Gender differences in the treatment of cerebrovascular disease

OBJECTIVE: Previous studies have shown that women receive fewer invasive procedures for the treatment of coronary artery disease than men, but gender differences in cerebrovascular disease have not been well studied. Our objective was to explore differences in the treatment of stroke between men and women. DESIGN: Secondary database analyses. STUDY PARTICIPANTS: We examined the use of carotid endarterectomy in a nationally representative sample of Medicare enrollees aged 65 to 84, hospitalized for a principal diagnosis of stroke in 1992, the "all strokes group". We also studied a subgroup of patients, the "carotid disease subgroup", admitted with a principal diagnosis of precerebral arterial occlusion and stenosis or transient cerebral ischemia. MEASUREMENTS: We determined rates of carotid endarterectomy for the all strokes group within gender and age groups and calculated corresponding female-to-male relative risks (RR) and 95% confidence intervals (CI). We also performed similar analyses for the carotid disease subgroup. We then used logistic regression to estimate the relative risk of use of carotid endarterectomy for women, controlling for age and comorbidity. RESULTS: The all-strokes group consisted of 3,356 women and 2,927 men, of whom 1,009 women and 990 men were in the carotid disease subgroup. The overall age-adjusted female-to-male relative risk of undergoing carotid endarterectomy for those aged 65 to 84 was 0.69 (95% CI, 0.64-0.74) in the all strokes group and 0.77 (95% CI, 0.72-0.82) in the carotid disease subgroup. In both analyses, the RR became more pronounced with increasing age. In the all strokes group, for example, the RR was 0.80 (0.70-0.92) for those aged 65 to 69 and 0.39 (0.32-0.48) for those aged 80 to 84. The RR for the all strokes group remained similar in magnitude even after controlling for comorbidity (RR, 0.63 and 95% CI, 0.59-0.70). CONCLUSION: We conclude that women hospitalized for strokes undergo fewer carotid endarterectomies than men. Further studies are needed to examine the reasons for and implications of this gender difference.     

Declining incidence and mortality of stroke in persons aged > or = 75 years in Finland; the FINSTROKE study.

BACKGROUND: The average life expectancy of a person aged 75 in Finland is approximately 10 years. A substantial threat to the quality of life during these years is stroke, which is common among the elderly, may hamper independent living and places a substantial burden on health care resources. The aim of the present study was to analyse the trends in incidence, mortality and prognosis of acute stroke events in persons aged > or = 75 years in Finland. DESIGN: A population-based stroke register study. METHODS: The FINSTROKE register recorded all stroke events in persons aged > or = 75 years (n=5493) among inhabitants of the town of Turku from 1982 to 1992 and again from 1996 to 1998, and in the Kuopio area from 1990 to 1997. RESULTS: At the end of the study period, the age group > or = 75 years constituted 3.8% of the population of study areas among men and 8.7% among women. This population segment contributed 35% of strokes among men and 66% among women. Of all strokes in this age group, 73% occurred among women. Data suggested that the mortality and incidence of acute stroke events were declining, but the 28-day case fatality did not change. At day 28 after the onset of stroke, only 26% of men and 19% of women had recovered well enough to be capable of independent living. CONCLUSIONS: Stroke mortality among the elderly is declining in Finland, which is mainly due to the decline in the incidence of stroke events.     

Trends in Stroke Rates,Risk, and Outcomes in the United States, 1988 to 2008

Background

Stroke is a major cause of morbidity and mortality. We describe trends in the incidence, outcomes, and risk factors for stroke in the US Medicare population from 1988 to 2008.

Methods

We analyzed data from a 20% sample of hospitalized Medicare beneficiaries with a principal discharge diagnosis of ischemic (n = 918,124) or hemorrhagic stroke (n = 133,218). Stroke risk factors were determined from the National Health and Nutrition Examination Survey (years 1988-1994, 2001-2008) and medication uptake from the Medicare Current Beneficiary Survey (years 1992-2008). Primary outcomes were stroke incidence and 30-day mortality after stroke hospitalization.

