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Insulin resistance (IR), the hallmark of type 2 diabetes, may be under epigenetic control. This study examines the association between global DNA methylation and IR using 84 monozygotic twin pairs. IR was estimated using homeostasis model assessment (HOMA). Global DNA methylation of Alu repeats in peripheral blood leukocytes was quantified by bisulfite pyrosequencing. The association between global DNA methylation and IR was examined using generalized estimating equation (GEE) and within-twin pair analyses, adjusting for potential confounders. Results show that methylation levels at all four CpG sites were individually associated with IR by GEE (all false discovery rate-adjusted P values≤0.026). A 10% increase in mean Alu methylation was associated with an increase of 4.55 units (95% CI 2.38-6.73) in HOMA. Intrapair difference in IR was significantly associated with intrapair difference in global methylation level. A 10% increase in the difference in mean Alu methylation was associated with an increase of 4.54 units (0.34-8.71; P=0.036) in the difference in HOMA. Confirmation of the results by intrapair analyses suggests that genetic factors do not confound the association between global DNA methylation and IR. Exclusion of twins taking diabetes medication (n=17) did not change our results. [ABSTRACT FROM AUTHOR]

BACKGROUND: alpha-Linolenic acid (ALA) is associated with a low risk of cardiovascular disease; however, the underlying mechanism is not completely known. OBJECTIVE: The objective was to examine whether habitual dietary ALA intake is associated with plasma concentrations of inflammatory biomarkers after control for shared genetic and common environmental factors. DESIGN: We cross-sectionally studied 353 middle-aged male twins. Habitual diet was assessed with the Willett food-frequency questionnaire. Fasting plasma concentrations of interleukin-6 (IL-6) and its soluble receptor (sIL-6R), high-sensitivity C-reactive protein (hsCRP), and tumor necrosis factor-alpha (TNF-alpha) were measured. Linear mixed-effect regression analysis was used to partition the overall association into within- and between-pair associations. RESULTS: A 1-g increment in habitual dietary ALA intake was associated with 11.0% lower concentrations of sIL-6R (P = 0.004) but not of IL-6 (P = 0.31), TNF-alpha (P = 0.16), or hsCRP (P = 0.36) after adjustment for energy intake, nutritional factors, known cardiovascular disease risk factors, and medications. After further control for shared genetic and common environmental factors by comparison of brothers within a twin pair, a twin with a 1-g higher ALA intake was likely to have 10.9% (95% CI: 3.7%, 17.6%; P = 0.004) lower sIL-6R concentrations than his co-twin with a low intake, whereas ALA intake was not significantly associated with plasma concentrations of IL-6, TNF-alpha, or hsCRP. These results were validated by using 1000 bootstrap samples. CONCLUSIONS: Habitual dietary ALA intake is inversely associated with plasma sIL-6R concentrations independent of shared genetic and common environmental influences. Lowering sIL-6R may be a mechanism underlying the cardioprotective properties of habitual dietary ALA. This study was registered at clinicaltrials.gov as NCT00017836. © 2010 American Society for Nutrition. [ABSTRACT FROM AUTHOR]

Serum phosphorus levels in the general population have been reported to be associated with cardiovascular morbidity and mortality and increased carotid intima-media thickness. The authors examined gender heterogeneity in the association of phosphorus with all-cause mortality and incident coronary artery disease using data from the Atherosclerosis Risk in Communities Study (1987-2001). Baseline phosphorus levels were higher in women and were associated differently among men and women with traditional atherosclerosis risk factors such as age, low density lipoprotein cholesterol, diabetes mellitus, and hypertension. In a multivariable-adjusted model, men in the highest quintile of serum phosphorus level (>3.8 mg/dL) had an increased mortality rate (hazard ratio = 1.45, 95% confidence interval: 1.12, 1.88), while women did not (hazard ratio = 1.18, 95% confidence interval: 0.89, 1.57). The multivariable likelihood ratio test of effect modification by gender was significant at alpha = 0.1 (P = 0.085) for all-cause mortality. Although the associations of phosphorus with coronary artery disease also appeared to differ substantially by gender, the multivariable test for effect modification suggested that the difference was consistent with random variation (P = 0.195). These results suggest the need for further investigation into gender differences in the contribution of mineral metabolism to cardiovascular disease in the general population. [ABSTRACT FROM AUTHOR]

Background:The cardioprotective property of the Mediterranean diet has been attributed to its antioxidant capacity, but direct investigation of this mechanism has been limited.Objective:We examined the association between the Mediterranean diet and an established plasma marker of oxidative stress, the ratio of reduced to oxidized glutathione (GSH/GSSG), in a well-controlled study of twins.Design:We administered the Willett food-frequency questionnaire to 138 monozygotic and dizygotic twin pairs and to 21 unpaired twins and derived a score measuring adherence to the Mediterranean diet. Fasting plasma GSH and GSSG concentrations were measured to calculate the GSH/GSSG ratio. The higher the ratio, the lower the oxidative stress. Mixed-effect regression analysis was used to partition the association into between- and within-twin pair differences. When within-pair effects are examined, twins are matched for sociodemographic and familial factors.Results:A one-unit increment in the diet score was associated with a 7% higher GSH/GSSG ratio (P = 0.03) after adjustment for energy intake, other nutritional factors, cardiovascular disease risk factors, and medication use. The association persisted within twin pairs: a one-unit within-pair absolute difference in the diet score was associated with a 10% (95% CI: 2.7, 18.0) higher GSH/GSSG ratio in the twin with the higher score than in the co-twin with the lower score (P = 0.007). Results were similar in monozygotic and dizygotic twin pairs.Conclusions:The association between the Mediterranean diet and plasma oxidative stress is robust and is not confounded by genetic or shared environmental factors. Decreased oxidative stress is a plausible mechanism linking the Mediterranean diet to reduced cardiovascular disease risk. © American Society for Nutrition [ABSTRACT FROM AUTHOR]

