Fruit and vegetable intake in relation to risk of ischemic stroke.

CONTEXT: Few studies have evaluated the relationship between fruit and vegetable intake and cardiovascular disease. OBJECTIVE: To examine the associations between fruit and vegetable intake and ischemic stroke. DESIGN, SETTING, AND SUBJECTS: Prospective cohort studies, including 75 596 women aged 34 to 59 years in the Nurses' Health Study with 14 years of follow-up (1980-1994), and 38683 men aged 40 to 75 years in the Health Professionals' Follow-up Study with 8 years of follow-up (1986-1994). All individuals were free of cardiovascular disease, cancer, and diabetes at baseline. MAIN OUTCOME MEASURE: Incidence of ischemic stroke by quintile of fruit and vegetable intake. RESULTS: A total of 366 women and 204 men had an ischemic stroke. After controlling for standard cardiovascular risk factors, persons in the highest quintile of fruit and vegetable intake (median of 5.1 servings per day among men and 5.8 servings per day among women) had a relative risk (RR) of 0.69 (95% confidence interval [CI], 0.52-0.92) compared with those in the lowest quintile. An increment of 1 serving per day of fruits or vegetables was associated with a 6% lower risk of ischemic stroke (RR, 0.94; 95 % CI, 0.90-0.99; P =.01, test for trend). Cruciferous vegetables (RR, 0.68 for an increment of 1 serving per day; 95% CI, 0.49-0.94), green leafy vegetables (RR, 0.79; 95% CI, 0.62-0.99), citrus fruit including juice (RR, 0.81; 95% CI, 0.68-0.96), and citrus fruit juice (RR, 0.75; 95% CI, 0.61-0.93) contributed most to the apparent protective effect of total fruits and vegetables. Legumes or potatoes were not associated with lower ischemic stroke risk. The multivariate pooled RR for total stroke was 0.96 (95% CI, 0.93-1.00) for each increment of 2 servings per day. CONCLUSIONS: These data support a protective relationship between consumption of fruit and vegetables-particularly cruciferous and green leafy vegetables and citrus fruit and juice-and ischemic stroke risk.     

Intake of fish and omega-3 fatty acids and risk of stroke in women

CONTEXT: Some prospective studies have shown an inverse association between fish intake and risk of stroke, but none has examined the relationship of fish and omega-3 polyunsaturated fatty acid intake with risk of specific stroke subtypes. OBJECTIVE: To examine the association between fish and omega-3 polyunsaturated fatty acid intake and risk of stroke subtypes in women. DESIGN, SETTING, AND SUBJECTS: Prospective cohort study of women in the Nurses' Health Study cohort, aged 34 to 59 years in 1980, who were free from prior diagnosed cardiovascular disease, cancer, and history of diabetes and hypercholesterolemia and who completed a food frequency questionnaire including consumption of fish and other frequently eaten foods. The 79 839 women who met our eligibility criteria were followed up for 14 years. MAIN OUTCOME MEASURE: Relative risk of stroke in 1980-1994 compared by category of fish intake and quintile of omega-3 polyunsaturated fatty acid intake. RESULTS: After 1 086 261 person-years of follow-up, 574 incident strokes were documented, including 119 subarachnoid hemorrhages, 62 intraparenchymal hemorrhages, 303 ischemic strokes (264 thrombotic and 39 embolic infarctions), and 90 strokes of undetermined type. Among thrombotic infarctions, 90 large-artery occlusive infarctions and 142 lacunar infarctions were identified. Compared with women who ate fish less than once per month, those with higher intake of fish had a lower risk of total stroke: the multivariate relative risks (RRs), adjusted for age, smoking, and other cardiovascular risk factors, were 0.93 (95% confidence interval [CI], 0.65-1.34) for fish consumption 1 to 3 times per month, 0.78 (95% CI, 0.55-1.12) for once per week, 0.73 (95% CI, 0.47-1.14) for 2 to 4 times per week, and 0.48 (95% CI, 0.21-1.06) for 5 or more times per week (P for trend =.06). Among stroke subtypes, a significantly reduced risk of thrombotic infarction was found among women who ate fish 2 or more times per week (multivariate RR, 0.49; 95% CI, 0.26-0.93). Women in the highest quintile of intake of long-chain omega-3 polyunsaturated fatty acids had reduced risk of total stroke and thrombotic infarction, with multivariate RRs of 0.72 (95% CI, 0.53-0.99) and 0.67 (95% CI, 0.42-1.07), respectively. When stratified by aspirin use, fish and omega-3 polyunsaturated fatty acid intakes were inversely associated with risk of thrombotic infarction, primarily among women who did not regularly take aspirin. There was no association between fish or omega-3 polyunsaturated fatty acid intake and risk of hemorrhagic stroke. CONCLUSIONS: Our data indicate that higher consumption of fish and omega-3 polyunsaturated fatty acids is associated with a reduced risk of thrombotic infarction, primarily among women who do not take aspirin regularly, but is not related to risk of hemorrhagic stroke.     

