Correlations between serum testosterone, estradiol, and sex hormone-binding globulin and bone mineral density in a diverse sample of men

CONTEXT: The relationship between hormones and bone mineral density (BMD) in men has received considerable attention. However, most studies have been conducted in homogenous populations, and it is not known whether differences in hormones impact racial and ethnic differences in BMD. OBJECTIVE: Our objective was to examine associations of testosterone, estradiol, and sex hormone-binding globulin (SHBG) with BMD in a racially and ethnically diverse population. DESIGN: This was a population-based, observational survey. PARTICIPANTS: A total of 976 Black, Hispanic, and white randomly selected men ages 30-79 yr from the Boston Area Community Health/Bone Survey were included. OUTCOME: BMD at the hip, wrist, and spine were calculated. RESULTS: The mean age of the sample was 46.7 +/- 12.4 yr. BMD levels were highest in black men, followed by Hispanic and then white men. Associations between hormones and BMD were consistent across racial and ethnic groups. Total and free testosterone was not correlated with BMD in age- or multivariate-adjusted models. SHBG was inversely correlated with total hip and ultradistal radius BMD after age adjustment, but not with multivariate adjustment for age, lean mass, fat mass, physical activity, self-rated health, and smoking. Total and free estradiol levels were positively and significantly correlated with femoral neck and total hip BMD, even with multivariate adjustment (partial correlations ranged between 0.11 and 0.16). However, estradiol levels failed to account for racial and ethnic differences in hip BMD. CONCLUSIONS: In our diverse population, neither serum total nor free testosterone levels were associated with BMD. Correlations between BMD and estradiol were significant but did not appear to account for any of the observed racial and ethnic differences in BMD. These findings suggest that differences in hormone levels are not a major contributor to the observed differences in BMD between Black, Hispanic, and white men.     

Racial/ethnic and sex differences in the relationship between uric acid and metabolic syndrome in adolescents: an analysis of National Health and Nutrition Survey 1999-2006

Among adolescents, uric acid is associated with insulin resistance, hypertension, and the metabolic syndrome (MetS); and in adults, high uric acid levels are an independent risk factor for cardiovascular disease and diabetes. The objective was to determine whether the relationship of uric acid with MetS varies in adolescents by race/ethnicity and sex. We used linear regression to evaluate associations between uric acid and other MetS-associated clinical and laboratory measures among 3296 non-Hispanic white, non-Hispanic black, and Hispanic adolescents aged 12 to 19 years participating in the National Health and Nutrition Evaluation Survey (1999-2006). Overall, non-Hispanic white males and females had the highest uric acid levels among the 3 racial/ethnic groups. In each racial/ethnic group, there were higher uric acid levels for those adolescents with vs without MetS. However, the extent of the MetS-related increase in uric acid level varied by race and sex. Among males, MetS was associated with the greatest increases in uric acid among non-Hispanic whites. However, among females the MetS-related increase in uric acid was greater among non-Hispanic blacks and Hispanics. Non-Hispanic white females exhibited the lowest degrees of correlation between levels of uric acid and MetS-associated variables. Uric acid levels did not correlate with insulin levels in non-Hispanic white females. These data suggest that the relationship between uric acid and MetS varies by race/ethnicity and sex. In particular, non-Hispanic white males exhibit a strong relationship and non-Hispanic white females exhibit a relatively poor correlation between uric acid and MetS-related factors. These data may have implications for the use of uric acid as a marker of future risk among adolescents.     

Association between thyroid hormone and components of metabolic syndrome in euthyroid Korean adults: A population-based study

