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Context: Prior studies have shown a cross-sectional association between body mass index (BMI) and salivary diurnal cortisol profile features (cortisol features); however, to our knowledge prior population-based studies have not examined the longitudinal association of body-mass index (BMI) with cortisol features., Objective: To examine the association of (1) prior annual BMI percent change over 7years with cortisol features, (2) baseline cortisol features with subsequent change in BMI over 6years and (3) the association of change in cortisol features with change in BMI over 6years., Design: Longitudinal study., Setting: Multi-Ethnic Study of Atherosclerosis (MESA) Stress I & II Studies (2004-2006 & 2010-2012)., Participants: 1685 ethnically diverse men and women attended either MESA Stress exam (mean age 65±10years at MESA Stress I; mean age 69±9years at MESA Stress II)., Outcome Measures: Log-transformed cortisol features including wake-up cortisol, cortisol awakening response, early decline slope (30min to 2h post-awakening), late decline slope (2h post-awakening to bedtime), bedtime, and total area under the curve (AUC) cortisol., Results: Over 7years, following multivariable adjustment, (1) a 1% higher prior annual BMI % increase was associated with a 2.9% (95% CI: -5.0%, -0.8%) and 3.0% (95% CI: -4.7%, -1.4%) lower current wake-up and total AUC cortisol, respectively; (2) there was no significant association between baseline cortisol features and subsequent change in BMI and (3) among participants with BMI≥30kg/m 2 , flattening of the late decline slope was associated with increases in BMI (every 1-unit increase late decline slope were associated with a 12.9% increase (95%CI: -1%, 26.8%) in BMI, respectively)., Conclusions: We found a significant association between prior annual BMI % change and cortisol features, but no significant association between baseline cortisol features and subsequent change in BMI. In participants with obesity increases in BMI were associated with less pronounced declined. Collectively, our results suggest that greater adiposity may lead to a blunted diurnal cortisol profile., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: Whether endogenous sex hormones play a role in cardiovascular disease (CVD) risk in men is unclear. Few studies have examined associations of sex hormones with atherosclerosis measured by coronary artery calcium score (CACS) and carotid intima-media thickness (cIMT). We evaluated the association of testosterone (T) and other sex hormones with CACS and cIMT., Methods: Using the large multi-ethnic cohort of 3164 men without known CVD in the Multi-Ethnic Study of Atherosclerosis (MESA), cross-sectional associations of tertiles of endogenous sex hormones with CACS and cIMT were analysed., Results: In regard to CAC, there was a significant negative trend (P-trend = 0·02) for CACS>0 over tertiles of free T (FT) with RRs (95% CI) for the lowest to highest tertiles. There was also a marginally significant positive trend (P-trend = 0·06) for CACS>0 over tertiles of sex hormone-binding globulin (SHBG) with RRs for the lowest to highest tertiles. There were no significant associations with CACS >0 for tertiles of TT (Total T), bioavailable T (BT), oestradiol (E2) and dehydroepiandrosterone (DHEA). There was significantly higher log CACS after adjustment for CVD risk factors for lower TT levels, compared to higher levels, using 9·54 and 10·4 nmol/l as cut-off points. In regard to cIMT, there was a significant positive trend (P = 0·003) in mean cIMT over the tertiles of BT, but not for TT, FT, E2, DHEA and SHBG. There was significantly lower cIMT after adjustment for CVD risk factors for lower TT levels compared to higher levels., Conclusion: In a population of male subjects with no known CVD, lower FT is associated with higher RR of CACS>0 and lower TT is associated with higher log CACS. Lower BT and TT are associated with lower cIMT. While these findings support the positive correlation between low T and coronary atherosclerosis, the opposite findings on cIMT warrant further evaluation., (© 2015 John Wiley & Sons Ltd.)