Results

Ischemic stroke incidence decreased from 927 per 100,000 in 1988 to 545 per 100,000 in 2008, and hemorrhagic stroke decreased from 112 per 100,000 to 94 per 100,000. Risk-adjusted 30-day mortality decreased from 15.9% in 1988 to 12.7% in 2008 for ischemic stroke and from 44.7% to 39.3% for hemorrhagic stroke. Although observed stroke rates decreased, the Framingham stroke model actually predicted increased stroke risk (mean stroke score 8.3% in 1988-1994, 8.8% in 2005-2008). Statin use in the general population increased (4.0% in 1992, 41.4% in 2008), as did antihypertensive use (53.0% in 1992, 73.5% in 2008).

Conclusions

Incident strokes in the Medicare population aged ≥65 years decreased by approximately 40% over the last 2 decades, a decline greater than expected on the basis of the population's stroke risk factors. Case fatality from stroke also declined. Although causality cannot be proven, declining stroke rates paralleled increased use of statins and antihypertensive medications.     

Atrial fibrillation: a major contributor to stroke in the elderly. The Framingham Study

Chronic atrial fibrillation without valvular disease has been associated with increased stroke incidence. The impact of atrial fibrillation on the risk of stroke with increasing age was examined in 5184 men and women in the Framingham Heart Study. After 30 years of follow-up, chronic atrial fibrillation appeared in 303 persons. Age-specific incidence rates steadily increased from 0.2 per 1000 for ages 30 to 39 years to 39.0 per 1000 for ages 80 to 89 years. The proportion of strokes associated with this arrhythmia was 14.7%, 68 of the total 462 initial strokes, increasing steadily with age from 6.7% for ages 50 to 59 years to 36.2% for ages 80 to 89 years. In contrast to the impact of cardiac failure, coronary heart disease, and hypertension, which declined with age, atrial fibrillation was a significant contributor to stroke at all ages.     

Hormone therapy and the risk of stroke after acute myocardial infarction in postmenopausal women.

OBJECTIVES: We examined the association of hormone therapy (HRT) with hemorrhagic and ischemic stroke among postmenopausal women with acute myocardial infarction (AMI). BACKGROUND: Hemorrhagic and ischemic strokes are common complications of AMI, and women are at increased risk for hemorrhagic stroke after thrombolytic therapy. This risk may be related to female hormones. METHODS: Using data from the National Registry of Myocardial Infarction-3, we studied 114,724 women age 55 years or older admitted to the hospital for AMI, of whom 7,353 reported HRT use on admission. We determined rates of in-hospital hemorrhagic and ischemic stroke stratified by HRT use and estimated the independent association of HRT with each stroke type using multivariable logistic regression. RESULTS: The HRT users were younger than non-users, had fewer risk factors for stroke including diabetes and prior stroke, and received more pharmacologic and invasive therapy including cardiac catheterization. A total of 2,152 (1.9%) in-hospital strokes occurred, with 442 (0.4%) hemorrhagic, 1,017 (0.9%) ischemic and 693 (0.6%) unspecified. Among HRT users and non-users, the rates of hemorrhagic stroke (0.40% vs. 0.42%, p = 1.00) and ischemic stroke (0.80% vs. 0.96%, p = 0.11) were similar. Among 13,328 women who received thrombolytic therapy, the rate of hemorrhagic stroke was not significantly different for users and non-users (1.6% vs. 2.1%, p = 0.22). After adjustment for baseline and treatment differences, HRT was not associated with hemorrhagic (odds ratio [OR], 0.88; 95% confidence intervals [CI], 0.58 to 1.35) or ischemic stroke (OR, 0.89; CI, 0.66 to 1.18). CONCLUSIONS: Acute myocardial infarction is a high-risk setting for stroke among postmenopausal women, but HRT does not appear to modify that risk. Clinicians should not alter their approach to thrombolytic therapy based on HRT use.     

The impact of C-reactive protein on risk of stroke, stroke subtypes, and ischemic heart disease in middle-aged Japanese: the Japan public health center-based study