Thyroid dysfunction increases the prevalence of metabolic syndrome. However, the link between thyroid hormones and metabolic syndrome remains debatable, and the effect of sex on their relationship is not completely understood. To elucidate the relationship of thyroid hormones with metabolic syndrome and its components according to sex in euthyroid individuals in South Korea. Adult participants who underwent thyroid tests at our institution between January 2015 and December 2018 and had thyroid-stimulating hormone (TSH; 0.270–4.200 μIU/mL) and free thyroxine (FT4; 0.93–1.70 ng/dL) levels in the normal range were included. After correcting for age and body mass index, multiple linear regression was performed to assess the association of TSH and FT4 with metabolic syndrome and its components, and logistic regression was performed to estimate the risk of developing metabolic syndrome and its components according to different thyroid hormone quartiles. We included 12,478 men and 7,575 women in this study. The prevalence of metabolic syndrome was 9.68%. In men, TSH was positively associated with blood pressure and triglycerides, and the odds ratio for high blood pressure and hypertriglyceridemia was approximately 1.3 times higher in the fourth quartile than in the first quartile. FT4 associated positively with waist circumference, and a high odds ratio for abdominal obesity in the fourth quartile was observed in both men (odds ratio [OR], 1.239; 95% confidence interval [CI], 1.045–1.470) and women (OR, 1.302; 95% CI, 1.029–1.649). A negative association was found between FT4 and triglycerides, and concurrently, the odds ratios for hypertriglyceridemia were lower in the fourth quartile in both men (OR, 0.692; 95% CI, 0.619–0.774) and women (OR: 0.641; 95% CI: 0.512–0.803). In addition, a higher odds ratio for high blood pressure was observed in the fourth quartiles of FT4 and TSH in women. However, there was no association between TSH and FT4 levels and the onset of metabolic syndrome in either of the sexes. Serum TSH and FT4 levels were associated with different metabolic syndrome components in men and women, but there was no association with the onset of metabolic syndrome.     

Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in nonobese men

BACKGROUND: The metabolic syndrome (MetS), characterized by central obesity, lipid and insulin dysregulation, and hypertension, is a precursor state for cardiovascular disease. The purpose of this analysis was to determine whether low serum sex hormone levels or clinical androgen deficiency (AD) predict the development of MetS. METHODS: Data were obtained from the Massachusetts Male Aging Study, a population-based prospective cohort of 1709 men observed at three time points (T1, 1987-1989; T2, 1995-1997; T3, 2002-2004). MetS was defined using a modification of the ATP III guidelines. Clinical AD was defined using a combination of testosterone levels and clinical signs and symptoms. The association between MetS and sex hormone levels or clinical AD was assessed using relative risks (RR), and 95% confidence intervals (95% CI) were estimated using Poisson regression models. RESULTS: Analysis was conducted in 950 men without MetS at T1. Lower levels of total testosterone and SHBG were predictive of MetS, particularly among men with a body mass index (BMI) below 25 kg/m2 with adjusted RRs for a decrease in 1 sd of 1.41 (95% CI, 1.06-1.87) and 1.65 (95% CI, 1.12-2.42). Results were similar for the AD and MetS association, with RRs of 2.51 (95% CI, 1.12-5.65) among men with a BMI less than 25 compared with an RR of 1.22 (95% CI, 0.66-2.24) in men with a BMI of 25 or greater. CONCLUSIONS: Low serum SHBG, low total testosterone, and clinical AD are associated with increased risk of developing MetS over time, particularly in nonoverweight, middle-aged men (BMI, <25). Together, these results suggest that low SHBG and/or AD may provide early warning signs for cardiovascular risk and an opportunity for early intervention in nonobese men.     

Association between metabolic syndrome and estimated glomerular filtration rate in older Koreans based on data from the third Korean National Health and Nutrition Examination Survey

Aim: To examine the association between metabolic syndrome (MetS) and renal function in older Koreans. Methods: A total of 1270 people aged 60 years and older who participated in the third Korean National Health and Nutrition Examination Survey were included in this study. Results: After adjusting for confounding factors, central obesity, high‐density lipoprotein cholesterol and fasting glucose were significantly associated with decreased renal function in men. In women, however, each component of MetS with the exception of fasting glucose was not associated with renal function. The odds ratios for MetS were 2.548 in men and 1.454 in women after adjustment for confounding variables; both were statistically significant. The odds ratio of decreased renal function increased as the number of components of MetS increased. Conclusion: The results of this study suggest that MetS may be an independent risk factor for decreased renal function in older population as well.     