Hypercortisolism is associated with insulin resistance (IR) and diabetes mellitus (DM); however, to our knowledge prior studies have not examined the association of diurnal cortisol curve features with measures of glycemia or IR in a population-based setting. Using log-transformed salivary cortisol data on 850 ethnically diverse men and women from the Multi-Ethnic Study of Atherosclerosis, we investigated the cross-sectional association of cortisol curve features with (1) glycemia in those with and without DM and (2) IR, in non-diabetic subjects. The log-transformed salivary cortisol curve features included wake-up cortisol, cortisol awakening response (CAR), early decline slope (30min to 2h post-awakening), late decline slope (2h post-awakening to bedtime), overall decline slope (0min to bedtime, excluding 30min cortisol), bedtime cortisol and total area under the curve (AUC). Overall, following multivariable adjustment, among those with diabetes mellitus (DM), early decline slope, overall decline slope, bedtime cortisol, and AUC were significantly and positively associated with a 5.4% (95% CI: 1.3, 9.7), 54.7% (95% CI: 12.4, 112.9), 4.0% (95% CI: 1.6,6.4), and 6.8% (95% CI: 3.3,10.4) higher HbA1c per 1 unit increase in log cortisol feature, respectively. Cortisol curve features were not associated with HbA1c among non-diabetic participants; however, wake-up cortisol and AUC were associated with a 8.2% lower (95% CI: -13.3,-2.7) and 7.9% lower (95% CI: -14.6, -0.6) log HOMA-IR, respectively. This was attenuated by adjustment for waist circumference. Among participants with DM, cortisol curve parameters suggestive of higher hypothalamic-pituitary-adrenal (HPA) axis activity and dysfunction were associated with higher HbA1c. In non-diabetic participants, greater HPA activity was paradoxically associated with lower insulin resistance., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Few studies have investigated the relationship of anthropometric measurements with computed tomography (CT) body fat composition, and even fewer determined if these relationships differ by sex and race., Methods: CT scans from 1,851 participants in the population based Multi-Ethnic Study of Atherosclerosis were assessed for visceral and subcutaneous fat areas by semi-automated segmentation of body compartments. Regression models were used to investigate relationships for anthropometry with visceral and subcutaneous fat separately by sex and race/ethnicity., Results: Participants were 50% female, 41% Caucasian, 13% Asian, 21% African American, and 25% Hispanic. For visceral fat, the positive relationship with weight (p = 0.028), waist circumference (p<0.001), waist to hip ratio (p<0.001), and waist to height ratio (p = 0.05) differed by sex, with a steeper slope for men. That is, across the range of these anthropometric measures the rise in visceral fat is faster for men than for women. Additionally, there were differences by race/ethnicity in the relationship with height (p<0.001), weight (p<0.001), waist circumference (p<0.001), hip circumference (p = 0.006), and waist to hip ratio (p = 0.001) with the Hispanic group having shallower slopes. For subcutaneous fat, interaction by sex was found for all anthropometric indices at p<0.05, but not for race/ethnicity., Conclusion: The relationship between anthropometry and underlying adiposity differs by sex and race/ethnicity. When anthropometry is used as a proxy for visceral fat in research, sex-specific models should be used.

Objective: Prior studies have shown a bidirectional association between depression and type 2 diabetes mellitus (T2DM); however, the prospective associations of anger and anxiety with T2DM have not been established. We hypothesized that trait anger and anxiety would predict incident T2DM, independently of depressive symptoms., Research Design and Methods: In the Multi-ethnic Study of Atherosclerosis (MESA), we prospectively examined the association of trait anger and trait anxiety (assessed via the Spielberger Trait Anger and Anxiety Scales, respectively) with incident T2DM over 11.4 years in 5598 White, Black, Hispanic, and Chinese participants (53.2% women, mean age 61.6 years) at baseline without prevalent T2DM or cardiovascular disease. We used Cox proportional hazards models to calculate the hazard ratios (HR) of incident T2DM by previously defined anger category (low, moderate, high), and anxiety quartile, as there were no previously defined categories., Results: High total trait anger was associated with incident T2DM (HR 1.50; 95% CI 1.08-2.07) relative to low total trait anger. The association was attenuated following adjustment for waist circumference (HR 1.32; 95% CI 0.94-1.86). Higher anger reaction was also associated with incident T2DM (HR=1.07; 95% CI 1.03-1.11) that remained significant after adjusting for potential confounders/explanatory factors. In contrast, trait anxiety did not predict incident T2DM., Conclusions: High total trait anger and anger reaction are potential modifiable risk factors for T2DM. Further research is needed to explore the mechanisms of the anger-diabetes relationship and to develop preventive interventions., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Context: Sex hormones may influence adipose tissue deposition, possibly contributing to sex disparities in cardiovascular disease risk., Objective: We hypothesized that associations of sex hormone levels with visceral and subcutaneous fat differ by sex., Design, Setting, and Participants: Participants were from the Multi-Ethnic Study of Atherosclerosis with sex hormone levels at baseline and visceral and subcutaneous fat measurements from computed tomography at visit 2 or 3 (n = 1835)., Main Outcome Measures: Multivariable linear regression was used to investigate the relationships between sex hormones and adiposity. Testing for interaction by sex, race/ethnicity, and age was conducted., Results: In adjusted models, there was a modest significant positive association between estradiol and visceral fat in both sexes (percent difference in visceral fat for 1% difference in hormone [95% confidence interval] in women, 5.44 [1.82, 9.09]; and in men, 8.22 [0.61, 16.18]). Higher bioavailable T was significantly associated with higher visceral and subcutaneous fat in women and with the reverse in men (women, 14.38 [10.23, 18.69]; men, -7.69 [-13.06, -1.00]). Higher dehydroepiandrosterone was associated with higher visceral fat in women (7.57 [1.71, 13.88]), but not in men (-2.47 [-8.88, 4.29]). Higher SHBG was associated with significantly lower levels of adiposity in both sexes (women, -24.42 [-28.11, -20.55]; men, -27.39 [-32.97, -21.34]). There was no significant interaction by race/ethnicity or age., Conclusion: Sex hormones are significantly associated with adiposity, and the associations of androgens differ qualitatively by sex. This heterogeneity may help explain the complexity of the contribution of sex hormones to sex differences in cardiovascular disease.

