beta-carotene and Cerebral-Hemorrhage

Observational data suggest that diets rich in fruits and vegetables and with high serum levels of antioxidants are associated with decreased incidence and mortality of stroke. We studied the effects of alpha-tocopherol and beta-carotene supplementation. The incidence and mortality of stroke were examined in 28 519 male cigarette smokers aged 50 to 69 years without history of stroke who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study). The daily supplementation was 50 mg alpha-tocopherol, 20 mg beta-carotene, both, or placebo. The median follow-up was 6.0 years. A total of 1057 men suffered from incident stroke: 85 men had subarachnoid hemorrhage; 112, intracerebral hemorrhage; 807, cerebral infarction; and 53, unspecified stroke. Deaths due to stroke within 3 months numbered 38, 50, 65, and 7, respectively (total 160). alpha-Tocopherol supplementation increased the risk of subarachnoid hemorrhage 50% (95% CI -3% to 132%, P=0.07) but decreased that of cerebral infarction 14% (95% CI -25% to -1%, P=0.03), whereas beta-carotene supplementation increased the risk of intracerebral hemorrhage 62% (95% CI 10% to 136%, P=0.01). alpha-Tocopherol supplementation also increased the risk of fatal subarachnoid hemorrhage 181% (95% CI 37% to 479%, P=0.01). The overall net effects of either supplementation on the incidence and mortality from total stroke were nonsignificant. alpha-Tocopherol supplementation increases the risk of fatal hemorrhagic strokes but prevents cerebral infarction. The effects may be due to the antiplatelet actions of alpha-tocopherol. beta-Carotene supplementation increases the risk of intracerebral hemorrhage, but no obvious mechanism is available.

Topics: Aged; beta Carotene; Cerebral Hemorrhage; Cerebral Infarction; Double-Blind Method; Humans; Male; Middle Aged; Smoking; Stroke; Subarachnoid Hemorrhage; Vitamin E

From a physiological perspective, physical activity might be expected to decrease the risk of developing stroke. However, epidemiological studies of physical activity and stroke risk have yielded divergent findings. We therefore sought to examine the association between exercise and stroke risk.. This was a prospective cohort study of 21 823 men, followed up for an average of 11.1 years. Participants were from the Physicians' Health Study, a randomized trial of low-dose aspirin and beta carotene. Men, aged 40 to 84 years at baseline, were free of self-reported myocardial infarction, stroke, transient ischemic attack, and cancer. At baseline, they reported on the frequency of exercise vigorous enough to work up a sweat. Stroke occurrence was reported by participants and confirmed after medical record review (n=533). We used Cox proportional hazards regression to analyze the data.. With adjustment for age, treatment assignment, smoking, alcohol intake, history of angina, and parental history of myocardial infarction, the relative risks of total stroke associated with vigorous exercise <1 time, 1 time, 2 to 4 times, and >/=5 times per week at baseline were 1.00 (referent), 0.79 (95% confidence interval [CI], 0.61 to 1. 03), 0.80 (95% CI, 0.65 to 0.99), and 0.79 (95% CI, 0.61 to 1.03), respectively; P for trend=0.04. In subgroup analyses, the inverse association appeared stronger with hemorrhagic than ischemic stroke. When we additionally adjusted for body mass index, history of hypertension, high cholesterol, and diabetes mellitus, corresponding relative risks for total stroke were 1.00 (referent), 0.81 (95% CI, 0.61 to 1.07), 0.88 (95% CI, 0.70 to 1.10), and 0.86 (95% CI, 0.65 to 1.13), respectively; P for trend=0.25.. Exercise vigorous enough to work up a sweat is associated with decreased stroke risk in men. In the present study, the inverse association with physical activity appeared to be mediated through beneficial effects on body weight, blood pressure, serum cholesterol, and glucose tolerance. Apart from its favorable influences on these variables, physical activity had no significant residual association with stroke incidence.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; beta Carotene; Brain Ischemia; Cerebral Hemorrhage; Cerebrovascular Disorders; Double-Blind Method; Exercise; Humans; Male; Middle Aged; Physicians; Platelet Aggregation Inhibitors; Prospective Studies; Risk Factors