Association between Relative Hypogonadism and Metabolic Syndrome in Newly Diagnosed Adult Male Patients with Impaired Glucose Tolerance or Type 2 Diabetes Mellitus

Sex steroid hormones are known to be important regulators of the lipid and glucose metabolism. Lower levels of testosterone (T) or sex hormone-binding globulin (SHBG) have been reported in men with type 2 diabetes. On the other hand, the relationship between relative hypogonadism and metabolic syndrome has not yet to be thoroughly studied. Ninety-eight Japanese adult (age 20-64) male patients with impaired glucose tolerance (IGT) or type 2 diabetes mellitus were divided into either an metabolic syndrome group (n = 42) or a non- metabolic syndrome (n = 56) group according to the definition of metabolic syndrome from WHO, or into three tertiles according to their sex hormone index level. The metabolic syndrome group had a significantly lower T/estradiol (E(2)) and SHBG level (p < 0.01). The age and subcutaneous fat surface area (SFA) were significantly different within the tertiles in SHBG and T/E(2). Logistic regression analyses were performed to investigate the association between the sex steroid hormone index level and the incidence of metabolic syndrome. Regarding the highest tertiles as a criterion, lower SHBG, T/E(2) or free T/E(2) had a higher odds ratio of prevalence of metabolic syndrome even after adjusting for age and SFA. Relative hypogonadism was strongly associated with the prevalence of metabolic syndrome in Japanese adult men who were newly diagnosed to have IGT or type 2 diabetes.     

Endogenous Sex Hormones,Metabolic Syndrome,and Diabetes in Men and Women

Endogenous sex hormones predict impairments of glucose regulation. Cross-sectional studies suggest that lower levels of testosterone in men and higher levels in women increase risk of metabolic syndrome and diabetes, whereas lower levels of sex hormone binding globulin in both men and women increase risk of metabolic syndrome and diabetes. In a systematic review, we summarize existing longitudinal studies, which suggest similar patterns. However, these studies are often limited to a single sex steroid measure. Whether these associations are primarily a marker of adiposity, and whether these associations differ between younger eugonadal vs older hypogonadal adults is also uncertain. The impact of exogenous sex steroid therapy may not reflect relationships between sex hormones and impaired glucose regulation that occur without supplementation. Therefore, examination of endogenous sex steroid trajectories and obesity trajectories within individuals might aid our understanding of how sex steroids contribute to glucose regulation.     

Associations of overweight/obesity and socioeconomic status with hypertension prevalence across racial and ethnic groups

Racial/ethnic disparities in the prevalence of diagnosed hypertension are persistent but may be partially explained by racial/ethnic differences in weight category and neighborhood socioeconomic status. The authors compared hypertension prevalence rates among 4 060 585 adults with overweight or obesity across 10 healthcare systems by weight category and neighborhood education level in geographically and racially diverse individuals. Data were obtained from electronic health records. Hypertension was defined as at least two outpatient visits or one inpatient hospitalization with a coded diagnosis. Logistic regression, adjusted for age, sex, and site, with two‐way interactions between race/ethnicity and weight category or neighborhood education, was used to examine the association between hypertension and race/ethnicity, with whites as the reference. Results documented that odds ratios for hypertension prevalence were greater for blacks, American Indians/Alaskan Natives, Asians, and Native Hawaiians/other Pacific Islanders compared with whites and lower for Hispanics in similar weight categories and neighborhood education levels. Although two‐way interactions were statistically significant, the magnitude of the odds of hypertension compared with whites did not substantially vary across weight or neighborhood education. Hypertension odds were almost double relative to whites for blacks and Native Hawaiians/other Pacific Islanders across most weight categories and all neighborhood education levels. Odds of hypertension were about 50% greater for Asians relative to whites across weight categories. Results suggest that other factors might be associated with racial/ethnic disparities in hypertension. More research is needed to understand the many factors that may contribute to variation in diagnosed hypertension across racial/ethnic groups with overweight or obesity.     

