Pediatric nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular risk

Nonalcoholic fatty liver disease(NAFLD) encompasses a range of liver histology severity and outcomes in the absence of chronic alcohol use.The mildest form is simple steatosis in which triglycerides accumulate within hepatocytes.A more advanced form of NAFLD,nonalcoholic steatohepatitis,includes inflammation and liver cell injury,progressive to cryptogenic cirrhosis.NAFLD has become the most common cause of chronic liver disease in children and adolescents.The recent rise in the prevalence rates of overweig...     

库欣综合征患者代谢紊乱及心血管危险因素分析

对173例库欣综合征患者的临床资料进行回顾性分析,并比较35例手术前后资料,发现库欣综合征常合并多种代谢紊乱及心血管危险因素,疾病治愈、皮质醇水平恢复正常后仍可能存在与活动期类似的代谢紊乱和心血管危险因素.     

From bench to bedside: what physicians need to know about endothelial progenitor cells

Since the discovery of endothelial progenitor cells in 1997, the scientific world has seen their ups and downs. There has been much discussion about the detection methods of endothelial progenitor cells and their diagnostic and predictive value. A lack of standardized methods to define endothelial progenitor cells has led to a number of nomenclatures and measuring methods that are difficult for clinicians to oversee. Therefore, only specialized hematologists and cardiologists were aware of their existence. Now it is time for a change: Most of the controversies have been eliminated by elaborate studies. This review aims to give an overview to the clinically working physician about the measurement, diagnostic potential, predictive value, and therapeutic potential of endothelial progenitor cells.     

Practical aspects of the control of cardiovascular risk in type 2 diabetes mellitus and the metabolic syndrome

Cardiovascular disease is unanimously recognized as the major burden in type 2 diabetes, in terms of both mortality and morbidity. There is an extensive evidence coming from epidemiological studies that supports this statement. The presence of the metabolic syndrome confers a higher risk of long-term death, and dysglycemia appears to be responsible for the most of the excess risk. The metabolic syndrome also has an essential role in the modern concept of cardiovascular prevention.     

Impact of metabolic syndrome criteria on cardiovascular disease risk in people with newly diagnosed type 2 diabetes

Aims/hypothesis We investigated the prognostic implication of metabolic syndrome according to modified National Cholesterol Education Program criteria and the implication of individual features of metabolic syndrome on cardiovascular disease (CVD) and CHD in a 5-year community-based study of people with newly diagnosed type 2 diabetes. Methods We entered 562 participants, aged 30–74 years, into a cross-sectional analysis and 428 participants (comprising those who were CVD-free at study entry) into a prospective analysis. In both analyses, the association of metabolic syndrome features with CVD/CHD was studied. Binary logistic regression, a Cox regression model and Fisher's exact test were used for statistical analyses. Results At diagnosis of type 2 diabetes, metabolic syndrome was independently associated with CVD (odds ratio [OR] 2.54; p=0.006) and CHD (OR 4.06; p=0.002). In the 5-year follow-up, metabolic syndrome at baseline was an independent predictor of incident CVD (hazard ratio [HR] 2.05; p=0.019). An increase in the number of individual features of the metabolic syndrome present at the time of diagnosis of type 2 diabetes was associated with a linear increase in incident CVD risk (trend p=0.044) with an almost five-fold increase when all five features were present, compared with hyperglycaemia alone (HR 4.76; p=0.042). Increasing age (HR 1.07; p<0.001), female sex (HR 0.62; p=0.032), total cholesterol (HR 1.43; p=0.01) and lipid-lowering therapy (HR 0.32; p<0.001) were also independent predictors of risk. Conclusions/interpretation Metabolic syndrome at baseline is associated with an increased risk of incident CVD in the 5 years following diagnosis of type 2 diabetes. CVD-free survival rates declined incrementally as the presence of metabolic syndrome features increased. Thus, identifying the features of metabolic syndrome at diagnosis of type 2 diabetes is potentially a useful prognostic tool for identifying individuals at increased risk of CVD.     