Long-term Intake of Dietary Fiber and Decreased Risk of Coronary Heart Disease Among Women

Context  Epidemiological studies of men suggest that dietary fiber intake protects against coronary heart disease (CHD), but data on this association in women are sparse. Objective  To examine the association between long-term intake of total dietary fiber as well as fiber from different sources and risk of CHD in women. Design and Setting  The Nurses' Health Study, a large, prospective cohort study of US women followed up for 10 years from 1984. Dietary data were collected in 1984, 1986, and 1990, using a validated semiquantitative food frequency questionnaire. Participants  A total of 68,782 women aged 37 to 64 years without previously diagnosed angina, myocardial infarction (MI), stroke, cancer, hypercholesterolemia, or diabetes at baseline. Main Outcome Measure  Incidence of acute MI or death due to CHD by amount of fiber intake. Results  Response rate averaged 80% to 90% during the 10-year follow-up. We documented 591 major CHD events (429 nonfatal MIs and 162 CHD deaths). The age-adjusted relative risk (RR) for major CHD events was 0.53 (95% confidence interval [CI], 0.40-0.69) for women in the highest quintile of total dietary fiber intake (median, 22.9 g/d) compared with women in the lowest quintile (median, 11.5 g/d). After controlling for age, cardiovascular risk factors, dietary factors, and multivitamin supplement use, the RR was 0.77 (95% CI, 0.57-1.04). For a 10-g/d increase in total fiber intake (the difference between the lowest and highest quintiles), the multivariate RR of total CHD events was 0.81 (95% CI, 0.66-0.99). Among different sources of dietary fiber (eg, cereal, vegetables, fruit), only cereal fiber was strongly associated with a reduced risk of CHD (multivariate RR, 0.63; 95% CI, 0.49-0.81 for each 5-g/d increase in cereal fiber). Conclusions  Our findings in women support the hypothesis that higher fiber intake, particularly from cereal sources, reduces the risk of CHD.      

Ischemic stroke risk with oral contraceptives: A meta-analysis

CONTEXT: The relationship between ischemic stroke and oral contraceptive (OC) use has been studied for 40 years, but disagreement about an association persists. OBJECTIVE: To review available literature to determine whether OC use is associated with increased stroke risk. DATA SOURCES: Studies published from January 1960 through November 1999 were identified from electronic databases (MEDLINE, BIOSIS, and Dissertation Abstracts Online), Index Medicus, bibliographies of pertinent review articles and pertinent original articles, textbooks, and expert consultation. STUDY SELECTION: From 804 potentially relevant references retrieved, 73 were studies investigating risk of ischemic stroke with OC use. Two reviewers independently applied the following inclusion criteria: more than 10 stroke cases sampled, clear stroke subtype differentiation, concurrent controls included, adequate data included to determine relative risks (RRs) and confidence intervals (CIs), analysis controlled for age, and no later publication of identical data. A third investigator adjudicated disagreements. Sixteen studies met all inclusion criteria and were included in the meta-analysis. DATA EXTRACTION: Two investigators independently extracted data, with disagreements resolved through discussion. DATA SYNTHESIS: The 16 studies were analyzed using random effects modeling. Current OC use was associated with increased risk of ischemic stroke (RR, 2.75; 95% CI, 2.24-3.38). Smaller estrogen dosages were associated with lower risk (P=.01 for trend), but risk was significantly elevated for all dosages. Studies that did not control for smoking (P=.01) and those using hospital-based controls (P<.001) found higher RRs, but no other patient characteristics or elements of study design were important. The summary RR was 1.93 (95% CI, 1.35-2.74) for low-estrogen preparations in population-based studies that controlled for smoking and hypertension. This translates to an additional 4.1 ischemic strokes per 100,000 nonsmoking, normotensive women using low-estrogen OCs, or 1 additional ischemic stroke per year per 24,000 such women. The RR of stroke due to OC use was not different in women who smoked, had migraines, or had hypertension. CONCLUSIONS: Summary results indicate that risk of ischemic stroke is increased in current OC users, even with newer low-estrogen preparations. However, the absolute increase in stroke risk is expected to be small since incidence is very low in this population. JAMA. 2000;284:72-78     

Fish consumption and risk of stroke in men

Context  The effect of fish consumption or long-chain omega-3 polyunsaturated fatty acid (PUFA) intake on risk of stroke remains uncertain. Objective  To examine the relation of fish consumption and long-chain omega-3 PUFA intake and risk of stroke in men. Design and Setting  The Health Professional Follow-up Study, a US prospective cohort study with 12 years of follow-up. Participants  A total of 43 671 men aged 40 to 75 years who completed a detailed and validated semiquantitative food frequency questionnaire and who were free of cardiovascular disease at baseline in 1986. Main Outcome Measure  Relative risk (RR) of stroke by subtype based on cumulative average fish consumption or long-chain omega-3 PUFA intake, ascertained in 1986, 1990, and 1994. Results  We documented 608 strokes during the 12-year follow-up period, including 377 ischemic, 106 hemorrhagic, and 125 unclassified strokes. Compared with men who consumed fish less than once per month, the multivariate RR of ischemic stroke was significantly lower among those who ate fish 1 to 3 times per month (RR, 0.57; 95% confidence interval [CI], 0.35-0.95). However, a higher frequency of fish intake was not associated with further risk reduction; the RR was 0.54 (95% CI, 0.31-0.94) for men who consumed fish 5 or more times per week. This lack of linearity was confirmed by spline analyses. By dichotomized fish intake, the multivariate RR for men who consumed fish at least once per month compared with those who ate fish less than once per month was 0.56 (95% CI, 0.38-0.83) for ischemic stroke and 1.36 (95% CI, 0.48-3.82) for hemorrhagic stroke. The inverse association between fish intake and risk of ischemic stroke was not materially modified by use of aspirin. No significant associations were found between fish or long-chain omega-3 PUFA intake and risk of hemorrhagic stroke. Conclusion  Our findings suggest that eating fish once per month or more can reduce the risk of ischemic stroke in men.      

Physical activity and coronary heart disease in women: is "no pain, no gain" passé?

