Georgios Georgiopoulos

Circulating androgen levels are associated with subclinical atherosclerosis and arterial stiffness in healthy recently menopausal women

Although increasing evidence supports an association between endogenous sex hormones and cardiovascular disease, the results still remain controversial. This study aims to examine the association between endogenous sex hormones and indices of vascular function and structure. Serum follicle-stimulating hormone, luteinizing hormone, estradiol, testosterone, sex hormone-binding globulin, dehydroepiandrosterone sulfate (DHEAS), and Δ4-androstenedione were measured in 120 healthy postmenopausal women aged 41 to 60 years. Possible associations with surrogate markers of subclinical atherosclerosis, arterial stiffness, and endothelial function were investigated. Indices of arterial structure included carotid and femoral intima-media thickness and atheromatous plaques presence. Indices of arterial function included flow-mediated dilation of the brachial artery, carotid-femoral pulse wave velocity (PWV), and augmentation index. Total testosterone and free androgen index (FAI) were the most important predictors of common carotid artery intima-media thickness (β = 0.376 and β = 0.236, P < .001 and P = .014, respectively). Similarly, FAI was the only significant independent predictor of PWV (β = 0.254, P = .027) after adjusting for age, smoking, body mass index, homeostasis model assessment of insulin resistance, and blood lipids. Free estrogen index showed a positive association with PWV, independently of age, smoking, and body mass index, but not of homeostasis model assessment of insulin resistance and blood lipids. Age-adjusted levels of DHEAS exhibited a significant independent negative association with measures of augmentation index. Follicle-stimulating hormone, luteinizing hormone, estradiol, sex hormone-binding globulin, and Δ4-androstenedione were not associated with any of the vascular parameters independently of traditional cardiovascular risk factors. Higher serum testosterone and FAI are associated with subclinical atherosclerosis in healthy recently menopausal women. This association is independent of traditional cardiovascular risk factors or insulin resistance. On the contrary, serum DHEAS exhibits a negative association with arterial stiffness.

Ten-year (2002–2012) cardiovascular disease incidence and all-cause mortality, in urban Greek population: The ATTICA Study

AIM The 10-year incidence of cardiovascular disease (CVD) and all-cause mortality, as well as its determinants, in a sample of men and women from Greece, was evaluated. METHODS From May 2001 to December 2002, 1514 men and 1528 women (>18y) without any clinical evidence of CVD or any other chronic disease, at baseline, living in greater Athens area, in Greece, were enrolled. In 2011-12, the 10-year follow-up was performed in 2583 participants (15% of the participants were lost to follow-up). Incidence of fatal or non-fatal CVD (coronary heart disease, acute coronary syndromes, stroke, or other CVD) was defined according to World Health Organization (WHO)-International Coding Diseases (ICD)-10 criteria. RESULTS The 10-year CVD incidence was 19.7% in men and 11.7% in women (p<0.001). Multi-adjusted analysis revealed that the determinants of CVD events were increased age (Hazard ratio (HR) per year=1.06, 95%Confidence Interval (CI): 1.04, 1.08), male sex (HR=1.40, 95%CI: 0.90, 2.19), smoking (HR=1.53, 95%CI: 1.03, 2.27), C-reactive protein levels (HR per 1mg/L=1.06, 95%CI: 1.02, 1.15), as well as adherence to Mediterranean diet (protective) (HR per 1/55 units=0.98, 95%CI: 0.95, 1.01). CONCLUSION The burden of CVD and its related risk factors is at emerging rates, in Greece, making the need for effective public health actions, more necessary than ever before.

Arterial Stiffness but Not Intima-Media Thickness Is Increased in Euthyroid Patients with Hashimoto's Thyroiditis: The Effect of Menopausal Status