Circulating CD34+ progenitor cells modulate host angiogenesis and inflammation in vivo

Within the phenotypically and functionally heterogeneous group of circulating progenitor cells (CPC), a subclass of cells with vascular repair potential have been identified. These CPC are detected and isolated based on single or combined expression of CD34, CD133 and VEGFR-2, and referred to as endothelial progenitor cells. Here we asked whether CPC subsets defined by single expression of these markers exhibit functional heterogeneity. As functional parameters, we chose the capacity of CPC to differentiate into endothelial cells. Moreover, we studied their role in remodeling by recruitment of inflammatory cells, an aspect that has been little explored. We established an in vivo model in which the intrinsic functional capacity of these human CPC subsets was studied. Human CD34+ CPC, but not CD133+ or VEGFR-2+ CPC, seeded in Matrigel pellets and transplanted subcutaneously in a nude mouse host, contributed little to donor-derived neovascularization. However, host angiogenesis in the Matrigel implant, as demonstrated by the presence of capillaries containing erythrocytes and expressing mouse CD31, was strong in response to implantation of human CD34+ CPC and significantly lower in response to the other two CPC subsets. Moreover, the CD34+ CPC subset was significantly superior to CD133+ CPC and VEGFR-2+ CPC in the recruitment of host monocytes/macrophages. These three CPC populations were further dissected into seven discrete subsets, based on three-parameter flow cytometry analysis of combined expression patterns of CD34, CD133 and VEGFR-2. In conclusion, in our system, CD34+ CPC contribute marginally to neovascularization by differentiation but are potent regulators of the host angiogenic and pro-inflammatory response, suggesting a possible role for these cells in the remodeling of vascular lesions.     

外周血CD34+细胞数在有危险因素的急性心肌梗死患者中的变化

目的:健康人外周血中前体CD34+细胞数目很少,但在急性缺血时,这些细胞可以从骨髓动员到外周血。研究发现,有心血管危险因素的患者,外周血CD34+细胞数目是减少的。然而,有心血管事件危险因素的患者,急性心肌梗死是否能促进CD34+细胞的动员,目前尚不完全清楚。方法:42例心血管事件危险因素患者被分成两组:急性心肌梗死组20例,无冠状动脉粥样硬化性心脏病组22例。同时,没有冠心病及任何心血管病危险因素的16例自愿者入选为健康对照组。流式细胞仪分析外周血CD34+细胞数目。结果:急性心肌梗死组,外周血CD34+细胞的数目为（1.915±0.667）/μl,与健康对照组（1.925±0.629）/μl值比较,P=0.963。无冠状动脉粥样硬化性心脏病组,外周血CD34+细胞的数目为（1.804±0.605）/μl。在心肌梗死组与无冠心病组间比较,外周血CD34+细胞的数目无明显不同（P=0.575）。而且,患者并存心血管危险因素的多少与外周血中CD34+细胞水平似乎成反向相关。结论:有心血管事件危险因素患者,发生急性心肌梗死后外周血前体CD34+细胞未发现增加。由此提示心血管病危险因素可能抑制急性缺血诱导的前体CD34+细胞的动员,且与危险因素多少相关。     

Visit-to-visit variability in the measurements of metabolic syndrome components and the risk of all-cause mortality,cardiovascular disease,and arterial stiffness

Background and aimsThe risk of adverse health conditions varied according to the number of metabolic syndrome components. We aimed to evaluate the risk of mortality and incident cardiovascular events according to the number of components with high variability.Methods and resultsA total of 43,737 Kailuan Study participants with ≥3 examinations of waist circumference, fasting blood glucose, systolic blood pressure, triglyceride, and high-density lipoprotein during 2006–2013 were included in the present study. Visit-to-visit variability in each parameter was defined by the intraindividual standard deviation across visits. High variability was defined as the highest quartile of variability. Participants were classified numerically according to the number of high-variability components (e.g., a score of 0 indicated no high-variability component). There were 1551 deaths during a median follow-up of 5.9 years, and 950 incident cardiovascular disease (CVD) cases during a median follow-up of 4.9 years. In the multivariable adjusted model, compared with participants with low variability for all components, participants with ≥3 high-variability components had significantly higher risks for all-cause mortality (hazards ratio [HR], 1.61; 95 % confidence interval [CI], 1.35–1.91) and incident CVD event (HR, 1.45; 95 % CI, 1.16–1.82). Additionally, participants with ≥3 high-variability components had increased odds of arterial stiffness, as measured by brachia-ankle pulse wave velocity (odds ratio [OR], 1.39; 95 % CI, 1.19–1.63).ConclusionsOur findings suggest that participants with at least three metabolic parameters with high variability experienced increased risk of CVD and all-cause mortality.     