CONTEXT: Physically active women have lower coronary heart disease (CHD) rates than inactive women. However, whether the association differs by intensity of activity or in women at high risk for CHD is unclear. OBJECTIVE: To examine the relation between physical activity, specifically investigating walking (a light-to-moderate activity depending on pace), and CHD among women, including those at high risk for CHD. DESIGN, SETTING, AND PARTICIPANTS: Cohort study of 39 372 healthy female health professionals aged 45 years or older, enrolled throughout the United States between September 1992 and May 1995, with follow-up to March 1999. Recreational activities, including walking and stair climbing, were reported at study entry. MAIN OUTCOME MEASURE: Correlation of CHD with energy expended on all activities, vigorous activities, and walking. RESULTS: A total of 244 cases of CHD occurred. Adjusting for potential confounders, the relative risks (RRs) of CHD for less than 200, 200-599, 600-1499, and 1500 or more kcal/wk expended on all activities were 1.00 (referent), 0.79 (95% confidence interval [CI], 0.56-1.12), 0.55 (95% CI, 0.37-0.82), and 0.75 (95% CI, 0.50-1.12), respectively (P for linear trend =.03). Vigorous activities were associated with lower risk (RR, 0.63; 95% CI, 0.38-1.04 comparing highest and lowest categories). Walking also predicted lower risk among women without vigorous activities. Among these women, the multivariate RRs for walking 1 to 59 min/wk, 1.0 to 1.5 h/wk, and 2 or more h/wk, compared with no regular walking, were 0.86 (95% CI, 0.57-1.29), 0.49 (95% CI, 0.28-0.86), and 0.48 (95% CI, 0.29-0.78), respectively. For walking paces of less than 3.2 km/h (2.0 mph), 3.2 to 4.7 km/h (2.0-2.9 mph), and 4.8 km/h (3.0 mph) or more, compared with no regular walking, RRs were 0.56 (95% CI, 0.32-0.97), 0.71 (95% CI, 0.47-1.05), and 0.52 (95% CI, 0.30-0.90), respectively. When analyzed simultaneously, time spent walking (P for linear trend =.01) but not walking pace (P for linear trend =.55) predicted lower risk. The inverse association between physical activity and CHD risk did not differ by weight or cholesterol levels (P for interaction =.95 and.71, respectively), but there were significant interactions by smoking and hypertension status. Physical activity was inversely related to risk in current smokers but not hypertensive women (P for interaction =.01 and.001, respectively). CONCLUSIONS: These data indicate that even light-to-moderate activity is associated with lower CHD rates in women. At least 1 hour of walking per week predicted lower risk. The inverse association with physical activity was also present in women at high risk for CHD, including those who were overweight, had increased cholesterol levels, or were smokers.     

Physical activity and risk of stroke in women

CONTEXT: Persuasive evidence has demonstrated that increased physical activity is associated with substantial reduction in risk of coronary heart disease. However, the role of physical activity in the prevention of stroke is less well established. OBJECTIVE: To examine the association between physical activity and risk of total stroke and stroke subtypes in women. DESIGN AND SETTING: The Nurses' Health Study, a prospective cohort study of subjects residing in 11 US states. SUBJECTS: A total of 72,488 female nurses aged 40 to 65 years who did not have diagnosed cardiovascular disease or cancer at baseline in 1986 and who completed detailed physical activity questionnaires in 1986, 1988, and 1992. MAIN OUTCOME MEASURE: Incident stroke occurring between baseline and June 1, 1994, compared among quintiles of physical activity level as measured by metabolic equivalent tasks (METs) in hours per week. RESULTS: During 8 years (560,087 person-years) of follow-up, we documented 407 incident cases of stroke (258 ischemic strokes, 67 subarachnoid hemorrhages, 42 intracerebral hemorrhages, and 40 strokes of unknown type). In multivariate analyses controlling for age, body mass index, history of hypertension, and other covariates, increasing physical activity was strongly inversely associated with risk of total stroke. Relative risks (RRs) in the lowest to highest MET quintiles were 1. 00, 0.98, 0.82, 0.74, and 0.66 (P for trend=.005). The inverse gradient was seen primarily for ischemic stroke (RRs across increasing MET quintiles, 1.00, 0.87, 0.83, 0.76, and 0.52; P for trend=.003). Physical activity was not significantly associated with subarachnoid hemorrhage or intracerebral hemorrhage. After multivariate adjustment, walking was associated with reduced risk of total stroke (RRs across increasing walking MET quintiles, 1.00, 0. 76, 0.78, 0.70, and 0.66; P for trend=.01) and ischemic stroke (RRs across increasing walking MET quintiles, 1.00, 0.77, 0.75, 0.69, and 0.60; P for trend=.02). Brisk or striding walking pace was associated with lower risk of total and ischemic stroke compared with average or casual pace. CONCLUSION: These data indicate that physical activity, including moderate-intensity exercise such as walking, is associated with substantial reduction in risk of total and ischemic stroke in a dose-response manner. JAMA. 2000.     

