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.     

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.     

Whole grain consumption and risk of ischemic stroke in women: A prospective study

CONTEXT: Although increased intake of grain products has been recommended to prevent cardiovascular disease (CVD), prospective data examining the relation of whole grain intake to risk of ischemic stroke are sparse, especially among women. OBJECTIVE: To examine the hypothesis that higher whole grain intake reduces the risk of ischemic stroke in women. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort of 75,521 US women aged 38 to 63 years without previous diagnosis of diabetes mellitus, coronary heart disease, stroke, or other CVDs in 1984, who completed detailed food frequency questionnaires (FFQs) in 1984, 1986, 1990, and 1994, and were followed up for 12 years as part of the Nurses' Health Study. MAIN OUTCOME MEASURE: Incidence of ischemic stroke, confirmed by medical records, by quintile of whole grain intake according to FFQ responses. RESULTS: During 861,900 person-years of follow-up, 352 confirmed incident cases of ischemic stroke occurred. We observed an inverse association between whole grain intake and ischemic stroke risk. The age-adjusted relative risks (RRs) from the lowest to highest quintiles of whole grain intake were 1.00 (referent), 0.68 (95% confidence interval [CI], 0.49-0.94), 0.69 (95% CI, 0.51-0.95), 0.49 (95% CI, 0.35-0.69), and 0.57 (95% CI, 0.42-0.78; P =.003 for trend). Adjustment for smoking modestly attenuated this association (RR comparing extreme quintiles, 0.64; 95% CI, 0.47-0.89). This inverse association remained essentially unchanged with further adjustment for known CVD risk factors, including saturated fat and transfatty acid intake (multivariate-adjusted RR comparing extreme quintiles, 0.69; 95% CI, 0.50-0.98). The inverse relation between whole grain intake and risk of ischemic stroke was also consistently observed among subgroups of women who never smoked, did not drink alcohol, did not exercise regularly, or who did not use postmenopausal hormones. No significant association was observed between total grain intake and risk of ischemic stroke. CONCLUSIONS: In this cohort, higher intake of whole grain foods was associated with a lower risk of ischemic stroke among women, independent of known CVD risk factors. These prospective data support the notion that higher intake of whole grains may reduce the risk of ischemic stroke.     

Alcohol intake and the risk of coronary heart disease mortality in persons with older-onset diabetes mellitus.

CONTEXT: Despite nutrition information and guidelines that advise against depriving diabetic patients of the potential benefit of moderate alcohol intake against cardiovascular events, the association between alcohol consumption and risk of cardiovascular outcomes in diabetic individuals has not been determined. OBJECTIVE: To examine the relationship between alcohol intake and coronary heart disease (CHD) mortality in persons with older-onset diabetes. DESIGN: Population-based, prospective cohort study conducted from 1984 through 1996, with a follow-up of up to 12.3 years. SETTING AND PARTICIPANTS: A total of 983 older-onset diabetic individuals (mean [SD] age, 68.6 [11.0] years; 45.2% male; 98.5% white) were interviewed about their past-year intake of alcoholic beverages during the 1984-1986 follow-up examination of a population-based study of diabetic persons in southern Wisconsin. MAIN OUTCOME MEASURE: Time to mortality from CHD by category alcohol intake. RESULTS: Alcohol use was inversely associated with risk of CHD mortality in older-onset diabetic subjects. The CHD mortality rates for never and former drinkers were 43.9 and 38.5 per 1000 person-years, respectively, while the rates for those with alcohol intakes of less than 2, 2 to 13, and 14 or more g/d were 25.3, 20.8, and 10.0 per 1000 person-years, respectively. Compared with never drinkers and controlling for age, sex, cigarette smoking, glycosylated hemoglobin level, insulin use, plasma C-peptide level, history of angina or myocardial infarction, digoxin use, and the presence and severity of diabetic retinopathy, former drinkers had a relative risk (RR) of 0.69 (95% confidence interval [CI], 0.43-1.12); for those who drank less than 2 g/d (less frequent than 1 drink a week), the RR was 0.54 (95% CI, 0.33-0.90); for 2 to 13 g/d, it was 0.44 (95% CI, 0.23-0.84); and for 14 or more g/d (about 1 drink or more a day), it was 0.21 (95% CI, 0.09-0.48). Further adjustments for blood pressure, body mass index, education, physical activity, diabetes duration, hypertension history, overt nephropathy, peripheral neuropathy, lipid measures, or intake of medications such as aspirin and antihypertensive agents did not change the associations observed. CONCLUSION: Our results suggest an overall beneficial effect of alcohol consumption in decreasing the risk of death due to CHD in people with older-onset diabetes.     

