Georgios Kaparos

The TyG Index as a Marker of Subclinical Atherosclerosis and Arterial Stiffness in Lean and Overweight Postmenopausal Women

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.

The metabolic syndrome is associated with carotid atherosclerosis and arterial stiffness in asymptomatic, nondiabetic postmenopausal women

Abstract The menopause transition is associated with adverse changes in cardiometabolic risk factors. We aimed to examine the association of the metabolic syndrome (MS) and its features with indices of vascular structure and function in a population of asymptomatic postmenopausal women. A total of 473 informed-consenting, nondiabetic postmenopausal women were included in the study. The MS was defined according to the Joint Definition. We evaluated the association between the presence of MS and indices of vascular structure (carotid artery intima-media thickness (IMT); atherosclerotic plaques) and function (flow-mediated dilatation (FMD); pulse wave velocity (PWV)). The mean age of women was 56.4 ± 6.7 and the mean menopausal age was 7.91 ± 6.31. The MS was present in 17.3% of our population. Mean values of PWV increased linearly with the accumulation of features of the MS. IMT was higher in women with the MS compared to women without the MS (0.78 ± 0.12 mm vs. 0.74 ± 0.11, p = .003). Multivariate analysis showed that the presence of the MS was independently associated with common carotid artery IMT (b = 0.149, p = .001), PWV (b = 0.114, p = .012) as well as central systolic and diastolic blood pressure (b = 0.293, p < .001 and b = 0.163, p < .001 respectively). The presence of the MS is associated with subclinical atherosclerosis already in the first postmenopausal decade of this sample of asymptomatic, nondiabetic women. Additional evidence is required to support the causative effect of these associations.

Genetic heterogeneity of platelet glycoproteins Ia and IIIa and the risk of spontaneous miscarriages

Abstract Objective: The aim of this study was to investigate the association between the genetic heterogeneity of platelet glycoproteins Ia (GpIa-C807T) and IIIa (GpIIIa-PlA1/PlA2) and spontaneous abortions. Study design: Two hundred and twenty two women with a history of unexplained spontaneous miscarriages and no successful pregnancy, and 60 fertile women serving as controls were genotyped for the GpIa-C807T and GpIIIa-PlA1/PlA2 polymorphisms by pyrosequencing. Results: In comparison with the common alleles homozygotes, GpIa-807T and GpIIIa-PlA2 carriers had an increased risk of fetal loss (OR = 3.36, 95%CI: 1.85–6.11, p < 0.001, and OR = 2.58, 95%CI: 1.30–5.13, p = 0.006, respectively). For subjects who were combined carriers of the GpIa-807T and GpIIIa-PlA2 alleles, the risk increased further (OR = 9.13, 95%CI: 2.99–27.82, p < 0.001). The above ORs were highest for women who were younger than 30 years of age. Conclusions: The GpIa-C807T and GpIIIa-PlA1/PlA2 polymorphisms and more pronouncedly their combination are associated with increased risk of spontaneous abortions. The correlations were stronger for younger patients. Our results indicate that GpIa-807T and GpIIIa-PlA2 are susceptibility alleles for fetal loss in the Greek population.

Effect of tibolone and raloxifene on serum markers of apoptosis in postmenopausal women

ABSTRACT Objectives To investigate the effect of tibolone and raloxifene on the serum apoptotic markers soluble Fas (sFas), soluble Fas ligand (sFasL) and cytochrome-c (cyt-c) in postmenopausal women. Methods A total of 89 healthy postmenopausal women, attending the University Menopause Clinic, were randomly allocated to tibolone (n =30), raloxifene (n =29) or no treatment (n =30). Serum apoptotic markers sFas, sFasL and cyt-c were measured at baseline and at 6 months. Results Serum sFasL decreased significantly in women receiving tibolone (baseline: 53.8±28.3 pg/ml, 6 months: 40.45±19.2 pg/ml, p =0.001), whilst sFas levels did not significantly change in this group. Serum sFas or sFasL did not change either in the raloxifene group or in the control group. Serum cyt-c concentrations were under the detection limit of the assay in all women assessed. Conclusions Tibolone use resulted in a significant decrease in serum sFasL, but not in serum sFas. Raloxifene had no effect on either sFas or sFasL. These results may indicate that tibolone use is associated with a decrease in receptor-mediated apoptosis.