High-density lipoprotein cholesterol and ischemic stroke in the elderly: the Northern Manhattan Stroke Study

CONTEXT: Elevated high-density lipoprotein cholesterol (HDL-C) levels have been shown to be protective against cardiovascular disease. However, the association of specific lipoprotein classes and ischemic stroke has not been well defined, particularly in higher-risk minority populations. OBJECTIVE: To evaluate the association between HDL-C and ischemic stroke in an elderly, racially or ethnically diverse population. DESIGN: Population-based, incident case-control study conducted July 1993 through June 1997. SETTING: A multiethnic community in northern Manhattan, New York, NY. PARTICIPANTS: Cases (n = 539) of first ischemic stroke (67% aged >/=65 years; 55% women; 53% Hispanic, 28% black, and 19% white) were enrolled and matched by age, sex, and race or ethnicity to stroke-free community residents (controls; n = 905). MAIN OUTCOME MEASURE: Independent association of fasting HDL-C levels, determined at enrollment, with ischemic stroke, including atherosclerotic and nonatherosclerotic ischemic stroke subtypes. RESULTS: After risk factor adjustment, a protective effect was observed for HDL-C levels of at least 35 mg/dL (0.91 mmol/L) (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.39-0.72). A dose-response relationship was observed (OR, 0.65; 95% CI, 0.47-0.90 and OR, 0.31; 95% CI, 0.21-0.46) for HDL-C levels of 35 to 49 mg/dL (0.91-1.28 mmol/L) and at least 50 mg/dL (1.29 mmol/L), respectively. The protective effect of a higher HDL-C level was significant among participants aged 75 years or older (OR, 0.51; 95% CI, 0.27-0.94), was more potent for the atherosclerotic stroke subtype (OR, 0.20; 95% CI, 0.08-0.50), and was present in all 3 racial or ethnic groups studied. CONCLUSIONS: Increased HDL-C levels are associated with reduced risk of ischemic stroke in the elderly and among different racial or ethnic groups. These data add to the evidence relating lipids to stroke and support HDL-C as an important modifiable stroke risk factor.     

A prospective study of folate intake and the risk of breast cancer

CONTEXT: Folate is involved in DNA synthesis and methylation and may reduce breast cancer risk, particularly among women with greater alcohol consumption. OBJECTIVES: To assess the association between folate intake and risk of breast cancer and whether higher folate intake may reduce excess risk among women who consume alcohol. DESIGN: Prospective cohort study performed in 1980, with 16 years of follow-up. SETTING AND PARTICIPANTS: A total of 88818 women who completed the dietary questionnaire section of the Nurses' Health Study in 1980. MAIN OUTCOME MEASURE: Incidence of invasive breast cancer by levels of folate and alcohol intake. RESULTS: A total of 3483 cases of breast cancer were documented. Total folate intake was not associated with overall risk of breast cancer. However, among women who consumed at least 15 g/d of alcohol, the risk of breast cancer was highest among those with low folate intake. For total folate intake of at least 600 microg/d compared with 150 to 299 microg/d, the multivariate relative risk (RR) was 0.55 (95% confidence interval [CI], 0.39-0.76; P for trend = .001). This association was only slightly attenuated after additional adjustment for intake of beta carotene, lutein/zeaxanthin, preformed vitamin A, and total vitamins C and E. The risk of breast cancer associated with alcohol intake was strongest among women with total folate intake of less than 300 microg/d (for alcohol intake > or =15 g/d vs <15 g/d, multivariate RR, 1.32; 95% CI, 1.15-1.50). For women who consumed at least 300 microg/d of total folate, the multivariate RR for intake of at least 15 g/d of alcohol vs less than 15 g/d was 1.05 (95% CI, 0.92-1.20). Current use of multivitamin supplements, the major source of folate, was associated with lower breast cancer risk among women who consumed at least 15 g/d of alcohol (for current users of supplements vs never users, RR, 0.74; 95% CI, 0.59-0.93). CONCLUSIONS: Our findings suggest that the excess risk of breast cancer associated with alcohol consumption may be reduced by adequate folate intake.     

Dietary sodium intake and subsequent risk of cardiovascular disease in overweight adults

CONTEXT: Dietary sodium is positively associated with blood pressure, and ecological and animal studies both have suggested that high dietary sodium intake increases stroke mortality. OBJECTIVE: To examine the risk of cardiovascular disease associated with dietary sodium intake in overweight and nonoverweight persons. DESIGN: Prospective cohort study. SETTING: The first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study, conducted in 1982-1984, 1986, 1987, and 1992. PARTICIPANTS: Of those aged 25 to 74 years when the survey was conducted in 1971 -1975 (14407 participants), a total of 2688 overweight and 6797 nonoverweight persons were included in the analysis. MAIN OUTCOME MEASURES: Dietary sodium and energy intake were estimated at baseline using a single 24-hour dietary recall method. Incidence and mortality data for cardiovascular disease were obtained from medical records and death certificates. RESULTS: For overweight and nonoverweight persons, over an average of 19 years of follow-up, the total number of documented cases were as follows: 680 stroke events (210 fatal), 1727 coronary heart disease events (614 fatal), 895 cardiovascular disease deaths, and 2486 deaths from all causes. Among overweight persons with an average energy intake of 7452 kJ, a 100 mmol higher sodium intake was associated with a 32% increase (relative risk [RR], 1.32; 95% confidence interval [CI], 1.07-1.64; P = .01) in stroke incidence, 89% increase (RR, 1.89; 95% CI, 1.31-2.74; P<.001) in stroke mortality, 44% increase (RR, 1.44; 95% CI, 1.14-1.81; P = .002) in coronary heart disease mortality, 61% increase (RR, 1.61; 95% CI, 1.32-1.96; P<.001) in cardiovascular disease mortality, and 39% increase (RR, 1.39; 95% CI, 1.23-1.58; P<.001) in mortality from all causes. Dietary sodium intake was not significantly associated with cardiovascular disease risk in nonoverweight persons. CONCLUSIONS: Our analysis indicates that high sodium intake is strongly and independently associated with an increased risk of cardiovascular disease and all-cause mortality in overweight persons.     