The objective was to examine the cross-sectional association of diurnal salivary cortisol curve components and urinary catecholamines with diabetes status. Up to 18 salivary cortisol samples over 3 days and overnight urinary catecholamines were collected from 1002 participants in the Multi-Ethnic Study of Atherosclerosis. Diabetes was defined as a fasting blood glucose of at least 126 mg/dL or medication use. Cortisol curve measures included awakening cortisol, cortisol awakening response, early decline, late decline, and cortisol area under the curve (AUC). Urinary catecholamines included epinephrine, norepinephrine, and dopamine. Participants with diabetes had significantly lower cortisol awakening response (β = -0.19; 95% confidence interval [CI], -0.34 to -0.04) than those without diabetes in multivariable models. Whereas men with diabetes had a nonsignificant trend toward lower total AUC (β = -1.56; 95% CI, -3.93 to 0.80), women with diabetes had significantly higher total AUC (β = 2.62; 95% CI, 0.72 to 4.51) (P = .02 for interaction) compared with those without diabetes. Men but not women with diabetes had significantly lower urinary catecholamines compared with those without diabetes (P < .05). Diabetes is associated with neuroendocrine dysregulation, which may differ by sex. Further studies are needed to determine the role of the neuroendocrine system in the pathophysiology of diabetes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To assess associations of sex hormones with impaired fasting glucose (IFG) and type 2 diabetes in men., Research Design and Methods: A total of 3,156 African American, Non-Hispanic white, Hispanic, and Chinese-American men aged 45-84 years who participated in the baseline visit of the Multi-Ethnic Study of Atherosclerosis (MESA) were included. Odd sratios and 95% CIs for type 2 diabetes and IFG compared with normal fasting glucose for quartiles of hormones were estimated., Results: After adjusting for age, ethnicity, BMI, and waist circumference, IFG and diabetes were associated inversely with total testosterone and sex hormone-binding globulin (SHBG) and positively with estradiol (E2). Dehydroepiandrosterone was positively associated with IFG but not with diabetes. Associations did not differ across ethnic groups., Conclusions: Regardless of obesity, total testosterone and SHBG were associated inversely and E2 was associated positively with IFG and diabetes in men. Further research is warranted to better understand the underlying biological mechanisms.

The traditional lipid profile differs by sex hormone levels. However, associations of sex hormones with lipoprotein subfractions, which may more accurately represent metabolic pathways to atherosclerosis, are not well studied. We quantified the cross-sectional associations of endogenous sex hormones with lipoprotein subfractions in 3143 men and 2038 postmenopausal women who were not on hormone replacement therapy, aged 45 to 84 years, in the Multi-Ethnic Study of Atherosclerosis baseline examination. Particle sizes and numbers of very low-density (VLDL), low-density (LDL), and high-density (HDL) lipoproteins were measured by nuclear magnetic resonance. In both men and women, after multivariable adjustment, higher sex hormone binding globulin (SHBG) levels are associated with smaller, fewer VLDL; larger, fewer LDL; and larger, more numerous HDL particles, whereas higher endogenous estradiol levels are associated with smaller VLDL and smaller, more numerous HDL and LDL particles (all P < .05). Testosterone (adjusted for SHBG) is associated with smaller VLDL particles in men but not women (sex difference P = .040). Higher dehydroepiandrosterone levels are associated with more numerous, smaller VLDL particles only in women (sex difference P = .030, .004, respectively). In conclusion, we found sex differences in the association of endogenous androgens with lipoprotein particle sizes and numbers. Higher endogenous estradiol, but lower SHBG, is associated with a more atherogenic lipoprotein particle profile. These findings highlight the potential to improve the lipoprotein profile with sex hormones, but emphasize the intricacies of the interactions.

Objective: To assess the cross-sectional association between depression and glucose tolerance status., Methods: We conducted a study of 6754 White, Black, Hispanic, and Chinese men and women aged 45 to 84 years in the Multiethnic Study of Atherosclerosis (MESA). Depression was defined as Center for Epidemiologic Studies Depression scale score of > or =16 and/or antidepressant use. Glucose tolerance status was defined as normal, impaired fasting glucose (IFG) or Type 2 diabetes mellitus (untreated and treated)., Results: In the minimally adjusted model, although depression was not associated with a greater odds of IFG (odds ratio (OR) = 1.01; 95% confidence interval (CI): 0.87-1.18) or untreated diabetes (OR = 1.03; 95% CI: 0.74-1.45), it was associated with a greater odds of treated diabetes (OR = 1.57; 95% CI: 1.27-1.96). This persisted following adjustment for body mass index (OR = 1.52; 95% CI: 1.22-1.90), metabolic (OR = 1.54; 95% CI: 1.23-1.93), and inflammatory (OR=1.53; 95% CI: 1.21-1.92) factors, daily caloric intake and smoking (OR = 1.48; 95% CI: 1.16-1.88), and socioeconomic markers (OR = 1.47; 95% CI: 1.17-1.85). Among individuals with treated diabetes, median depression scores were higher in those with microalbuminuria compared with those without microalbuminuria (median = 7; interquartile range: 3-13 versus median = 6; interquartile range: 2-11; p = .046). Depression scores were not associated with homeostatic model assessment of insulin resistance among individuals without diabetes., Conclusions: In MESA, depression was significantly associated with treated diabetes. Further studies are needed to determine the temporality of this association.