Associations of combined polymorphisms of the platelet membrane glycoproteins Ia and IIIa and the platelet-endothelial cell adhesion molecule-1 and P-Selectin genes with IVF implantation failures

Abstract The aim of the study was to investigate the combined impact of the genetic heterogeneity of the glycoproteins Ia (GpIa) and IIIa (GpIIIa) and the platelet-endothelial cell adhesion molecule-1 (PECAM-1) and P-Selectin genes on IVF embryo transfer implantation failures (IVF-ET failures). Sixty nulligravida women with previous IVF-ET failures and 60 fertile controls were genotyped for the GpIa-C807T, GpIIIa-PlA1/PA2, PECAM-1-C373G (Leu125Val) and P-Selectin-A37674C (Thr715Pro) polymorphisms by pyrosequencing. Compared with wild-type combined homozygotes, carriers of combinations of risk alleles in two gene loci were at significantly increased risk for IVF-ET failure, whereas carriers of the combination of GpIa-807T, GpIIIa-PlA2 and PECAM-1-373G alleles had OR = 52.50 (95%CI: 4.05–680.95, p < .001). The area under the receiver-operating characteristic curve (AUC) based on the number of polymorphisms and the number of risk alleles per subject was 75.4% (95%CI: 66.7%–82.8%, p < .001) and 72.5% (95%CI: 63.6%–80.3%, p < .001), respectively. The OR per polymorphism and risk allele increase was 4.26 (95%CI: 2.15–8.41, p < .001) and 2.85 (95%CI: 1.71–4.76, p < .001), respectively. The above associations were more robust among younger women. The combined analysis of these polymorphisms revealed strong association of combined carriers with IVF-ET failures especially for younger women and provided a genetic risk score with good diagnostic accuracy in the prediction of IVF-ET failures.

The intensity of menopausal symptoms is associated with episodic memory in postmenopausal women

Abstract Objective: The adaptation of the brain to aging is subject to the impact of psychological and environmental factors and possibly climacteric symptomatology. We aimed to determine the association of climacteric symptomatology with different aspects of episodic memory in a sample of Greek menopausal women. Methods: This cross-sectional study included 39 postmenopausal women with subjective memory complaints. Memory performance was evaluated using the Hopkins Verbal Learning Test (HVLT) and the revised Brief Visuospatial Memory Test (BVMT), assessing verbal and visuospatial episodic memory, respectively. We evaluated general cognitive status using the Mini-Mental State Examination (MMSE) and the Clock Drawing Test. Menopausal symptoms were assessed using Greene’s Climacteric scale. Results: In the multivariate approach, vasomotor symptoms predicted independently HVLT (retained percentage and delayed recall: b-coefficient = −0.568, p = 0.009 and b-coefficient = −0.563, p = 0.012, respectively). Psychological symptoms predicted independently MMSE (b-coefficient = −0.391, p = 0.024); and in combination with free estrogens (logFEI), psychological symptoms predicted BVMT (total and delayed recall: b-coefficient = −0.558, p = 0.001 and b-coefficient = −0.474, p = 0.005) and HVLT discrimination index (b-coefficient = −0.390, p = 0.023). Combined symptomatology predicted independently MMSE (b-coefficient = −0.457, p = 0.006) and HVLT total (b-coefficient = −0.557, p = 0.034); combined symptomatology predicted in combination with logFEI scores of BVMT total (b-coefficient = −0.593, p < 0.001), BVMT delayed recall (b-coefficient = −0.492, p = 0.002). Conclusion: The intensity of psychological, vasomotor and combined climacteric symptoms predicted cognitive performance in this sample of postmenopausal women. A differential contribution of vasomotor symptoms to episodic memory is described, with the negative impact being more pronounced in visuospatial rather than verbal episodic memory.

Variations in glomerular filtration rate are associated with subclinical atherosclerosis in healthy postmenopausal women.

ObjectiveThis study aims to evaluate the potential effects of renal function variations on vascular structure before the development of hypertension. MethodsThis pilot study included 141 postmenopausal women without evidence of renal dysfunction or hypertension. Markers of renal function and levels of glomerular filtration rate (GFR)—using standard calculations (GFR based on levels of creatinine [GFRepi]) and newer creatinine and/or cystatin calculations (GFR based on levels of creatinine and cystatin [GFRcr cystatin] and GFR based on levels of cystatin [GFRcystatin])—were associated with hemodynamic parameters and markers of vascular structure (intima-media thickness [IMT] and presence of atheromatous plaques in carotid and femoral arteries). ResultsLevels of GFRepi, GFRcr cystatin, and GFRcystatin exhibited a significant negative correlation with femoral artery IMT, whereas levels of GFRepi correlated significantly with mean carotid bulb (CB) IMT. Multivariate analysis showed that CB-IMT was predicted by GFRepi levels and age (&bgr;-coefficient = −0.212, P = 0.020), whereas femoral artery IMT was predicted by GFRepi levels (&bgr;-coefficient = −0.293, P = 0.001). GFRepi levels lower than the 25th percentile were associated with higher CB-IMT (P = 0.009), femoral artery IMT (P = 0.001), and combined IMT (P = 0.035) compared with higher GFRepi levels. Moreover, GFRepi levels greater than the 25th percentile were associated with lower odds for the presence of atherosclerotic plaques at the CB and carotid arteries combined (CB: odds ratio, 0.146; P = 0.006; combined: odds ratio, 0.249; P = 0.043) compared with lower GFRepi levels. ConclusionsA mild decrease in renal function within normal limits of GFR is independently associated with the presence of subclinical atherosclerosis in a sample of apparently healthy young postmenopausal women. Assessment of GFR using creatinine (vs cystatin C) levels is a more sensitive marker of its association with IMT and atherosclerotic plaques in this postmenopausal population.