Testosterone, cardiovascular disease and the metabolic syndrome

Recent evidence suggests that low, rather than high, testosterone (T) is associated with increased male morbidity and mortality. We reviewed relationships between hypogonadism, metabolic syndrome (MetS) and cardiovascular (CV) disease (CVD), along with erectile dysfunction (ED), a common condition in the three diseases. Although several experimental data indicate that T exerts a protective effect on vascular function, epidemiological studies do not support a link between hypogonadism and CVD and three meta-analyses found no significant effect of testosterone replacement therapy (TRT) on CV events. Low T is associated with increased risk of CV death in community-dwelling men, and in men with ED. It is possible that both low T and CVD are associated with another, still unknown (or not assessed) factor, thus explaining the association, in the absence of any causal relationship. A meta-analysis on the effect of TRT in MetS-associated hypogonadism demonstrated positive effects of T on some of the components of MetS. Large-scale interventional studies with TRT are therefore advisable.     

The link between abdominal obesity, metabolic syndrome and cardiovascular disease

AimThe prevalence of metabolic syndrome has increased dramatically in recent years, and the cluster of metabolic abnormalities it encompasses results in increased cardiovascular morbidity and mortality. The role of abdominal (visceral) obesity and the underlying molecular and cellular mechanisms central to this association have been the subject of intensive research in recent times. The aim of this review is to correlate data in this area, highlighting the central role of excess visceral fat and its secreted adipokines, and to review existing and emerging therapies.Data synthesisData were generated from a search of the PubMed database using the terms ‘abdominal obesity’, ‘metabolic syndrome’, ‘insulin resistance’, ‘adipokines’, ‘interleukin-6 (IL-6)’, ‘adiponectin’, ‘tumour necrosis factor-alpha (TNF-α)’ and ‘cardiovascular disease’.ConclusionMetabolic syndrome is associated with a pro-inflammatory state, and the role of visceral obesity is thought to be central to this. Visceral obesity leads to alteration of the normal physiological balance of adipokines, insulin resistance, endothelial dysfunction and a pro-atherogenic state. In association with this, the presence of conventional cardiovascular risk factors such as hypertension, dyslipidaemia and smoking results in a significantly elevated cardiovascular and metabolic (cardiometabolic) risk. Better understanding of the molecular mechanisms central to this association has led to the development of potential therapeutic agents.     

Metabolic syndrome and risk of cardiovascular disease: a meta-analysis

Purpose

The use of different definitions of the metabolic syndrome has led to inconsistent results on the association between the metabolic syndrome and risk of cardiovascular disease. We examined the association between the metabolic syndrome and risk of cardiovascular disease.

Methods

A MEDLINE search (1966-April 2005) was conducted to identify prospective studies that examined the association between the metabolic syndrome and risk of cardiovascular disease. Information on sample size, participant characteristics, metabolic syndrome definition, follow-up duration, and endpoint assessment was abstracted.

Results

Data from 21 studies met the inclusion criteria and were included. Individuals with the metabolic syndrome, compared to those without, had an increased mortality from all causes (relative risk [RR] 1.35; 95% confidence interval [CI], 1.17-1.56) and cardiovascular disease (RR 1.74; 95% CI, 1.29-2.35); as well as an increased incidence of cardiovascular disease (RR 1.53; 95% CI, 1.26-1.87), coronary heart disease (RR 1.52; 95% CI, 1.37-1.69) and stroke (RR 1.76; 95% CI, 1.37-2.25). The relative risk of cardiovascular disease associated with the metabolic syndrome was higher in women compared with men and higher in studies that used the World Health Organization definition compared with studies that used the Adult Treatment Panel III definition.