东亚男性饮酒和卒中关系的前瞻性队列研究荟萃分析

目的 系统评价源自于中、日、韩关于饮酒和卒中关系的前瞻性队列研究,探讨东亚男性饮酒和卒中及全因死亡的关系.方法 检索Pubmed等数据库,纳入符合入选条件的前瞻性队列研究,记录研究来源国家、研究对象例数、性别、年龄(均数或中位数及间距)、随访期限、饮酒量(g/d)、与饮酒相关的卒中或死亡相对风险(RR)及95%可信区间(CI)等.根据异质性检验结果,采用随机或固定效应模型,以RR作为评价饮酒量与缺血性卒中或出血性卒中发病率及全因死亡率的风险效应指标.结果 共纳入17项前瞻性队列研究.样本量最小1 322人,最大108 461人,9项研究报道了全因死亡;7项报道了缺血性卒中、7项报道了出血性卒中.随访期间4.1～19.0年.分层比较显示每日饮酒量≤20、21～40、41～60、＞60 g/d的各组与不饮酒者比较,缺血性卒中风险(RR及95%CI)分别为0.85(0.78～0.93;P=0.0002)、0.94(0.79～1.11;P=0.46)、1.08(0.86～1.37;P=0.50)和1.24(0.96～1.59;P=0.10);出血性卒中风险分别为0.92(0.75～1.12;P=0.40)、1.11(0.96～1.28;P=0.17)、1.20(0.92～1.56;P=0.18)和1.74(1.32～2.28;P＜0.01);全因死亡风险分别为0.83(0.75～0.91,P=0.01)、0.93(0.87～0.99,P=0.03)、1.01(0.95～1.07;P=0.86)和1.32(1.29～1.36;P＜0.01).结论 在东亚男性人群中,少量饮酒(≤20 g/d)降低缺血性卒中的风险,过量饮酒使卒中(尤其是出血性卒中)、全因死亡的风险明显增加.适量饮酒的范围应每日酒精量不超过40g.     

Effect of treating isolated systolic hypertension on the risk of developing various types and subtypes of stroke: the Systolic Hypertension in the Elderly Program (SHEP)

CONTEXT: The Systolic Hypertension in the Elderly Program (SHEP) demonstrated that treating isolated systolic hypertension in older patients decreased incidence of total stroke, but whether all types of stroke were reduced was not evaluated. OBJECTIVE: To investigate antihypertensive drug treatment effects on incidence of stroke by type and subtype, timing of strokes, case-fatality rates, stroke residual effects, and relationship of attained systolic blood pressure to stroke incidence. DESIGN: The SHEP study, a randomized, double-blind, placebo-controlled trial began March 1, 1985, and had an average follow-up of 4.5 years. SETTING AND PARTICIPANTS: A total of 4736 men and women aged 60 years or older with isolated systolic hypertension at 16 clinical centers in the United States. INTERVENTIONS: Patients were randomly assigned to receive treatment with 12.5 mg/d of chlorthalidone (step 1); either 25 mg/d of atenolol or 0.05 mg/d of reserpine (step 2) could be added (n = 2365); or placebo (n = 2371). MAIN OUTCOME MEASURES: Occurrence, type and subtype, and timing of first strokes and stroke fatalities; and change in stroke incidence for participants (whether in active treatment or placebo groups) reaching study-specific systolic blood pressure goal (decrease of at least 20 mm Hg from baseline to below 160 mm Hg) compared with participants not reaching goal. RESULTS: A total of 85 and 132 participants in the active treatment and placebo groups, respectively, had ischemic strokes (adjusted relative risk [RR], 0.63; 95% confidence interval [CI], 0.48-0.82); 9 and 19 had hemorrhagic strokes (adjusted RR, 0.46; 95% CI, 0.21-1.02); and 9 and 8 had strokes of unknown type (adjusted RR, 1.05; 95% CI, 0.40-2. 73), respectively. Four subtypes of ischemic stroke were observed in active treatment and placebo group participants, respectively, as follows: for lacunar, n = 23 and n = 43 (adjusted RR, 0.53; 95% CI, 0.32-0.88); for embolic, n = 9 and n = 16 (adjusted RR, 0.56; 95% CI, 0.25-1.27); for atherosclerotic, n = 13 and n = 13 (adjusted RR, 0. 99; 95% CI, 0.46-2.15); and for unknown subtype, n = 40 and n = 60 (adjusted RR, 0.64; 95% CI, 0.43-0.96). Treatment effect was observed within 1 year for hemorrhagic strokes but was not seen until the second year for ischemic strokes. Stroke incidence significantly decreased in participants attaining study-specific systolic blood pressure goals. CONCLUSIONS: In this study, antihypertensive drug treatment reduced the incidence of both hemorrhagic and ischemic (including lacunar) strokes. Reduction in stroke incidence occurred when specific systolic blood pressure goals were attained. JAMA. 2000;284:465-471     

