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Open access

Xia Wu, Zhiling Li, Wenjiang Sun, and Huan Zheng

Polycystic ovary syndrome (PCOS) is associated with an increased risk of cardiovascular disease in women. Hyperhomocysteinemia (H-Hcy) is closely related to arterial stiffness (AS) in patients with cardiovascular disease. This study aimed to investigate the relationship between serum homocysteine(Hcy) level and brachial-ankle pulse wave velocity (baPWV) in Chinese women with PCOS. A total of 124 PCOS women were enrolled and divided into two groups according to their baPWV values: normal, baPWV < 1400 cm/s and high AS, baPWV ≥ 1400 cm/s. Univariate analysis was performed to investigate the relative factors for baPWV, and multiple regression analysis was used to evaluate the association of Hcy with baPWV. The group with high AS (n = 35) had higher Hcy levels than the other group (n = 89; P < 0.05). Moreover, univariate analysis revealed that serum Hcy was positively correlated with baPWV (r = 0.133, P < 0.01). In multiple regression analysis, the age-adjusted serum Hcy level was positively correlated with baPWV (β = 0.201, P < 0.01). It remained positively associated with baPWV (β = 0.145, P < 0.01) after further adjustments for age, BMI, PCOS duration, systolic blood pressure, and homeostasis model assessment-insulin resistance as well as several other factors correlated with baPWV. Our results demonstrated that H-Hcy was significantly and independently related to elevated baPWV, suggesting that Hcy might play a role in the pathologic process of AS in women with PCOS. Further researches with more subjects are needed to explore whether Hcy would be a promising biomarker for the stratification management of PCOS women.

Open access

Xiaomin Nie, Yiting Xu, Xiaojing Ma, Yun Shen, Yufei Wang, and Yuqian Bao

Background

A high level of free triiodothyronine (FT3) within the reference range may be a potential metabolic risk marker. However, the relationship between different fat depots and FT3 has remained unclear.

Objective

We aimed to explore the relationships between segmental fat distribution and FT3 in euthyroid middle-aged and elderly men and postmenopausal women.

Methods

A total of 891 subjects (394 men and 497 women) were enrolled. A bioelectrical impedance analyzer was used to measure total, trunk, arm and leg fat mass (FM) and fat percentage (fat%). The leg fat mass to trunk fat mass ratio (LTR) was calculated to evaluate the relative distribution of leg fat compared with that of trunk fat. Thyroid hormones were measured by electrochemical luminescence immunoassay.

Results

FT3 in men did not change significantly with increases in LTR quartiles, while FT3 in women decreased significantly (P for trend = 0.004). In multivariate linear regression analysis, multiple metabolic and cardiovascular risk factors were adjusted. The LTR was negatively related to FT3 in women (P < 0.05). After further mutual adjustment for trunk fat and leg fat parameters, trunk FM and fat% were positively related to FT3, while leg FM and fat% were negatively related to FT3 in women (all P < 0.05).

Conclusions

In euthyroid postmenopausal women, trunk fat was positively correlated with FT3, whereas leg fat was negatively correlated with FT3. Our findings supported that a high level of FT3 within the reference range was related to adverse fat distribution.

Open access

Kristin Godang, Karolina Lundstam, Charlotte Mollerup, Stine Lyngvi Fougner, Ylva Pernow, Jörgen Nordenström, Thord Rosén, Svante Jansson, Mikael Hellström, Jens Bollerslev, Ansgar Heck, and the SIPH Study Group

Context

Mild primary hyperparathyroidism has been associated with increased body fat mass and unfavorable cardiovascular risk factors.

Objective

To assess the effect of parathyroidectomy on fat mass, glucose and lipid metabolism.

Design, patients, interventions, main outcome measures

119 patients previously randomized to observation (OBS; n = 58) or parathyroidectomy (PTX; n = 61) within the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH) trial, an open randomized multicenter study, were included. Main outcome measures for this study were the differences in fat mass, markers for lipid and glucose metabolism between OBS and PTX 5 years after randomization.

