Association of the A1330V and V667M polymorphisms of LRP5 with bone mineral density in Greek peri- and postmenopausal women

Wnt signaling through low-density lipoprotein receptor-related protein 5 (LRP5) is an important determinant of bone mass regulation.

Objective

To explore the influence of two LRP5 single nucleotide polymorphisms (SNPs) A1330V and V667M on bone mineral density (BMD) and serum levels of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL) and bone metabolic markers in a Greek female population.

Study design

Two hundred and nine postmenopausal and twelve perimenopausal women aged 40–63 years were enrolled. All participants underwent spinal BMD evaluation. Genotyping of A1330V and V667M polymorphisms was performed by real-time polymerase chain reaction. Levels of OPG, soluble RANKL (sRANKL) and bone metabolic markers were measured.

Results

As regards A1330V SNP, women carrying CT/TT genotypes had lower spinal BMD than women with CC (p < 0.0001). Regarding V667M SNP, spinal BMD was lower in women with GA/AA than in women with GG genotypes (p < 0.0001). These differences remained significant after adjustment for age, years since menopause and body mass index. The A1330V and V667M polymorphisms were in strong linkage disequilibrium. A significant interaction between A1330V and V667M SNPs on spinal BMD was revealed. The haplotype with both risk alleles of the two SNPs (AT) conferred more risk for low BMD than the haplotypes with one risk allele (GT or AC) or the haplotype-reference (GC) (p = 0.046, p = 0.045, and p = 0.010, respectively). No effect was observed on circulating OPG, sRANKL levels and bone metabolic markers.

Conclusions

These findings demonstrate that the A1330V and V667M polymorphisms are associated with low BMD in peri- and postmenopausal Greek women.     

DNA repair gene ERCC2 polymorphisms and risk of squamous cell carcinoma of the head and neck

Introduction

Genetic aberrations of DNA repair enzymes are known to be common events and to be associated with different cancer entities. Aim of the following study was to analyze the genetic association of single nucleotide polymorphisms (SNP) of the DNA repair genes with the risk of squamous cell carcinoma of the head and neck (HNSCC).

Materials and methods

Genetic variants ERCC2 Lys751Gln (rs13181), ERCC2 Asp312Asn (rs1799793), XRCC1 Arg194Trp (rs1799782); XRCC1 Gln399Arg (rs25487), XRCC1 Arg280His (rs25489) and XRCC3 Thr241Met (rs861539) were analyzed in a primary study group comprising 169 patients with histologically confirmed HNSCC and 463 healthy control subjects. Polymorphisms associated with HNSCC were furthermore analyzed in an independent replication study including 125 HNSCC.

Results

Only the ERCC2 751 Gln/Gln genotype was associated with HNSCC in the primary study (p = 0.033) and in the replication study (p = 0.023), resulting in an overall odds ratio of 0.54 (95% confidence interval 0.35–0.92; p = 0.006).

Conclusion

Carriers of the homozygous ERCC2 751 Gln/Gln genotype may be at lower risk for HNSCC.     

Testosterone, SHBG and differential white blood cell count in middle-aged and older men

Objective

Low-grade chronic inflammation is increasingly being implicated in cardiovascular disease (CVD) etiology and may represent an alternative pathway through which testosterone and sex hormone-binding globulin (SHBG) influence CVD risk. We examined the associations between endogenous testosterone, SHBG and total and differential white blood cell (WBC) counts in men.

Methods

Cross-sectional study of 2418 men aged 40–78 years from the Norfolk population of European Prospective Investigation into Cancer (EPIC-Norfolk) who had no history of CVD or cancer and complete data on sex hormones (total testosterone (TT), SHBG and free testosterone (FT)) and WBC counts. Associations between sex hormones and WBC counts were assessed using linear regression models.

Results

Higher SHBG and TT levels were associated with lower WBC counts. After adjustment for age, BMI, smoking, physical activity and diabetes status, total WBC count decreased by 0.163 (95% CI −0.236; −0.091) and 0.102 (−0.170; −0.034) per standard deviation (SD) increase in SHBG and TT respectively. Associations of SHBG and TT with total WBC count were mainly accounted for by a lower granulocyte count (β coefficient = −0.132 (−0.194; −0.070) per SD increase in SHBG and β coefficient = −0.104 (−0.161; −0.046) per SD increase in TT). No associations between FT and total and differential WBC counts were found.