Trials of intensive glucose control have not improved cardiovascular disease (CVD) risk in populations with type 2 diabetes; however, in the general population, reports are inconsistent about the effects of maintaining lower glucose levels. Some speculate that low glycemic values are associated with increased glycemic variability, which is in turn associated with higher CVD risk. It has also been suggested that fasting glucose and hemoglobin A1c (HbA1c) in the lower ranges have a different relationship with CVD and mortality. In 4990 participants from the Multi-Ethnic Study of Atherosclerosis, we used logistic regression to investigate associations of low fasting glucose (

Latino immigrants have lower prevalence of depression, obesity and cardiovascular disease than US-born Latinos when they are recently arrived in the US, but this health advantage erodes with increasing duration of US residence. Cumulative exposure to psychosocial stress and its physiological sequelae may mediate the relationship between nativity and duration of US residence and poor health. We used data from Latino cohort study participants ages 45-84 to examine cross-sectional (n=558) and longitudinal (n=248) associations between nativity and duration of US residence and features of the diurnal cortisol curve including: wake-up cortisol, cortisol awakening response (CAR, wake-up to 30min post-awakening), early decline (30min to 2h post-awakening) and late decline (2h post-awakening to bed time), wake-to-bed slope, and area under the curve (AUC). In cross-sectional analyses, US-born Latinos had higher wake-up cortisol than immigrants with fewer than 30 years of US residence. In the full sample, over 5 years the CAR and early decline became flatter and AUC became larger. Over 5 years, US-born Latinos had greater increases in wake-up cortisol and less pronounced flattening of the early diurnal cortisol decline than immigrants with fewer than 30 years of US residence. Immigrants with 30 or more years of US residence also had less pronounced flattening of the early decline relative to more recent immigrants, and also had a less pronounced increase in AUC. In sum, we saw limited cross-sectional evidence that US-born Latinos have more dysregulated cortisol than recently-arrived Latino immigrants, but over time US-born Latinos had slower progression of cortisol dysregulation.

ContextPrior studies have shown a cross-sectional association between body mass index (BMI) and salivary diurnal cortisol profile features (cortisol features); however, to our knowledge prior population-based studies have not examined the longitudinal association of body-mass index (BMI) with cortisol features.ObjectiveTo examine the association of (1) prior annual BMI percent change over 7years with cortisol features, (2) baseline cortisol features with subsequent change in BMI over 6years and (3) the association of change in cortisol features with change in BMI over 6years.DesignLongitudinal study.SettingMulti-Ethnic Study of Atherosclerosis (MESA) Stress I & II Studies (2004-2006 & 2010-2012).Participants1685 ethnically diverse men and women attended either MESA Stress exam (mean age 65±10years at MESA Stress I; mean age 69±9years at MESA Stress II).Outcome measuresLog-transformed cortisol features including wake-up cortisol, cortisol awakening response, early decline slope (30min to 2h post-awakening), late decline slope (2h post-awakening to bedtime), bedtime, and total area under the curve (AUC) cortisol.ResultsOver 7years, following multivariable adjustment, (1) a 1% higher prior annual BMI % increase was associated with a 2.9% (95% CI: -5.0%, -0.8%) and 3.0% (95% CI: -4.7%, -1.4%) lower current wake-up and total AUC cortisol, respectively; (2) there was no significant association between baseline cortisol features and subsequent change in BMI and (3) among participants with BMI≥30kg/m2, flattening of the late decline slope was associated with increases in BMI (every 1-unit increase late decline slope were associated with a 12.9% increase (95%CI: -1%, 26.8%) in BMI, respectively).ConclusionsWe found a significant association between prior annual BMI % change and cortisol features, but no significant association between baseline cortisol features and subsequent change in BMI. In participants with obesity increases in BMI were associated with less pronounced declined. Collectively, our results suggest that greater adiposity may lead to a blunted diurnal cortisol profile.

