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Genetic variations of genes encoding the endothelial nitric oxide synthase (eNOS) and the NADH/NADPH oxidase system are related with atherosclerosis in the general population, but their significance in women is not sufficiently assessed. We investigated the potential association between the G894T polymorphism of the NOS3 gene and the C242T polymorphism of the CYBA gene with subclinical vascular disease. Seventy (70) healthy, normally ovulating, premenopausal women were recruited for this study. Venous blood samples were obtained for biochemical/hormonal assessment as well as for genotyping, using real-time PCR. Sonographically assessed indices of vascular structure and function included carotid and femoral intima-media thickness (IMT), flow-mediated dilation (FMD), carotid-femoral pulse-wave velocity (PWV), and augmentation index. The prevalence of wild type, heterozygote, and homozygote genotype was 44.3% (31/70), 54.3% (38/70), and 1.4% (1/70) for the G894T polymorphism and 38.6% (27/70), 31.4% (22/70), and 30.0% (21/70) for the C242T polymorphism, respectively. After multivariable adjustment, the hC242T polymorphism was a predictor of both internal carotid IMT (b-coefficient − 0.119, p = 0.011) and combined-IMT (b-coefficient − 0.061, p = 0.015). Systolic blood pressure, lipids, and hC242T determined values of FMD (b-coefficient − 1.604, p = 0.034). Concerning the NOS3 G894T polymorphism, carriers of the polymorphic variant had higher values of IMT and PWV compared to the wild-type subgroup (carotid bulb-IMT and PWV, heterozygotes/homozygotes vs wild type 0.7 ± 0.2 vs 0.6 ± 0.1 mm; 7.1 ± 0.8 vs 6.6 ± 0.7 m/s; p = 0.048 and p = 0.029, respectively). These differences, however, were rendered non-significant in the multivariable analysis. In healthy premenopausal women, the CYBA C242T polymorphism is an independent determinant of endothelial function and subclinical atherosclerosis of the carotid arteries. The NOS3 G894T polymorphic variant also correlated with atherosclerosis, an association probably mediated by the traditional risk factors for CVD. The relevance of these findings in the clinical setting remains to be elucidated. [ABSTRACT FROM AUTHOR]

Atherosclerosis is the principal cause of cardiovascular disease (CVD) and has many risk factors, among which is diabetes. Osteoprotegerin (OPG) is a soluble g lycoprotein, involved in bone metabolism. OPG is also found in other tissues, and studies have shown that it is expressed in vascular smooth muscle cells. OPG has been implicated in various infiammations and also has been linked to diabetes mellitus. Increased serum OPG levels were found in patients with diabetes and poor glycemic control. Furthermore, prepubertal children with type 1 diabetes have significantly increased OPG levels. Receptor activator of nuclear factor kappa-B ligand (RANKL) is not found in the vasculature in normal conditions, but may appear in calcifying areas. OPG and RANKL are important regulators of mineral metabolism in both bone and vascular tissues. Few data are available on the relationship between plasma OPG/RANKL levels and endothelial dysfunction as assessed using noninvasive methods like ultrasound indexes, neither in the general population nor, more specifically, in diabetic patients. The aim of our review study was to investigate, based on the existing data, these interrelationships in order to identify a means of predicting, via noninvasive methods, later development of endothelial dysfunction and vascular complications in diabetic patients. [ABSTRACT FROM AUTHOR]

Aims. To evaluate carotid intima-media thickness (cIMT) and biomarkers of the osteoprotegerin/receptor activator of nuclear factor-kB ligand (OPG/RANKL) system in type 1 diabetes (T1DM) children and adolescents and controls. Subjects and Methods. Fifty six T1DM patients (mean ± SD age: 12.0 ± 2.7 years, diabetes duration: 5.42 ± 2.87 years and HbA1c: 8.0 ± 1.5%) and 28 healthymatched controls, were studied with anthropometric and laboratory measurements, including serumOPG, soluble RANKL (sRANKL) and cIMT. Results. Anthropometric, laboratory, and cIMT measurements were similar between T1DM youngsters and controls. However patients with longer diabetes duration (>/7.0 years) had indicatively higher cIMT (cIMT = 0.49 vs 0.44 mm, P0.072) and triglyceride levels than the rest of the patients (93.7 vs 64.6mg/dl, P0.025). Both in the total study population (β 0.418, P0.027) and among T1DM patients separately (β 0.604, P 0.013), BMI was the only factor associated with cIMT. BMI was further associated with OPGin both groups (β-0.335, P 0.003 and β-0.356, P 0.008 respectively), while sRANKL levels were not associated with any factor. Conclusions. BMI was the strongest independent predictor of cIMT among the whole population, and especially in diabetics, suggesting a possible synergistic effect of diabetes and adiposity on atherosclerotic burden. BMI was overall strongly associated with circulating OPG, but the causes of this association remain unclear. [ABSTRACT FROM AUTHOR]

Background: The present study aims to examine the association of the metabolic syndrome (MS) as well as of the triglyceride-glucose index (TyG-Index), a novel marker of insulin resistance, with subclinical atherosclerosis in a cohort of postmenopausal women, stratified according to their body mass index.Methods: A total of 473 informed-consenting, non-diabetic postmenopausal women, without overt cardiovascular disease, were included in this study. We aimed to compare the association between structural and functional indices of subclinical atherosclerosis (i.e. carotid artery intima-media thickness (IMT), flow-mediated dilation of the brachial artery, pulse wave velocity (PWV)) with the TyG-index or MS, separately for lean and overweight/obese women.Results: The TyG-Index correlated significantly with carotid IMT (r=0.155, p=0.012) and PWV (r=0.157, p=0.013) only in the group of lean women. Multivariate analysis showed that subclinical atherosclerosis was predicted by MS, in the overweight/obese group (OR=2.517, 95% CI: 1.078-5.878, p=0.033), and by the TyG-Index the lean group (OR=3.119, 95% CI: 1.187-8.194, p<0.001). Using a TyG-Index cut-off value of 8.0 in the lean subpopulation, women above the cut-off had 44.1% prevalence of subclinical atherosclerosis compared to 29.4% in women below the cut-off (p=0.043).Conclusions: The TyG-Index is associated with carotid atherosclerosis and arterial stiffness mainly in lean postmenopausal women, while the MS serves as a better predictor of subclinical atherosclerosis in overweight/obese women. The TyG-Index may prove a useful marker for identifying high-risk women in the normal-weight postmenopausal population. [ABSTRACT FROM AUTHOR]

Abstract: 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 41–60years 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 37–278mg/dl), waist circumference (62–114cm), fasting blood glucose (69–114mg/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 4years 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. [Copyright &y& Elsevier]

Abstract: 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>0.9mm) 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±0.119mm and 1.47±1.6 versus 0.717±0.138mm 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. [Copyright &y& Elsevier]