Conclusions

Endogenous TT and SHBG levels are inversely associated with total WBC and granulocyte count in middle-aged and older men. Even though the underlying mechanism and causal directionality requires further exploration, these results support a link between hormonal status and low-grade inflammation.     

A J-shaped association between plasma testosterone and risk of ischemic arterial event in elderly men: The French 3C cohort study

Objectives

Low plasma testosterone is associated with increased mortality in men. However, the relation between testosterone and cardiovascular disease is uncertain. We assessed the association of plasma sex hormones with the incidence of ischemic arterial disease (IAD) in elderly men.

Methods

We used data from the French Three-City prospective cohort study (3650 men aged >65 years). A case-cohort design was set up including a random sample of 495 men and 146 incident cases of first IAD event (112 coronary heart disease (CHD) and 34 strokes) after a 4-year follow-up. Plasma total and bioavailable testosterone, total estradiol and sex hormone-binding globulin (SHBG) were measured at baseline. Multivariate hazard ratios (HRs) and 95% confidence intervals for IAD were assessed using Cox model.

Results

After adjustment for cardiovascular risk factors, a J-shaped association between plasma total testosterone and IAD risk was found (p < 0.01). The HRs associated with the lowest and the highest total testosterone quintiles relative to the second quintile were 2.23 (95% CI: 1.02; 4.88) and 3.61 (95% CI: 1.55; 8.45) respectively. Additional analysis for CHD showed similar results (HR: 3.11, 95% CI: 1.27; 7.63 and HR: 4.75, 95% CI: 1.75; 12.92, respectively). Similar J-shaped association was observed between bioavailable testosterone and IAD risk (p = 0.01). No significant association of estradiol and SHBG with IAD was found.

Conclusion

High and low plasma testosterone levels are associated with an increased risk of IAD in elderly men. Optimal range of plasma testosterone may confer cardiovascular protection and these results may have clinical implications in the management of testosterone deficiency.     

Association between CDH13 Variants and Cardiometabolic and Vascular Phenotypes in a Korean Population

Purpose

Although some CDH13 single nucleotide polymorphisms (SNPs) have been shown to be determinants of blood adiponectin levels, the clinical implications of CDH13 variants are not yet completely understood. The purpose of this study was to evaluate the effects of SNPs of CDH13 on metabolic and vascular phenotypes.

Materials and Methods

We included 238 hypertensive subjects and 260 age- and sex-matched controls. Seven tagging-SNPs were identified in the CDH13 gene by whole gene sequencing. The association between these SNP variants and the risk of hypertension, metabolic traits, and carotid intima-media thickness (IMT) was examined.

Results

Minor allele carriers of rs12444338 had a lower risk of hypertension, but the association turned out just marginal after adjusting confoudners. Blood glucose levels were higher in the minor allele carriers of c.1407C>T (p=0.01), whereas low-density lipoprotein-cholesterol levels were greater in those of rs6565105 (p=0.02). The minor allele of rs1048612 was associated with a higher body mass index (p=0.01). In addition, the mean carotid IMT was significantly associated with rs12444338 (p=0.02) and rs1048612 (p=0.02).

Conclusion

These results provide evidence that CDH13 variants are associated with metabolic traits and carotid atherosclerosis in Koreans. This study shows the multifaceted effects of CDH13 variants on cardiometabolic risk.     

Hormone therapy and coronary heart disease risk by vasomotor menopausal symptoms

Objectives

We examined whether the association between hormone therapy (HT) use and coronary heart disease (CHD) risk differed between women with and without vasomotor symptoms (VMS).

Study design

We used data from a Dutch (EPOS) and Swedish (WHILA) population-based sample of 8865 women, aged 46–64 years, and free of CHD, stroke, venous thrombosis/pulmonary embolism or cancer at baseline. Data on HT use, VMS and potential confounders were collected by questionnaires.

Main outcome measures

CHD endpoints, obtained via registries.

Results

252 CHD cases occurred during 10.3 years of follow-up. Neither for women with nor for women without flushing or (night) sweats ever HT use was associated with CHD risk, compared with never HT use. Among women with intense VMS, ever HT use borderline significantly decreased CHD risk compared with never HT use (HR 0.48 [95% CI 0.20–1.03]). Among women without intense VMS, ever HT use was associated with a borderline significant increased CHD risk (HR 1.28 [95% CI 0.96–1.70]; P for interaction = 0.02). However, after multivariate adjustment, as compared to never HT use, ever HT use was not associated with risk of CHD among women with or without intense VMS.