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.     

Sex differences in evaluation and outcome of unstable angina

CONTEXT: The existence of sex bias in the delivery of cardiac care is controversial, and little is known about the association between sex and delivery of care and outcomes at an early point in the diagnostic sequence, such as when patients present for the evaluation of chest pain. OBJECTIVE: To test the hypothesis that female sex is negatively associated with care delivered to and outcomes of persons diagnosed as having unstable angina. DESIGN: Inception population-based cohort study with an average of 6 years of follow-up. SETTING: Emergency departments (EDs) in Olmsted County, Minnesota. PATIENTS: A total of 2271 Olmsted County residents (1306 men and 965 women) who presented to the ED for the first time with symptoms meeting criteria for unstable angina between 1985 and 1992. MAIN OUTCOME MEASURES: Use of cardiac procedures within 90 days of ED visit, overall mortality, and cardiac events (cardiac death, nonfatal myocardial infarction, nonfatal cardiac arrest, and congestive heart failure), compared by sex and Agency for Health Care Policy and Research cardiovascular risk category (low, intermediate, or high). RESULTS: Women were older (P<.001), more likely to have a history of hypertension (P = .001), and less likely to present with typical angina (P = .004) than men. Men were more likely than women to undergo noninvasive cardiac tests (relative risk [RR], 1.27; 95% confidence interval [CI], 1.14-1.40) as well as invasive cardiac procedures (RR, 1.72; 95% CI, 1.51-1.97). After adjustment, male sex was associated with a 24% increase in the use of cardiac procedures. Survival of both men and women in the high and intermediate risk categories was significantly lower than expected per the general population (P<.001). Women had a worse outcome than men, but after multivariate adjustment, male sex was associated with a trend toward an increase in the risk of death (RR, 1.23; 95% CI, 0.99-1.54) and significantly associated with increased risk of cardiac events (RR, 1.21; 95% CI, 1.03-1.42). CONCLUSIONS: Our population-based data indicate that after an ED visit for symptoms of unstable angina, the use of cardiac procedures was lower in women, but after taking into account baseline characteristics, men experienced worse outcomes.     

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.     

The definition of anemia in older persons.

CONTEXT: Whether hemoglobin concentrations defined as anemia by the World Health Organization (WHO) are associated with increased mortality in older persons is not known. OBJECTIVE: To investigate the association between hemoglobin concentration and cause-specific mortality in older persons. DESIGN: Community-based study conducted from 1986 to 1996 (follow-up period, 10 years). SETTING: Leiden, the Netherlands. PARTICIPANTS: A total of 1016 community residents aged 85 years and older were eligible and 872 agreed to have a blood sample taken. Hemoglobin concentration was measured in 755 persons (74%). MAIN OUTCOME MEASURES: Hemoglobin concentration, 10-year survival, and primary cause of death. According to the WHO criteria, anemia was defined as a hemoglobin concentration below 7.5 mmol/L (120 g/L) in women and below 8.1 mmol/L (130 g/L) in men. RESULTS: Compared with persons with a normal hemoglobin concentration, the mortality risk was 1.60 (95% confidence interval [CI], 1.24-2.06; P<.001) in women with anemia, and 2.29 (95% CI, 1.60-3.26; P<.001) in men with anemia. In both sexes, the mortality risk increased with lower hemoglobin concentrations. In persons without self-reported clinical disease at baseline, the mortality risk of anemia was 2.21 (95% CI, 1.37-3.57; P=.002). Mortality from malignant and infectious diseases was higher in persons with anemia. CONCLUSIONS: Anemia defined by the WHO criteria was associated with an increased mortality risk in persons aged 85 years and older. The criteria are thus appropriate for older persons. A low hemoglobin concentration at old age signifies disease.     

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.     

Influence of dietary patterns on the risk of acute myocardial infarction in China population: the INTERHEART China study

Background Some dietary patterns are risk factors for acute myocardial infarction (AMI).Chinese traditional food and habits vary from other cultures.The present study determined whether different dieta...