The Effect of Curcumin on Serum Copper and Zinc and Zn/Cu Ratio in Individuals with Metabolic Syndrome: A Double-Blind Clinical Trial.

Metabolic syndrome is a complex disorder with high socioeconomic costs and a high global prevalence. The serum concentrations of some trace elements are higher in people with metabolic syndrome compared to normal individuals. Curcumin is derived from turmeric and has antioxidant and anti-inflammatory properties. Curcumin may therefore have a potential role in the management of cardiovascular risk. The aim of this study was to investigate the effects of curcumin on serum copper (Cu), zinc (Zn), and Zn/Cu ratio levels in patients with metabolic syndrome. A double-blind clinical trial was designed in which 120 individuals with metabolic syndrome were randomly assigned to one of three groups: curcumin 1gr/day, phospholipidated curcumin 1gr/day, or a placebo, each taken for 6 weeks. Serum copper and zinc were measured before and after intervention. At baseline, in addition to obtaining the anthropometric characteristics of participants, a fasting blood sample was taken from each participant, and the concentrations of serum Cu and Zn were measured by atomic absorption (Varian AA 240 FS model). Serum Zn concentrations rose significantly in the phospholipidated curcumin and curcumin groups, being significantly higher (p <.001) in the phospholipidated curcumin group than in the curcumin group (p <.05). Serum Zn concentration fell in the control group (p <.05). Changes in serum Zn level from baseline to the levels after six weeks' intervention were significantly different between the groups, but changes in serum Cu from between baseline until after intervention were not significantly different. The serum Zn/Cu level in phospholipidated curcumin and curcumin groups after intervention was higher than for the control group, but it was more significant in the group taking phospholipidated curcumin (p <.001). Curcumin and phospholipidated curcumin complex, given at a dose of 1 g per day for six weeks, were associated with an increase in serum zinc and consequently zinc-to-copper ratio.

Is echocardiographic epicardial fat thickness increased in patients with coronary artery disease? A systematic review and meta-analysis.

BACKGROUND: The relation of epicardial fat thickness (EFT) to coronary artery disease (CAD) has recently been reported in multiple studies. Echocardiography is a safe and relatively inexpensive and accessible approach to assess regional EFT, which can be performed easily in many centers. OBJECTIVE: To determine the association between echocardiographic EFT and the presence or the absence of CAD. METHODS: This was a systematic review and meta-analysis conducted on literature available in electronic databases up to March 2018. The articles measuring EFT by echocardiography in the right ventricular (RV) free wall were included in the study. The quality of the enrolled items was assessed using the Methodological Index for Non-Randomized Studies (MINORS) checklist. The analyses were performed using the Comprehensive Meta-Analysis version 2 software. Cochran's Q test and I2 index were used to evaluate heterogeneity. RESULTS: This meta-analysis was performed on 13 studies involving 2,436 patients (1,622 with CAD, and 814 without CAD). The maximum EFT reported by echocardiography was 12.9±2.7 mm in the CAD group and 8.4±2.5 mm in the non-CAD group. The minimum EFT reported by echocardiography was 2.2±1.8 mm in the CAD group and 1.8±1.4 mm in the non-CAD group. The heterogeneity was found among the researched studies (I2=91.8%, p=0.000, Q-value=146.43, df [Q] =12) using the random effect model. The patients with CAD had a significantly higher echocardiographic EFT than those without CAD (SMD=1.03, 95% CI= 0.70-1.37, p=0.000). CONCLUSION: According to the findings of this meta-analysis, the echocardiographic EFT in the subjects with CAD was significantly higher than that of those without CAD. The measurement of echocardiographic EFT seems to be an acceptable strategy for risk stratification of heart diseases considering ease of use, cost-effectiveness and non-exposure characteristics, compared to other imaging interventions.

Association between serum 25-hydroxyvitamin D concentrations and prevalence of metabolic syndrome.