The validity of stroke diagnosis in the National Hospital Discharge Register and the Register of Causes of Death was examined among 546 middle-aged men in Finland. The subjects were cases of cerebrovascular diseases of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and identified by record linkage to the registers. In all, 375 events with cerebrovascular disease as hospital discharge diagnosis and 218 events with cerebrovascular disease as the underlying cause of death were reviewed using specific criteria modified from the classifications of the National Survey of Stroke and the WHO MONICA Study. For hospital stroke diagnoses, there was agreement on diagnosis for all strokes in 90%, for subarachnoid hemorrhage in 79%, intracerebral hemorrhage in 82%, and cerebral infarction in 90%. The respective agreement rates for stroke as the underlying cause of death were 97%, 95%, 91%, and 92%. The data were insufficient for review in 1% and 3% of the stroke events, respectively. Age, observation year and trial supplementation with alphatocopherol or beta-carotene had no effect on validity. In conclusion, the validity of stroke diagnosis was good in registers of hospital diagnoses and causes of death justifying their use for endpoint assessment in epidemiological studies.

Topics: Age Factors; Aged; beta Carotene; Cause of Death; Cerebral Hemorrhage; Cerebral Infarction; Cerebrovascular Disorders; Classification; Double-Blind Method; Finland; Humans; Lung Neoplasms; Male; Medical Record Linkage; Middle Aged; Patient Discharge; Placebos; Registries; Reproducibility of Results; Smoking; Subarachnoid Hemorrhage; Vitamin E

The evaluation of cerebrovascular end points in prospective studies is often based exclusively on medical record examination and may be made by more than one observer over time. To address the issues of adequacy of medical record information and consistency in diagnosis over time, we evaluated interobserver agreement for the main items of the stroke classification system used in the Physicians' Health Study. This trial included 22,071 physicians randomly assigned in 1982 to receive either aspirin or placebo to assess the subsequent risk of cardiovascular events, including stroke.. Stroke subtype, stroke severity, and certainty of diagnosis were first classified from medical records from the years 1982 through 1988. The 216 stroke events reported in this period were independently reclassified in 1994 and compared with the initial classification using kappa statistics.. Overall agreement in major stroke types (hemorrhagic, ischemic, undetermined stroke) as well as in hemorrhagic stroke subtypes was excellent (kappa = 0.81 and kappa = 0.95, respectively). A wide range of values for the ischemic stroke subtypes (kappa = 0.13 to kappa = 0.96) was obtained. Agreement was substantial in assessment of stroke severity (kappa = 0.71), and it was fair (kappa = 0.33) for certainty of diagnosis.. Interobserver agreement is high for major stroke types as well as for categories of hemorrhagic stroke on the basis of review of medical records and results of imaging data. The classification of ischemic stroke subtypes, however, is subject to substantial interobserver disagreement. Periodic reclassification of random samples of end points might be considered in long-term prospective studies to assess potential misclassification of events by different observers.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; beta Carotene; Carotenoids; Cerebral Hemorrhage; Cerebral Infarction; Cerebrovascular Disorders; Drug Therapy, Combination; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged; Observer Variation; Patient Discharge; Physicians; Placebos; Prospective Studies; Severity of Illness Index

In the Alpha Tocopherol, Beta Carotene Cancer Prevention Study, alpha tocopherol supplementation decreased risk of cerebral infarction by 14% (95% CI, -25% to -1%), and beta carotene increased risk of intracerebral hemorrhage by 62% (95% CI, 10% to 132%). We report here the 6-year postintervention effects of alpha tocopherol and beta carotene supplementation on stroke and its subtypes.. A total of 29,133 male smokers, aged 50 to 69 years, were randomized to receive 50 mg of alpha tocopherol, 20 mg of beta carotene, both, or placebo daily for 5 to 8 years. At the beginning of the post-trial follow-up, 24 382 men were still at risk for first-ever stroke. During the post-trial follow-up, 1327 men experienced a stroke: 1087 cerebral infarctions, 148 intracerebral hemorrhages, 64 subarachnoid hemorrhages, and 28 unspecified strokes.. Post-trial risk for cerebral infarction was elevated among those who had received alpha tocopherol compared with those who had not (relative risk [RR], 1.13; 95% CI, 1.00 to 1.27), whereas beta carotene had no effect (RR, 0.97; 95% CI, 0.86 to 1.09). Alpha tocopherol supplementation was associated with a postintervention RR of 1.01 (95% CI, 0.73 to 1.39) for intracerebral hemorrhage and 1.38 (95% CI, 0.84 to 2.26) for subarachnoid hemorrhage. The corresponding RRs associated with beta carotene supplementation were 1.38 (95% CI, 0.99 to 1.91) and 1.09 (95% CI, 0.67 to 1.77), respectively.. Neither alpha tocopherol nor beta carotene supplementation had any postintervention preventive effects on stroke. The post-trial increase in cerebral infarction risk among recipients of alpha tocopherol may present a rebound of the reduced risk of cerebral infarction during the intervention.