Results

In the OBS group, total cholesterol (Total-C) decreased from mean 5.9 (±1.1) to 5.6 (±1.0) mmol/L (P = 0.037) and LDL cholesterol (LDL-C) decreased from 3.7 (±1.0) to 3.3 (±0.9) mmol/L (P = 0.010). In the PTX group, the Total-C and LDL-C remained unchanged resulting in a significant between-group difference over time (P = 0.013 and P = 0.026, respectively). This difference was driven by patients who started with lipid-lowering medication during the study period (OBS: 5; PTX: 1). There was an increase in trunk fat mass in the OBS group, but no between-group differences over time. Mean 25(OH) vitamin D increased in the PTX group (P < 0.001), but did not change in the OBS group. No difference in parameters of glucose metabolism was detected.

Conclusion

In mild PHPT, the measured metabolic and cardiovascular risk factors were not modified by PTX. Observation seems safe and cardiovascular risk reduction should not be regarded as a separate indication for parathyroidectomy based on the results from this study.

Open access

M A Webb, H Mani, S J Robertson, H L Waller, D R Webb, C L Edwardson, D H Bodicoat, T Yates, K Khunti, and M J Davies

Aims

Physical activity has been proposed to be an effective non-pharmacological method of reducing systemic inflammation and therefore may prove particularly efficacious for women with polycystic ovary syndrome (PCOS) who have been shown to have high levels of inflammation and an increased risk of type 2 diabetes (T2DM) and cardiovascular disease (CVD). Therefore, the aim of the present study was to assess whether modest changes in daily step count could significantly reduce levels of inflammatory markers in women with PCOS.

Subjects and Methods

Sixty-five women with PCOS were assessed at baseline and again at 6 months. All had been provided with an accelerometer and encouraged to increase activity levels. Multivariate linear regression analyses (adjusted for age, ethnicity, baseline step count, change in BMI and change in accelerometer wear-time) were used to assess changes in daily step count against clinical and research biomarkers of inflammation, CVD and T2DM.

Results

Mean step count/day at baseline was 6337 (±270). An increase in step count (by 1000 steps) was associated with a 13% reduction in IL6 (β: −0.81 ng/L; 95% CI, −1.37, −0.25, P = 0.005) and a 13% reduction in CRP (β: −0.68 mg/L; 95% CI, −1.30, −0.06, P = 0.033). Additionally, there was a modest decrease in BMI (β: 0.20 kg/m2; 95% CI, −0.38, −0.01, P = 0.038). Clinical markers of T2DM and CVD were not affected by increased step count.

Conclusions

Modest increases in step count/day can reduce levels of inflammatory markers in women with PCOS, which may reduce the future risk of T2DM and CVD.

Open access

Mírian Romitti, Vitor C Fabris, Patricia K Ziegelmann, Ana Luiza Maia, and Poli Mara Spritzer

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder affecting women of reproductive age. PCOS has been associated with distinct metabolic and cardiovascular diseases and with autoimmune conditions, predominantly autoimmune thyroid disease (AITD). AITD has been reported in 18–40% of PCOS women, depending on PCOS diagnostic criteria and ethnicity. The aim of this systematic review and meta-analysis was to summarize the available evidence regarding the likelihood of women with PCOS also having AITD in comparison to a reference group of non-PCOS women. We systematically searched EMBASE and MEDLINE for non-interventional case control, cross-sectional or cohort studies published until August 2017. The Ottawa–Newcastle Scale was used to assess the methodological quality of studies. Statistical meta-analysis was performed with R. Thirteen studies were selected for the present analysis, including 1210 women diagnosed with PCOS and 987 healthy controls. AITD was observed in 26.03 and 9.72% of PCOS and control groups respectively. A significant association was detected between PCOS and chance of AITD (OR = 3.27, 95% CI 2.32–4.63). Notably, after geographical stratification, the higher risk of AITD in PCOS women persisted for Asians (OR = 4.56, 95% CI 2.47–8.43), Europeans (OR = 3.27, 95% CI 2.07–5.15) and South Americans (OR = 1.86, 95% CI 1.05–3.29). AIDT is a frequent condition in PCOS patients and might affect thyroid function. Thus, screening for thyroid function and thyroid-specific autoantibodies should be considered in patients with PCOS even in the absence of overt symptoms. This systematic review and meta-analysis is registered in PROSPERO under number CRD42017079676.