BACKGROUND Hashimotos thyroiditis (HT) is an autoimmune disorder associated with increased cardiovascular risk, mainly as a result of accelerated atherosclerosis. The aim of this study was to determine the effect of HT on carotid atherosclerosis and arterial stiffness, as possible mediators of this vascular impairment. Menopausal status was also considered in this setting since HT is mainly prevalent in women. METHODS Fifty-four women with HT and normal thyroid function (thyrotropin [TSH] < 4.5 mU/L) and 72 healthy controls with comparable age and risk factor prevalence were examined in this cross-sectional study. Intima-media thickness (IMT) in the carotid arteries averaged from six sites and carotid-femoral pulse wave velocity (PWV) were measured. RESULTS Although both groups had TSH levels within normal limits, TSH was higher in HT patients (2.1 +/- 1.16 vs. 1.5 +/- 0.8 mU/L, p = 0.001). PWV (7.95 +/- 2.02 vs. 7.21 +/- 1.24 m/s, p = 0.021), but not IMT (0.644 +/- 0.144 vs. 0.651 +/- 0.169 mm, p = 0.798), was significantly higher in HT patients compared to controls. When the women were divided according to menopausal status, only premenopausal women without HT had significantly lower PWV when compared with the three other subgroups (6.51 +/- 1.09 m/s premenopausal controls vs. 7.64 +/- 2.05 m/s premenopausal HT vs. 7.69 +/- 1.11 m/s postmenopausal controls vs. 8.3 +/- 1.97 m/s postmenopausal HT, p < 0.001). By multivariate analysis PWV independently correlated with age (p = 0.042), the presence of HT (p = 0.002), TSH (p = 0.003), and menopause (p < 0.001) in the whole population while HT was an independent determinant of PWV only in premenopausal women. CONCLUSIONS HT is associated with increased PWV independent of arterial atheromatosis, indicating a direct impact of this disorder on arterial stiffening. This effect may be masked in postmenopausal women possibly due to their heavier cardiovascular risk profile.

Subclinical atherosclerosis in menopausal women with low to medium calculated cardiovascular risk

BACKGROUND The menopausal status is closely related with cardiovascular disease (CVD). Nevertheless, it is still not included in risk stratification by total cardiovascular risk estimation systems. The present study aimed to evaluate the extent of subclinical vascular disorders in young healthy postmenopausal women. METHODS This cross-sectional study consecutively recruited 120 healthy postmenopausal women without clinically overt CVD or diabetes, aged 41-60 years and classified as not high-risk by the Heartscore (<5%). In addition to risk factors used for Heartscore calculations, years since menopause and associated risk factors (triglycerides (range 37-278 mg/dl), waist circumference (62-114 cm), fasting blood glucose (69-114 mg/dl) and HOMA-IR (0.44-5)) were also assessed. Carotid-femoral pulse wave velocity, carotid and femoral intima-media thickness in the abnormal range as well as atheromatous plaques both in carotid and femoral arteries were used to define the presence of subclinical atherosclerosis. RESULTS Subclinical atherosclerosis and the presence of at least one plaque were identified in 55% and 28% of women, respectively. Subjects with subclinical atherosclerosis had higher age, years since menopause, HOMA-IR and blood pressure. By multivariate analysis years since menopause and systolic blood pressure independently determined subclinical atherosclerosis while 79% of intermediate-risk women (Heartscore 2-4.9%) being in menopause for at least 4 years would be reclassified to a higher risk for the presence of atherosclerosis. CONCLUSION Subclinical atherosclerosis was highly prevalent in postmenopausal women with low to medium Heartscore. Thus our data suggest that menopausal status and associated risk factors should be additionally weighted in risk calculations, regarding primary prevention strategies in this population.

Mechanisms in endocrinology: primary HT and risk for breast cancer: a systematic review and meta-analysis.

OBJECTIVE The association between hypothyroidism and breast cancer has been described from very early on. Breast and thyroid tissue are interconnected on a molecular level mainly through activation of thyroid hormone receptors expressed on cells of the mammary gland as well as on the plasma membrane of breast cancer cells. Despite the experimental evidence the true value of hypothyroidism as a risk factor for breast cancer remains controversial. METHODS We searched the PubMed database through February 2011 to identify studies that evaluated the association between hypothyroidism and risk for breast cancer as well as the effect of thyroid hormone replacement therapy on breast cancer incidence. RESULTS A meta-analysis performed in 12 studies showed that hypothyroidism was not associated with risk for breast cancer (pooled risk ratio (RR)=1.06, 95% confidence intervals (CIs) 0.82-1.35, P = 0.672). The effect of treatment was assessed in seven studies and no evidence for an association between thyroid hormone replacement and breast cancer was observed with an overall RR of 0.99 (95% CI 0.73-1.35, P = 0.965). CONCLUSIONS Our meta-analysis showed that hypothyroidism is not associated with increased risk for breast cancer and thyroid hormone replacement therapy does not reduce breast cancer prevalence; however, the heterogeneity of the studies analyzed precludes firm conclusions.