An examination of sex and racial/ethnic differences in the metabolic syndrome among adults: A confirmatory factor analysis and a resulting continuous severity score

Objective

The metabolic syndrome (MetS) is typically diagnosed based on abnormalities in specific clustered clinical measures that are associated with increased risk for coronary heart disease (CHD) and Type 2 diabetes mellitus (T2DM). However, current MetS criteria result in racial/ethnic discrepancies. Our goals were to use confirmatory factor analysis (CFA) to delineate differential contributions to MetS by sub-group, and if contributions were discovered, develop sex and racial/ethnic-specific equations to calculate MetS severity.

Research Design and Methods

Using data on adults from the National Health and Nutrition Examination Survey 1999–2010, we performed a CFA of a single MetS factor that allowed differential loadings across groups, resulting in a sex and race/ethnicity-specific continuous MetS severity score.

Results

Loadings to the single MetS factor differed by sub-group for each MetS component (p < 0.001), with lower factor loadings among non-Hispanic-blacks for triglycerides and among Hispanics for waist circumference. Systolic blood pressure exhibited low factor loadings among all groups. MetS severity scores were correlated with biomarkers of future disease (high-sensitivity C-reactive-protein, uric acid, insulin resistance). Non-Hispanic-black-males with diabetics had a low prevalence of MetS but high MetS severity scores that were not significantly different from other racial/ethnic groups.

Conclusions

This analysis among adults uniquely demonstrated differences between sexes and racial/ethnic groups regarding contributions of traditional MetS components to an assumed single factor. The resulting equations provide a clinically-accessible and interpretable continuous measure of MetS for potential use in identifying adults at higher risk for MetS-related diseases and following changes within individuals over time. These equations hold potential to be a powerful new outcome for use in MetS-focused research and interventions.     

Endogenous sex hormones and metabolic syndrome in aging men

BACKGROUND: Sex hormone levels in men change during aging. These changes may be associated with insulin sensitivity and the metabolic syndrome. METHODS: We studied the association between endogenous sex hormones and characteristics of the metabolic syndrome in 400 independently living men between 40 and 80 yr of age in a cross-sectional study. Serum concentrations of lipids, glucose, insulin, total testosterone (TT), SHBG, estradiol (E2), and dehydroepiandrosterone sulfate (DHEA-S) were measured. Bioavailable testosterone (BT) was calculated using TT and SHBG. Body height, weight, waist-hip circumference, blood pressure, and physical activity were assessed. Smoking and alcohol consumption was estimated from self-report. The metabolic syndrome was defined according to the National Cholesterol Education Program definition, and insulin sensitivity was calculated by use of the quantitative insulin sensitivity check index. RESULTS: Multiple logistic regression analyses showed an inverse relationship according to 1 sd increase for circulating TT [odds ratio (OR) = 0.43; 95% confidence interval (CI), 0.32-0.59], BT (OR = 0.62; 95% CI, 0.46-0.83), SHBG (OR = 0.46; 95% CI, 0.33-0.64), and DHEA-S (OR = 0.76; 95% CI, 0.56-1.02) with the metabolic syndrome. Each sd increase in E2 levels was not significantly associated with the metabolic syndrome (OR = 1.16; 95% CI, 0.92-1.45). Linear regression analyses showed that higher TT, BT, and SHBG levels were related to higher insulin sensitivity; beta-coefficients (95% CI) were 0.011 (0.008-0.015), 0.005 (0.001-0.009), and 0.013 (0.010-0.017), respectively, whereas no effects were found for DHEA-S and E2. Estimates were adjusted for age, smoking, alcohol consumption, and physical activity score. Further adjustment for insulin levels and body composition measurements attenuated the estimates, and the associations were similar in the group free of cardiovascular disease and diabetes. CONCLUSIONS: Higher testosterone and SHBG levels in aging males are independently associated with a higher insulin sensitivity and a reduced risk of the metabolic syndrome, independent of insulin levels and body composition measurements, suggesting that these hormones may protect against the development of metabolic syndrome.     