PURPOSE: There is now good evidence that 25-hydroxyvitamin D (25OHD) status may have an important impact on the development and progression of cardiovascular disease. Because of the potential involvement of vitamin D deficiency in blood pressure control and immune responses, we aimed to investigate whether there was a relationship between 25OHD status and the prevalence of metabolic syndrome in an Iranian population. MATERIAL/METHODS: The study was carried out on a sample of 846 subjects [357(42.19%) males and 489(57.80%) females], derived from MASHAD STUDY. Serum 25OHD levels were measured using a competitive electroluminescence protein binding assay. Anthropometric indices were measured using standard protocols. RESULTS: Serum 25OHD was 12.7 (6.8-18.4) ng/ml in the metabolic syndrome (MetS) group and 14.1 (8.8-19.0) ng/ml in the group without metabolic syndrome (P=0.43). The frequency of vitamin D deficiency was 80.7% and 79.0% in subjects with or without metabolic syndrome in Iranian population. CONCLUSIONS: We found no significant difference in serum 25OHD concentrations between individuals with or without MetS and no significant linear relationship between serum 25OHD and several CVD risk factors.

Association of heat shock protein70-2 (HSP70-2) gene polymorphism with obesity.

BACKGROUND: Obesity is a major risk factor of chronic-diseases, including cardiovascular-diseases (CVD). Increasing evidence is showing the association of heat-shock protein (HSP) with type-2 diabetes and CVD; however, there is little data on the relationship between the genetic-polymorphisms of HSP70-2 with obesity. AIM: The present study has investigated the association between 1267HSP70-2 genetic polymorphism and obesity in an Iranian population with 317 subjects. SUBJECTS AND METHODS: Anthropometric parameters and biochemical measurements were measured in all the samples, while genotypes were determined using PCR-RFLP. Univariate/multivariate analyses were conducted to explore the relationship between the genetic-polymorphisms and obesity. RESULTS: The data showed a significant association between 1267HSP70-2 polymorphism in obese subjects, compared to the non-obese group. Moreover, it was observed that this polymorphism was associated with obesity in the CAD + group, which had a high BMI compared to non-obese controls. CONCLUSION: The 1267HSP70-2 polymorphism is associated with obesity in an Iranian population, supporting a possible potential genetic link between obesity and cardiovascular diseases.

Cytokine and growth factor profiling in patients with the metabolic syndrome.

The metabolic syndrome (MetS) is associated with a pro-inflammatory milieu that may partially account for its association with an increased cardiovascular risk. We aimed to (1) evaluate the serum concentrations of twelve cytokines and growth factors (epidermal growth factor (EGF), interferon-γ (IFN-γ), IL-1α/-1ß/-2/-4/-6/-8/-10, monocyte chemoattractant protein-1 (MCP-1), TNF-α and vascular endothelial growth factor (VEGF)) in 303 individuals with or without the MetS; and (2) explore their relationship with the presence of the MetS. Patients with the MetS had significantly higher serum concentrations of IFN-γ, EGF, IL-1α/-1ß/-2/-4/-6/-8/-10, MCP-1 and TNF-α, whilst serum VEGF concentrations were markedly lower compared with the control group (e.g. 38·55 v. 82·18 pg/ml; P< 0·05). Amongst these parameters, IFN-γ and IL-1α emerged as the most significant independent predictors of the MetS. In conclusion, our findings demonstrate that patients with the MetS had an altered blood cytokine and growth factor profile that may partially account for its adverse clinical outcomes. Further prospective studies in larger multi-centre settings are required to unravel the role and association of the emerging biomarkers with the MetS and their implication in therapeutic intervention.

Relationship between serum cytokine and growth factor concentrations and coronary artery disease.

BACKGROUND: We have assessed the association between serum concentrations of 12 cytokines/growth factors and angiographically-defined coronary artery disease, comparing the concentrations in four groups (one control group and three case groups). METHODS: We studied a total of 426 subjects including; 98 control subjects and 3 case groups. The patient groups consisted of: coronary artery bypass graft (CABG) candidates (n=48) and patients undergoing coronary angiography, with, or without obstructive coronary artery disease. Twelve cytokines (IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, MCP-1, IFN-γ, EGF, and VEGF) were measured using a sandwich chemi-luminescence assays, on the Evidence Investigator® system. RESULTS: The four groups were well matched for demographic and clinical characteristics, except waist circumference, fasting blood glucose (FBG), total and LDL cholesterol and diastolic blood pressure that were significantly higher in case groups compared to the control group (P<0.05 for all). There were significant differences between control group and the other three groups regarding the measured cytokines, such as IL-1α, IL-8, MCP-1, and VEGF (P<0.01). Furthermore, IL-4, IL-6 and EGF were also significantly different between the control, obstructive coronary disease and CABG candidate groups (P<0.01). Analysis of the ROC curve showed 92.1% sensitivity, 99.2% specificity and 100% positive predictive value (PPV) for VEGF in its ability to distinguish the CABG group at the cut-off point of 37.18 pg/ml. CONCLUSION: The results of this study suggest that cytokines such as IL-1α, IL-4, IL-8, IL-10 and VEGF may play major roles in pathogenesis of CAD.