Open access

Julia Kubiak, Per Medbøe Thorsby, Elena Kamycheva, and Rolf Jorde

Objective

Low serum 25(OH)D levels are associated with cardiovascular disease (CVD) and some of its risk factors. However, in interventional studies, the effects of vitamin D supplementation have been uncertain, possibly due to inclusion of vitamin D-sufficient subjects. Our aim was therefore to examine effects of vitamin D supplementation on CVD risk factors in vitamin D-insufficient subjects.

Design

Double-blinded randomized controlled trial.

Methods

A 4-month interventional study with high-dose vitamin D (100,000 IU loading dose, followed by 20,000 IU/week) or placebo with measurements of blood pressure, lipids (total-, LDL- and HDL-cholesterol, triglycerides, apolipoproteins A1 and B), and glucose metabolism parameters (blood glucose, HbA1c, serum human receptors for advanced glycation end products (sRAGE), insulin, C-peptide and HOMA-IR).

Results

A total of 422 subjects with mean serum 25(OH)D level 34 nmol/L were included, with 411 subjects completing the study. Serum 25(OH)D levels increased with 56 nmol/L and decreased with 4 nmol/L in the vitamin D and placebo group, respectively. We found no statistically significant differences between the two groups in any of the measured CVD risk factors, except for a minor increase in sRAGE in the vitamin D group. Stratified analyses of subjects with low baseline serum 25(OH)D levels alone, or combined with blood pressure, lipid and HOMA-IR values above the median for the cohort, did not skew the results in favour of vitamin D supplementation.

Conclusion

Supplementation with vitamin D in subjects with baseline vitamin D insufficiency does not improve CVD risk factor profile.

Open access

Christine Rode Andreasen, Andreas Andersen, Filip Krag Knop, and Tina Vilsbøll

In recent years, glucagon-like peptide 1 receptor agonists (GLP-1RAs) have become central in the treatment of type 2 diabetes (T2D). In addition to their glucose-lowering properties with low risk of hypoglycaemia, GLP-1RAs reduce body weight and show promising results in reducing cardiovascular risk and renal complications in high-risk individuals with T2D. These findings have changed guidelines on T2D management over the last years, and GLP-1RAs are now widely used in overweight patients with T2D as well as in patients with T2D and cardiovascular disease regardless of glycaemic control. The currently available GLP-1RAs have different pharmacokinetic profiles and differ in their ability to improve glycaemia, reduce body weight and in their cardio- and renal protective potentials. Understanding how these agents work, including insights into their pleiotropic effects on T2D pathophysiology, may improve their clinical utilisation and be useful for exploring other indications such as non-alcoholic steatohepatitis and neurodegenerative disorders. In this review, we provide an overview of approved GLP-1RAs, their clinical effects and mode of action, and we offer insights into the potential of GLP-1RAs for other indications than T2D. Finally, we will discuss the emerging data and therapeutic potential of using GLP-1RAs in combinations with other receptor agonists.

Open access

Xiuzhen Zhang, Dan Xu, Ping Xu, Shufen Yang, Qingmei Zhang, Yan Wu, and Fengyi Yuan

Introduction

Metformin has been demonstrated to enhance cardioprotective benefits in type 1 diabetes (T1DM). Although glycemic variability (GV) is associated with increased risk of CVD in diabetes, there is a scarcity of research evaluating the effect of metformin on GV in T1DM.

Objectives

In the present study, the effects of adjuvant metformin therapy on GV and metabolic control in T1DM were explored.

Patients and methods

A total of 65 adults with T1DM were enrolled and subjected to physical examination, fasting laboratory tests, and continuous glucose monitoring, and subsequently randomized 1:1 to 3 months of 1000–2000 mg metformin daily add-on insulin (MET group, n = 34) or insulin (non-MET group, n = 31). After, baseline measurements were repeated.

Results

The mean amplitude of glycemic excursions was substantially reduced in MET group, compared with non-MET group (–1.58 (–3.35, 0.31) mmol/L vs 1.36 (–1.12, 2.24) mmol/L, P = 0.004). In parallel, the largest amplitude of glycemic excursions (–2.83 (–5.47, –0.06) mmol/L vs 0.45 (–1.29, 4.48) mmol/L, P = 0.004), the s.d. of blood glucose (–0.85 (–1.51, 0.01) mmol/L vs –0.14 (–0.68, 1.21) mmol/L, P = 0.015), and the coefficient of variation (–6.66 (–15.00, 1.50)% vs –1.60 (–6.28, 11.71)%, P = 0.012) all demonstrated improvement in the MET group, compared with the non-MET group. Significant reduction in insulin dose, BMI, and body weight was observed in patients in MET, not those in non-MET group.