Conclusions

In both groups of women with and without VMS, HT use does not seem to be associated with the risk of CHD. Hence, our findings do not support the view that HT use increases the CHD risk among women with an indication, i.e. VMS, but this needs to be confirmed in specifically designed studies.     

Risk factor reduction in progression of angiographic coronary artery disease

Introduction

To investigate differences between outpatients with progressive and nonprogressive coronary artery disease (CAD) measured by coronary angiography.

Material and methods

Chart reviews were performed in patients in an outpatient cardiology practice having ≥ 2 coronary angiographies ≥ 1 year apart. Progressive CAD was defined as 1) new non-obstructive or obstructive CAD in a previously disease-free vessel; or 2) new obstruction in a previously non-obstructive vessel. Coronary risk factors, comorbidities, cardiovascular events, medication use, serum low-density lipoprotein cholesterol (LDL-C), and blood pressure were used for analysis.

Results

The study included 183 patients, mean age 71 years. Mean follow-up duration was 11 years. Mean follow-up between coronary angiographies was 58 months. Of 183 patients, 108 (59%) had progressive CAD, and 75 (41%) had nonprogressive CAD. The use of statins, β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and aspirin was not significantly different in patient with progressive CAD or nonprogressive CAD Mean arterial pressure was higher in patients with progressive CAD than in patients with nonprogressive CAD (97±13 mm Hg vs. 92±12 mm Hg) (p<0.05). Serum LDL-C was insignificantly higher in patients with progressive CAD (94±40 mg/dl) than in patients with nonprogressive CAD (81±34 mg/dl) (p=0.09).

Conclusions

Our data suggest that in addition to using appropriate medical therapy, control of blood pressure and serum LDL-C level may reduce progression of CAD.     

Serum p-cresyl sulfate predicts cardiovascular disease and mortality in elderly hemodialysis patients

Introduction

Previous studies have shown that serum p-cresyl sulfate (PCS) and indoxyl sulfate (IS) were significantly related to clinical outcomes in patients on hemodialysis (HD). However, evidence for the relationship in elderly HD patients remains scarce. We explore whether the two toxins can predict clinical outcomes in elderly HD patients.

Material and methods

Fifty stable HD patients more than 65 years old were enrolled from a single medical center. Serum total and free PCS, IS levels and biochemistry were measured concurrently. The clinical outcomes including cardiovascular events and all-cause mortality were analyzed after 38-month follow-up.

Results

Univariate Cox proportional hazard ratio analysis revealed that cardiovascular events were associated with gender (p = 0.02), diabetes (p < 0.01), calcium (p = 0.01), total PCS (p < 0.01), free PCS (p < 0.01) and total IS (p = 0.05). Multivariate analysis showed that diabetes (p = 0.01), total PCS (p = 0.01) and free PCS (p = 0.04) were related to cardiovascular events. For all-cause mortality, only total PCS (p = 0.01) reached significance after adjusting other confounding factors. However, Kaplan-Meier analysis indicated that free PCS (p = 0.02) and total PCS (p < 0.01) were significantly associated with cardiovascular events and total PCS (p = 0.048) was related to all-cause mortality during 38-month follow-up.

Conclusions

Our results indicate that total PCS is a valuable marker in predicting cardiovascular event and all-cause mortality in elderly HD patients.     

IL10 polymorphisms associated with Behçet’s disease in Chinese Han

Objective

IL-10 is a potent anti-inflammatory cytokine that plays important roles in the pathogenesis of Behçet’s disease (BD). Two genome-wide association studies have identified IL10 as a potential risk factor for BD. Here, we investigated the association between IL10 polymorphisms and BD in Chinese Han.

Methods

407 BD patients and 679 healthy controls were enrolled, and genotyped by Sequenom MassArray system (Sequenom iPLEX assay, San Diego, CA).