Prevalence of metabolic syndrome and its relationship to white blood cell count in a population of Thai men and women receiving routine health examinations

BACKGROUND: Patients with metabolic syndrome (MetS) are at increased risk for developing diabetes mellitus and cardiovascular disease. Limited information is available about the prevalence of MetS among Thai men and women. In this study we sought to estimate the prevalence of MetS among a population of patients receiving annual health exams. We also studied the relationship between MetS and elevated white blood cell (WBC) count. METHODS: This was a cross-sectional study of 1,383 patients (375 men and 1,008 women) who participated in annual health examinations at the Preventive Medicine Clinic of the King Chulalongkorn Memorial Hospital in Bangkok, Thailand, from July 1999 through February 2000. The presence of MetS was defined using the modified criteria of the National Cholesterol Education Program Adult Treatment Panel III. RESULTS: Overall, the prevalence of the MetS was 12.8% and was more common among men than women (15.7% v 11.7%). Advanced age and elevated WBC counts were the only statistically significant risk factors of MetS in this population. The WBC count was statistically significantly correlated with high-density lipoprotein-cholesterol and triglyceride (P = .05). Men with highest WBC count (>or=7.50 x 10(3) cell/microL) had a 2.98-fold increased in risk of MetS (odds ratio 2.98, 95% confidence interval 1.29 to 6.87), as compared with men in the lowest quartile (<5.40 x 10(3) cell/microL). Among women, the risk of MetS increased across successive quartiles of WBC counts (1.00, 2.26, 2.88, and 4.30, with the lowest quartile as the referent group). CONCLUSIONS: In this study of Thai men and women receiving routine health examinations, MetS was found to be prevalent. In addition, WBC count (indicative of systemic chronic inflammation) is positively associated with MetS.     

Race/ethnicity and the receipt of watchful waiting for the initial management of prostate cancer

INTRODUCTION: Several recent studies have noted that African Americans disproportionately receive "watchful waiting" for the initial management of their prostate cancer. To determine whether racial/ethnic differences in the receipt of watchful waiting are explained by differences in clinical presentation and life expectancy at the time of diagnosis, we examined Surveillance, Epidemiology, and End Results (SEER)-Medicare data for men diagnosed with prostate cancer in 1994 to 1996. METHODS: Race/ethnicity, comorbidity, stage, grade, age, and expected lifespan and their association with the receipt of watchful waiting were examined in multivariate logistic regression analyses. Race-stratified logistic regression analyses were also used to examine racial/ethnic variation in the association of clinical and demographic factors with the receipt of watchful waiting among African-American, Hispanic, and non-Hispanic white men. RESULTS: African-American (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.3 to 1.6) and Hispanic men (OR, 1.3; 95% CI, 1.1 to 1.5) were significantly more likely than non-Hispanic white men to receive watchful waiting in a multivariate model adjusted for age, comorbidity, stage, grade, and life expectancy. Advanced stage and grade, lower life expectancy, older age, and high comorbidity indices were also significantly associated with an increase in the odds of receipt of watchful waiting in multivariate analyses. In general, the association between the receipt of watchful waiting and the clinical characteristics (i.e., stage, grade, and age) were similar for the three racial/ethnic groups. In race-stratified logistic regression analyses, life expectancy was associated with an increase in the odds of receiving watchful waiting but results were statistically significant for whites only. There was also a statistically significant increase in the odds of receiving watchful waiting for African-American and white men with high comorbidity indices but not Hispanic men. The odds of receiving watchful waiting were also higher for African-American and Hispanic men who resided in census tracts where a large percentage of residents had not completed high school than for white men who resided in similar census tracts. CONCLUSION: The disproportionate receipt of watchful waiting among African Americans and Hispanics is not completely explained by racial/ethnic variation in clinical characteristics or life expectancy as measured in this study. These data suggest that there are other factors that contribute to racial/ethnic differences in receipt of watchful waiting that warrant investigation.     