Conclusion

Additional metformin therapy improved GV in adults with T1DM, as well as improving body composition and reducing insulin requirement. Hence, metformin as an adjunctive therapy has potential prospects in reducing the CVD risk in patients with T1DM in the long term.

Open access

Ling-Jun Li, Izzuddin M Aris, Lin Lin Su, Yap Seng Chong, Tien Yin Wong, Kok Hian Tan, and Jie Jin Wang

Aims

The cumulative effect of gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) on postpartum cardio-metabolic diseases is equivocal. We aimed to assess the associations of GDM and HDP’s individual and synergic contribution to risks of postpartum cardio-metabolic diseases (metabolic syndrome (MetS), abnormal glucose metabolism and hypertension (HTN)).

Methods

Of participants from a Singapore birth cohort, 276 mothers attending the 5-year postpartum visit were included in this study. During this visit, we collected mothers’ history of GDM and HDP in all live births in a chronicle sequence and assessed the cardio-metabolic risks based on blood pressure, anthropometry and a panel of serum biomarkers. We diagnosed MetS, abnormal glucose metabolism and HTN according to Adult Treatment Panel III 2000 and World Health Organization guidelines.

Results

Of 276 mothers, 157 (56.9%) had histories of GDM while 23 (8.3%) had histories of HDP. After full adjustment, we found associations of GDM episodes with postpartum abnormal glucose metabolism (single episode: relative risk (RR) 2.9 (95% CI: 1.7, 4.8); recurrent episodes (≥2): RR = 3.8 (2.1–6.8)). Also, we found association between histories of HDP and HTN (RR = 3.6 (1.5, 8.6)). Having either (RR 2.6 (1.7–3.9)) or both gestational complications (RR 2.7 (1.6–4.9)) was associated with similar risk of postpartum cardio-metabolic disease.

Conclusions

Mothers with GDM or HDP had a threefold increased risk of postpartum abnormal glucose metabolism or HTN, respectively. Having both GDM and HDP during past pregnancies was not associated with additional risk of postpartum cardio-metabolic diseases beyond that associated with either complication alone.

Open access

Marc Blondon, Emmanuel Biver, Olivia Braillard, Marc Righini, Pierre Fontana, and Alessandro Casini

Objective

Vitamin D deficiency is associated with increased risks of arterial and venous cardiovascular events. Hypothetically, supplementation with vitamin D may lead to a less prothrombotic phenotype, as measured by global coagulation assays and fibrin clot structure.

Methods

In this prospective cohort study, we enrolled adult outpatients attending the Primary Care Division of the Geneva University Hospitals with a severe vitamin D deficiency (25-hydroxyvitamin-D3 (25-OHD) <25 nmol/L), excluding obese patients or with a recent acute medical event. We evaluated changes in coagulation times, thrombin generation assay, clot formation and clot lysis time, 25-OHD and parathormone before and 1–3 months after cholecalciferol oral supplementation with one-time 300,000 IU then 800 IU daily. Paired t-tests with a two-sided alpha of 0.05 compared absolute mean differences.

Results

The 48 participants had a mean age of 43.8 ± 13.8 years. After supplementation, 25-OHD levels increased from 17.9 ± 4.6 nmol/L to 62.5 ± 20.7 nmol/L 6.4 ± 3.0 weeks after inclusion. Endogenous thrombin potential and thrombin generation peak values both decreased significantly (−95.4 nM × min (95%CI −127.9 to −62.8), P < 0.001; −15.1 nM (−23.3 to −6.8), P < 0.001). The maximum absorbance by turbidimetry decreased significantly (P = 0.001) after supplementation. There was no change in clot lysis time, coagulation times or plasminogen activator inhibitor-1 and homocysteine levels.

Conclusions

In severe vitamin D deficiency, a high-dose cholecalciferol supplementation was associated with a reduction in thrombin generation and an average decreased number of fibrin protofibrils per fibers and fibrin fiber size measured by turbidimetry. This suggests that severe vitamin D deficiency may be associated with a potentially reversible prothrombotic profile.