Aim: To examine the impact of C-reactive protein on the risks of stroke and its subtypes, particularly among Asian populations in which median C-reactive protein levels are typically lower than in Western populations.Methods: A prospective, nested case-control study was conducted to examine the associations between high sensitivity-CRP (hs-CRP) and risks of cardiovascular disease within a cohort of 29,876 men and women aged 40-69 years, with no history of stroke, ischemic heart disease or cancer, who submitted blood samples between 1990 and 1993. Systematic cardiovascular surveillance was performed throughout 2007. One control for each stroke and two controls for each ischemic heart disease were matched for sex, age, date of blood drawing, time since last meal and study location.Results: We documented 1,132 incident strokes (638 ischemic and 494 hemorrhagic strokes) and 209 ischemic heart diseases (168 myocardial infarctions and 41 sudden cardiac deaths), and observed a linear association between hs-CRP levels and risks of ischemic stroke and ischemic heart disease, more specifically myocardial infarction. The multivariable odds ratios associated with 1-SD increment of logarithmically transformed hs-CRP were 1.13 (0.99-1.29),p= 0.07 for ischemic stroke, 1.16 (0.96-1.41),p= 0.13 for lacunar infarction, 1.41 (0.98-2.01),p= 0.06 for embolic infarction, and 1.28 (1.03-1.59),p= 0.03 for myocardial infarction. The predictive value of hs-CRP for ischemic stroke was reduced primarily after adjustment for hypertensive status and body mass index. No association was found between hs-CRP levels and the risk of hemorrhagic or total stroke.Conclusions: High serum hs-CRP levels were associated with the risk of myocardial infarction and more weakly with the risk of ischemic stroke among middle-aged Japanese men and women.     

Is insulin resistance or diabetes mellitus associated with stroke? An 18-year follow-up study

Insulin resistance and/or diabetes are risk factors for coronary artery disease. However, it is still controversial whether they are associated with the development of stroke. A total of 304 Japanese men and women, aged 20-69 years, were selected on the basis of casual high blood glucose concentrations from 2732 participants of a population-based health examination in 1980. They all underwent a 50 g oral glucose tolerance test in 1981. Homa IR (index of insulin resistance) and Homa beta-cells (index of beta-cell function) were calculated from their fasting insulin and glucose using the formulas for the homeostasis model. They were followed-up for 18 years. Incidence of stroke was investigated by computed tomography. During 18 years, 28 subjects had a stroke; 21 had ischemic and nine had hemorrhagic strokes (two had both). Baseline variables, which showed an independent association with the incidence of stroke in the Cox proportional hazard model, were blood pressure, use of anti-hypertensive medications, and Homa beta-cell index (inversely) after adjustments for age and sex. After further adjustment for blood pressure using a step-forward method, Homa beta-cell was significantly related to the incidence of stroke (Hazard ratio: 0.65, 95% confidence interval: 0.44-0.95). In addition to hypertension, diabetes but not insulin resistance, is a risk factor for stroke.     

Comparison of blood pressure-associated risk of intracerebral hemorrhage and subarachnoid hemorrhage: Korea Medical Insurance Corporation study

Intracerebral hemorrhage and subarachnoid hemorrhage have different pathogeneses and risk factor profiles. However, little information is available on the difference between intracerebral and subarachnoid hemorrhages in relation to blood pressure. We prospectively investigated the relationships between blood pressure and risks of stroke subtypes. We measured blood pressure and other cardiovascular risk factors in 100,147 men and 59,558 women 35 to 59 years of age in 1990 and 1992. Outcomes were fatal and nonfatal events of stroke and its subtypes from 1993 to 2002. Independent relationships between baseline blood pressure and stroke subtypes were assessed using Cox's proportional hazard models. During the 10 years, 1714 ischemic and 1159 hemorrhagic strokes (742 intracerebral and 308 subarachnoid hemorrhages) occurred. Blood pressure was related more closely with hemorrhagic stroke than ischemic stroke, and the difference was more prominent in women. Among the subtypes of hemorrhagic stroke, intracerebral hemorrhage was more closely related with blood pressure than subarachnoid hemorrhage. For each 20 mm Hg increase in systolic blood pressure, adjusted relative risks of ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage were 1.79 (95% confidence interval, 1.68 to 1.90), 2.48 (2.30 to 2.68), and 1.65 (1.38 to 1.97) in men, and 1.64 (1.42 to 1.89), 3.15 (2.61 to 3.80), and 2.29 (1.82 to 2.89) in women, respectively. In conclusion, blood pressure is more closely related with intracerebral hemorrhage than subarachnoid hemorrhage, thus proportion of intracerebral hemorrhage in hemorrhagic stroke may affect the association between blood pressure and hemorrhagic stroke. Our data also emphasize the importance of blood pressure control for the prevention of stroke, especially in countries with a high incidence of intracerebral hemorrhage.     

