Frequency and Structure of Cerebral Strokes and Their Risk Factors: Measures for the Prevention of Recurrent Strokes at the Outpatient Stage

Marc Fisher MD Kennedy Lees MD Section Editors: Hypertension is the most important modifiable risk factor for stroke.1,2 It is estimated that 25% or more of strokes may be attributable to hypertension. Because many patients with stroke have mild hypertension or prehypertension, we have shifted our focus and now think of stroke on a continuum of risk based on blood pressure (BP) level rather than on a threshold effect.3 Because high BP may not exist in isolation, a wider definition of hypertension has been proposed that also takes into account the absolute risk of cardiovascular events and associated metabolic factors or early disease markers.3 Lowering BP reduces the risk of stroke. Epidemiological studies have shown that for each 10 mm Hg lower systolic blood pressure (SBP), there is a decrease in risk of stroke of approximately one third in persons aged 60 to 79 years. This association is continuous down to levels of at least 115/75 mm Hg and is consistent across sexes, regions, stroke subtypes, and for fatal and nonfatal events.4 Lowering diastolic blood pressure (DBP) was once the main target to achieve stroke and other cardiovascular event reduction, but SBP has now become the target.3 As recently shown, even the elderly with sustained SBP elevation may gain from BP reduction in relation to less fatal or nonfatal stroke, death, and heart failure.5 Although the role of longer-term BP control to improve outcomes in patients with stroke is undisputed, BP management immediately after a stroke remains controversial. In an effort to resolve this controversy, several pilot clinical trials have been initiated. In this review, we discuss the results of some of these trials and available evidence-based guidelines for BP control in the settings of acute ischemic and hemorrhagic stroke (excluding subarachnoid hemorrhage) and …

Objective To explore sex differences in risk factors for recurrent stroke in patients with H-type hypertension and stroke. Methods This was an observational study of 1407 patients with H-type hypertension and stroke based on medical record review from an electronic clinical information system. The median follow-up period was 4.9 years. The cumulative incidences of recurrent stroke were compared in different sex-group by using Kaplan-Meier survival analysis. Multivariable Cox analysis was used to evaluate sex differences in independent risk factors and their interactions on recurrent stroke. Results The recurrent stroke rates were slightly higher in men (20.4%) than women (18.3%), which were not significantly different (P>0.05). Kaplan-Meier survival analysis showed that a higher risk of recurrent stroke in the homocysteine (Hcy)≥19 μmol/L group (vs Hcy<19 μmol/L group) of men and diabetes mellitus (DM) group (vs non-DM group), atrial fibrillation (AF) group (vs non-AF group) or ≥60 years group (vs <60 years group) of women (P<0.05). Fasting plasma glucose (FPG) ≥7.0 mmol/L group (vs FPG<7.0 mmol/L group) had an increased risk of recurrent stroke in both women and men (P<0.05). Multivariable Cox proportional hazards model showed that DM and elevated Hcy levels were independent risk factors for recurrent stroke in men, and older age, AF and elevated FPG levels in women (P<0.05). The DM-sex interaction and AF-sex interaction were confirmed, which suggested a higher risk of recurrent stroke in women with DM or AF compared with men (P<0.05). The interactions between DM and other risk factors on recurrent stroke were statistically significant: body mass index and Hcy in men, and systolic blood pressure, diastolic blood pressure and Hcy in women (P<0.05). Conclusion It is recommended that the effectiveness of risk factors alone and the interactions between them for prevention of recurrent stroke in patients with H-type hypertension and stroke should be fully evaluated. There is a need for a stroke risk score for each sex. Multiple cardiovascular risk factors should be controlled simultaneously to better reduce the risk of recurrent stroke. Key words: Hypertension; Stroke; Homocysteine; Recurrence

Major Ongoing Stroke Trials

Major Ongoing Stroke Trials

Major Ongoing Stroke Trials

New information about therapeutic interventions regarding several important aspects of cerebrovascular disease has appeared recently. This short review will focus on new therapeutic developments concerning the prevention of ischemic stroke, acute ischemic stroke therapy trials, and, lastly, the management of patients with intracranial aneurysms. Great strides have been made in the pharmacological management of patients to reduce the risk for developing ischemic stroke. Stroke prevention is now clearly a multimodal endeavor that encompasses not only the use of antithrombotic agents but also the identification and treatment of multiple, potential stroke risk factors.1 While the precise relationship of elevated total and LDL cholesterol to stroke risk remains to be determined, prior studies clearly demonstrated substantial primary stroke risk reduction with the use of various statins in patients with cardiovascular disease.2 A recent report by the Heart Protection Study Collaborative Group (HPS) suggests that the benefits of at least 1 statin, simvastatin, extend to stroke patients as well.3 In this study, 20 536 patients with 1 form of vascular disease or diabetes mellitus were randomized to 40 mg of simvastatin daily or placebo in addition to their baseline medications and followed on average for 5 years. Of patients randomized, 1820 had stroke alone and 1460 had stroke and coronary artery disease. Allocation to simvastatin was associated with an overall 25% reduction in first stroke. Patients with stroke in the study had a similar benefit for subsequent major vascular events, although precise characterization of risk reduction for secondary stroke was not provided. The results may in fact underestimate the benefits of simvastatin because on average 17% of placebo allocated patients took a nonstudy statin. The result of this study led to a change in the indications for simvastatin by the FDA, and the medication is now indicated in stroke patients, …

