Demetrios Rizos

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.

Placental growth factor and soluble fms-like tyrosine kinase-1 are useful markers for the prediction of preeclampsia but not for small for gestational age neonates: a longitudinal study

OBJECTIVE To determine maternal serum concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) longitudinally in normal pregnancies, pregnancies that developed preeclampsia and pregnancies that deliver a small for gestational age (SGA) infant, in order to evaluate them as markers for the prediction of preeclampsia. STUDY DESIGN In this case-control study we included 12 singleton pregnancies that developed preeclampsia and 104 randomly selected singleton normal pregnancies. Fourteen of the normal pregnancies gave birth to an SGA infant. Blood samples and ultrasonographic data were collected during the 1st, 2nd and 3rd trimesters of pregnancy. RESULTS In preeclamptic pregnancies, PlGF (pg/mL) (median; inter-quartile range) was significantly lower in the 2nd (208; 84-339) (p=0.035) and in the 3rd trimester (202; 109-284) (p=0.002) while sFlt-1 was significantly higher only in the 3rd trimester (2521; 2101-3041) (p=0.011) compared to normal pregnancies (PlGF 2nd: 311; 243-440, PlGF 3rd: 780; 472-1037, sFlt-1 3rd: 1616; 1186-2220). In pregnancies with SGA infants, PlGF and sFlt-1 did not differ significantly from normal pregnancies in any trimester. The sFlt-1 to PlGF ratio was significantly higher in preeclamptic pregnancies than in normal pregnancies, in both the 2nd and 3rd trimesters. The relative difference and the slope of PlGF concentration between 1st and 2nd trimester were significantly reduced in preeclampsia compared to normal pregnancies. A logistic regression model with predictors BMI, 2nd trimester Doppler PI and relative difference of PlGF from the 1st to the 2nd trimester gave 46% sensitivity and 99% specificity for the prediction of preeclampsia, with a very high negative predictive value of 98.3%. CONCLUSIONS Our study confirms that maternal serum PlGF concentration is significantly lower, at least after 20th week, while sFlt-1 concentration is significantly higher in 3rd trimester, in pregnancies destined to develop preeclampsia. Pregnancies that gave birth to SGA infants do not have altered angiogenic factor concentrations throughout pregnancy. The relative difference of PlGF from the 1st to the 2nd trimester, uterine artery Doppler PI in the 2nd trimester and BMI are the most powerful markers for the prediction of preeclampsia.

Endogenous sex steroids and bone mineral density in healthy Greek postmenopausal women

The aim of this study was to assess the association of endogenous sex steroids with bone mineral density (BMD) in healthy postmenopausal women not on hormone therapy. A total of 884 postmenopausal women aged 42–71 years were studied in a cross-sectional design. Parameters assessed were follicle-stimulating hormone, luteinizing hormone, estradiol, total testosterone, sex hormone-binding globulin, free estrogen index (FEI), free androgen index (FAI), Δ4-androstendione (Δ4A), dehydroepiandrosterone sulfate (DHEAS), bone alkaline posphatase, and bone mineral density at the lumbar spine (L-BMD) and femoral neck (N-BMD). Estradiol and FEI associated positively with both L-BMD and N-BMD (r = 0.21–0.47, P < 0.01). These associations remained significant after adjustment for age, years since menopause, and body mass index. FAI correlated positively with both L-BMD and N-BMD (r = 0.18 and 0.33, respectively; P < 0.01). At the multivariate analysis, however, FAI remained the significant determinant only for N-BMD. Δ4A associated positively with N-BMD (r = 0.27, P = 0.001), whereas DHEAS showed no association with BMD at either site. Thus, endogenous steroids are significant determinants of postmenopausal BMD. Endogenous estradiol may be more important for lumbar spine BMD, whereas endogenous androgens are associated mainly with femoral neck BMD.

Arterial stiffness is increased in asymptomatic nondiabetic postmenopausal women with a polycystic ovary syndrome phenotype.