Results

The frequency of risk allele of rs1800871 was notably higher in BD patients than in controls (71.9% vs. 66.2%, OR: 1.30, 95%CI: 1.08–1.58, p_c = 0.024). Similarly, rs1518111, which showed strong linkage disequilibrium (r² = 1) with allele rs1800871, was also associated with BD (p_c = 0.026). Rs3021094 was in association with BD in a dominant model (p_c = 0.035), and the haplotype (GACC) formed by rs1518111, rs3021094, rs3790622, and rs1800871 was associated with BD (p_c = 0.023). Results obtained from meta-analysis combined with our data showed that rs1800871 and rs1518111 were associated with BD.

Conclusion

IL10 may be the susceptibility gene for BD in Chinese Han population.     

Psychological factors and subclinical atherosclerosis in postmenopausal Chinese women in Hong Kong

Background

Substantial evidence shows that psychological factors are associated with cardiovascular diseases. However, data on the association between psychological factors and subclinical atherosclerosis is lacking in postmenopausal Chinese women.

Objectives

To examine the associations of perceived stress and trait anxiety with subclinical atherosclerosis in postmenopausal Chinese women in Hong Kong. Their relationships with biological and behavioral risk factors were also examined.

Methods

Between 2002 and 2004, we recruited 518 postmenopausal women aged 50–64 years. Perceived stress and trait anxiety were evaluated by the perceived stress scale and the state-trait anxiety inventory, respectively. Subclinical atherosclerosis was determined by measuring carotid intima-media thickness (IMT) and plaque using B-mode ultrasonography.

Results

Perceived stress and trait anxiety showed no significant association with IMT or plaque. Multivariate analyses showed high perceived stress scores were associated with an increased risk of elevated total cholesterol (OR = 2.10; 95% CI = 1.17–3.77) and elevated low-density lipoprotein cholesterol (LDL-C) (OR = 2.39; 95% CI = 1.36–4.21). High trait anxiety scores were associated with a 2.7-fold risk of elevated LDL-C (OR = 2.74; 95% CI = 1.56–4.80). Women with high perceived stress or trait anxiety scores were more likely to be physically inactive.

Conclusions

Perceived stress and trait anxiety were associated with atherogenic lipid levels, but not subclinical atherosclerosis. Maintaining high physical activity may help alleviate psychological stress and anxiety.     

Wellness in community living adults: the Weigh to Life program

Objective

To examine physiological and health-related quality of life (HRQOL) outcomes in community living adults attending a 12-week combined lifestyle wellness program.

Methods

A sample of overweight and obese adults (n = 319) and a subgroup who also had diabetes (n = 46 of 319) were studied. The program focuses on dietary, physical activity, and behavioral strategies to promote cardiovascular health. Baseline and 12-week measures were obtained.

Results

In the total sample, all physiological and HRQOL outcomes improved (p < .05), except HDL. High attendance was associated with the highest weight loss. In the diabetic subgroup, weight, steps/day, low density lipoprotein, and most aspects of HRQOL improved significantly.

Conclusion

Physiological and HRQOL benefits can be gained from a 12-week combined lifestyle program; greater benefits were obtained with higher attendance. Although the diabetic subgroup was not large, positive outcomes were realized.

Practice implications

The 12-week combined lifestyle program shows promise for improving outcomes in community living overweight and obese adults who may also be diabetic. By attending class, participants are reminded about strategies they are to apply during the 12-week program and, by program end, they are equipped with a tool kit of strategies for use in everyday life.     

Do cognitive perceptions influence CPAP use?

Objective

Nonadherence to CPAP increases health and functional risks of obstructive sleep apnea. The study purpose was to examine if disease and treatment cognitive perceptions influence short-term CPAP use.

Methods

A prospective longitudinal study included 66, middle-aged (56.7 ± 10.7 yr) subjects (34 [51.5%] Caucasians; 30 [45.4%] African Americans) with severe OSA (AHI 43.5 events/hr ± 24.6). Following full-night diagnostic/CPAP polysomnograms, home CPAP use was objectively measured at 1 week and 1 month. The Self Efficacy Measure for Sleep Apnea (SEMSA) questionnaire, measuring risk perception, outcome expectancies, and self-efficacy, was collected at baseline, post-CPAP education, and after 1 week CPAP treatment. Regression models were used.