Sex hormones, inflammation and the metabolic syndrome: a population-based study

OBJECTIVE: Mild hypoandrogenism in men is associated with features of the metabolic syndrome, but the association with the metabolic syndrome itself using an accepted definition has not been described. DESIGN: Men with the metabolic syndrome were identified and testosterone and sex hormone-binding globulin (SHBG) levels were determined in a population-based cohort of 1896 non-diabetic middle-aged Finnish men. RESULTS: Calculated free testosterone and SHBG were 11% and 18% lower (P<0.001) in men with the metabolic syndrome (n=345, World Health Organisation definition). After categorisation by tertiles and adjusting for age and body mass index, total and free testosterone and SHBG were inversely associated with concentrations of insulin, glucose, triglycerides, C-reactive protein (CRP) and CRP-adjusted ferritin and positively associated with high-density lipoprotein cholesterol. Men with free testosterone levels in the lowest third were 2.7 (95% confidence interval (CI) 2.0-3.7) times more likely to have the metabolic syndrome in age-adjusted analyses, and 1.7 (95% CI 1.2-2.4) times more likely even after further adjusting for body mass index. Exclusion of men with cardiovascular disease did not alter the association. The inverse association of SHBG with the metabolic syndrome was somewhat stronger. CONCLUSIONS: Low testosterone and SHBG levels were strongly associated not only with components of the metabolic syndrome, but also with the metabolic syndrome itself, independently of body mass index. Furthermore, sex hormones were associated with inflammation and body iron stores. Even in the absence of late-stage consequences such as diabetes and cardiovascular disease, subtle derangements in sex hormones are present in the metabolic syndrome, and may contribute to its pathogenesis.     

Testosterone,Sex Hormone-Binding Globulin and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

Introduction and aimEndogenous sex hormones are associated with the risk of diabetes and metabolic syndrome. Recent studies suggested the role of these hormones in nonalcoholic fatty liver disease (NAFLD). We conducted a systematic review and meta-analysis of observational studies investigating the association between sex hormones and NAFLD.Material and MethodsA comprehensive search of the databases of the MEDLINE and EMBASE was performed from inception through April 2016. The inclusion criterion was the observational studies that assessed the association of serum total testosterone (TT) and sex-hormone binding globulin (SHBG) and NAFLD. We calculated pooled effect estimates of TT and SHBG with 95% confidence intervals (CI) comparing between subjects with and without NAFLD by using random-effects model.ResultsSixteen trials comprising 13,721 men and 5,840 women met the inclusion criteria. TT levels were lower in men with NAFLD (MD = -2.78 nmol/l, 95%CI -3.40 to -2.15, I² = 99%) than in those without. Men with higher TT levels had lower odds of NAFLD whereas higher TT levels increased the odds of NAFLD in women. In both sexes, SHBG levels were lower in patients with NAFLD than controls and this inverse association was stronger in women than men and higher SHBG levels were associated with reduced odds of NAFLD.ConclusionOur meta-anal-ysis demonstrated a sex-dependent association between TT and NAFLD. Lower TT levels are associated with men with NAFLD and inversely associated with women with NAFLD, whereas higher SHBG levels are associated with lower NAFLD odds in both men and women.     

Sex-specific association of the androgen to oestrogen ratio with adipocytokine levels in older adults: the Rancho Bernardo Study

OBJECTIVE: Androgens and oestrogens have opposing effects on some adipocyte functions. Thus, the androgen to oestrogen balance may be as important as the individual hormones in determining the biological interaction between endogenous sex hormones and adipocyte-derived factors such as adiponectin and leptin. We tested this hypothesis by evaluating the sex-specific, cross-sectional association of sex hormones and androgen to oestrogen ratios with serum adiponectin and leptin in older men and postmenopausal women. DESIGN: Cross-sectional. PARTICIPANTS: A total of 1510 community dwelling men and postmenopausal women aged 50-92 years. MEASUREMENTS: Serum leptin, adiponectin and sex hormone levels. RESULTS: Adiponectin and leptin levels were higher in women than men (P < 0.001). In both sexes, adiponectin concentrations were lower, and leptin levels higher, with increasing BMI and waist girth (all P < 0.001). Although the ratio of total testosterone to total oestradiol was significantly associated with both adipocytokines in both sexes, the strongest and most consistent hormone-adipocytokine associations were observed when the androgen to oestrogen ratio was expressed as total testosterone to bioavailable oestradiol. In linear regressions, the testosterone to bioavailable oestradiol ratio was positively related to adiponectin and inversely related to leptin, with nearly identical standardized beta-coefficients for men and women (all P < 0.001). The strength of the hormone ratio-adipocytokine associations was reduced, but not eliminated, after adjustment for age, adiposity and cardiovascular disease risk factors, including insulin resistance. CONCLUSIONS: The striking similarity of the hormone ratio-adipocytokine associations for men and women, despite wide differences in sex hormone and adipocytokine levels, suggests these results reflect underlying physiological mechanisms common to both sexes.     