Migraine and risk of cardiovascular disease in women

Context  Migraine with aura has been associated with an adverse cardiovascular risk profile and prothrombotic factors that, along with migraine-specific physiology, may increase the risk of vascular events. Although migraine with aura has been associated with increased risk of ischemic stroke, an association with cardiovascular disease (CVD) and, specifically, coronary events remains unclear. Objective  To evaluate the association between migraine with and without aura and subsequent risk of overall and specific CVD. Design, Setting, and Participants  Prospective cohort study of 27 840 US women aged 45 years or older who were participating in the Women's Health Study, were free of CVD and angina at study entry (1992-1995), and who had information on self-reported migraine and aura status, and lipid measurements. This report is based on follow-up data through March 31, 2004. Main Outcome Measures  The primary outcome measure was the combined end point of major CVD (first instance of nonfatal ischemic stroke, nonfatal myocardial infarction, or death due to ischemic CVD); other measures were first ischemic stroke, myocardial infarction, coronary revascularization, angina, and death due to ischemic CVD. Results  At baseline, 5125 women (18.4%) reported any history of migraine; of the 3610 with active migraine (migraine in the prior year), 1434 (39.7%) indicated aura symptoms. During a mean of 10 years of follow-up, 580 major CVD events occurred. Compared with women with no migraine history, women who reported active migraine with aura had multivariable-adjusted hazard ratios of 2.15 (95% confidence interval [CI], 1.58-2.92; P<.001) for major CVD, 1.91 (95% CI, 1.17-3.10; P = .01) for ischemic stroke, 2.08 (95% CI, 1.30-3.31; P = .002) for myocardial infarction, 1.74 (95% CI, 1.23-2.46; P = .002) for coronary revascularization, 1.71 (95% CI, 1.16-2.53; P = .007) for angina, and 2.33 (95% CI, 1.21-4.51; P = .01) for ischemic CVD death. After adjusting for age, there were 18 additional major CVD events attributable to migraine with aura per 10 000 women per year. Women who reported active migraine without aura did not have increased risk of any vascular events or angina. Conclusions  In this large, prospective cohort of women, active migraine with aura was associated with increased risk of major CVD, myocardial infarction, ischemic stroke, and death due to ischemic CVD, as well as with coronary revascularization and angina. Active migraine without aura was not associated with increased risk of any CVD event.      

Combined Effects of Family History of Cardiovascular Disease and Serum C-reactive Protein Level on the Risk of Stroke: A 9.2-year Prospective Study among Mongolians in China

Objective We aimed to evaluate the combined effect of a family history of cardiovascular disease(CVD) and high serum C‐reactive protein(CRP) on the stroke incidence in an Inner Mongolian population in China. Methods A prospective cohort study was conducted from June 2002 to July 2012, with 2,544 participants aged 20 years and over from Inner Mongolia, China. We categorized participants into four groups based on the family history of CVD and CRP levels. Results We adjusted for age; sex; smoking; drinking; hypertension; body mass index; waist circumference; and blood glucose, triglycerides, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol levels. Compared with the group with no family history of CVD/low CRP levels, the group with family history of CVD/high CRP levels had a hazard ratio(HR) of 1.78 [95% confidence interval(CI), 1.03‐3.07; P = 0.039] of stroke, and an HR of 2.14(95% CI, 1.09‐4.20; P = 0.027) of ischemic stroke. The HRs of hemorrhagic stroke for the other three groups were not statistically significant(all P 0.05). Conclusion Participants with both a family history of CVD and high CRP levels had the highest stroke incidence, suggesting that high CRP levels may increase stroke risk, especially of ischemic stroke, among individuals with a family history of CVD.     

Homocysteine and risk of cardiovascular disease among postmenopausal women.

CONTEXT: Individuals with elevated levels of homocysteine tend to have higher prevalence of cardiovascular disease. However, prospective studies of homocysteine are inconsistent and data among women are limited. OBJECTIVE: To determine whether elevated homocysteine levels in healthy postmenopausal women predict risk of developing cardiovascular disease. DESIGN: Prospective, nested case-control study with a mean 3-year follow-up. SETTING: The Women's Health Study, an ongoing US primary prevention trial initiated in 1993. PARTICIPANTS: From a total cohort of 28,263 postmenopausal women with no history of cardiovascular disease or cancer at baseline, 122 women who subsequently experienced cardiovascular events were defined as cases, and 244 age- and smoking status-matched women who remained free of disease during follow-up were defined as controls. MAIN OUTCOME MEASURES: Incidence of death due to cardiovascular disease, nonfatal myocardial infarction (MI), stroke, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft by baseline homocysteine level. RESULTS: Of the 122 cases, there were 85 events of MI or stroke and 37 coronary revascularizations. Case subjects had significantly higher baseline homocysteine levels than controls (14.1 vs 12.4 micromol/L; P = .02). Subjects with homocysteine levels in the highest quartile had a 2-fold increase in risk of any cardiovascular event (relative risk [RR], 2.0; 95% confidence interval [CI], 1.1-3.8). This effect was largely due to an excess of cases with high levels of homocysteine; the RR for those with homocysteine levels at or higher than the 95th percentile (20.7 micromol/L) was 2.6 (95% CI, 1.1-5.7). Risk estimates were independent of traditional risk factors and were greatest for the end points of MI and stroke (RR for those with baseline homocysteine levels in the top quartile, 2.2; 95% CI, 1.1-4.6). Self-reported multivitamin supplement use at study entry was associated with significantly reduced levels of homocysteine (P<.001). However, the association between increasing quartile of homocysteine level and risk of MI or stroke remained significant in analyses controlling for baseline multivitamin supplement use (P = .003 for trend), and subgroup analyses limited to women who were (P = .02 for trend) or were not (P = .04 for trend) taking multivitamin supplements. CONCLUSIONS: Among healthy postmenopausal US women, elevated levels of homocysteine moderately increased the risk of future cardiovascular disease. Whether lowering the homocysteine level reduces risk of cardiovascular events requires testing in randomized controlled trials.     