Results

CPAP use at one week was 3.99 ± 2.48 h/night and 3.06 ± 2.43 h/night at one month. No baseline SEMSA domains influenced CPAP use. Post-education self-efficacy influenced one week CPAP use (1.52 ± 0.53, p = 0.007). Self-efficacy measured post-education and after one week CPAP use also influenced one month CPAP (1.40 ± 0.52, p = 0.009; 1.20 ± 0.50, p = 0.02, respectively).

Conclusion

Cognitive perceptions influence CPAP use, but only within the context of knowledge of CPAP treatment and treatment use.

Practice implications

Patient education is important to OSA patients’ formulation of accurate and realistic disease and treatment perceptions which influence CPAP adherence.     

Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age

Background: The risk of intrauterine cytomegalovirus (CMV) infection and disease in the fetus or newborn largely depends on time of primary maternal infection during pregnancy.

Objectives

Prospective cohort study of pregnancy outcome in relation to gestational age at primary maternal CMV infection.

Study design

In a total of 248 pregnancies with primary infection the onset of infection was determined by IgG seroconversion, IgG avidity and/or onset of clinical symptoms. Congenital infection was diagnosed by CMV detection in amniotic fluid, fetal tissue or urine of the neonate in the first 2 weeks of life. Clinical symptoms were retrieved from ultrasound and medical records.

Results

The intrauterine transmission rates following primary CMV infection in the pre- and periconceptional period were 16.7% (4/24) and 34.5% (10/29), respectively. For the first, second and third trimester of pregnancy transmission rates were 30.1% (25/83), 38.2% (29/76) and 72.2% (26/36), respectively. The rate of symptomatically infected fetuses or newborns at birth was 22.8% for any symptoms and 10.3% for severe manifestations. No symptoms were observed in infected newborns of mothers with primary infection in the preconceptional period and in the third trimester.

Conclusions

The risk of intrauterine transmission following primary maternal infection in the third trimester is high, but the risk of neonatal disease is low. The highest risk of severe symptoms in the fetus and newborn exists around conception and in the first trimester of pregnancy.     

Triptolide inhibits rat vascular smooth muscle cell proliferation and cell cycle progression via attenuation of ERK1/2 and Rb phosphorylation

Background

Drug-eluting stents have demonstrated a substantial reduction of restenosis and currently are gaining a leading position in the intervention field. Triptolide, a purified extract from Chinese herb medicine Tripterygium wilfordii hook F, exhibits antiproliferative and pro-apoptotic function in vitro and in vivo. In the present study, we investigated effects of triptolide on in-stent restenosis in vivo and in vitro, and study the biological mechanism of this drug.

Methods

Rat aortic smooth muscle cells were cultured and treated with different concentration of triptolide (0, 1, 10, and 50 nM). For cell viability, we used trypan blue exclusion (TBE) survival assay. Flow cytometry was used to study the influence of triptolide on VSMCs cell cycle. Signal proteins were detected by western blotting analysis. Triptolide coated stents had been implanted in the iliac arteries of New Zealand rabbits. After 4 weeks, the stented iliac artery segments were processed for embedding, staining and histomorphometric analysis.

Results

Triptolide of concentration 10 nM, 50 nM significantly inhibited fetal calf serum-induced VSMC proliferation (p < 0.05). The accumulation of triptolide-treated cells at the G1/S-interphase was dose dependent. Triptolide completely blocked the cell cycle progression at 50 nM. Western blotting analysis showed decreased ERK1/2 MAP kinase phosphorylation level, significantly increased p21^cip1 expression and reduced retinoblastoma protein (pRb) phosphorylation after 24 h of triptolide treatment. 4 weeks after the surgery, the arterial wall morphology was shown that triptolide-coated stent has less neointimal vs bare metal stent.

Conclusions

Our study indicates that triptolide exert inhibitory effect on VSMC proliferation, inactivation of MAPK pathway and modulation of cell cycle proteins p21^cip1 and Rb are relating mechanisms. Triptolide drug-eluting stents attenuated neointimal formation after stent implantation in rabbit vessel. We believe that triptolide may potentially be useful in treating cardiovascular restenosis after PCI.     

High prevalence of HTLV-I infection in Mashhad, Northeast Iran: A population-based seroepidemiology survey

Background

Mashhad, in the northeast of Iran has been suggested as an endemic area for human T cell lymphotropic virus type I (HTLV-I) infection since 1996.

Objectives

We performed a community-based seroepidemiology study to examine the prevalence and risk factors for HTLV-I infection in the city of Mashhad.