Background: The cross-sectional area of total muscle mass has been reported to decrease by about 40% for those 20-60 years of age. Depressive symptoms may discourage motivation to engage in physical activity such as strength training shown to negate muscle loss. Inflammation related to depressive symptoms may also contribute to muscle atrophy. Physiological differences by sex and race/ethnicity may also modify the association between depression and muscle mass. Evidence on the relationship between depression (or depressive symptoms) and adiposity has been mounting; however, little is known about the depressive symptoms-muscle mass association. We sought to determine the association between elevated depressive symptoms (EDS) and lean muscle mass and whether this varies by sex and race/ethnicity. Methods: Evaluating 1605 adults (45-84 years of age) from the Multi-ethnic Study of Atherosclerosis Abdominal Body Composition, Inflammation and Cardiovascular Disease Study, we examined the cross-sectional association between EDS (Center for Epidemiologic Studies for Depression Scale score = 16 and/or antidepressant use) and computed tomography-measured abdominal lean muscle mass using linear regression. Muscles were evaluated as a whole and by functionality (locomotion vs. stabilization/posture). Covariates included height, body mass index, sociodemographics, comorbidities, inflammatory markers and health behaviors (pack-years of smoking, alcohol locomotion compared to men, total intentional exercise, daily caloric intake). Sex and race/ethnicity were assessed as potential modifiers. Statistical significance was at a p < 0.05 for main effects and < 0.20 for interaction. Results: Men with elevated depressive symptoms had 5.9 cm² lower lean muscle mass for locomotion compared to men without EDS, fully-adjusted (CI = -10.5, -1.4, p = 0.011). This was statistically significantly different from the null finding among women (interaction p = 0.05). Chinese participants with EDS had 10.2 cm² lower abdominal lean muscle mass for locomotion compared to those without EDS (fully-adjusted, CI = -18.3, -2.1, p = 0.014), which was significantly different from the null relationship among White participants (interaction p = 0.04). No association was observed between elevated depressive symptoms and muscle for stabilization/posture evaluating the whole population or stratified by sex or race/ethnicity. Conclusions: In the presence of elevated depressive symptoms, men and Chinese participants may have lower muscle mass, particularly for locomotion. [ABSTRACT FROM AUTHOR]

Summary: Collection of salivary cortisol has become increasingly popular in large population-based studies. However, the impact of protocol compliance on day-to-day reliabilities of measures, and the extent to which reliabilities differ systematically according to socio-demographic characteristics, has not been well characterized in large-scale population-based studies to date. Using data on 935 men and women from the Multi-Ethnic Study of Atherosclerosis, we investigated whether sampling protocol compliance differs systematically according to socio-demographic factors and whether compliance was associated with cortisol estimates, as well as whether associations of cortisol with both compliance and socio-demographic characteristics were robust to adjustments for one another. We further assessed the day-to-day reliability for cortisol features and the extent to which reliabilities vary according to socio-demographic factors and sampling protocol compliance. Overall, we found higher compliance among persons with higher levels of income and education. Lower compliance was significantly associated with a less pronounced cortisol awakening response (CAR) but was not associated with any other cortisol features, and adjustment for compliance did not affect associations of socio-demographic characteristics with cortisol. Reliability was higher for area under the curve (AUC) and wake up values than for other features, but generally did not vary according to socio-demographic characteristics, with few exceptions. Our findings regarding intra-class correlation coefficients (ICCs) support prior research indicating that multiple day collection is preferable to single day collection, particularly for CAR and slopes, more so than wakeup and AUC. There were few differences in reliability by socio-demographic characteristics. Thus, it is unlikely that group-specific sampling protocols are warranted. [ABSTRACT FROM AUTHOR]

Summary: Cumulative cortisol burden is known to influence neuropsychiatric and metabolic disorders. To better understand the relationship between daily cortisol exposure and measures of the diurnal circadian cortisol rhythm, we examined the cross-sectional association of the cortisol awakening response (CAR) with wake-up cortisol, bedtime cortisol, diurnal slope, and total cortisol area under the curve (AUC). Up to 18 salivary cortisol samples were collected over 3 days from 935 White, Hispanic, and Black individuals (mean age 65±9.8 years) in the Multi-Ethnic Study of Atherosclerosis. Outcome measures included awakening cortisol, CAR (awakening to 30min post-awakening), early decline (30min to 2h post-awakening), late decline (2h post-awakening to bedtime), and the corresponding AUCs. Total cortisol AUC was a summary measure of cumulative cortisol exposure. Higher CAR was associated with significantly lower wake-up cortisol (β =−0.56; 95% CI: −0.59 to −0.53) and a higher early decline AUC (β =0.38; 95% CI: 0.34–0.42) but was not associated with total cortisol AUC (β =0.04; 95% CI: −0.01 to 0.09), or other diurnal cortisol curve components following multivariable adjustment. Total cortisol AUC was significantly and positively associated with wake-up cortisol (β =0.36; 95% CI: 0.32–0.40), bedtime cortisol (β =0.61; 95% CI: 0.58–0.64), and other AUC measures, following multivariable adjustment. Associations were similar by sex, race/ethnicity, and age categories. We conclude that bedtime cortisol showed the strongest correlation with total cortisol AUC, suggesting it may be a marker of daily cortisol exposure. [ABSTRACT FROM AUTHOR]

