The relationship between reduced testosterone, stimulated growth hormone secretion and increased carotid intima-media thickness in obese men.

OBJECTIVE: Obesity is associated with reduced testosterone and growth hormone (GH). However, the interrelationship between these axes and their independent contributions to cardiovascular risk is unknown. The objectives of this study were to determine (1) the association between testosterone and GH in obesity, (2) whether excess adiposity mediates this association and (3) the relative contribution of reduced testosterone and GH to increased carotid intima-media thickness (cIMT) in obesity. DESIGN: Fifty obese men were studied with GH-releasing hormone-arginine testing, and morning free testosterone (FT) was measured by equilibrium dialysis. Metabolic, anthropometric and cardiovascular risk indices, including cIMT were measured. Twenty-six normal weight men served as controls. RESULTS: Obese subjects demonstrated lower mean (±SEM) peak stimulated GH (5·9 ± 0·6 vs 36·4 ± 3·9 µg/l; P < 0·0001) and FT (0·41 ± 0·03 vs 0·56 ± 0·03 nmol/l; P = 0·0005) compared to controls. GH was significantly associated with FT (r = +0·44; P < 0·0001) and both were inversely related to visceral adipose tissue (VAT) (GH: r = -0·65; P < 0·0001; FT: r = -0·51; P < 0·0001). In multivariate regression analysis controlling for VAT, FT was no longer related to GH. Both GH and FT were associated with cIMT in univariate analysis. However, in multivariate modelling including traditional cardiovascular risk markers, GH (ß = 0·003; P = 0·04) but not FT (P = 0·35) was associated with cIMT. CONCLUSIONS: These results demonstrate a strong relationship between FT and GH in obesity and suggest that this relationship is more a function of excess adiposity rather than a direct relationship. While reduced FT and GH are both related to increased cIMT, the relationship with reduced GH remains significant controlling for reduced FT and traditional cardiovascular disease risk markers.

Effects of obesity, body composition, and adiponectin on carotid intima-media thickness in healthy women.

CONTEXT: Increased common carotid intima-media thickness (IMT) is predictive of coronary artery disease and stroke. OBJECTIVE: In this study, we investigated common carotid IMT by obesity category in a cohort of healthy women without previously known cardiovascular disease. DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOME MEASURES: One hundred healthy women (aged 24-59 yr) from the general community enrolled in an observational study conducted at an academic medical center participated in the study. B-mode ultrasound imaging of the common carotid arteries was used to measure common carotid IMT in 99 subjects. Fat distribution was determined by computed tomography. Hormonal and inflammatory parameters related to cardiovascular disease and obesity were measured. RESULTS: IMT was higher in obese [body mass index (BMI) >or= 30 kg/m(2)], compared with overweight women (BMI >or= 25 and < 30 kg/m(2)) [0.69 mm, interquartile range (IQR) 0.60-0.75 mm] vs. 0.62 mm [IQR 0.56-0.68 mm), P = 0.044] and in comparison with lean women (BMI < 25 kg/m(2)) [0.69 mm (IQR 0.60-0.75 mm) vs. 0.59 mm (IQR 0.54-0.67 mm), P = 0.016]. In multivariate modeling, age (beta = 0.0050 mm change in IMT per year of age, P = 0.003), smoking (beta = 0.0044 mm change in IMT per pack-year, P = 0.046), and sc abdominal adiposity (beta = 0.00026 mm change in IMT per square centimeter, P = 0.010) were positively associated with IMT, whereas adiponectin (beta = -0.0042 mm change in IMT per milligram per liter, P = 0.045) was negatively associated with IMT. Visceral adiposity (beta = 0.00048 mm change in IMT per square centimeter, P = 0.092) was not significantly associated with IMT after adjusting for age, race, smoking, sc abdominal adiposity, and adiponectin. CONCLUSIONS: Obesity is associated with increased common carotid IMT in young and middle-aged women. Adiponectin and sc abdominal adiposity are associated with carotid IMT in this population.

Carotid intimal medial thickness in human immunodeficiency virus-infected women: effects of protease inhibitor use, cardiac risk factors, and the metabolic syndrome.