Acute stroke in a metropolitan area, 1970 and 1980. The Minnesota Heart Survey

Mortality rates for stroke, and hospitalization and case fatality rates for acute stroke in 1970 and 1980 were obtained for residents aged 30-74 of the Twin Cities (Minneapolis--St Paul) metropolitan area to determine whether improved hospital care contributed to the decline in stroke mortality. Age-adjusted mortality rates per 100,000 declined significantly in that decade for men (1970, 89.4; 1980, 47.5; p less than 0.01) and women (1970, 72.6; 1980, 40.9; p less than 0.01). Age-adjusted hospitalization rates per 100,000 population also declined significantly for men (1970, 438; 1980, 323; p less than 0.01) and women (1970, 331; 1980, 203; p less than 0.01). Age-adjusted mean length of hospital stay did not change significantly. Hospital case fatality declined for men aged 30-64 years (1970, 22.5%; 1980, 15.1%; p less than 0.01) but did not change significantly for 65 to 74 year-old men (1970, 16.5%; 1980, 20.0%; p = 0.09) or for all women (age-adjusted rates: 1970, 13.6%; 1980, 16.0%; p = 0.17). There was no change in the distribution of severity of hospitalized cases between years. Therefore, the decline in stroke mortality is consistent with a decreased incidence of stroke resulting from improved hypertension control. Improvements in hospital medical care appear not to have contributed substantially to the decline in stroke mortality.     

农民脑卒中发病率及影响因素

对35～59岁农民4332人进行脑卒中发病率的10年随访．随访率97．17％，10年发生脑卒中86例．年标化发病率1．94‰；．男性标化率2.40‰。，女性1．90‰。发现基线收缩压、舒张压水平与脑卒中发病呈正相关。男性大量吸烟组发病率（5．37％），较不吸烟组（1．90％）高，RR2．83；男性大量饮酒组发病率5.59％，不饮酒为1．72％，RR3．25；高血压大量饮酒组脑卒中发生率46.47％．较正常血压不饮酒组（0．74％）显著高，RR63．07。血清胆固醇的均值女性高于男性（P＜0.01）。女性基线血压水平及高血压患病率明显高于男性，但脑卒中发病率及低于男性，分析其原因．女性有多于男性的有利因素，即血TC高，少量吸烟，不饮或少量饮酒。     

Exploring contrary trends in bladder cancer incidence,mortality and survival: implications for research and cancer control

Aim: To investigate trends in bladder cancer incidence, mortality and survival, and cancer–control implications. Methods: South Australian Registry data were used to calculate age‐standardized incidence and mortality rates from 1980 to 2004. Sociodemographic predictors of invasive as opposed to in situ disease were examined. Determinants of disease‐specific survival were investigated using Kaplan–Meier estimates and proportional hazards regression. Results: Incidence rates for invasive cancers decreased by 21% between 1980–84 and 2000–04, similarly affecting men and women. Meanwhile increases occurred for combined in situ and invasive disease. While mortality rates decreased by approximately a third in men and women less than 70 years of age after the early 1990s, no changes were evident for older residents. The proportion of cancers found at an in situ stage was higher in younger ages and more recent diagnostic periods. Five‐year survivals of invasive cases decreased from 64% for 1980–84 diagnoses to 58% for 1995–2004. Multivariable analysis showed that diagnostic period was not predictive of survival after age adjustment (P= 0.719), with lower survival relating to older age, transitional compared with papillary transitional cancers, female sex, indigenous status and a country as opposed to metropolitan residence. Conclusions: Reductions in invasive disease incidence may be due to increased detection at an in situ stage. The decline in survival from invasive disease in more recent periods is explained by increased age at diagnosis. Poorer outcomes of invasive cases remain for women after adjusting for age, histology, indigenous status and residential location.     

Fish consumption and stroke risk in elderly individuals: the cardiovascular health study

