemic heart disease, heart failure, atrial fibrillation and lack of physical activity. Age is the strongest risk factor for both ischemic and haemorrhagic stroke with its incidence doubling for each successive decade after the age of fifty-five years. However, there is a substantial portion of patients with significant cerebrovascular disease who do not have any of these stroke risk-factors, leading to the speculation that there are other factors that have not been identified yet So as to improve diagnosis and treatment strategies, as well as to reduce the related public health burden, it could be helpful to successfully identify its extremely complex genetic determinants (polygenic, multiple genes play a role). Pharmacogenetics is the field of pharmacology that deals with the influence of genetic variation on drug response by correlating gene expression and gene variants with the efficacy or toxicity of drugs. The principle drugs in stroke medicine are antithrombotics. The aim of this paper was to review the most commonly used drugs for stroke such as rtPA in the acute phase as well as antiplatelets and wafarin for secondary prophylaxis.

Acute hyperglycemia and early hemorrhagic transformation in ischemic stroke.

BACKGROUND: Hyperglycemia has been claimed to be associated with hemorrhagic transformation (HT) in patients with acute ischemic stroke treated with thrombolysis. The aim of this study was to assess whether the admission blood glucose level is related to HT in a prospective study in consecutive patients with acute ischemic stroke. METHODS: Consecutive patients admitted for ischemic stroke to 4 Italian hospitals were included in this prospective cohort study. RESULTS: Among 1,125 consecutive patients included in the analysis, 98 (8.7%) had HT: 62 (5.5%) had hemorrhagic infarction (HI) and 36 (3.2%) parenchymal hematoma (PH). A blood glucose level >110 mg/dl was found in 42.4% of the patients, a level between 110 and 149 mg/dl in 25.2%, and a level >150 mg/dl in 17.2%. At 3 months, 7 patients were lost at follow-up, 326 patients (29.2%) were disabled (modified Rankin score > or = 3) and 129 died (11.5%). PH was associated with an increased risk of death or disability (OR 15.29, 95% CI 2.35-99.35). However, this was not the case for HT overall and HI. At logistic regression analysis, PH was predicted by high levels of admission blood glucose (OR 1.01, 95% CI 1.00-1.01 for 1 added mg/dl). The rate of PH was 2.1% in patients with <110 mg/dl, 3.6% in patients with a level between 110 and 149 mg/dl and 6.4% in patients with a level >150 mg/dl. The curve estimation regression model showed a significant linear increase in the risk of PH related to an increase in blood glucose levels (R(2) = 0.007, p = 0.007). CONCLUSIONS: Hyperglycemia during acute ischemic stroke predisposes to PH, which in turn determines a non-favorable outcome at 3 months. This relationship seems to be linear.

Hormone replacement therapy and stroke.

UNLABELLED: Stroke is the third most common cause of death in women and a major cause of disability. Stroke occurs in older age in women compared with men. High premenopausal estrogen concentrations in women are thought to be protective against stroke and cardiovascular disease. Estrogens are essential for normal reproductive function and they exert complex and diverse non reproductive actions on multiple tissues such as neuroprotective effects, vasodilatation, improved vascular reactivity, antithrombotic effects and lipid lowering effects. After menopause estrogen concentrations are depleted and in the past estrogen replacement therapy was considered as a potential protective agent against both cardiovascular disease and stroke. Although the use of hormone therapy was originally associated with a reduction in the risk of heart disease by about 50% in observational studies, the results regarding stroke have been less clear. In order to investigate the effect of hormone therapy on stroke risk, randomized controlled trials of cardio-and/or cerebrovascular-disease prevention in women with established heart disease have been designed. The Heart Estrogen-Progestin Replacement Study included stroke as secondary outcome. This study did not show any differences in myocardial infarction (MI) or coronary death (HR 0.99; 95%CI 0.80-1.22) and in stroke rate. In another study, the Women Estrogen Stroke Trial, 17 beta estradiol 1 mg/placebo was administered to women with previous ischemic stroke or transient ischaemic attack (TIA) having a mean age 71. No differences in stroke rate (RR 1.1; 95% CI 0.8-1.4) and in mortality rate (RR 1.2; 95% CI 0.8-1.8) were found, while a trend showing an increased rate of fatal strokes (RR 2.9; 95% CI 0.9-9.0) and for more severe non-fatal strokes (% patients with final National Institutes of Health Stroke Scale (NIHSS) 0-1: 19 % vs. 33%; p = 0.12) was observed. The Women's Health Initiative, a primary prevention study, where conjugated equine estrogen (CEE) plus medroxyprogesterone acetate/placebo was utilized, was stopped because of an excess in breast cancer and increased stroke rates (RR 1.4; 95% CI 1.1-1.8). Recently, a meta-analysis including 39,769 women participating in 28 trials has been published. Twelve studies were of secondary prevention and the overall stroke rate was 2%. In the hormone replacement therapy (HRT) arm there was a 29% increased rate of ischemic stroke (Number Needed to Harm, NNH:147). Furthermore, a 56% increased rate of death or dependency after stroke and a tendency of more fatal stroke were observed. Additionally, a higher stroke risk was reported in the first year of treatment. CONCLUSIONS: There seems to be no indication for hormone replacement therapy in the prevention of stroke in women. Further studies are needed to discover why estrogens have different effects on the heart and brain. Conventional risk-factors which could increase the risk of estrogen therapy need to be identified and as well as more restrictive inclusion and exclusion criteria such as coagulation parameters and intimal thickness should be adopted before new randomized trials are started.

Effect of on-admission antiplatelet treatment on patients with cerebral hemorrhage.

BACKGROUND: Antiplatelet treatment remains the first choice for primary and secondary prevention of vascular diseases; even so, expected benefits may be offset by risk of bleeding, particularly cerebral hemorrhage. The aim of this study was to assess the influence of antiplatelet treatment on clinical outcome at hospital discharge. MATERIALS AND METHODS: Consecutive patients with first-ever stroke due to a primary intraparenchymal hemorrhage were prospectively identified over a 4-year period (2000-2003). Data on hemorrhage location, vascular risk factors, and antiplatelet and anticoagulant treatment were collected. At discharge, outcome was measured using the modified Rankin Scale (disabling stroke > or =3). Patients treated with anticoagulant therapy were excluded from the study. RESULTS: Of 457 consecutive patients with cerebral hemorrhage, 94 (20.5%) had been taking antiplatelet agents. The treated patients (mean age for antiplatelet group 78.9 +/- 9.0 years) were older than the nontreated patients (73.8 +/- 9.4, p = 0.02). In-hospital mortality was 23.4 and 23.1% (p = n.s.) for patients who had been taking antiplatelet agents or no treatment. Poor outcome at discharge was found in 52.1 and 59.7% (p = n.s.), respectively. Univariate analysis showed that age and coma at admission were predictors of disability at discharge, but antiplatelet treatment was not. Additionally, age and coma were shown to be determinants of disability at discharge after multivariate analysis: OR 1.03 per year (95% CI: 1.018-1.049), p < 0.001 and OR 1.68 (95% CI: 1.138-2.503), p = 0.009, respectively. CONCLUSIONS: Hemorrhagic stroke continues to be responsible for a high percentage of disability and death. Furthermore, it was seen here that functional outcome was independent of previous antiplatelet treatment.