CONTEXT: Little is known regarding carotid intimal medial thickness (IMT) in HIV-infected women and the risk factors for subclinical atherosclerosis in this population, including antiretroviral therapy and the metabolic syndrome. OBJECTIVE: Our objective was to assess carotid IMT in relationship to HIV status and antiretroviral therapy in HIV-infected women in comparison with healthy age- and body mass index (BMI)-matched control subjects. SETTING AND SUBJECTS: The study took place at an academic medical center and included 97 HIV-infected women compared with 86 age- and BMI-matched healthy control subjects. MAIN OUTCOME MEASURES: We assessed carotid IMT, metabolic syndrome, and risk factors for increased IMT. RESULTS: Carotid IMT was not increased in HIV-infected women [0.62 mm (0.57-0.68); median (IQR)] compared with non-HIV-infected women [0.61 mm (0.55-0.68)] matched for age and BMI (P = 0.07) but was increased significantly among HIV patients receiving a protease inhibitor (PI) [0.65 (0.59-0.71) mm] vs. non-PI-treated patients [0.61 (0.57-0.66) mm] (P < 0.05) and vs. control subjects [0.61 (0.55-0.68) mm] (P < 0.05). The prevalence of metabolic syndrome was significantly increased among the HIV-infected women compared with control subjects and particularly in PI- vs. non-PI-treated HIV patients (45 vs. 19%, P = 0.001). Metabolic syndrome score correlated with IMT among non-HIV patients but not among the HIV group. Individual risk factors most strongly associated with IMT in multivariate regression modeling in the control group were age and waist-to-hip ratio, and among the HIV group age and waist circumference. CONCLUSIONS: These data demonstrate increased carotid IMT in HIV-infected women receiving PI therapy, which may be due to associated metabolic abnormalities related to PI therapy or more direct effects of this medication class on the vasculature. Additional studies of the mechanisms by which PI uses results in subclinical atherosclerosis are needed.

Increased skeletal muscle phosphocreatine recovery after sub-maximal exercise is associated with increased carotid intima-media thickness.

BACKGROUND: The association between skeletal muscle mitochondrial function and CVD risk in healthy subjects is unknown. METHODS: Forty subjects were evaluated for CVD risk with lipid profile, oral glucose tolerance test and measurement of carotid intima-media thickness (cIMT). Skeletal muscle mitochondrial function was determined by phosphocreatine recovery after sub-maximal exercise with (31)Phosphorous-MRS and represented as τPCr. RESULTS: τPCr was positively associated with age (r=+0.41; P=0.009) and cIMT (r=+0.50; P=0.001) on univariate analyses. In multivariate regression analysis controlling for age, the association between τPCr and cIMT remained significant (ß=0.003; P=0.03). This association remained significant after controlling for traditional risk factors for CVD including age, gender, tobacco use, BMI, blood pressure, cholesterol and fasting glucose in a combined model (ß=0.003; P=0.04; R(2)=0.53; P=0.008 for overall model). CONCLUSIONS: These data suggest a novel association between skeletal muscle τPCr and increased cIMT, independent of age or traditional CVD risk factors.

Reduced growth hormone secretion is associated with increased carotid intima-media thickness in obesity.

CONTEXT: Obesity is associated with reduced GH. OBJECTIVE: The aim of the study was to determine whether reduced GH is associated with increased carotid intima-media thickness (cIMT) in obesity. DESIGN: A total of 102 normal-weight and obese men and women without known hypopituitarism were studied. Subjects underwent GH stimulation testing with GHRH-arginine. Lipid profile, inflammatory markers, oral glucose tolerance test, abdominal computed tomography, dual-energy x-ray absorptiometry, and cIMT were measured. Relative GH deficiency was defined as peak GH of 4.2 microg/liter or less. Subjects were separated based on BMI and GH testing into three groups: normal weight, obese GH sufficient (GHS), and obese relative GH deficient (GHD). Age, gender, and race were similar between the groups. BMI, percentage body fat, and visceral adiposity did not differ between obese GHS and relative GHD. RESULTS: Peak GH was associated with cIMT, IGF-I, high-density lipoprotein, low-density lipoprotein, triglycerides, adiponectin, C-reactive protein, and TNF-alpha (all P < 0.05). Obese GHS subjects had similar cIMT compared to normal-weight subjects (P = not significant), whereas obese GHD subjects had higher cIMT compared to normal-weight subjects (P < 0.05) (normal weight, 0.645 +/- 0.023, vs. obese GHS, 0.719 +/- 0.021, vs. obese GHD, 0.795 +/- 0.063 mm; P = 0.01 by ANOVA). Similar results were seen in sensitivity analyses with less stringent cutoffs (< 5, < or = 8, < 9 microg/liter) to define GHD. In multivariate modeling, peak GH remained significantly associated with cIMT after controlling for age, gender, race, tobacco, blood pressure, cholesterol, and fasting glucose (R(2) for model, 0.35; P < 0.0001). CONCLUSIONS: These results suggest that reduced GH secretion is associated with a more abnormal metabolic phenotype in obesity, characterized by increased cIMT, dyslipidemia, insulin resistance, and inflammation.