The ACE insertion/deletion polymorphism and its association with metabolic syndrome

The angiotensin-1-converting enzyme (ACE) gene has been suggested to be involved in the development of metabolic syndrome (MetS). However, results have been inconsistent. In this study, a meta-analysis was performed to investigate the association between ACE insertion/deletion (I/D) polymorphism and MetS. Published literature from PubMed, EMBASE, and ISI Web of Science databases was searched for eligible publications. All studies assessing the association between ACE I/D polymorphism and MetS were included. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated using a fixed- or random-effects model. Ten studies (1939 cases/2845 controls) for ACE I/D polymorphism were included in this meta-analysis. Most of the studies were performed in whites. The ACE I/D polymorphism was associated with an increased OR of MetS under a dominant model (DD + ID vs II: OR = 1.39; 95% CI, 1.22-1.60; P < .001). Using this model, similar results were found among studies using different ethnic populations, studies using different MetS definitions, and studies with more than 100 cases. This meta-analysis indicated that the D allele of the ACE gene, known to be related to higher levels of angiotensinogen, is associated with an increased OR of MetS. However, given the limited sample size, this association warrants further investigation.     

Elevated serum uric acid in nondiabetic people mark pro-inflammatory state and HDL dysfunction and independently predicts coronary disease

We explored the association of serum uric acid (UA) concentrations with pro-inflammatory state and high-density lipoprotein (HDL) dysfunction. UA tertiles in tracked 1,508 nondiabetic participants were analyzed cross-sectionally for associations with inflammation biomarkers and protective proteins over a mean follow-up of 4.9 years for incident coronary heart disease (CHD) using Cox proportional hazards regression. In the absence of metabolic syndrome (MetS), UA tertiles significantly distinguished, in each sex, increasing categories of three MetS components (inflammation/oxidation markers, apolipoprotein (apo)B) and (inversely) current smoking (but not protective proteins such as HDL, apoA-I, and adiponectin). Distinctions attenuated in the presence of MetS. Linear regression model revealed fasting triglycerides (1.86 mg/dl variance), male sex, and gamma-glutamyl transferase and age as covariates of UA levels in women. In Cox analysis, incident CHD (n?=?137) was predicted by mid and upper UA tertile in men alone at significant hazard ratios of 2.7, additively to conventional risk factors. Elevated serum UA levels, linked to triglycerides, mark in nondiabetic people pro-inflammatory state, and, notably, HDL dysfunction. CHD risk is independently predicted by elevated UA levels in nondiabetic men and is modulated by MetS and gender.     

Testosterone is associated with the cardiovascular autonomic response to a stressor in healthy men

Abstract

Objective: Men have high cardiovascular risk and unfavourable cardiac autonomic tone compared to premenopausal women. The role of sex hormones in control of autonomic tone is unclear. We sought to determine the association between sex hormones and cardiosympathovagal tone at baseline and in response to a physiological stressor. Methods: Forty-eight healthy subjects (21 men, 27 premenopausal women) were studied in high-salt balance. Cardiac autonomic tone was assessed by heart rate variability, calculated by spectral power analysis (low frequency (LF, a measure of sympathetic modulation), high frequency (HF, a measure of vagal modulation) and LF:HF (a measure of cardiosympathovagal balance)) at baseline and in response to graded Angiotensin II (AngII) infusion (3?ng/kg/min?×?30?min, 6?ng/kg/min?×30?min) were measured. The primary outcome was association between endogenous sex hormone levels and measures of cardiac autonomic tone. Results: All subjects had sex hormone levels in the normal range. No associations were observed between sex hormones and baseline cardiac autonomic tone in men or women. Men with lower testosterone levels, however, were unable to maintain both cardiosympathetic (p?=?0.045) and cardiovagal tone (p?=?0.035) in response to AngII even after adjustments for covariates. No association was observed between estradiol and progesterone and cardiac autonomic response to AngII in either sex. Conclusion: An unfavourable shift in the cardiac autonomic tone in men with lower testosterone levels was observed in response to a stressor. Understanding the role of sex hormones in modulation of cardiac autonomic tone may help guide risk reduction strategies in men.     

