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Background: Variants in the advanced glycosylation end product-specific receptor (AGER) gene have been associated with diabetic vasculopathy, however their role in the pathogenesis of insulin resistance and type 2 diabetes mellitus (T2DM) are uncertain. We investigated the relationship of 3 polymorphisms (rs1800625, rs1800624 and rs2070600) in the AGER gene and their haplotypes with T2DM as well as insulin resistance., Methods: A case-control study from community-based population sample of the Boston metropolitan area was performed in 637 diabetic patients and 596 controls (non-diabetic). The relationships between genotypes and T2DM were evaluated by linear and logistic regression models. Associations with insulin resistance [using corrected insulin response (CIR-30), insulin sensitivity index (ISI-120) and oral glucose tolerance test] were also examined among controls., Results: We found no consistent association between prevalent type 2 diabetes mellitus, and "insulin indices" (CIR-30, ISI-120 and oral glucose tolerance test) and the AGER polymorphisms. The A allele in the rs1800624 was modestly associated with a progressive decrease in CIR-30 levels only among Black controls (p=0.03)., Conclusions: A suggestive association between the A allele in the rs1800624 and CIR-30 levels was found. Further large and multiethnic studies should be performed to clarify these relationships.

Objective: Diabetes-related metabolic abnormality may aggravate the adverse effects of iron overload on cardiovascular health. However, little is known about whether iron consumption affects coronary heart disease (CHD) risk in diabetes., Research Design and Methods: We prospectively assessed the associations of long-term intakes of dietary iron and red meat with CHD risk among 6,161 women who reported a diagnosis of type 2 diabetes., Results: During 54,455 person-years of follow-up from 1980 through 2000, we documented 550 incident cases of CHD. After adjustment for age and BMI, high intakes of both heme iron and red meat were associated with a significantly increased risk of fatal CHD (P for trend = 0.003 and 0.018), coronary revascularization (P for trend = 0.02 and 0.06), and total CHD (P for trend = 0.0009 and 0.007). Women with the highest intake of heme iron had 50% (6-94%) increased risk of total CHD compared with those with the lowest intake. Further adjustment for other lifestyle and dietary factors did not appreciably change the associations. The positive association between heme iron and red meat intakes and CHD was more evident among postmenopausal women compared with premenopausal women., Conclusions: Our data indicate that higher consumption of heme iron and red meat may increase CHD risk among women with type 2 diabetes.

Context: Several case-control studies suggest an association between analgesic use and increased risk of chronic renal disease, but few cohort studies have examined this association., Objective: To determine whether analgesic use is associated with risk of renal dysfunction., Design and Setting: Cohort study of analgesic use data from the Physicians' Health Study, which lasted 14 years from September 1982 to December 1995 with annual follow-up., Participants: A total of 11 032 initially healthy men who provided blood samples and self-report of analgesic use., Main Outcome Measures: Elevated creatinine level defined as 1.5 mg/dL (133 micromol/L) or higher and a reduced creatinine clearance defined as 55 mL/min (0.9 mL/s) or less, and self-reported use of acetaminophen, aspirin, and other nonsteroidal anti-inflammatory drugs (never [<12 pills]; 12-1499 pills; 1500-2499 pills; and >/=2500 pills)., Results: A total of 460 men had elevated creatinine levels (4.2%) and 1258 had reduced creatinine clearance (11.4%). Mean creatinine levels and creatinine clearances were similar among men who did not use analgesics and those who did, even at total intakes of 2500 or more pills. In multivariable analyses adjusted for age; body mass index; history of hypertension, elevated cholesterol, and diabetes; occurrence of cardiovascular disease; physical activity; and use of other analgesics, the relative risks of elevated creatinine level associated with intake of 2500 or more pills were 0.83 (95% confidence interval [CI], 0.50-1.39; P for trend =.05) for acetaminophen, 0.98 (95% CI, 0.53-1.81; P for trend =.96) for aspirin, and 1.07 (95% CI, 0.71-1.64; P for trend =.86) for other nonsteroidal anti-inflammatory drugs. No association was observed between analgesic use and reduced creatinine clearance., Conclusions: Moderate analgesic use in this cohort study of initially healthy men was not associated with increased risk of renal dysfunction.

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 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.

Context: Obesity is a well-established risk factor for coronary heart disease (CHD), but whether regional fat distribution contributes independently to risk remains unclear., Objective: To compare waist-hip ratio (WHR) and waist circumference in determining risk of CHD in women., Design and Setting: Prospective cohort study among US female registered nurses participating in the Nurses' Health Study conducted between 1986, when the nurses completed a questionnaire, and follow-up in June 1994., Participants: A total of 44702 women aged 40 to 65 years who provided waist and hip circumferences and were free of prior CHD, stroke, or cancer in 1986., Main Outcome Measures: Incidence of CHD (nonfatal myocardial infarction or CHD death)., Results: During 8 years of follow-up 320 CHD events (251 myocardial infarctions and 69 CHD deaths) were documented. Higher WHR and greater waist circumference were independently associated with a significantly increased age-adjusted risk of CHD. After adjusting for body mass index (BMI) (defined as weight in kilograms divided by the square of height in meters) and other cardiac risk factors, women with a WHR of 0.88 or higher had a relative risk (RR) of 3.25 (95% confidence interval [CI], 1.78-5.95) for CHD compared with women with a WHR of less than 0.72. A waist circumference of 96.5 cm (38 in) or more was associated with an RR of 3.06 (95% CI, 1.54-6.10). The WHR and waist circumference were independently strongly associated with increased risk of CHD also among women with a BMI of 25 kg/m2 or less. After adjustment for reported hypertension, diabetes, and high cholesterol level, a WHR of 0.76 or higher or waist circumference of 76.2 cm (30 in) or more was associated with more than a 2-fold higher risk of CHD., Conclusions: The WHR and waist circumference are independently associated with risk of CHD in women.

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.