Conclusion

This analysis strongly suggests that the metabolic syndrome is an important risk factor for cardiovascular disease incidence and mortality, as well as all-cause mortality. The detection, prevention, and treatment of the underlying risk factors of the metabolic syndrome should become an important approach for the reduction of the cardiovascular disease burden in the general population.     

Predictors of cardiovascular risk among patients with type 1 diabetes: A critical analysis of the metabolic syndrome and its components

Patients with type 1 diabetes (T1D) are at increased risk for cardiovascular diseases. The metabolic syndrome (MetS), a complex disorder defined by a cluster of interconnected factors including abdominal obesity, hypertension, dyslipidaemia and insulin resistance, has been proposed to identify patients with T1D at high cardiovascular risk. The MetS has been identified in 8–45% of patients with T1D, depending on the definition and cohort studied. However, clinicians and researchers face several issues with the criteria for MetS in patients with T1D, therefore questioning its value in routine care. For example, three criteria can lead to overestimation of MetS prevalence; the impaired fasting glucose criterion is irrelevant as it is automatically fulfilled; and the widespread use of antihypertensive and lipid-lowering medications for cardiac and renal preventative purposes can contribute to overestimations of the prevalence of raised blood pressure and elevated triglycerides. In cross-sectional studies, the MetS has been associated mostly with an increased risk of microvascular complications whereas, in prospective cohorts, the predictive value of MetS for micro- and macrovascular outcomes has been inconsistent. While identifying diabetes patients at increased risk for cardiovascular complications and early mortality is crucial from a prevention standpoint, for patients with T1D, the current definition of MetS may not be the most suitable tool. The aims of the present report are to review the applicability and limitations of the MetS in patients with T1D, and to discuss alternative avenues to identify high-risk patients.     

Circulating human CD34+ progenitor cells modulate neovascularization and inflammation in a nude mouse model

CD34+ progenitor cells hold promise for therapeutic neovascularization in various settings. In this study, the role of human peripheral blood CD34+ cells in neovascularization and inflammatory cell recruitment was longitudinally studied in vivo. Human CD34+ cells were incorporated in Matrigel, implanted subcutaneously in nude mice, and explanted after 2, 4, 7, or 14 days. Cell-free Matrigels served as controls. Histochemical analyses demonstrated that neovascularization occurred almost exclusively in CD34+ implants. Cellular and capillary density were increased in cell-loaded Matrigels after 2 days and further increased at 14 days. Human CD34+ cells did not incorporate in neovessels, but formed vWF+/CD31+/VEGF+ cell clusters that were present up to day 14. However, CD34+ cells induced host neovascularization, as demonstrated by increased presence of murine CD31+ and vWF+ vasculature from day 7 to 14. Moreover, recruitment of murine monocytes/macrophages was significantly enhanced in CD34+ implants at all time points. Gene expression of chemotactic cytokines MCP-1 and IL-8 was detected on CD34+ cells in vitro and confirmed immunohistochemically in cell-loaded explants at all time points. Our data indicate that human CD34+ cells, implanted in a hypoxic environment, generate an angiogenic niche by secreting chemotactic and angiogenic factors, enabling rapid neovascularization, possibly via recruitment of monocytes/macrophages.     

Endothelial impairment and bone marrow‐derived CD34+/133+ cells in diabetic patients with erectile dysfunction

Aims/Introduction

The present study was undertaken to determine vascular endothelial impairment and endothelial progenitor cells (EPCs) in patients with type 2 diabetes mellitus and erectile dysfunction (ED).

Materials and Methods

A total of 100 type 2 diabetic men were enrolled. Flow‐mediated dilatation (FMD) and anaerobic threshold (AT) were measured. Also, EPCs in the peripheral blood were determined by flow cytometry.