BACKGROUND: Associations between fish consumption and stroke risk have been inconsistent, possibly because of the differences in types of fish meals consumed. Additionally, such relationships have not been specifically evaluated in the elderly, in whom disease burden may be high and diet less influential. METHODS: Among 4775 adults 65 years or older (range, 65-98 years) and free of known cerebrovascular disease at baseline in 1989-1990, usual dietary intake was assessed using a food frequency questionnaire. In a subset, consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches (fish burgers), correlated with plasma phospholipid long-chain n-3 fatty acid levels. Incident strokes were prospectively ascertained. RESULTS: During 12 years of follow-up, participants experienced 626 incident strokes, including 529 ischemic strokes. In multivariate analyses, tuna/other fish consumption was inversely associated with total stroke (P = .04) and ischemic stroke (P = .02), with 27% lower risk of ischemic stroke with an intake of 1 to 4 times per week (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55-0.98) and 30% lower risk with intake of 5 or more times per week (HR, 0.70; 95% CI, 0.50-0.99) compared with an intake of less than once per month. In contrast, fried fish/fish sandwich consumption was positively associated with total stroke (P = .006) and ischemic stroke (P = .003), with a 44% higher risk of ischemic stroke with consumption of more than once per week (HR, 1.44; 95% CI, 1.12-1.85) compared with consumption of less than once per month. Fish consumption was not associated with hemorrhagic stroke. CONCLUSIONS: Among elderly individuals, consumption of tuna or other broiled or baked fish is associated with lower risk of ischemic stroke, while intake of fried fish or fish sandwiches is associated with higher risk. These results suggest that fish consumption may influence stroke risk late in life; potential mechanisms and alternate explanations warrant further study.     

Diabetes as a risk factor for stroke. A population perspective

Summary Stroke incidence, case fatality and mortality in diabetic patients were compared to non-diabetic subjects in a 35–74-year-old population in northern Sweden (target population 241,000). During an 8-year period, 1,544 stroke events in diabetic patients and 4,826 events in non-diabetic subjects were recorded. The crude incidence of stroke was 1,000 per 100,000 in the diabetic men vs 247 in the non-diabetic men (relative risk 4.1; 95% confidence interval 3.2–5.2). Among diabetic women, the crude incidence was 757 per 100,000 and 152 in non-diabetic women (relative risk 5.8; 95% confidence interval 3.7–6.9). The 28-day case fatality among men was similar in the diabetic and non-diabetic stroke patients (18.6 vs 17.1%; p=0.311), but significantly higher in diabetic women compared with non-diabetic women (22.2 vs 17.9%; p=0.02). When compared with the non-diabetic population, the overall mortality from stroke in the diabetic population (first and recurrent) was 4.4-times higher in male and 5.1-times higher in the female patients. Hypertension, atrial fibrillation, heart failure or myocardial infarction were all significantly more common in diabetic than in non-diabetic stroke patients. The population attributable risk, a crude estimate of all strokes ascribed to diabetes mellitus, was 18% in men and 22% in women. In Sweden, about 50 strokes are annually directly attributed to diabetes in a population of 100,000 in this age group.Abbreviations MONICA Multinational Monitoring of Trends and Determinants in Cardiovascular Disease - ICD International Classification of Diseases - CT computerised tomography - CI confidence interval - RR relative risk - CF case fatality     

The incidence of stroke after myocardial infarction: a meta-analysis

Purpose

While the risk of stroke after myocardial infarction (MI) is increased compared with the risk among those without MI, the magnitude of this risk remains unclear. Although numerous clinical trials have reported the incidence of stroke following MI, these are among selected populations. We reviewed cohort studies reporting the incidence of stroke after MI to better define the risk of ischemic stroke in an unselected population.

Methods

A computerized literature search (MEDLINE and PubMed) and manual review of reference lists of identified articles were conducted. Population-based studies published from 1978-2004 with at least 100 subjects that reported number or percent of ischemic strokes experienced by MI survivors were identified. Data were extracted using standardized forms, and study quality was assessed by 2 independent reviewers. Ischemic stroke rates were reported as number of events per 1000 MI with 95% confidence intervals (CI) calculated by Poisson distribution. A combined stroke rate was calculated for in-hospital, 30 days, and 1-year post-MI using weights of 1/variance. A random-effects model also was created to estimate in-hospital stroke rate. Variability in study designs and outcome definitions limit synthesis of available data.

Results

During hospitalization for the index MI, 11.1 ischemic strokes occurred per 1000 MI compared with 12.2 at 30 days and 21.4 at 1 year. Using a random-effects model, 14.5 strokes occurred per 1000 MI. Positive predictors of stroke after MI included: advanced age, diabetes, hypertension, history of prior stroke, anterior location of index MI, prior MI, atrial fibrillation, heart failure, and nonwhite race.