Objective: The metabolic dysfunction accompanying the polycystic ovary syndrome (PCOS) may increase the risk of hypertension and cardiovascular disease (CVD). Although menopause per se may be an additional risk factor of CVD, the association between PCOS in postmenopausal women and cardiovascular risk has not been adequately investigated. We aimed to evaluate the effect of PCOS on markers of subclinical atherosclerosis in nondiabetic postmenopausal women. Methods: This cross-sectional study included 286 postmenopausal women with intact ovaries. PCOS phenotype was defined if three of the following were present: insulin resistance, current hyperandrogenism or history of clinical androgen excess, history of infertility, central obesity and history of irregular menses. Traditional CVD risk factors, as well as indices of arterial structure (intima–media thickness, atheromatous plaques presence) and function [flow-mediated dilation, pulse wave velocity (PWV), augmentation index] were compared between women with a PCOS phenotype and the rest of the sample, who served as controls. Results: Women with the PCOS phenotype (N = 43) had higher SBP and triglycerides and lower high-density lipoprotein (HDL)-cholesterol than controls. Mean values of PWV differed significantly between PCOS cases and controls (9.46 ± 1.74 vs. 8.60 ± 1.51 m/s, P = 0.001, univariate). Multivariate regression analysis showed that the PCOS phenotype, age and SBP were the only independent predictors of PWV. Conclusion: Arterial stiffness is increased in asymptomatic, nondiabetic women with a putative PCOS phenotype, independently of age, BMI or blood pressure. This might present one mechanism through which PCOS increases the risk of CVD and hypertension later in life.

Levels of asymmetric dimethylarginine throughout normal pregnancy and in pregnancies complicated with preeclampsia or had a small for gestational age baby

Objective: The aim of this study was to investigate maternal asymmetric dimethylarginine (ADMA) concentrations at the three trimesters of pregnancy in uncomplicated pregnancies and in women who developed preeclampsia or had small for gestational age infants (SGA) without preeclampsia. Methods: ADMA concentrations were retrospectively determined in the first, second and third trimester of pregnancy in 41 uncomplicated pregnancies, 10 pregnancies complicated with preeclampsia and 14 pregnancies that delivered a SGA baby. ADMA was measured with an ELISA kit. Results: Mean (±SD) concentrations of ADMA (µmol/L) in uncomplicated l pregnancies were: 0.51 ± 0.14; 0.52 ± 0.13; 0.58 ± 0.16 in the three trimesters, respectively. ADMA concentrations in SGA pregnancies were significantly lower in each trimester compared to uncomplicated pregnancies: (0.40 ± 0.10, p = 0.005 1st trim; 0.42 ± 0.10, p = 0.007 2nd trim; 0.45 ± 0.10, p = 0.007 3rd trim). Although pregnancies that developed preeclampsia had higher ADMA concentration in all trimesters compared to uncomplicated pregnancies (0.58 ± 0.10; 0.63 ± 0.14; 0.68 ± 0.11), the difference was statistically significant only in the 2nd trimester (p = 0.02). Conclusions: Maternal serum ADMA concentration tends to increase during normal pregnancy. Pregnancies with SGA infants had significantly lower ADMA levels in all trimesters of pregnancy. ADMA concentrations in the 2nd trimester was significantly elevated in pregnancies that later developed preeclampsia.

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.

Thyroid function and postpartum mood disturbances in Greek women

BACKGROUND Postpartum mood disturbances are very common with postpartum blues being as high as 44.5% among Greek women. This study aimed to investigate whether thyroid function within the normal range affects the incidence of postpartum mood disturbances. METHODS In a cross-sectional study in the maternity ward of Aretaieion Hospital, 57 Greek women were evaluated for postpartum mood swings by the Maternity Blues Questionnaire and the Edinburgh Postnatal Depression Scale on the first and sixth week postpartum. Serum Free T4, Free T3 and TSH concentrations as well as thyroglobulin and thyroid peroxidase antibodies were measured on admission for delivery and daily until the fourth postpartum day. We examined the association between hormone and antibody levels, and scores in the two scales evaluating postpartum mood disturbances. RESULTS Prepartum serum FT3 and FT4 correlated negatively with blues scores in the first week postpartum (blues on day 4: with FT3, rho=-0.44, p < or = 0.01; with FT4 rho=-0.36, p < or = 0.01). Women with lower FT3 and FT4 levels belonged to the high scoring group (high scoring group: FT3=1.22 pg/ml, FT4=0.66 ng/dl; low scoring group: FT3=1.64 pg/ml, FT4=0.73 ng/dl). Serum FT3 showed a negative independent correlation with postpartum blues scores in the first postpartum days. No association was found between thyroid antibody levels and mood scores. CONCLUSION Our findings indicate an association between the occurrence of postpartum mood disorders and antenatal thyroid function. Within normal limits, lower levels of serum FT3 and FT4 are associated with increased incidence of mood disturbances in the first postpartum week.