Objective To investigate the correlation of microembolic signals （MES） and outcome in patients with acute ischemic stroke. Methods The patients with acute ischemic stroke were enrolled in the study. The MES of middle cerebral artery was monitored dynamically using transcranial color Doppler ultrasound. The early lesions of ischemic stroke were evaluated by MRI. The National Institutes of Health Stroke Scale （NIHSS） was used to evaluate neurological deficits. The modified Rankin scale was used to evaluate the outcome, and the stroke recurrence was recorded. Results A total of 135 patients with acute ischemic stroke were enrolled, in which, 33 were cardiogenic cerebral embolism, 49 were large artery atherosclerotic stroke, 24 were small medal occlusive stroke, and 29 were other clear causes or cryptogenic stroke. Multivariate logistic regression analysis showed that coronary heart disease （odds ratio [ OR], 5. 862, 95% confidence interval [ CI] 2. 008 - 17. 114; P = 0. 000） was the independent risk factor for positive MES within 48 hours after stroke onset, while the history of antithrombotic treatment （OR O. 376, 95% C10. 141 - 0. 998; P = 0. 045） was its independent protective factor. In addition, coronary heart disease （OR 4. 879, 95% CI 1. 257 - 18. 939; P = 0. 033）, hypertension （OR 4. 958, 95% C1 1. 029 - 23. 882; P = 0. 030） , and diabetes （OR 3. 659, 95% C11. 027 - 13. 034; P = 0. 050） were the independent risk factors for positive MES within 1 week after stroke onset. The NIHSS scores of the patients of the positive MES at baseline and 1 week and the clinical outcome at 3 months had no significant differences with the patients of negative MES, however, stroke recurrence and deaths increased significantly （P =0. 019）. Conelmiom MES within 48 hours of onset was not associated with the outcome in patients with acute ischemic stroke at 3 months, however, the incidence of endpoint events such as recurrence and death was sigaificantly higher in patients of positive MES within 3 months. Key words: Intracranial Embolism and Thrombosis; Stroke; Brain Ischemia; Ultrasonoraphy, Doppler,Transcranial; Cerebrovascular Circulation; Risk Factors

Vasculocentricity Versus Cerebrocentricity: What Stroke-Related Baroreceptor Reflex Sensitivity Changes Might Be Telling Us

Intracranial bleeding is the most feared complication of thrombolytic therapy in acute stroke. The risk of brain hemorrhage is the main argument of the European authorities not to approve recombinant tissue plasminogen activator (rtPA), and the fear of hurting patients with rtPA explains its limited use in North America. The common argument is, “Treatment with rt-PA may have some beneficial effect, but that is traded off by a considerable risk of symptomatic hemorrhage.” This argument is false and based on misunderstanding and misconception. The misunderstanding: There is no such trade-off. The National Institute of Neurological Disorders and Stroke (NINDS) rtPA Stroke Study Group observed 2 patients (0.6%) with symptomatic and 1 patient (0.3%) with fatal hemorrhages in the placebo group (n=312) and 20 patients (6.4%) with symptomatic and 9 patients (2.9%) with fatal hemorrhages in the rtPA group (n=312).1 Despite this supposed excess in risks caused by rtPA treatment (odds ratios [OR], 10.6 and 9.2), rtPA treatment significantly reduced the risk for disability and death (modified Rankin Scale >1 at 12 months after stroke) from 73% to 59% (reduction for death alone: 28% to 24%).2 In both European Cooperative Acute Stroke Studies (ECASS) 1 and 2, rtPA increased the risk for parenchymal hematomas (OR, 3.0 and 4.2), but reduced the overall risk for disability and death by 6% and 8% (NS).3,4⇓ A similar observation—an overall risk reduction for disability and death despite an increased risk for intracranial hemorrhages—was made in the Multicenter Acute Stroke Trials (MAST) -Europe and -Italy. Why …