Recently postmenopausal women have the same prevalence of subclinical carotid atherosclerosis as age and traditional risk factor matched men

OBJECTIVE To compare the prevalence of subclinical atherosclerosis between postmenopausal women and men of similar age early after the onset of menopause. METHODS In the first part of this cross-sectional study 186 non-diabetic young postmenopausal women (n = 101, menopausal age ≤ 10 years) and men (n = 85) aged 40-60 years without overt CVD were consecutively recruited from the outpatients clinics of an academic hospital. Subclinical carotid atherosclerosis was assessed by high-resolution ultrasonography. The presence of carotid atherosclerosis was defined as either increased carotid intima-media thickness (IMT>0.9 mm) and/or the presence of plaques. In the second part, 1:1 matching for age and traditional risk factors (hyperlipidemia, smoking, hypertension and BMI) was performed between men and women of this cohort resulting in a matched sub-sample of 76 subjects. RESULTS By multivariate analysis, gender was not an independent determinant of any measure of carotid atherosclerosis. In the matched sub-sample, carotid IMT and the number of segments with atherosclerosis did not significantly differ between women and men (0.734 ± 0.119 mm and 1.47 ± 1.6 versus 0.717 ± 0.138 mm and 1.47 ± 1.5, p = 0.575 and p = 0.999, respectively). Also, the prevalence of increased IMT (60.5% in both genders), carotid plaques and subclinical atherosclerosis (31.6% and 63.2% versus 28.9% and 65.8%, p = 0.803 and p = 0.811, respectively) was similar between men and women. CONCLUSIONS The prevalence and severity of carotid atherosclerosis was similar between men and young postmenopausal women matched for traditional risk factors. Whether these women may be better risk stratified irrespective of gender should be further assessed in prospective studies.

Menopausal symptoms are associated with subclinical atherosclerosis in healthy recently postmenopausal women

ABSTRACT Objectives To determine whether menopausal symptoms are associated with changes in arterial structure and function in healthy, recently postmenopausal women. Methods One hundred and ten postmenopausal women aged 45–55 years were included in the present cross-sectional study. Menopausal symptoms were recorded by the Greene Climacteric Scale. Anthropometric measures, blood pressure, serum lipids, glucose, insulin, sex and thyroid hormones were determined in each individual. Arterial structure, function and stiffness were assessed by intima–media thickness (IMT), flow-mediated dilation and pulse-wave velocity, respectively. Results Women with moderate to severe hot flushes had increased IMT compared to women with no or mild hot flushes (IMT in women with no hot flushes 0.61±0.08 mm, IMT in women with mild hot flushes 0.62±0.11 mm, IMT in women with moderate to severe hot flushes 0.67±0.11 mm; p = 0.034). This difference was independent of cardiovascular risk factors like age, menopausal age, smoking, blood pressure, adiposity, lipid levels, insulin resistance or hormone levels. No association was detected between psychological or psychosomatic symptoms and arterial indices. Furthermore, menopausal symptoms were not associated with serum sex steroids or thyroid hormone levels. Conclusions Carotid IMT, a surrogate marker of subclinical atherosclerosis and cardiovascular risk, was found to be increased in women with vasomotor symptoms as compared to asymptomatic women. This association was independent of cardiovascular risk factors or endogenous hormone levels. It remains to be elucidated whether the presence of menopausal symptoms is an additional cardiovascular risk factor requiring preventive intervention.

Frequent conversion of tuberculosis screening tests during anti-tumour necrosis factor therapy in patients with rheumatic diseases

Objectives To determine the rate of tuberculosis (TB) screening test conversion during anti-tumour necrosis factor (TNF) therapy in rheumatic patients with negative baseline screening. Methods This was a prospective study of rheumatic patients with negative baseline TB screening (tuberculin skin test (TST): <5 mm, and negative T-SPOT.TB, QuantiFERON-TB Gold In Tube (QFT-GIT) and chest X-ray) treated with anti-TNF agents. All patients underwent re-screening for TB with all assays 1 year later. Factors associated with TB test conversion were analysed and compared between ‘converters’ and ‘non-converters’. Results Seventy patients (mean age 50.6±15.5 years) with rheumatic disease (33 with rheumatoid arthritis, 33 with spondyloarthropathies and 4 with other conditions) were enrolled. Patients were treated with different anti-TNFs (27 with adalimumab, 14 etanercept, 16 infliximab, 8 golimumab, 5 certolizumab pegol) for 1 year. Twenty patients (29%) displayed conversion of at least one screening assay 12 months after anti-TNF therapy: conversion of TST occurred in 9 (13%), T-SPOT.TB in 7 (10%) and QFT-GIT in 5 (7%). Only one patient had concomitant conversion of more than one screening test. Univariate and multivariate analysis revealed that only infliximab was associated with a decreased rate of TB screening assay conversion (OR 0.048, 95% CI 0.004 to 0.606, p=0.017). No patient (40% received isoniazid therapy) developed active TB during follow-up (27±12 months). Conclusions Approximately one third of patients with negative baseline TB screening develop conversion of at least one screening test during anti-TNF treatment. These findings should be considered when designing re-screening strategies and contemplating latent TB therapy.