Conclusions

The public health implications of stroke among MI survivors, as well as the large number of MI survivors, underscore the need to be aware of this devastating complication. Further research is needed to determine the optimal stroke prevention strategies for MI survivors.     

Atrial fibrillation as a risk factor for stroke recurrence

BACKGROUND: Although atrial fibrillation is a well-known risk factor for ischemic stroke, the extent to which it increases the risk of stroke recurrence, particularly in elderly patients, is less certain. METHODS: We performed a retrospective cohort study of 915 patients aged 50 to 94 years who were admitted with an ischemic stroke. The rates of recurrent strokes and recurrent severe strokes were estimated with the Kaplan-Meier method. The effects of atrial fibrillation on stroke risk were analyzed with proportional hazards models. RESULTS: Of the 829 patients who survived the initial hospitalization, 163 (20%) had a stroke during follow-up. Of the 203 patients with atrial fibrillation during index hospitalization who were not anticoagulated, 54 (27%) had recurrent strokes, compared with 18% (19/103) among those with atrial fibrillation who were anticoagulated and 17% (90/523) among those without atrial fibrillation. The age-adjusted hazard ratio for recurrent stroke among those with atrial fibrillation who were not treated with anticoagulants was 2.1 (95% confidence interval [CI]: 1.4 to 2.9; P <0.001), whereas the hazard ratio for recurrent severe stroke was 2.4 (95% CI: 1.6 to 3.6; P <0.001). The increased risk was observed even in patients aged > or = 80 years and persisted during the follow-up for more than 5 years. CONCLUSION: Atrial fibrillation was an independent risk factor for stroke recurrence over a wide age range.     

Incidence of Kaposi's sarcoma and HHV-8 seroprevalence among homosexual men with known dates of HIV seroconversion. Italian Seroconversion Study

OBJECTIVES: To evaluate temporal trends of Kaposi's sarcoma (KS) and of the KS-related human herpesvirus (HHV-8) among homosexual men who seroconverted for HIV between 1984 and 1997. METHODS: The study participants were 387 homosexual men. Changes over a period of time were assessed by estimating KS incidence rates per 1000 person-years for the periods 1984-1989, 1990-1992, 1993-1995, and 1996-1997. The proportional incidence of KS as the AIDS-defining disease for the same periods was also calculated. To evaluate a cohort effect of calendar period, Kaplan-Meier curves were used to estimate the risk of KS by period of HIV seroconversion [i.e. before 1990 (median year of seroconversion) versus later]. Relative hazards for the four periods were estimated using competitive-risks models. We also estimated HHV-8 seroprevalence over the study period. RESULTS: Forty-eight participants developed KS. Between 1984 and 1995, the incidence rate of KS per 1000 person-years increased from 3.9 to 32.8, whereas the proportional incidence decreased from 33.3 to 24.3%. The risk of developing KS after HIV seroconversion did not change when comparing the seroconversion periods (i.e. before 1990 versus later). HHV-8 seroprevalence also remained stable. The rates of KS and the relative hazards dramatically decreased after 1995. CONCLUSIONS: Although KS incidence rates increased up to 1995, the proportional incidence decreased, due to the higher increase in rates of other AIDS-defining diseases. The finding that the risk of developing KS after HIV seroconversion remained stable over time is consistent with the stable trend of HHV-8 seroprevalence. The dramatic decrease in KS incidence rates after 1995 coincides with combined antiretroviral therapy.     

Mixed comparison of stroke prevention treatments in individuals with nonrheumatic atrial fibrillation