Major Ongoing Stroke Trials

Major Ongoing Stroke Trials

Objective To respectively analyze the patterns and possible predictors of recurrent strokes among patients with initial ischemic stroke. Methods Three hundred and sixty-one patients with recurrent strokes (acute ischemic stroke or intracerebral hemorrhage) after initial ischemic strokes were collected from Jan 2004 to Dec 2009. The data about conventional risk factors such as smoking, heavy alcohol drinking, hypertension, diabetes, hyperlipidemia, heart diseases, head trauma, migraine, family history of cardiovascular disease, and the use of preventive medications were collected and analyzed among patients with different types of recurrent strokes. Results Patients (n=361) were divided into ischemic stroke group (n=321) and hemorrhagic stroke group (n=40) according to the recurrent stroke type. The ischemic stroke group was further divided into the anterior circulation stroke subgroup (n=234) , the posterior circulation stroke subgroup (n=75) and watershed cerebral infarction or multiple infarction subgroup (n=12) . Multivariate logistic regression analysis revealed that older age at initial stroke onset (OR=1.036,95%CI 1.006—1.067，P=0.02) and hyperlipidemia (OR=2.253,95%CI 1.092—4.647，P=0.028) were both the independent risk factors for the recurrent ischemic stroke. Comparing the subgroups, multivariate logistic regression analysis showed that atrial fibrillation (OR=4.217,95%CI 1.489—11.942，P=0.007) was the independent risk factor for the recurrent ischemic stroke in the posterior circulation territory. Conclusion Aging and hyperlipidemia are possible predictors of recurrent ischemic stroke after the initial ischemic stroke which would be useful for individualized secondary prevention of stroke. Key words: Brain ischemia; Stroke; Recurrence; Risk factors

Abstracts of literature

Stroke is the third leading cause of death in the United States.1 2 3 4 A decline in the age-adjusted death rate for nonwhite women began in 1924, for nonwhite men in 1930, and for whites by 1918.5 The rate of decline accelerated in the 1970s, probably because of improved hypertension control, but slowed in the 1980s for reasons that remain unclear.6 Recently published statistics suggest that the long-term decline in stroke mortality rates in the United States may have ceased. There is unmistakable evidence for a marked slowdown in the decline in stroke mortality.6 The age-adjusted US stroke mortality rate increased between 1992 and 1993; a recent report documented another rise in the preliminary rate for 1995 (percent change from 1994 to 1995, +0.8).7 Age-adjusted rates per 100 000 for 1991 to 1995 were 26.8, 26.2, 26.5, 26.5, and 26.7, respectively (Table 1⇓). It is important to view these increases in proper perspective while in no way diminishing the serious impact of the slowdown in the decline of stroke mortality in the United States since 1978.6 To this end, we tested the hypotheses (1) that the rate of decline of age-adjusted mortality rates in 1987 to 1994, the period since the previous report,6 has returned to that seen in the 1960s before the widespread availability of antihypertensive therapy, and (2) that this occurred in each sex/race group. In 1987 to 1994, the mean annual absolute and percent decline in age-adjusted death rates for stroke was less than observed in 1979 to 1986 for each sex/race group (Table 2⇓).6 It was comparable to that observed in the 1960s, before the rapid decline of the 1970s that was commonly attributed to marked improvements in hypertension detection and treatment.2 This …

85 BACKGROUND AND PURPOSE: Sleep patterns may independently affect morbidity and mortality. However, the effect of habitual sleep patterns on the risk for stroke and carotid atherosclerosis is undetermined. METHODS: We evaluated the association of nocturnal snoring, sleep duration, and daytime somnolence with stroke and carotid artery stenosis in 1,348 adults who participated in a stroke screening program in Buffalo, New York. A standard questionnaire was used for each person to report sleep habits and cardiovascular risk factors. Each participant underwent carotid Doppler ultrasound testing and an interview by a neurologist or neurosurgeon to determine the presence of carotid stenosis or history of stroke. Logistic regression analyses were used to examine these relationships. RESULTS: Of the 1348 persons evaluated, 82 (6%) had a previous stroke and 96 (7.1%) had significant carotid stenosis (stenosis > 60%). The frequency of prior stroke was higher in individuals who routinely slept for more than 8 hours per night (14%) than in those who either slept for 6–8 hours (5.4%) or less than 6 hours (5.4%). Persons who experienced daytime somnolence regularly had a higher frequency of stroke (14%) than those who did not (4%). After adjusting for differences in age, race, gender, cigarette smoking, hyperlipidemia, hypertension, and diabetes mellitus, the risk for stroke was significantly associated with daytime somnolence (Wald s chi-square test 11.8, p=0.018), average hours of sleep (Wald s chi-square test 14.7, p=0.002), and frequency of nocturnal snoring (Wald s chi-square test 13.3, p=0.009). After adjusting for other cardiovascular risk factors, daytime somnolence, average hours of sleep, and frequency of nocturnal snoring were not associated with carotid atherosclerosis. CONCLUSIONS: Daytime somnolence, sleeping more than 8 hours per night, and frequent nocturnal snoring increase the likelihood for stroke but not carotid atherosclerosis. This increased likelihood for stroke appears to be independent of atherosclerotic mechanisms and other cardiovascular risk factors.