Objective: Neuroendocrine abnormalities, such as activation of the hypothalamic-pituitary-adrenal (HPA) axis, are associated with obesity; however, few large-scale population-based studies have examined HPA axis and markers of obesity. We examined the cross-sectional association of the cortisol awakening response (CAR) and diurnal salivary cortisol curve with obesity. Design and Methods: The Multiethnic Study of Atherosclerosis Stress Study includes 1,002 White, Hispanic, and Black men and women (mean age 65 ± 9.8 years) who collected up to 18 salivary cortisol samples over 3 days. Cortisol profiles were modeled using regression spline models that incorporated random parameters for subject-specific effects. Cortisol curve measures included awakening cortisol, CAR (awakening to 30-min postawakening), early decline (30 min to 2-h postawakening), late decline (2-h postawakening to bedtime), and the corresponding areas under the curve (AUC). Body mass index (BMI) and waist circumference (WC) were used to estimate adiposity. Results: For the entire cohort, both BMI and WC were negatively correlated with awakening cortisol ( P < 0.05), AUC during awakening rise, and early decline and positively correlated to the early decline slope ( P < 0.05) after adjustments for age, race/ethnicity, gender, diabetes status, socioeconomic status, β-blockers, steroids, hormone replacement therapy, and smoking status. No heterogeneities of effects were observed by gender, age, and race/ethnicity. Conclusions: Higher BMI and WC are associated with neuroendocrine dysregulation, which is present in a large population sample, and only partially explained by other covariates. [ABSTRACT FROM AUTHOR]

The article presents a study examining the biodirectional association between depressive symptoms and type 2 diabetes. The design and setting of the Multi-Ethnic Study of Atherosclerosis, which involved U.S. men and women aged 45 to 84 is described. The main outcomes measured include elevated depressive symptoms, use of antidepressant drugs, fasting glucose levels and type 2 diabetes. Researchers report a modest link between baseline depressive symptoms and incidence of type 2 diabetes which was partly explained by lifestyle factors.

Summary: Objective: Trait anger has been shown to predict coronary heart disease; however, there are no prior studies evaluating anger as a risk factor for type 2 diabetes. The objective of this study was to determine if anger proneness predicted type 2 diabetes using prospective analyses. Methods: We analyzed data on trait anger, assessed by questionnaire, in a longitudinal, bi-racial cohort study of 11,615 initially non-diabetic adults aged 48–67, who were subsequently followed for 6 years for the development of type 2 diabetes. Results: There was no relation between overall trait anger and the subsequent risk of diabetes; however, individuals in the highest tertile of trait anger temperament scores had a 34% increased risk of developing diabetes compared to those in the lowest tertile (Relative hazard [RH]=1.34; 95% confidence interval: 1.10, 1.62), following adjustment for age, race, gender, and education. The relation between anger temperament and diabetes remained significant following adjustment for behavioral factors (smoking, physical activity, and caloric intake) (RH=1.31; 95% CI: 1.08, 1.60) but was non-significant after additional adjustment for waist-to-hip ratio and body-mass index (RH=1.18; 95% CI: 0.97, 1.44). Conclusions: While we found no relation between overall trait anger and incident diabetes, persons who had higher anger temperament subscale scores had a slightly increased risk of type 2 diabetes, which was largely explained by adiposity. Anger temperament may deserve further attention as a potential risk factor for type 2 diabetes. [Copyright &y& Elsevier]

OBJECTIVE -- To assess the magnitude of the association between the National Cholesterol Education Program's Third Adult Treatment Panel Report (ATP III) definition of the metabolic syndrome and cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS -- Cox regression was used to estimate the relative risk of incident coronary heart disease (CHD) and stroke among 12,089 black and white middle-aged individuals in the Atherosclerosis Risk in Communities (ARIC) study. RESULTS -- The metabolic syndrome was present in ∼23% of individuals without diabetes or prevalent CVD at baseline. Over an average of 11 years of follow-up, 879 incident CHD and 216 ischemic stroke events occurred. Among the components of the metabolic syndrome, elevated blood pressure and low levels of HDL cholesterol exhibited the strongest associations with CHD. Men and women with the metabolic syndrome were ∼1.5 and 2 times more likely to develop CHD than control subjects after adjustment for age, smoking, LDL cholesterol, and race/ARIC center (sex interaction P < 0.03). Similar associations were found between the metabolic syndrome and incident ischemic stroke. Comparison of receiver operating characteristic curves indicated that the metabolic syndrome did not materially improve CHD risk prediction beyond the level achieved by the Framingham Risk Score (FRS). CONCLUSIONS -- Individuals without diabetes or CVD, but with the metabolic syndrome, were at increased risk for long-term cardiovascular outcomes, although statistical models suggested that most of that risk was accounted for by the FRS. Nevertheless, identification of individuals with the metabolic syndrome may provide opportunities to intervene earlier in the development of shared disease pathways that predispose individuals to both CVD and diabetes. [ABSTRACT FROM AUTHOR]

