Calcium supplement intake and risk of cardiovascular disease in women.

UNLABELLED: Some recent reports suggest that calcium supplement use may increase risk of cardiovascular disease. In a prospective cohort study of 74,245 women in the Nurses' Health Study with 24 years of follow-up, we found no independent associations between supplemental calcium intake and risk of incident coronary heart disease (CHD) and stroke. INTRODUCTION: Some recent reports suggest that calcium supplements may increase cardiovascular disease (CVD) risk. The objective was to examine the independent associations between calcium supplement use and risk of CVD. METHODS: We conducted a prospective cohort study of supplemental calcium use and incident CVD in 74,245 women in the Nurses' Health Study (1984-2008) free of CVD and cancer at baseline. Calcium supplement intake was assessed every 4 years. Outcomes were incident CHD (nonfatal or fatal MI) and stroke (ischemic or hemorrhagic), confirmed by medical record review. RESULTS: During 24 years of follow-up, 4,565 cardiovascular events occurred (2,709 CHD and 1,856 strokes). At baseline, women who took calcium supplements had higher levels of physical activity, smoked less, and had lower trans fat intake compared with those who did not take calcium supplements. After multivariable adjustment for age, body mass index, dietary calcium, vitamin D intake, and other CVD risk factors, the relative risk of CVD for women taking >1,000 mg/day of calcium supplements compared with none was 0.82 (95% confidence interval [CI] 0.74 to 0.92; p for trend <0.001). For women taking >1,000 mg/day of calcium supplements compared with none, the multivariable-adjusted relative risk for CHD was 0.71 (0.61 to 0.83; p for trend < 0.001) and for stroke was 1.03 (0.87 to 1.21; p for trend = 0.61). The relative risks were similar in analyses limited to non-smokers, women without hypertension, and women who had regular physical exams. CONCLUSIONS: Our findings do not support the hypothesis that calcium supplement intake increases CVD risk in women.

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.

Baseline characteristics of participants in the Women's Health Study.

The Women's Health Study (WHS) is a randomized, double-blind, placebo-controlled trial designed to evaluate the balance of benefits and risks of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer in women. A total of 39,876 female health professionals, age 45 years or older and without a history of cardiovascular disease or cancer (other than nonmelanoma skin cancer), were randomized in a 2x2 factorial design to one of four treatment groups: active aspirin and vitamin E placebo, aspirin placebo and active vitamin E, both active agents, or both placebos. The process of randomization was successful, as evidenced by the equal distribution of a large number of baseline demographic, lifestyle, and health history characteristics among the four treatment groups. Similar distribution of known potential confounders, as well as the large sample size, provides reassuring evidence that unmeasured or unknown potential confounders are also equally distributed. As expected in a clinical trial, the women in the study are healthier in some respects than the general population, but they have very comparable rates of obesity, hypertension, and elevated cholesterol. With adequate duration of treatment and follow-up, this trial will provide important and relevant information on the balance of benefits and risks of aspirin and vitamin E supplementation in the primary prevention of cardiovascular disease and cancer in women.

Antioxidants and coronary heart disease: observational studies.

Observational studies have found that persons who consume large amounts of fruit and vegetables have lower rates of coronary heart disease. The strength of epidemiologic evidence, however, differs for each of the antioxidant vitamins. High intake of vitamin E from food or supplements has generally been associated with a lower incidence of coronary heart disease. The evidence for beta-carotene intake is inconsistent, with several studies finding a modest reduction in risk among persons with high intake, and others failing to find an association. Although many studies have examined the relationship between vitamin C intake and cardiovascular disease, no significant benefit was seen in any of the large studies that were able to control for other antioxidant intake or multivitamin use. Observational studies cannot discern whether the decreased risk observed is caused by the antioxidants themselves or other characteristics of the individuals who consume them. The epidemiologic associations may be due to other nutrients in antioxidant-rich foods, or other dietary or lifestyle factors. Randomized controlled trials are necessary to confirm or refute the observational data. On the basis of available evidence, we should recommend a healthy diet, rich in fruit and vegetables, but should not endorse vitamin supplementation unless conclusive evidence of benefit is demonstrated in clinical trials.