MTHFR C677T polymorphism modifies the effect of HRT on metabolic parameters in postmenopausal women

Abstract Objective To assess the interaction of the MTHFR C677T polymorphism with changes in lipid and glucose metabolism effected by oral hormone replacement therapy (HRT) in postmenopausal women. Methods In this open-label, prospective, interventional study, parameters of lipid and glucose metabolism, as well as homocysteine, were assessed in 97 postmenopausal women at baseline and 1 year after the initiation of HRT. Participants were stratified into three subgroups, according to the MTHFR C677T polymorphism (wild-type: CC genotype; heterozygous: CT genotype; homozygous for the mutant variable: TT genotype). Results The TT genotype was associated with an elevation of total and low density lipoprotein (LDL) cholesterol, while CT and CC genotypes were associated with a reduction of total cholesterol and LDL cholesterol after 1 year of HRT (p = 0.032 for total cholesterol and p = 0.002 for LDL cholesterol). Women with the TT genotype had higher glucose levels in contrast to women with the CC genotype who had lower glucose levels after 1 year of HRT (p = 0.011). Additionally, CC carriers under HRT had a significant elevation of apolipoprotein A1 levels (p = 0.018), contrarily to CT and TT genotypes. Conclusion While HRT was associated with favorable changes in lipid and metabolic parameters in carriers of the CC genotype, this effect was not evident in carriers of the T allele. The MTHFR C677T polymorphism may modify the effect of HRT on lipid and metabolic parameters in postmenopausal women.

Re: Alan J. Wolfe, Linda Brubaker. “Sterile Urine” and the Presence of Bacteria. Eur Urol 2015;68:173–4

We read with great interest the article by Wolfe and Brubaker [1] and their conclusion that the sterile urine paradigm is no longer valid. As highlighted by the authors, newer techniques involving DNA sequence-based analyses can identify bacteria in cases in which traditional culturing methods are not efficient. However, is this really the case? First, to question the dogma that normal urine is sterile, one should be sure that the specimens collected are not contaminated. According to Wolfe and Brubaker [1], urine collection for bacteria detection in several studies—including their own—consisted of suprapubic aspiration or transurethral catheterization to avoid contamination and produce safe results. Moreover, the authors state that transurethral samples are similar to suprapubic samples, bypassing any source of contamination. However, the hypothesis that contamination of the catheter tip while it is being inserted is a possible means by which bacteria gain access to the bladder has been confirmed [2]. Kaye et al [3] noted that even a single bladder catheterization could initiate a urinary tract infection, as insertion of a catheter through the urethra is likely to introduce pathogens from the anterior urethra into the bladder. In this way, bacteria find a suitable culture environment once they reach the bladder. As a result, sensitive detection protocols such as ribosomal RNA gene analysis could easily produce false positive results for bladder colonization. In a previous study we collected urethral swabs and urine specimens for polymerase chain reaction (PCR) analysis [4]. PCR on urethral specimens yielded positive results in 98.3% of symptomatic males with Chlamydia trachomatis infection, which was higher than the 93.1% positivity for simple urine samples. Tosif et al [5] also found that contamination rates were much higher for clean-catch urine specimens than for samples obtained via transurethral and

Matrix metalloproteinase-3 gene promoter polymorphisms: A potential risk factor for pelvic organ prolapse.

Pelvic organ prolapse (POP) is a common multifactorial condition. Matrix metalloproteinases (MMPs) are enzymes capable of breaking down various connective tissue elements. Single-nucleotide polymorphisms (SNPs) in regulatory areas of MMP-encoding genes can alter their transcription rate, and therefore the possible effect on pelvic floor supporting structures. The insertion of an adenine (A) base in the promoter of the MMP-3 gene at position −1612/−1617 produces a sequence of six adenines (6A), whereas the other allele has five (5A). The aim of the present study was to investigate the possible association of MMP-3 gene promoter SNPs with the risk of POP. The patient group comprised 80 women with clinically significant POP [Stage II, III or IV; POP quantification (POP-Q) system]. The control group consisted of 80 females without any or important pelvic floor support defects (Stages 0 or I; POP-Q system). All the participants underwent the same preoperative evaluation. SNP detection was determined with whole blood sample DNA analysis by quantitative polymerase chain reaction (PCR) in LightCycler® PCR platforms, using the technique of sequence-specific hybridization probe-binding assays and melting temperature curve analysis. The results showed there was no statistically significant difference between 5A/5A, 5A/6A and 6A/6A MMP-3 gene promoter variants in the two study groups (P=0.4758). Therefore, MMP-3 gene promoter SNPs alone is insufficient to increase the genetic susceptibility to POP development.