Background: Poor prognosis in heart failure (HF) patients with diabetes is often attributed to increased co-morbidity and advanced disease. Further, this effect may be worse in women.Objective: To determine whether the effect of diabetes on outcomes and the sex-related variation persisted in a propensity score-matched HF population, and whether the sex-related variation was a function of age.Methods: Of the 7788 HF patients in the Digitalis Investigation Group trial, 2218 had a history of diabetes. Propensity score for diabetes was calculated for each patient using a non-parsimonious logistic regression model incorporating all measured baseline covariates, and was used to match 2056 (93%) diabetic patients with 2056 non-diabetic patients.Results: All-cause mortality occurred in 135 (25%) and 216 (39%) women without and with diabetes (adjusted HR = 1.67; 95% CI = 1.34 to 2.08; p<0.001). Among men, 535 (36%) and 609 (41%) patients without and with diabetes died from all causes (adjusted HR = 1.21; 95% CI = 1.07 to 1.36; p = 0.002). Sex-diabetes interaction (overall adjusted p<0.001) was only significant in patients > or = 65 years (15% absolute risk increase in women; multivariable p for interaction = 0.005), but not in younger patients (2% increase in women; p for interaction = 0.173). Risk-adjusted HR (95% CI) for all-cause hospitalisation for women and men were 1.49 (1.28 to 1.72) and 1.21 (1.11 to 1.32), respectively, also with significant sex-diabetes interaction (p = 0.011).Conclusions: Diabetes-associated increases in morbidity and mortality in chronic HF were more pronounced in women, and theses sex-related differences in outcomes were primarily observed in elderly patients. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to examine prospectively whether inflammation explains the relationship between depression and cardiovascular disease (CVD). Background: It is unclear whether inflammation is a mechanism linking depression to CVD. Methods: We measured C-reactive protein (CRP) and interleukin (IL)-6 in 559 women with suspected coronary ischemia who completed the Beck Depression Inventory (BDI) at baseline and were followed over 5.9 years. We considered indicators of past and current depression to classify women into 3 groups: 1) depression, having both elevated depressive symptoms (BDI > or =10) and a previous diagnosis of depression requiring treatment; 2) possible depression, having either indicator but not both; and 3) no depression, having neither indicator of depression. The main outcome was incidence of CVD events (hospital stays for nonfatal myocardial infarction, stroke, congestive heart failure, and CVD-related mortality). Results: Compared with women without depression, women with depression had a 70% higher CRP (p = 0.0008) and a 25% higher IL-6 (p = 0.04), whereas women with possible depression had 30% higher CRP (p = 0.02) and 28% higher IL-6 (p = 0.01). Depression was a significant predictor of CVD (hazard ratio 2.58, p = 0.0009), but possible depression was not (hazard ratio 1.12, p = 0.68). Adjustment for other patient factors did not substantially affect the results. Addition of CRP decreased the estimate for depression by 13% and addition of IL-6 decreased it by 4%. Both depression and inflammatory biomarkers remained independent predictors of outcome. Conclusions: Despite their robust association with depression, inflammatory biomarkers explain only a small portion of the association between depression and CVD incidence. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the relation between bone mass and the incidence of coronary heart disease in women and men. Participants included 2,059 cohort members of the Framingham Study (1,236 women and 823 men aged 47-80 years) who underwent posteroanterior hand radiography and were free from cardiovascular disease at baseline (1967-1970) and who were then followed for 30 years through the end of 1997 for the incidence of coronary heart disease. The incidence of coronary heart disease decreased from 15.65/1,000 person-years among women in the lowest metacarpal cortical area quartile to 11.76/1,000 person-years among women in the highest quartile (p(trend) = 0.03), and the inverse relation persisted after adjustment for confounders (highest vs. lowest quartile of metacarpal cortical area: hazard ratio = 0.73, 95% confidence interval: 0.53, 1.00; p(trend) = 0.03). In contrast, no association was present in men (highest vs. lowest quartile of metacarpal cortical area: hazard ratio = 1.14, 95% confidence interval: 0.84, 1.56; p(trend) = 0.55). [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine the association of age with the change in quality of life (QOL) after valve surgery.Background: Improvement in QOL is one of the principal goals of valve surgery. These procedures are being done with increasing frequency for older patients.Methods: We prospectively studied 148 patients with aortic valve procedures and 72 patients with mitral valve procedures. Patients' QOL was measured at baseline and at 18 months using the Medical Outcomes Trust Short Form 36-Item (SF-36) Health Survey (response rate 90%). The association of age with change in QOL was measured by multiple regression analysis and based on two meta-scores of the SF-36: the Mental Component Summary (MCS) and the Physical Component Summary (PCS).Results: Overall improvement in most domains of the SF-36, including the MCS and the PCS scores, was substantial. Improvement in the MCS score was not influenced by age in either aortic (0.09 score point improvement per 10-year age increments; p = 0.9) or mitral (0.90 score point improvement per 10-year age increments; p = 0.3) patients. Similarly, improvement in the PCS score did not vary by age in aortic patients (-1.00 score points per 10-year age increments; p = 0.2) and only slightly varied by age in mitral patients (-1.90 score points per 10-year age increments, p = 0.02). In the latter, despite statistical significance, the association was not substantial or clinically important.Conclusions: Among patients referred for cardiac valve surgery, age does not appear to limit the QOL benefits of surgery. [ABSTRACT FROM AUTHOR]