Results

In the 42 ED diabetic patients, FMD and AT were significantly less than those in the 58 patients with normal erectile function (FMD 2.84 vs 3.82%, P = 0.038, and AT 11.2 vs 12.7 mL/kg/min, P = 0.022). Exercise tolerance significantly increased the number of EPCs in the patients with and without ED (49–60 cells/100 μL, P = 0.015, and 72–99 cells/100 μL, P = 0.003). In the diabetic patients without autonomic neuropathy, FMD was significantly reduced in the patients with ED than those without ED (P = 0.015). In response to exercise tolerance, the number of EPCs increased in both the diabetic patients with ED (P = 0.003) and without ED (P = 0.007). In contrast, in the diabetic patients with autonomic neuropathy, there was no difference in FMD between the patients with and without ED. The exercise tolerance increased the number of EPCs in the patients without ED (P = 0.023), but it disappeared in those with ED.

Conclusions

ED diabetic patients have endothelial impairment during the early period of diabetic complications, whose deranged endothelial function is concomitantly repaired by promoting bone marrow‐derived EPCs.     

Serum uric acid and its relationship with metabolic syndrome and cardiovascular risk profile in patients with hypertension: Insights from the I-DEMAND study

Background and aimsThe independent role of serum uric acid (SUA) as a marker of cardio-renal risk is debated. The aim of this study was to assess the relationship between SUA, metabolic syndrome (MS), and other cardiovascular (CV) risk factors in an Italian population of hypertensive patients with a high prevalence of diabetes.Methods and resultsA total of 2429 patients (mean age 62 ± 11 years) among those enrolled in the I-DEMAND study were stratified on the basis of SUA gender specific quartiles. MS was defined according to the NCEP-ATP III criteria, chronic kidney disease (CKD) as an estimated GFR (CKD-Epi) <60 ml/min/1.73 m² or as the presence of microalbuminuria (albumin-to-creatinine ratio ≥2.5 mg/mmol in men and ≥3.5 mg/mmol in women).The prevalence of MS, CKD, and positive history for CV events was 72%, 43%, and 20%, respectively. SUA levels correlated with the presence of MS, its components, signs of renal damage and worse CV risk profile. Multivariate logistic regression analysis revealed that SUA was associated with a positive history of CV events and high Framingham risk score even after adjusting for MS and its components (OR 1.10, 95% CI 1.03–1.18; P = 0.0060; OR 1.28, 95% CI 1.15–1.42; P < 0.0001). These associations were stronger in patients without diabetes and with normal renal function.ConclusionsMild hyperuricemia is a strong, independent marker of MS and high cardio-renal risk profile in hypertensive patients under specialist care. Intervention trials are needed to investigate whether the reduction of SUA levels favorably impacts outcome in patients at high CV risk.     

Efficacy of IVRS-based mHealth intervention in reducing cardiovascular risk in metabolic syndrome: A cluster randomized trial

AimsEfficacy of mobile-phone based intervention for reducing cardiovascular risk in metabolic syndrome (MetSyn).MethodsWe screened adults 20–60 years in 10 villages in India for MetSyn using stratified cluster sampling. Lifestyle and biochemical risk factors were assessed. International Harmonized Criteria were used for diagnosis. Villages were randomized with 5 each in control and intervention groups. Interactive voice response system (IVRS) in Hindi was developed. In intervention clusters two messages for promotion of healthy lifestyle and medical treatment were broadcast daily over 12-months and risk factors reassessed.Results1012/1200(84%) persons were screened and MetSyn diagnosed in 286(28.3%). Villages were divided into 5 control(n = 136) and 5 intervention(n = 147) clusters. Baseline characteristics in both clusters were similar. Acceptability of intervention was >60% in 80% participants. At 12 months, significantly greater participants in intervention vs control clusters had healthier lifestyle (healthy diet 28.8vs14.7%, physical activity 25.9vs13.1%, tobacco 13.7vs32.5%), anthropometry (waist circumference 85.7 ± 6.3vs88.6 ± 14.0 cm, body mass index 21.9 ± 2.8vs23.1 ± 2.9 kg/m²), systolic BP 123.6 ± 7.7vs128.6 ± 14.1 mmHg, fasting glucose 95.6 ± 19.4vs109.4 ± 43.7 mg/dl, cholesterol 175.5 ± 36.5vs186.4 ± 43.3 mg/dl, and triglycerides 147.6 ± 48.3vs159.5 ± 60.7 mg/dl (p < 0.01). Prevalence of metabolic syndrome declined in intervention group by 22.3%vs3.9%, p < 0.001).ConclusionAn interactive voice response system based technology significantly reduced multiple cardiovascular risk factors and prevalence of metabolic syndrome.     