In 1990–1992, the authors investigated the association of total and free testosterone with the metabolic syndrome in postmenopausal US women not taking hormone replacement therapy (n = 362) in a prevalent case-control study of carotid atherosclerosis. Free testosterone was estimated by using the free androgen index (FAI) (total testosterone/sex hormone-binding globulin ratio). The metabolic syndrome was defined as the presence of three or more of the following criteria: waist circumference ≥35 inches (88.9 cm), triglycerides ≥150 mg/dl, high density lipoprotein cholesterol <40 mg/dl, blood pressure >130/80 mmHg, fasting insulin ≥100 pmol/liter, or impaired glucose homeostasis (fasting glucose ≥110 mg/dl or diagnosed diabetes mellitus). FAI, but not total testosterone, was strongly associated with the metabolic syndrome. Compared with women in the lowest FAI quartile, those in the highest quartile had a fivefold greater odds of having the metabolic syndrome (odds ratio = 5.38, 95% confidence interval: 2.70, 10.7) after adjustment for age, race, and carotid atherosclerosis status. In multivariate analyses, the three-component metabolic syndrome combinations that contained both hyperinsulinemia and hyperglycemia were most strongly associated with increased FAI (absolute increase = 0.41–0.54 compared with that for women who did not have these combinations; all p’s < 0.001). Higher FAI was associated with the hyperinsulinemia and hyperglycemia components of the metabolic syndrome. The role of androgens in glucose homeostasis in postmenopausal women requires further study. [ABSTRACT FROM AUTHOR]

OBJECTIVE — The goal of this study was to determine whether depressive symptoms predict type 2 diabetes. RESEARCH DESIGN AND METHODS — We analyzed data on depressive symptoms (including recent fatigue, sleep disturbance, feelings of hopelessness, loss of libido, and increased irritability) in a longitudinal, biracial cohort study of 11,615 initially nondiabetic adults aged 48-67 years, who were subsequently followed for 6 years for the development of type 2 diabetes. RESULTS — At baseline, depressive symptoms were positively associated with BMI, fasting insulin, systolic blood pressure, caloric intake, physical inactivity, and current smoking (all P < 0.05). In prospective analyses, after adjusting for age, race, sex, and education, individuals in the highest quartile of depressive symptoms had a 63% increased risk of developing diabetes compared with those in the lowest quartile (relative hazard [RH] 1.63, 95% CI 1.31-2.02). This relation persisted after adjustment for stress-associated lifestyle factors (smoking, physical activity, caloric intake, and adiposity) (1.28, 1.02-1.60) and metabolic covariates (fasting insulin and glucose, lipids, blood pressure, and adiposity) (1.38, 1.10-1.73). CONCLUSIONS — In this cohort, depressive symptoms predicted incident type 2 diabetes. This relation is only partially explained by demographic, metabolic, and lifestyle factors. Possible neuroendocrine mediators of the stress-obesity-diabetes relationship require further evaluation in prospective cohort studies that use an established tool to assess depression and incorporate neurohormonal measurements. [ABSTRACT FROM AUTHOR]

The extent to which groupings of insulin resistance-related cardiovascular risk factors synergize to produce atherosclerosis beyond what is expected from their additive effects is uncertain. The objective of this study was to measure interactions among groupings of the features of the insulin resistance syndrome (IRS) on carotid intimal-medial thickness (IMT). This cross-sectional study used baseline data from the Atherosclerosis Risk in Communities Study on 11,790 adults aged 45-64 years without diagnosed diabetes, treated dyslipidemia, or coronary heart disease. The main outcome was carotid IMT, assessed using B-mode ultrasound. The excess carotid IMT attributable to each IRS grouping was determined using multiple linear regression models. There were 57 possible combinations of six IRS components (hypertension, hyperinsulinemia, obesity, hypertriglyceridemia, low HDL cholesterol, and hyperglycemia). In multivariate analysis, 29 of the 57 groupings were associated with excess carotid IMT. Individuals with all six IRS components had the greatest excess IMT compared with those without this grouping (71 micro m; 95% CI 40-102 micro m). The groupings most strongly associated with excess carotid IMT included hypertension and hypertriglyceridemia. Interventions aimed at ameliorating the IRS may produce reductions in atherosclerotic risk beyond that predicted by treatment of individual IRS-related risk factors. [ABSTRACT FROM AUTHOR]

Studies examining the relation between endogenous postmenopausal hormone levels and cardiovascular disease have yielded conflicting results. After excluding women with a history of hormone replacement therapy (HRT) use, the authors conducted a US case-control study in 1987–1992 comparing endogenous postmenopausal hormone levels in women with and without significant carotid atherosclerosis in the Atherosclerosis Risk in Communities (ARIC) cohort. Atherosclerosis was assessed by using B-mode ultrasound to measure carotid artery intimal-medial thickness (IMT). Cases (n = 182) were postmenopausal women with average IMT measurements ≥ the 95th percentile. Controls (n = 182) were frequency matched to cases on age and ARIC center and had IMT measurements < the 75th percentile. After adjustment for cardiovascular risk factors, no association was found between the odds of atherosclerosis and increasing quartiles of estrone, dehydroepiandrosterone sulfate, or androstenedione. Compared with participants in the lowest quartile of sex hormone-binding globulin (SHBG), those in the highest quartile had a significantly lower odds of atherosclerosis (odds ratio = 0.48, 95% confidence interval: 0.24, 0.97). Similarly, participants in the highest quartile of total testosterone had a lower odds of atherosclerosis (odds ratio = 0.38, 95% confidence interval: 0.20, 0.74). The authors found higher total testosterone and SHBG to be inversely related to carotid atherosclerosis, suggesting their potential importance in reducing atherosclerotic risk in postmenopausal women not using HRT. [ABSTRACT FROM PUBLISHER]