An imbalance in serum concentrations of inflammatory and anti-inflammatory cytokines in hypertension.

Hypertension is an important risk factor for cardiovascular disease and there is increasing evidence that inflammation and abnormal immune responses are involved in the pathogenesis of hypertension. However, the data on the association between specific cytokine concentrations and hypertension are inconsistent. We have evaluated the association between 12 cytokines/growth factors and the presence of different degrees of hypertension, comparing these concentrations to values in a healthy group of subjects. The concentrations of interleukin (IL)-1α, -1ß, -2, -4, -6, -8, -10, tumor necrosis factor (TNF-α), interferon-γ (IFN-γ), monocyte chemoattractant protein (MCP-1), epidermal growth factor, and vascular endothelial growth factor were measured in 155 hypertensive patients and 148 healthy subjects, using EV-3513 cytokine biochip arrays, a competitive chemiluminescence immunoassay. Univariate and multivariate analyses were used to evaluate the association of specific cytokines and growth factors with systolic blood pressure (SBP) and diastolic blood pressure (DBP). Hypertensive subjects had higher serum concentrations of IL-1α, -2, -8, vascular endothelial growth factor, IFN-γ, TNF-α, MCP-1, and epidermal growth factor; and lower concentrations of anti-inflammatory cytokine, IL-10 (P < .05), compared with the healthy individuals. The serum concentrations of IL-4, -6, and -1ß did not differ between the hypertensive subjects and control group. Univariate and multivariate analyses revealed that IL-1α and IFN-γ were independent predictors of a high SBP, while IFN-γ, IL-1α, TNF-α, and MCP-1 remained statistically significant for DBP after correction for age, gender, Body mass index, smoking, fasting blood glucose, and triglycerides. There was a significant association between the concentrations of several cytokines and hypertension. These associations may either be related to common underlying factors that cause hypertension and may also be proinflammatory or because these inflammatory cytokines might directly be involved in the etiology of hypertension.

Association of heat shock protein70-2 (HSP70-2) gene polymorphism with coronary artery disease in an Iranian population.

BACKGROUND: Coronary artery disease (CAD) is an inflammatory process and a major cause of mortality and morbidity. The (heat shock protein70-2) HSP70-2 gene is reported to be associated with coronary artery disease possibly by affecting the regulation of pro-inflammatory cytokines such as TNF-α. The association between CAD and the HSP70-2 gene +1267A>G polymorphism has been studied in some populations but there are no data about this association in the Iranian population. AIM: We have investigated the association between the HSP70-2 gene +1267A>G polymorphism and angiographically defined CAD within an Iranian population. METHODS: We determined the presence of the HSP70-2 gene +1267A>G polymorphism in 628 patients with CAD and 307 healthy individuals using PCR-RFLP. Of the patients, 433 (68%) had >50% stenosis (CAD+) and the remaining 195 patients had <50% stenosis (CAD-), based on coronary angiography. Angiogram positive patients were subdivided into three groups: those with single (n=113), double (n=134), and triple vessels (n=186) disease. RESULTS: A significant higher frequency of AG+GG genotypes (G allele carriers) was observed in angiogram positive and angiogram negative groups compared to controls in a dominant analysis model of the HSP70-2 gene +1267A>G position (51.2 vs. 43.2, P=0.002, OR=1.37) (51.0 vs. 43.2, P=0.01, OR=1.37). The allele frequency of the HSP70-2 G was also significantly higher in angiogram positive and angiogram negative groups compared to the control group (51.2 vs. 43.2, P=0.002, OR=1.37) (51.0 vs. 43.2, P=0.01, OR=1.37). CONCLUSION: These results suggest that HSP70-2 +1267 polymorphism may influence the risk of CAD in Iranian population, however further studies are needed to clarify the role of other HSP70-2 gene polymorphisms in the pathogenesis of the CAD.