Metabolic syndrome, diabetes, and cardiovascular disease in an elderly Caucasian cohort: the Italian Longitudinal Study on Aging

BACKGROUND: The metabolic syndrome (MetS) is represented by a cluster of risk factors for cardiovascular diseases (CVDs). In spite of its high frequency and strong association with morbidity and mortality in the adult population, little is known about its magnitude in elderly persons. METHODS: We assessed the prevalence of MetS by diabetic status and sex in the participants in the Italian Longitudinal Study on Aging (ILSA), a population-based study on a sample of 5632 individuals 65-84 years old at baseline (1992). We measured the association of MetS with stroke, coronary heart disease, and diabetes at baseline and with CVD mortality at 4-year follow-up. RESULTS: The prevalence of MetS was 25.9% in nondiabetic men and 55.2% in nondiabetic women; in diabetic individuals it was 64.9% and 87.1% in men and women, respectively. At baseline, in both men and women there was a significant association with stroke (odds ratio [OR]=1.67, 95% confidence interval [CI], 1.02-2.75 in men and OR=1.72, CI, 1.01-2.93 in women) and diabetes (OR=4.58, CI, 3.12-6.74 in men and OR=5.15, CI, 3.23-8.20 in women). A significant association with chronic heart disease was found in men only (OR=1.40; CI, 1.02-1.97). During the approximately 4-year follow-up, nondiabetic men with MetS had a risk of CVD mortality 12% higher compared to those without MetS, whereas no significant differences were found in women. CONCLUSIONS: MetS is very common in aged Italians, and it is associated with stroke and diabetes in both sexes, and with chronic heart disease in men. In men, it increases significantly the risk of CVD mortality.     

The associations of leptin and adiponectin with the metabolic syndrome in an Indonesian and a Dutch population

Background and aimsAt the same BMI, Asian populations develop cardiometabolic complications earlier than Western populations. We hypothesized that a different secretion of the adipocyte-derived hormones leptin and adiponectin plays a role and investigated the associations of the two hormones with the metabolic syndrome (MetS) in an Indonesian and a Dutch population.Methods and resultsWe performed cross-sectional analyses of the Netherlands Epidemiology of Obesity Study (n = 6602) and the SUGAR Scientific Programme Indonesia–Netherlands Study (n = 1461). We examined sex-stratified associations of leptin and adiponectin with MetS, using multivariate logistic regression including adjustment for total body fat. The mean (SD) leptin (mcg/L) were 4.7 (6.0) in Indonesian men, 18.6 (12.0) in Indonesian women, 9.1 (7.7) in Dutch men, and 23.4 (17.4) in Dutch women. The mean (SD) adiponectin (mg/L) were 5.7 (5.4), 7.5 (7.1), 6.6 (3.3), and 11.3 (4.9), respectively. Within the same BMI category, leptin concentrations were similar in the two populations, whereas adiponectin was lower in the Indonesian population. Per SD of leptin, adjusted prevalence odds ratios (ORs, 95%CI) of MetS were 0.9 (0.6–1.2) in Indonesian men, 1.1 (0.9–1.4) in Indonesian women, 2.2 (1.6–2.8) in Dutch men, and 1.2 (1.0–1.5) in Dutch women. Per SD of adiponectin, the ORs were 0.9 (0.7–1.2), 0.8 (0.7–1.0), 0.6 (0.6–0.8), and 0.4 (0.4–0.5), respectively.ConclusionsDespite lower adiponectin levels, adiponectin was not related to the MetS in the Indonesian population and can not explain their increased cardiometabolic risk at the same BMI.