Latino immigrants have lower prevalence of depression, obesity and cardiovascular disease than US-born Latinos when they are recently arrived in the US, but this health advantage erodes with increasing duration of US residence. Cumulative exposure to psychosocial stress and its physiological sequelae may mediate the relationship between nativity and duration of US residence and poor health. We used data from Latino cohort study participants ages 45–84 to examine cross-sectional (n = 558) and longitudinal (n = 248) associations between nativity and duration of US residence and features of the diurnal cortisol curve including: wake-up cortisol, cortisol awakening response (CAR, wake-up to 30 min post-awakening), early decline (30 min to 2 h post-awakening) and late decline (2 h post-awakening to bed time), wake-to-bed slope, and area under the curve (AUC). In cross-sectional analyses, US-born Latinos had higher wake-up cortisol than immigrants with fewer than 30 years of US residence. In the full sample, over 5 years the CAR and early decline became flatter and AUC became larger. Over 5 years, US-born Latinos had greater increases in wake-up cortisol and less pronounced flattening of the early diurnal cortisol decline than immigrants with fewer than 30 years of US residence. Immigrants with 30 or more years of US residence also had less pronounced flattening of the early decline relative to more recent immigrants, and also had a less pronounced increase in AUC. In sum, we saw limited cross-sectional evidence that US-born Latinos have more dysregulated cortisol than recently-arrived Latino immigrants, but over time US-born Latinos had slower progression of cortisol dysregulation. [ABSTRACT FROM AUTHOR]

Abstract: We examined cross-sectional associations between sex hormones and carotid artery intimal-medial thickness (cIMT) and coronary artery calcium in women in the Multi-Ethnic Study of Atherosclerosis. Serum testosterone, estradiol, sex hormone binding globulin (SHBG), and dehydroepiandrosterone levels were measured in 1947 postmenopausal women aged 45–84 years (30% White, 14% Chinese-American, 31% Black, and 25% Hispanic) and not on hormone therapy. Using multiple linear regression we evaluated associations between log(sex hormone) levels and log(cIMT) adjusted for age, ethnicity, body mass index (BMI) and cardiac risk factors. Associations between sex hormone levels and the presence and extent of coronary calcium were evaluated. Total and bioavailable testosterone were positively associated with common cIMT independent of age, BMI, hypertension, smoking, HDL-cholesterol, LDL-cholesterol and insulin sensitivity (p =0.009 and p =0.002, respectively). SHBG was negatively associated with common cIMT (p =0.001) but further adjustment for BMI, cardiovascular risk factors, and LDL- and HDL-cholesterol removed significance. Estradiol and dehydroepiandrosterone were not associated with common cIMT. Sex hormones were not associated with presence of coronary calcium. Among women with measurable coronary calcium, higher SHBG (p =0.012) and lower bioavailable testosterone (p =0.007) were associated with greater coronary calcium score. No heterogeneity by ethnicity was found. In postmenopausal women, testosterone is independently associated with greater common cIMT. SHBG is negatively associated and this may be mediated by LDL- and HDL-cholesterol. In contrast, SHBG and testosterone were associated with extent of coronary calcium but in the opposite direction compared to carotid intimal-medial thickness. These differences warrant further evaluation. [Copyright &y& Elsevier]

We determined the prevalence of the metabolic syndrome (MS) with the criteria recommended by the National Cholesterol and Education Program, Adult Treatment Panel III report and estimated the magnitude of cross-sectional associations between the MS, coronary heart disease (CHD), and atherosclerosis in 14,502 black and white middle-age patients in the Atherosclerosis Risk in Communities Study. CHD was ascertained by standardized procedures and subclinical atherosclerosis was determined by measuring carotid intimal medial wall thickness using B-mode ultrasonography. The prevalence of MS was 30%, with substantial variation across race and gender subgroups. Among women but not among men, MS was significantly associated with increasing low-density lipoprotein cholesterol. CHD prevalence was 7.4% among those with the MS compared with 3.6% in comparison subjects (p &#60;0.0001). After adjustment for established risk factors, subjects who had MS were 2 times more likely to have prevalent CHD than were those who did not have the syndrome. Among individuals free of CHD and stroke, after adjustment for age, gender, and race/center, the average intimal-medial wall thickness of carotid arteries was greater among those with versus those without MS (747 vs 704 μm, p &#60;0.0001). Thus, MS was significantly associated with the presence of CHD and carotid intimal medial wall thickness. Identification of patients who have MS may provide opportunities to initiate CHD prevention strategies. [Copyright &y& Elsevier]