Topics: alpha-Tocopherol; Antioxidants; beta Carotene; Cerebral Hemorrhage; Cerebral Infarction; Dietary Supplements; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk; Smoking; Stroke; Subarachnoid Hemorrhage

Smoking is an established risk factor for ischemic stroke and subarachnoid hemorrhage (SAH), but the impact of smoking on intracerebral hemorrhage (ICH) is less clear.. Prospective cohort study among 22,022 US male physicians participating in the Physicians' Health Study. Incidence of stroke was measured by self-report and confirmed by medical record review. We used Cox proportional-hazards models to evaluate the association of smoking with risk of total hemorrhagic stroke, ICH, and SAH. We categorized smoking into 4 groups: never, past, or current smokers of <20 or of >or=20 cigarettes per day.. During 17.8 years of follow-up, 108 ICHs and 31 SAHs occurred. Never smokers and past smokers had equal rates of ICH and SAH. Current smokers of <20 cigarettes per day had multivariable-adjusted relative risks of 1.65 (95% CI, 0.61 to 4.50) for total hemorrhagic stroke, 1.60 (95% CI, 0.50 to 5.07) for ICH, and 1.75 (95% CI, 0.24 to 13.09) for SAH when compared with never smokers. Current smokers of >or=20 cigarettes had relative risks of 2.36 (95% CI, 1.38 to 4.02) for total hemorrhagic stroke, 2.06 (95% CI, 1.08 to 3.96) for ICH, and 3.22 (95% CI, 1.26 to 8.18) for SAH when compared with never smokers.. This prospective study suggests an increased risk of total hemorrhagic stroke, ICH, and SAH in current cigarette smokers with a graded increase in risk that depended on how many cigarettes were smoked. The effect of smoking on ICH is of about the same magnitude as the effect of smoking on ischemic stroke. Our results add to the multiple health benefits that can be accrued by abstaining from cigarette smoking.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Alcohol Drinking; Aspirin; beta Carotene; Body Mass Index; Brain Ischemia; Cardiovascular Diseases; Cerebral Arteries; Cerebral Hemorrhage; Cohort Studies; Comorbidity; Confounding Factors, Epidemiologic; Diabetes Mellitus; Exercise; Follow-Up Studies; Humans; Hypercholesterolemia; Hypertension; Incidence; Male; Medical Records; Middle Aged; Multivariate Analysis; Neoplasms; Physicians; Proportional Hazards Models; Prospective Studies; Randomized Controlled Trials as Topic; Risk; Smoking; Stroke; Subarachnoid Hemorrhage; United States

Antioxidants may protect against atherosclerosis and thus prevent cerebrovascular disease. We studied the association between dietary antioxidants and subtypes of stroke.. The study cohort consisted of 26 593 male smokers, aged 50 to 69 years, without a history of stroke. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire at baseline. Incident cases were identified through national registers.. During a 6.1-year follow-up, 736 cerebral infarctions, 83 subarachnoid hemorrhages, and 95 intracerebral hemorrhages occurred. Neither dietary flavonols and flavones nor vitamin E were associated with risk for stroke. The dietary intake of beta-carotene was inversely associated with the risk for cerebral infarction (relative risk [RR] of highest versus lowest quartile 0.74, 95% CI 0.60 to 0. 91), lutein plus zeaxanthin with risk for subarachnoid hemorrhage (RR 0.47, 95% CI 0.24 to 0.93), and lycopene with risks of cerebral infarction (RR 0.74, 95% CI 0.59 to 0.92) and intracerebral hemorrhage (RR 0.45, 95% CI 0.24 to 0.86). Vitamin C intake was inversely associated with the risk for intracerebral hemorrhage (RR 0.39, 95% CI 0.21 to 0.74). After simultaneous modeling of the antioxidants, a significant association remained only between beta-carotene intake and risk for cerebral infarction (RR 0.77, 95% CI 0.61 to 0.99).. Dietary intake of beta-carotene was inversely associated with the risk for cerebral infarction. No association was detected between other dietary antioxidants and risk for stroke.

Topics: Aged; Ascorbic Acid; beta Carotene; Carotenoids; Cerebral Hemorrhage; Cerebral Infarction; Cohort Studies; Comorbidity; Diet; Finland; Flavonoids; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Risk; Risk Assessment; Smoking; Stroke; Subarachnoid Hemorrhage; Vitamin E; Vitamins