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Objective: Few studies have examined the association between genetic variants of the estrogen receptor beta (ESR2) and obesity in postmenopausal women., Methods: The relationship of three polymorphisms (rs1271572, rs1256049 and rs4986938) and their associated haplotypes in the ESR2 gene with obesity and overweight were evaluated in 561 apparently healthy women (median age 63 years) from the Women's Health Study. Most of the women were postmenopausal (99.1%). The associations between genotypes and haplotypes with obesity (BMI> or =30kg/m(2)) and overweight (BMI> or =25kg/m(2)) were evaluated by logistic regression, assuming an additive model., Results: No association was observed for any of the three polymorphisms with BMI, overweight or obesity. In haplotype analyses, one haplotype (major allele for all polymorphisms) was associated with a borderline inverse association with overweight but not obesity (OR=0.62, 95% CI=0.39-0.98)., Conclusions: An inverse and borderline significant association was found between the ESR2 G-G-G haplotype and overweight in postmenopausal women. Further investigation regarding the association between ESR2 and adiposity should be performed to confirm these findings.

Background: Waist circumference is a simpler measure of abdominal adiposity than waist/hip ratio (WHR), but few studies have directly compared the two measures as predictors of coronary heart disease (CHD) in men. In addition, whether the association of abdominal adiposity is independent of total adiposity as measured by body mass index (BMI) in men remains uncertain., Objective: To compare waist circumference and WHR as predictors of CHD in men, and to determine whether the association is independent of BMI., Design: Prospective cohort study., Methods: We compared WHR, waist circumference and BMI with risk of CHD (myocardial infarction or coronary revascularization) among men in the Physicians' Health Study, a randomized trial of aspirin and beta-carotene among 22 071 apparently healthy US male physicians, aged 40-84 y at baseline in 1982. Men reported height at baseline, and weight, waist and hip measurements on the 9 y follow-up questionnaire., Results: Among the 16 164 men who reported anthropometric measurements and were free from prior CHD, stroke or cancer, a total of 552 subsequent CHD events occurred during an average follow-up of 3.9 y. After adjusting for age, randomized study agent, smoking, physical activity, parental history of myocardial infarction, alcohol intake, multivitamin and aspirin use, men in the highest WHR quintile (>or=0.99) had a relative risk (RR) for CHD of 1.50 (95% CI 1.14-1.98) compared with those in the lowest quintile (<0.90). Men in the highest waist circumference quintile (>or=103.6 cm) had a RR of 1.60 (CI, 1.21-2.11) for CHD compared with men in the lowest quintile (<88.4 cm). Further adjustment for BMI substantially attenuated these associations: men in the highest WHR and waist circumference quintiles had relative risks for CHD of 1.23 (CI, 0.92-1.66) and 1.06 (CI, 0.74-1.53), respectively. Men in the highest BMI quintile (>or=27.6 kg/m(2)) had a multivariate RR of CHD of 1.73 (CI, 1.29-2.32), after adjustment for WHR. No significant effect modification by age of the relationship between either measure of abdominal adiposity and risk of CHD was observed., Conclusions: These data support a modest relationship between abdominal adiposity, as measured by either WHR or waist circumference, and risk of CHD both in middle-aged and older men. However, abdominal adiposity did not remain an independent predictor of CHD after adjustment for BMI.

Objective: To examine the associations of body mass index (BMI) and weight change with risk of stroke in women., Setting and Design: Prospective cohort study among US female registered nurses participating in the Nurses' Health Study., Participants: A total of 116759 women aged 30 to 55 years in 1976 who were free from diagnosed coronary heart disease, stroke, and cancer., Main Outcome Measure: Incidence of ischemic stroke, hemorrhagic stroke (subarachnoid or intraparenchymal hemorrhage), and total stroke., Results: During 16 years of follow-up, 866 total strokes (including 403 ischemic strokes and 269 hemorrhagic strokes) were documented. In multivariate analyses adjusted for age, smoking, postmenopausal hormone use, and menopausal status, women with increased BMI (> or =27 kg/m2) had significantly increased risk of ischemic stroke, with relative risks (RRs) of 1.75 (95% confidence interval [CI], 1.17-2.59) for BMI of 27 to 28.9 kg/m2; 1.90 (95% CI, 1.28-2.82) for BMI of 29 to 31.9 kg/m2; and 2.37 (95% CI, 1.60-3.50) for BMI of 32 kg/m2 or more (P for trend<.001), as compared with those with a BMI of less than 21 kg/m2. For hemorrhagic stroke there was a nonsignificant inverse relation between obesity and hemorrhagic stroke, with the highest risk among women in the leanest BMI category (P for trend=.20). For total stroke the RRs were somewhat attenuated compared with those for ischemic stroke but remained elevated for women with higher BMI (P for trend<.001). In multivariate analyses that also adjusted for BMI at age 18 years, weight gain from age 18 years until 1976 was associated with an RR for ischemic stroke of 1.69 (95% CI, 1.26-2.29) for a gain of 11 to 19.9 kg and 2.52 (95% CI, 1.80-3.52) for a gain of 20 kg or more (P for trend<.001), as compared with women who maintained stable weight (loss or gain <5 kg). Although weight change was not related to risk of hemorrhagic stroke (P for trend=.20), a direct relationship was observed between weight gain and total stroke risk (P for trend<.001)., Conclusions: These prospective data indicate that both obesity and weight gain in women are important risk factors for ischemic and total stroke but not hemorrhagic stroke. The relationship between obesity and total stroke depends on the distribution of stroke subtypes in the population.

Obesity is strongly associated with cardiac risk factors including elevated blood pressure, glucose intolerance, and dyslipidemia. Clinical trials have indicated that weight loss significantly improves these risk profiles. Epidemiologic studies consistently have shown that obesity is a strong risk factor for coronary heart disease in both men and women. In addition, abdominal adiposity may confer added risk for coronary heart disease. Although obesity is a modifiable and preventable cardiac risk factor, management of this disorder remains both challenging and vexing to clinicians. To prevent cardiovascular disease we must find ways to decrease the rising prevalence of obesity and to help overweight individuals achieve and sustain weight loss.