The significance of Chlamydia pneumoniae in symptomatic carotid stenosis

An association between symptomatic carotid stenosis and recent infection with Chlamydia pneumoniae is reported. Thirty-five patients (20 symptomatic and 15 asymptomatic) with carotid stenosis of 70% to 90% underwent carotid endarterectomy. Endarterectomy was performed without patch and shunt; the average occlusion time of the internal carotid artery was 14 ±3 min. The atheromatic plaque and a portion of the thyroid artery were examined with polymerase chain reaction and peripheral vein blood was obtained for serologic detection of systematic infection, and IgG and IgM antibodies to C. pneumoniae by enzyme-linked immunosorbent assay. Twenty of 35 patients (57.1 %) had increased titers of IgG antibodies to C, pneumoniae. Eight patients revealed IgG plus IgM antibodies; two of the eight had IgG, IgM, and positive findings on polymerase chain reaction. No C pneumoniae was detected on the thyroid arteries. Sixty-five percent (13/20) of the patients with increased IgG antibodies to C. pneumoniae, 87.5% (7/8) with IgG + IgM, and 100% with IgG + IgM + positive polymerase chain reaction were symptomatic. Plaque morphology in association with symptoms did not reveal a significant correlation between soft plaques and symptoms, whereas the majority of the symptomatic patients had plaques of type III-V. Patients having recent contamination and positive poly merase chain reaction had a significant relationship between C. pneumoniae infection and symptomatic carotid disease. This supports the hypothesis that C. pneumoniae infection can produce a kind of instability of the carotid plaque. The results of this study demonstrate that patients with advanced atherosclerotic carotid disease have an increased incidence of C. pneu moniae infection. Recent infection could be responsible for instability of the carotid plaque, causing cerebral ischemic episodes.

Vitamin D receptor Bsm1 polymorphism, calcium metabolism and bone mineral density in patients with multiple sclerosis: a pilot study

Vitamin D receptor’s (VDR) genotypes have been associated both with the development of bone disease and the pathogenesis of multiple sclerosis (MS). We aimed to evaluate the association between the presence of Bsm1 restriction fragment length polymorphism of VDR and bone loss in ambulatory patients with MS. This cross-sectional study included 82 adult patients with relapsing-remitting MS. Fasting blood samples were obtained for biochemical–hormonal assessment and genotyping. Bone mineral density (BMD) was assessed at the lumbar spine (LS) and the femoral neck (FN), using dual energy X-ray absorptiometry. Possible associations between VDR’s genotypes and BMD levels as well as biochemical and hormonal indices were evaluated. Among premenopausal women and men, carriers of the B allele exhibited higher BMD and Z score at the FN and a trend toward higher BMD at the LS, compared to patients with the bb genotype, after adjusting for age, BMI, sex, EDSS scoring, interferon administration, duration of MS and total steroids intake. Among postmenopausal women, the presence of the B allele was not associated with BMD or T score at any site, whereas carriers of the B allele exhibited higher levels of calcium (p value 0.008, univariate). No other significant differences were exhibited between levels of electrolytes, parathormone, 25-hydroxyvitamin D3 and the genotype of VDR, in any of the groups. VDR’s Bsm1 polymorphism is associated with a mild effect on BMD in younger patients with MS. Larger studies are necessary to corroborate these findings.

Reproductive hormones and postpartum mood disturbances in Greek women.

Aim. Postpartum mood disturbances are common among Greek women, with postpartum depression (PPD) being as high as 19%. This study aimed to investigate whether sex steroid hormone levels affect the incidence of postpartum mood disturbances. Materials and methods. Fifty-seven women were evaluated for postpartum mood disturbances using the Postpartum Blues Questionnaire and the Edinburgh Postnatal Depression Scale on the 1st and 6th week. Serum estradiol, progesterone and testosterone concentrations were measured upon admission for delivery and daily until the fourth postpartum day. We then studied the association between hormone levels and the scores in the two psychometric scales. Results. Testosterone was the only hormone that was marginally associated with psychometric scoring in simple regression analysis. (Postpartum Blues during days 1–4: b = 4.291, 95% C.I. −0.796 to 9.377 and p-value = 0.096). Women with lower testosterone drops had higher scores in Postpartum Blues Questionnaire. This association, however, lost statistical significance in the multivariable analysis after adjusting for pregnancy duration. In multiple regression analysis, only pregnancy duration had the most constant adverse effect on psychometric scores: The shorter the duration of pregnancy, the higher the scores for Postpartum Blues. (r = −0.39, p < 0.01). Conclusions. Our findings do not indicate an association between the occurrence of postpartum mood disorders and sex steroid hormone levels. Preterm labour may be associated with a higher risk of postpartum mood disturbances.