Smoking and atherosclerotic cardiovascular disease in men with low levels of serum cholesterol: the Korea Medical Insurance Corporation Study

CONTEXT: Few studies have examined the interactive effects of smoking and serum cholesterol level on morbidity and mortality from cardiovascular dieseases. In East Asia, where the prevalence of smoking is among the highest in the world, morbidity and mortality from ischemic heart disease (IHD) is rapidly escalating. OBJECTIVES: To determine whether cigarette smoking is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in the Republic of Korea (South Korea), a population that has relatively low levels of serum cholesterol, and to determine whether serum cholesterol levels modify the risk relationship between smoking and ASCVD. DESIGN: Prospective cohort study with a follow-up period of 6 years (1993-1998). SETTING AND SUBJECTS: A total of 106745 Korean men aged 35 to 59 years who received health insurance from the Korea Medical Insurance Corporation and who had biennial medical evaluations in 1990 and 1992. MAIN OUTCOME MEASURES: Hospital admissions and deaths from IHD, cerebrovascular disease (CVD), and total ASCVD. RESULTS: At baseline, 61389 (58%) were current cigarette smokers and 64482 (60%) had a total cholesterol level of less than 5.17 mmol/L (200 mg/dL). Between 1993 and 1998, 1006 IHD events (176 per 100000 person-years), 1364 CVD events (238 per 100000 person-years), and 716 other ASCVD events (125 per 100000 person-years) occurred. In multivariate Cox proportional hazard models controlling for age, hypertension, hypercholesterolemia, and diabetes, current smoking increased the risk of IHD (risk ratio [RR], 2.2; 95% confidence interval [CI], 1.8-2.8), CVD (RR, 1.6; 95% CI, 1.4-1.8), and total ASCVD (RR, 1.6; 95% CI, 1.5-1.8). For each outcome, there were significant dose-response relationships with amount and duration of smoking. Throughout the range of serum cholesterol levels, current smoking significantly increased the risk of IHD and CVD. In the lowest quartile of serum cholesterol levels (<4.42 mmol/L [171 mg/dL]), the RR from current smoking was 3.3 (95% CI, 1.7-6.2) for IHD and 1.6 (95% CI, 1.2-2.3) for CVD. There was no evidence of an interaction between smoking and serum cholesterol (P for interaction = .75, .87, and .92 for IHD, CVD, and total ASCVD, respectively). CONCLUSIONS: This study demonstrates that in Korea smoking is a major independent risk factor for IHD, CVD, and ASCVD and that a low cholesterol level confers no protective benefit against smoking-related ASCVD.     

Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis

CONTEXT: Establishing relative benefit or harm from specific antihypertensive agents is limited by the complex array of studies that compare treatments. Network meta-analysis combines direct and indirect evidence to better define risk or benefit. OBJECTIVE: To summarize the available clinical trial evidence concerning the safety and efficacy of various antihypertensive therapies used as first-line agents and evaluated in terms of major cardiovascular disease end points and all-cause mortality. DATA SOURCES AND STUDY SELECTION: We used previous meta-analyses, MEDLINE searches, and journal reviews from January 1995 through December 2002. We identified long-term randomized controlled trials that assessed major cardiovascular disease end points as an outcome. Eligible studies included both those with placebo-treated or untreated controls and those with actively treated controls. DATA EXTRACTION: Network meta-analysis was used to combine direct within-trial between-drug comparisons with indirect evidence from the other trials. The indirect comparisons, which preserve the within-trial randomized findings, were constructed from trials that had one treatment in common. DATA SYNTHESIS: Data were combined from 42 clinical trials that included 192 478 patients randomized to 7 major treatment strategies, including placebo. For all outcomes, low-dose diuretics were superior to placebo: coronary heart disease (CHD; RR, 0.79; 95% confidence interval [CI], 0.69-0.92); congestive heart failure (CHF; RR, 0.51; 95% CI, 0.42-0.62); stroke (RR, 0.71; 0.63-0.81); cardiovascular disease events (RR, 0.76; 95% CI, 0.69-0.83); cardiovascular disease mortality (RR, 0.81; 95% CI, 0.73-0.92); and total mortality (RR, 0.90; 95% CI, 0.84-0.96). None of the first-line treatment strategies-beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs), alpha-blockers, and angiotensin receptor blockers-was significantly better than low-dose diuretics for any outcome. Compared with CCBs, low-dose diuretics were associated with reduced risks of cardiovascular disease events (RR, 0.94; 95% CI, 0.89-1.00) and CHF (RR, 0.74; 95% CI, 0.67-0.81). Compared with ACE inhibitors, low-dose diuretics were associated with reduced risks of CHF (RR, 0.88; 95% CI, 0.80-0.96), cardiovascular disease events (RR, 0.94; 95% CI, 0.89-1.00), and stroke (RR, 0.86; 0.77-0.97). Compared with beta-blockers, low-dose diuretics were associated with a reduced risk of cardiovascular disease events (RR, 0.89; 95% CI, 0.80-0.98). Compared with alpha-blockers, low-dose diuretics were associated with reduced risks of CHF (RR, 0.51; 95% CI, 0.43-0.60) and cardiovascular disease events (RR, 0.84; 95% CI, 0.75-0.93). Blood pressure changes were similar between comparison treatments. CONCLUSIONS: Low-dose diuretics are the most effective first-line treatment for preventing the occurrence of cardiovascular disease morbidity and mortality. Clinical practice and treatment guidelines should reflect this evidence, and future trials should use low-dose diuretics as the standard for clinically useful comparisons.     