Objectives: This study was designed to examine whether female gender is associated with poorer recovery after coronary artery bypass graft (CABG) surgery.Background: The risks and benefits associated with CABG surgery in women are not as well established as they are in men, and there are concerns that women may have worse outcomes. The recovery period after CABG (the first four to eight weeks after the surgery) is a vulnerable time, with higher risks of complications and hospital readmission. There is little information on patients' experiences during this phase, particularly among women.Methods: We prospectively followed 1,113 patients (804 men and 309 women) who underwent first CABG consecutively between February 1999 and February 2001. Patients were interviewed at baseline and between six and eight weeks after surgery. Clinical data were abstracted from medical records.Results: Compared with men, women were older and more often had unstable angina and congestive heart failure, lower physical function (PF), and more depressive symptoms in the month before surgery. At six to eight weeks after CABG surgery, after adjustment for baseline characteristics, the rate of hospital readmission was 20.5% in women and 11.0% in men (p = 0.005), and the mean number of physical symptoms and side effects was 2.5 in women and 2 in men (p = 0.0009). Whereas, on average, PF remained unchanged in men (an increase in score of 0.3 points, 95% confidence interval [CI], -1.1 to 1.8) and depressive symptoms improved (a decrease of 0.2 depressive symptoms, 95% CI, -0.4 to -0.04), women showed, on average, a 13-point decline in physical function (95% CI, -15.8 to -10.4) and an increase of 0.5 in depressive symptoms (95% CI, 0.1 to 0.9).Conclusions: After CABG surgery, women have a more difficult recovery compared with men, which is not explained by illness severity, presurgery health status, or other patient characteristics. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study examined the associations of poverty income ratio (PIR), education, and occupational status with type 2 diabetes prevalence among African American and non-Hispanic White (White) women and men aged 40 to 74 years. METHODS: We analyzed cross-sectional data from the Third National Health and Nutrition Examination Survey, controlling for age and examination-related variables. RESULTS: Among African American women, there was a strong, graded association between PIR and diabetes, which remained significant after other risk factors were adjusted for. All 3 variables were significantly associated with diabetes among White women. Among White men, only PIR was significantly associated with diabetes. Controlling for risk factors substantially attenuated these associations among White women. There were no significant associations for African American men. CONCLUSIONS: Socioeconomic status is associated with type 2 diabetes prevalence among women, but not consistently among men. Diabetes prevalence is more strongly associated with PIR than with education or occupational status. These associations are largely independent of other risk factors, especially among African American women. Economic resources should be addressed in efforts to explain and reverse the increasing prevalence of diabetes in the United States. [ABSTRACT FROM AUTHOR]

To examine whether socioeconomic status (SES) explains differences in the prevalence of type 2 diabetes between African-American and non-Hispanic white women and men. Cross sectional study of diabetes prevalence, SES, and other risk factors ascertained by physical examination and interview. Interviews were conducted in subjects' homes; physical examinations were conducted in mobile examination centres. 961 African-American women, 1641 non-Hispanic white women, 839 African-American men and 1537 non-Hispanic white men, aged 40 to 74 years, examined in the Third National Health and Nutrition Examination Survey (NHANES III), a representative sample of the non-institutionalised civilian population of the United States, 1988-1994. Among women, African-American race/ethnicity was associated with an age adjusted odds ratio of 1.76 (95% confidence intervals 1.21, 2.57), which was reduced to 1.42 (95% confidence intervals 0.95, 2.13) when poverty income ratio was controlled. Controlling for education or occupational status had minimal effects on this association. When other risk factors were controlled, race/ethnicity was not significantly associated with type 2 diabetes prevalence. Among men, the age adjusted odds ratio associated with African-American race/ethnicity was 1.43 (95% confidence intervals 1.03, 1.99). Controlling for SES variables only modestly affected the odds ratio for African/American race/ethnicity among men, while adjusting for other risk factors increased the racial/ethnic differences. Economic disadvantage may explain much of the excess prevalence of type 2 diabetes among African-American women, but not among men. [ABSTRACT FROM AUTHOR]