BACKGROUND: We aimed to identify different stroke prevention treatments for atrial fibrillation assessed in randomized controlled trials and to compare them within a single evidence synthesis framework. METHODS: We updated the Cochrane review on anticoagulants and antiplatelet therapy for nonrheumatic atrial fibrillation to include randomized controlled trials published between January 2000 and March 2005 identified via the CENTRAL database and MEDLINE. A mixed-treatment comparison method was used to combine direct within-trial, between-treatment comparisons with indirect trial evidence while maintaining randomization. RESULTS: Data were combined from 19 clinical trials that included 17 833 patients randomized to 9 treatment strategies, including placebo. For prevention of ischemic stroke, adjusted standard-dose warfarin sodium (relative rate [RR], 0.35; 95% credible interval [CrI], 0.24 to 0.52), adjusted low-dose warfarin (RR, 0.35; 95% CrI, 0.19 to 0.60), ximelagatran (RR, 0.34; 95% CrI, 0.18 to 0.61), and aspirin (RR, 0.64; 95% CrI, 0.44 to 0.88) were all associated with a significantly lower rate of ischemic stroke compared with placebo. For major and fatal bleeding episodes, there was some evidence of an increased risk for all treatments but none were statistically significant. Assuming a baseline risk of 51 ischemic stroke events per 1000 person-years, it can be estimated that adjusted standard-dose warfarin could prevent 28 (95% CrI, -37 to -19) ischemic strokes at the expense of 11 (95% CrI, -1 to +39) major or fatal bleeding episodes. In comparison, aspirin could prevent 16 (95% CrI, -26 to -5) ischemic strokes at the expense of 6 (95% CrI, -3 to +27) major or fatal bleeding episodes. CONCLUSIONS: A lower rate of ischemic stroke and a higher rate of major bleeding episodes were found to be associated with oral anticoagulants compared with aspirin, and both anticoagulants and aspirin were found to be associated with a reduction in the rate of stroke compared with placebo.     

Hormone replacement therapy and associated risk of stroke in postmenopausal women

BACKGROUND: There is little information about the risk of stroke in relation to time since initiation of hormone therapy and in relation to estrogen dose. METHODS: We conducted a population-based case-control study at Group Health Cooperative (GHC), a health maintenance organization in the greater Seattle (Wash) area, to assess the association of hormone replacement therapy with the risks of incident ischemic and hemorrhagic stroke. Cases were all postmenopausal women with incident stroke at GHC during July 1989 through December 1998 (726 ischemic strokes and 213 hemorrhagic strokes). Controls were randomly selected from GHC enrollees and frequency matched to cases on age and calendar year (n = 2525). Hormone use was assessed from computerized pharmacy data. We reviewed the medical record to confirm eligibility and assess other risk factors. RESULTS: After risk factor adjustment, ischemic stroke was not associated with current use of estrogen with progestin (odds ratio [95% confidence interval]: 0.97 [0.69-1.37]) or without (0.94 [0.72-1.23]) compared with never use. Similarly, hemorrhagic stroke was not associated with current use of estrogen with progestin (0.74 [0.43-1.28]) or without (1.06 [0.71-1.56]). However, the risks of ischemic stroke and hemorrhagic stroke were increased 2-fold during the first 6 months of hormone use (ischemic stroke: 2.16 [1.04-4.49], hemorrhagic stroke: 2.20 [0.83-5.81]). Risk of ischemic stroke also increased with estrogen dose (P for trend =.03). CONCLUSION: The transitory increase in risks of ischemic stroke and hemorrhagic stroke associated with initiation of hormone replacement therapy merits further investigation.     

Associations of dietary magnesium intake with mortality from cardiovascular disease: the JACC study

The authors sought to investigate the relationship between dietary magnesium intake and mortality from cardiovascular disease in a population-based sample of Asian adults. Reported findings are based on dietary magnesium intake in 58,615 healthy Japanese aged 40-79 years, in the Japan Collaborative Cohort (JACC) Study. Dietary magnesium intake was assessed by a validated food frequency questionnaire administered between 1988 and 1990. During the median 14.7-year follow-up, we documented 2690 deaths from cardiovascular disease, comprising 1227 deaths from strokes and 557 deaths from coronary heart disease. Dietary magnesium intake was inversely associated with mortality from hemorrhagic stroke in men and with mortality from total and ischemic strokes, coronary heart disease, heart failure and total cardiovascular disease in women. The multivariable hazard ratio (95% CI) for the highest vs. the lowest quintiles of magnesium intake after adjustment for cardiovascular risk factor and sodium intake was 0.49 (0.26-0.95), P for trend = 0.074 for hemorrhagic stroke in men, 0.68 (0.48-0.96), P for trend = 0.010 for total stroke, 0.47 (0.29-0.77), P for trend < 0.001 for ischemic stroke, 0.50 (0.30-0.84), P for trend = 0.005 for coronary heart disease, 0.50 (0.28-0.87), P for trend = 0.002 for heart failure and 0.64 (0.51-0.80), P for trend < 0.001 for total cardiovascular disease in women. The adjustment for calcium and potassium intakes attenuated these associations. In conclusion, dietary magnesium intake was associated with reduced mortality from cardiovascular disease in Japanese, especially for women.