High normal thyroid-stimulating hormone is associated with arterial stiffness in healthy postmenopausal women.

Objective: Apart from the effects of a dysfunctional thyroid gland on the cardiovascular system, thyroid function within the reference range may have an impact on the vasculature. The present study aimed to evaluate the association between thyroid function and markers of arterial structure and function in euthyroid postmenopausal women. Methods: The present cross-sectional study recruited 106 healthy postmenopausal women with a mean age of 55.0 years and thyroid-stimulating hormone (TSH) levels within the laboratory reference range (0.4–4.5 &mgr;IU/ml). Anthropometric and biochemical measures as well as blood pressure were determined in each individual. Vascular structure and function were assessed by intima–media thickness, pulse wave velocity (PWV), augmentation index and flow-mediated dilation, respectively. We evaluated the associations between arterial markers and serum TSH, free triiodothyronine, free thyroxin, as well as serum thyroid peroxidase and thyroglobulin autoantibodies. Results: Mean levels of PWV increased linearly across increasing TSH quartiles (P value = 0.014). Individuals with serum TSH greater than 2.5 &mgr;IU/ml had significantly higher values of PWV when compared with individuals with TSH levels below 2.5 &mgr;IU/ml (9.68 ± 1.97 vs. 8.54 ± 1.83 m/s; P = 0.030). In multivariate analysis, age, insulin resistance and TSH above 2.5 &mgr;IU/ml were the only significant predictors of PWV (TSH, &bgr;-coefficient = 0.222; P = 0.014). No associations were found between the remaining markers and levels of thyroid hormones, whereas thyroid antibodies were not associated with any of the arterial markers. Conclusion: Women with TSH levels in the upper reference range have increased arterial stiffness compared to women with lower TSH. The upper limit of normal TSH in postmenopausal women may need re-evaluation with respect to the effects on the vasculature.

Exploring the path of Mediterranean diet on 10-year incidence of cardiovascular disease: The ATTICA study (2002–2012)

BACKGROUND AND AIMS A Mediterranean diet has been associated with lower all-cause and cardiovascular disease (CVD) morbidity and mortality, but the clinical and behavioral pathway has not been well understood and appreciated. The aim of this work was to explore the path between adherence to a Mediterranean-type diet, lifestyle behaviors, clinical status, and a 10-year incidence of CVD. METHODS AND RESULTS The ATTICA study was carried out in the Athens area during 2001-2002 and included 3042 participants free of CVD at baseline (49.8% men, aged 18-89). Adherence to a Mediterranean diet was assessed using the MedDietScore (range 0-55). During 2011-2012, 2583 out of the 3042 participants were found during the 10-year follow-up (15% lost to follow-up). Adherence to a Mediterranean diet decreased CVD risk (relative Risk (RR) per 1/55 unit = 0.96, 95% confidence interval (CI): 0.93, 1.00), independently of various sociodemographic, lifestyle, and clinical factors. Subgroup analyses revealed that participants with an unhealthy lifestyle (i.e., smokers, and obese and sedentary persons) remained protected from CVD through a greater adherence to a Mediterranean diet (RR for smokers = 0.92, 95%CI: 0.88, 0.97; RR for obese participants = 0.90, 95%CI: 0.82, 0.979; and RR for sedentary participants = 0.95, 95%CI: 0.90, 0.99). Path analysis revealed that adherence to a Mediterranean diet not only decreases the levels of C-reactive protein and interleukin-6 but also has an independent protective role against CVD risk per se (total effect of the MedDietScore on CVD = -0.003, 95%CI: -0.005 to 0.000). CONCLUSION Adherence to a Mediterranean diet confers a considerable reduction on CVD risk, independent of various factors. Therefore, even subjects with unhealthy lifestyle behaviors may benefit from adherence to this diet, suggesting another dimension to prevention strategies.