Study design

Between May and September 2009, overall 1678 subjects from all the 12 geographical area of Mashhad were selected randomly by multistage cluster sampling for HTLV antibody. The study population included 763 males and 915 females, with the mean age of 29.1 ± 18.5 years. 1654 serum samples were assessed for HTLV antibody using ELISA and reactive samples were confirmed by Western blot and PCR.

Results

The overall prevalence of HTLV-I infection in whole population was 2.12% (95% CI, 1.48–2.93) with no significant difference between males and females (p = 0.093) and the prevalence of HTLV-II seropositivity was 0.12% (95% CI, 0.02–0.44).The HTLV-I Infection was associated with age (p < 0.001), marital status (p < 0.001), education (p = 0.047), and history of blood transfusion (p = 0.009), surgery (p < 0.001), traditional cupping (p = 0.002), and hospitalization (p = 0.004). In logistic regression analysis, age was the only variable that had a significant relation with the infection (p = 0.006, OR = 4.33).

Conclusions

Our results demonstrated that Mashhad still remains an endemic area for HTLV-I infection despite routine blood screening. Thus, further strategies are needed for prevention of the virus transmission in whole population.     

Testosterone improves verbal learning and memory in postmenopausal women: Results from a pilot study

Objective

To explore the effects of testosterone on cognitive performance in healthy postmenopausal women.

Study design

Open-label pilot study. Nine postmenopausal women on non-oral hormone replacement therapy, aged 47–60 years received transdermal testosterone spray for 26 weeks. A control group of 30 women provided normative data for comparison.

Main outcome measures

Scores from a computerized cognitive test battery performed pre- and post treatment, at 0 and 26 weeks.

Results

There were no differences between treatment/normative groups in any parameter at baseline. At week 26 scores for the International Shopping list task including delayed recall (verbal learning and memory) and the continuous paired associate learning task (visual learning and memory) were significantly higher in the treatment group as compared to the normative group (p < 0.05). Significant improvements from baseline were observed for the International Shopping list delayed recall (verbal learning and memory) and Groton Maze recall tasks (visual learning and memory) for the treatment group (both p < 0.05), after 26 weeks. There were no significant differences between baseline and week 26 in the normative group. In the regression analysis which modeled the score at week 26, and which included a bootstrapping approach, the beta coefficient for the treatment group was statistically significant when age and baseline score were taken into account for the International Shopping list task including delayed recall (both p < 0.02).

Conclusion

Testosterone improved cognitive performance in the domain of verbal learning and memory in a pilot study of healthy postmenopausal women and is worthy of further exploration in a randomized placebo controlled study.     

Caregiver rating of provider participatory decision-making style and caregiver and child satisfaction with pediatric asthma visits

Objective

The purpose of this study was to examine the relationship between caregiver ratings of provider use of a participatory decision-making style and caregiver and child satisfaction with their pediatric asthma visits.

Methods

Children ages 8 through 16 with persistent asthma and their caregivers were recruited at five pediatric practices. Children were interviewed and caregivers completed questionnaires after their child's medical visits. Generalized estimating equations were used to analyze the data.

Results

Three hundred and twenty children were recruited. Caregivers were significantly more satisfied with providers who they perceived as using more of a participatory decision-making style (beta = 17.80, p < 0.001). Children (beta = −0.10, p < 0.05) and caregivers (beta = −0.21, p < 0.01) were significantly more satisfied with younger providers. Children were significantly more satisfied with providers who knew them better as a person (beta = 2.87, p < 0.001).

Conclusions

Caregivers were more satisfied with providers who they perceived as involving them more during treatment decisions made during pediatric asthma visits.

Practice implications

Providers should attempt to use a more participatory decision-making style with families during pediatric asthma visits.     

Metabolic syndrome component combinations and chronic kidney disease: The severance cohort study

Objectives

The effects of ethnicity and gender can produce varying results when evaluating risk of chronic kidney disease (CKD) development and metabolic syndrome (MetS) components. The risks of specific MetS component combinations and incident CKD are unclear. The aim of this study was to investigate the relationship between the combination of MetS components and CKD.

Methods

This prospective cohort study included 15,401 participants. Koreans 20–84 years of age were followed for 5.2 years. The NCEP-ATP III definition of MetS was used. CKD was defined as an estimated glomerular filtration rate of <60 ml/min/1.73 m² by the simplified Modification of Diet in Renal Disease equation.