Different modalities of exercise to reduce visceral fat mass and cardiovascular risk in metabolic syndrome: the RESOLVE* randomized trial

Background

Opinions differ over the exercise modalities that best limit cardiovascular risk (CVR) resulting from visceral obesity in individuals with metabolic syndrome (MetS). As little is known about the combined effects of resistance and endurance training at high volumes under sound nutritional conditions, we aimed to analyze the impact of various intensities of physical activity on visceral fat and CVR in individuals with MetS.

Methods

100 participants, aged 50–70 years, underwent a diet restriction (protein intake 1.2 g/kg/day) with a high exercise volume (15–20 h/week). They were randomized to three training groups: moderate-resistance–moderate-endurance (re), high-resistance–moderate-endurance (Re), or moderate-resistance–high-endurance (rE). A one-year at-home follow-up (M12) commenced with a three-week residential program (Day 0 to Day 21). We measured the change in visceral fat and body composition by DXA, MetS parameters, fitness, the Framingham score and carotid-intima–media-thickness.

Results

78 participants completed the program. At D21, visceral fat loss was highest in Re (− 18%, p < .0001) and higher in rE than re (− 12% vs. − 7%, p < .0001). Similarly, from M3, visceral fat decreased more in high-intensity-groups to reach a visceral fat loss of − 21.5% (Re) and − 21.1% (rE) > − 13.0% (re) at M12 (p < .001). CVR, MetS parameters and fitness improved in all groups. Visceral fat loss correlated with changes in MetS parameters.

Conclusion

Increased intensity in high volume training is efficient in improving visceral fat loss and carotid-intima–media-thickness, and is realistic in community dwelling, moderately obese individuals. High-intensity-resistance training induced a faster visceral fat loss, and thus the potential of resistance training should not be undervalued (ClinicalTrials.gov number: NCT00917917).     

White fish reduces cardiovascular risk factors in patients with metabolic syndrome: The WISH-CARE study,a multicenter randomized clinical trial

Background and aimsReduction of cardiovascular risk with high consumption of fish in diet is still a matter of debate, and concerns about heavy metal contamination have limited consumption of oily fish. We aimed to evaluate the effect of regular ingestion of white fish on cardiovascular risk factors in patients with metabolic syndrome.Methods and resultsMulticenter randomized crossover clinical trial including 273 individuals with metabolic syndrome. An 8-week only-one dietary intervention: 100 g/d of white fish (Namibia hake) with advice on a healthy diet, compared with no fish or seafood with advice on a healthy diet. Outcomes were lipid profile, individual components of the metabolic syndrome, serum insulin concentrations, homeostasis model of insulin resistance, serum C-reactive protein and serum fatty acid levels. We found a significant lowering effect of the intervention with white fish on waist circumference (P < 0.001) and diastolic blood pressure (P = 0.014). A significant lowering effect was also shown after the dietary intervention with fish on serum LDL concentrations (P = 0.048), whereas no significant effects were found on serum HDL or triglyceride concentrations. A significant rise (P < 0.001) in serum EPA and DHA fatty acids was observed following white fish consumption. Overall adherence to the intervention was good and no adverse events were found.ConclusionIn individuals with metabolic syndrome, regular consumption of hake reduces LDL cholesterol concentrations, waist circumference and blood pressure components of the metabolic syndrome.Clinical trial registryWhite Fish for Cardiovascular Risk Factors in Patients with Metabolic Syndrome Study, Registered under ClinicalTrials.gov Identifier: NCT01758601.