老年阻塞性睡眠呼吸暂停患者远期缺血性脑卒中的风险评分模型： 多中心前瞻性队列研究

目的 基于临床资料分析老年阻塞性睡眠呼吸暂停（OSA）患者远期缺血性脑卒中发生的独立危险因素,构建老年OSA患者缺血性脑卒中风险评分模型并进行验证,为相关临床治疗提供参考。方法 采用多中心前瞻性队列设计。2015年1月~2017年10月,多中心连续纳入年龄≥60岁、基线无明显心脑血管病史且无重要临床指标缺失的的首次确诊为OSA的老年患者进行随访,随访结局为缺血性脑卒中的发生情况。收集所有纳入研究对象的基线人口学资料、临床特征、睡眠参数指标、实验室和超声检查结果,以3∶1的比例将其随机分为建模组856例和验证组258例。采用LASSO回归用于变量的降维和筛选,并基于Cox比例风险回归构建老年OSA相关的缺血性脑卒中风险评分预测模型。结果 共入组1141例研究对象,中位随访42（41,54）月内,58例发生缺血性脑卒中,累计发病率为5.08%,其中建模组和验证组缺血性脑卒中的累计发病率分别为5.14%和4.91%（P<0.05）。多变量逐步Cox比例风险回归的变量筛选结果显示,年龄（HR=3.44,95% CI：2.38~7.77）、空腹血糖（FPG）（HR=2.13,95% CI：1.22~3.72）、升主动脉内径（HR=2.60,95% CI：1.04~4.47）、左心房前后径（HR=1.98,95% CI：1.75~2.25）和最低氧饱和度（LSpO2）（HR=1.57,95% CI：1.20~1.93）是缺血性脑卒中发生风险的独立危险因素（P<0.05,P<0.01）;利用ROC曲线分析进行比变量转化,以这5个风险变量的回归系数比取整数构建老年OSA患者远期缺血性脑卒中风险评分模型。Bootstrap 法（自抽样次数=500）前后,建模组队列风险评分模型的ROC曲线下面积（AUC）分别为0.84（95% CI：0.78~0.90）和0.85（95% CI：0.78~0.89）,验证组队列风险评分模型的ROC曲线下面积（AUC）分别为0.83（95% CI：0.73~0.93）和0.82（95% CI：0.72~0.90）,提示模型预测效能较好且稳健性高。以模型最佳临床截点的对应值进行风险分层后的生存分析结果显示,高风险组OSA患者的缺血性脑卒中累积发生率高于低风险组（P=0.021）。结论 该模型有助于在老年人群中识别高风险OSA患者进行早期干预,以降低今后与OSA潜在相关的缺血性脑卒中风险。     

脑梗死和脑出血患者的临床特点及长期预后观察

目的 探讨不同类型卒中的危险因素、病因、死亡原因和预后.方法 基于华西医院卒中登记,脑卒中分为出血性和缺血性,缺血性卒中亚型是依据牛津郡社区卒中项目分类原则.分析住院患者的人口学特点、危险因素、死亡原因和1年末结局.结果 2002年3月至2005年9月,共纳入1913例资料完整的卒中患者,其中脑出血599例(31.3%);缺血性脑卒中1314例(68.7%).后者中完全前循环梗死209例(15.9%),部分前循环梗死417例(31.7%),后循环梗死186例(14.2%),腔隙性梗死502例(38.2%).校正年龄和性别,多因素分析显示,房颤是完全前循环梗死的独立预测因素(OR=1.42,95% CI=1.25～2.31);高血压和饮酒是腔隙性梗死(OR=1.24,95% CI=1.02～2.18;OR=1.12,95% CI=1.03～3.04)和脑出血(OR=1.84,95% CI=1.31～3.02;OR=1.04,95% CI=1.01～4.13)的独立预测因素.完全前循环梗死与高血压呈负相关(OR=0.62,95% CI=0.34～0.72),腔隙性梗死与房颤呈负相关(OR=0.46,95% CI=0.26～0.82),脑出血与糖尿病亦呈负相关(OR=0.56,95% CI=0.42～0.76).以腔隙性梗死为参照,完全前循环梗死(OR=6.21,95% CI=2.86～8.42)和脑出血(OR=5.86,95% CI=2.46～8.52)明显增加患者1年死亡风险.结论 不同类型卒中的危险因素、病因和结局不同.确定卒中亚型对于急性期治疗和预防有重要意义.     

Intake of fruits and vegetables and risk of breast cancer: a pooled analysis of cohort studies

CONTEXT: Some epidemiologic studies suggest that elevated fruit and vegetable consumption is associated with a reduced risk of breast cancer. However, most have been case-control studies in which recall and selection bias may influence the results. Additionally, publication bias may have influenced the literature on associations for specific fruit and vegetable subgroups. OBJECTIVE: To examine the association between breast cancer and total and specific fruit and vegetable group intakes using standardized exposure definitions. DATA SOURCES/STUDY SELECTION: Eight prospective studies that had at least 200 incident breast cancer cases, assessed usual dietary intake, and completed a validation study of the diet assessment method or a closely related instrument were included in these analyses. DATA EXTRACTION: Using the primary data from each of the studies, we calculated study-specific relative risks (RRs) that were combined using a random-effects model. DATA SYNTHESIS: The studies included 7377 incident invasive breast cancer cases occurring among 351 825 women whose diet was analyzed at baseline. For comparisons of the highest vs lowest quartiles of intake, weak, nonsignificant associations were observed for total fruits (pooled multivariate RR, 0.93; 95% confidence interval [CI], 0.86-1.00; P for trend =.08), total vegetables (RR, 0.96; 95% CI, 0.89-1.04; P for trend =.54), and total fruits and vegetables (RR, 0.93; 95% CI, 0.86-1.00; P for trend =.12). No additional benefit was apparent in comparisons of the highest and lowest deciles of intake. No associations were observed for green leafy vegetables, 8 botanical groups, and 17 specific fruits and vegetables. CONCLUSION: These results suggest that fruit and vegetable consumption during adulthood is not significantly associated with reduced breast cancer risk.