Results

The incidence rate per 1000 person-years of CKD was determined in men (13.8) and women (14.1) with MetS. In a multivariate Cox proportional hazard model controlling for age and lifestyle variables, increased CKD risk in men (hazard ratio 1.45, 95% confidence interval 1.20–1.76) and women (1.52, 1.19–1.93) with Mets was found compared to those without MetS. Incidence and HRs for CKD elevated with increasing numbers of MetS components in men and women (P for trend <0.0001). The risks associated with MetS varied by combination of causative factors. High blood pressure (BP) and low high-density lipoprotein (HDL) were more likely to be associated with risk of CKD development.

Conclusions

BP and HDL were the leading risk factors for CKD development in healthy Koreans. The association between MetS and kidney dysfunction were significantly independent of traditional cardiovascular risk factors.     

The relationship of vitamin D with non-traditional risk factors for cardiovascular disease in subjects with metabolic syndrome

Introduction

Several studies implicate an inverse relationship between 25-hydroxy vitamin D (25(OH)Vit D) serum levels and metabolic syndrome (MetS). We sought to investigate a possible relationship between 25(OH)Vit D and emerging risk factors associated with MetS, such as small dense low-density lipoprotein cholesterol (sdLDL-C) concentration, lipoprotein-associated phospholipase A₂ (Lp-PLA₂) activity and high-sensitivity C-reactive protein (hsCRP) levels.

Material and methods

We studied 110 consecutive otherwise healthy individuals. Of these, 52 were diagnosed with MetS and 58 who did not meet the MetS criteria served as controls. Low-density lipoprotein (LDL) subclass analysis was performed by polyacrylamide gel electrophoresis. Lp-PLA₂ activity was determined in total plasma by the trichloroacetic acid precipitation procedure. Serum 25(OH)Vit D was determined quantitatively by an enzyme immunoassay method.

Results

Metabolic syndrome subjects had significantly lower 25(OH)Vit D levels (11.8 [0.6-48.3] ng/ml; 29.5 [1.5-120.75] nmol/l) compared with controls (17.2 [4.8-62.4] ng/ml; 43 [12-156] nmol/l, p = 0.027). Univariate regression analysis showed that 25(OH)Vit D concentration was inversely related to triglycerides (r= − 0.416, p = 0.003) and sdLDL-C (r= − 0.305, p = 0.004). There was no association of 25(OH)Vit D with waist circumference, blood pressure, high-density lipoprotein cholesterol (HDL-C), fasting glucose, Lp-PLA₂ and hsCRP. In multivariate regression analysis the relationship between 25(OH)Vit D and sdLDL-C became insignificant when triglycerides were included in the model.

Conclusions

Subjects with MetS exhibit lower 25(OH)Vit D serum levels compared with non-MetS individuals. Low 25(OH)Vit D is associated with higher sdLDL-C levels possibly through elevated triglycerides. No association between 25(OH)Vit D and Lp-PLA₂ or hsCRP was found.     

Association of circulating adiponectin with testosterone in women during the menopausal transition

Objective

We examined (1) the change in circulating adiponectin in women during the menopausal transition and (2) the associations of adiponectin levels with estrogen, androgen and sex hormone-binding globulin (SHBG) in women during the menopausal transition.

Methods

We conducted a cross-sectional study in 235 healthy women and divided them into 7 stages by menstrual regularity and follicle-stimulating hormone (FSH) level. Serum levels of adiponectin, estradiol, total testosterone, dehydroepiandrosterone-sulfate (DHEA-S) and SHBG were measured. Levels of free and bioavailable testosterone were calculated by using total testosterone, albumin and SHBG.

Results

Serum adiponectin levels showed a U-curve, levels being low in early and late menopausal transition and gradually becoming higher after menopause. Adiponectin levels were negatively correlated with levels of free testosterone, bioavailable testosterone and DHEA-S and were positively correlated with SHBG in postmenopausal women for whom more than 1 year had passed since menopause. Adiponectin level was not correlated with estradiol level.

Conclusion

Circulating adiponectin level shows a U-curve during the menopausal transition and adiponectin level is associated with levels of free and bioavailable testosterone and DHEA-S in postmenopause.