E-selectin and TFPI are associated with carotid intima-media thickness in stable IHD patients: the baseline findings of the MIAMI study

ObjectiveMIAMI was a prospective multicenter clinical study designed to investigate the relationship between changes in carotid intima-media thickness (C-IMT) and those in the levels of circulating markers of inflammation, thrombosis and endothelial dysfunction. The study was performed in a group of stable coronary patients treated for two years with a moderate dosage of atorvastatin (20 mg/day). In this paper the cross-sectional relationship between C-IMT and the same circulating markers of inflammation, thrombosis and endothelial dysfunction measured at baseline was investigated.MethodsEighty-five subjects that had not used statins for at least two months were enrolled in the study. At time of enrollment, the levels of vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), E-selectin, interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, high-sensitivity C-reactive protein (hs-CRP), tissue factor (TF), tissue factor pathway inhibitor (TFPI), von Willebrand factor (vWF), fibrinogen, total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL), and triglycerides were measured, in parallel with C-IMT assessment.ResultsIn cross-sectional analyses, markers of endothelial perturbation (i.e. E-selectin) and TFPI were more strongly correlated with arherosclerotic burden than markers of inflammation. The baseline picture in this study indicates that E-selectin and TFPI are linked with atherosclerotic burden.     

Serum visfatin as a non-traditional biomarker of endothelial dysfunction in chronic kidney disease: an Egyptian study

BackgroundEndothelial dysfunction (ED) is closely linked to cardiovascular disease and outcome in patients with chronic kidney disease (CKD). Visfatin is an adipocytokine that recently generated much interest; however, its role in CKD remains to be clarified. This study aimed to assess visfatin in correlation with markers of ED and inflammation in Egyptian patients with CKD.MethodsThe study included 40 non-diabetic, clinically stable CKD patients and 20 healthy volunteers. Serum levels of visfatin, markers of ED (intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) and markers of inflammation (interleukin-6 (IL-6), and C-reactive protein (CRP)) were measured. Endothelial function was evaluated using brachial artery flow-mediated dilatation (FMD).ResultsSerum visfatin, ICAM-1, VCAM-1, CRP, and IL-6 levels were significantly elevated and FMD% was decreased in CKD patients as compared to controls. Visfatin correlated positively with ICAM-1, VCAM-1, CRP, and IL-6 and negatively with FMD% in CKD patients. In a multiple regression model, visfatin was strongly and independently associated with FMD (Beta = ?0.02, P < 0.001) in CKD patients.ConclusionsSerum visfatin is strongly associated with endothelial adhesion molecules and FMD%, suggesting that visfatin is an important promising biomarker for prediction of ED and future cardiovascular risk in CKD patients. Moreover, the relationship between visfatin and IL-6 indicates that circulating visfatin may reflect the sub-clinical inflammatory status. Thus, visfatin might be involved in the complex interactions between ED, inflammation, and atherosclerosis and their major clinical consequences; however, further prospective studies are required to prove this hypothesis.     

Soluble CD40 ligand,interleukin (IL)-6, and hemostatic parameters in metabolic syndrome patients with and without overt ischemic heart disease

Background and aimSoluble CD40 ligand (sCD40L, also known as CD154) is a marker for platelet activation which could increase coagulation and inflammation. In this case-control study, we aimed to assess the levels of plasma sCD40L, IL-6, and some hemostatic parameters in patients with metabolic syndrome (MetS) whether or not associated with overt ischemic heart disease (IHD).Subjects and methodsWe measured plasma sCD40L (an index of platelet activation), interleukin (IL)-6 (a proinflammatory cytokine), and some hemostatic parameters (tissue factor [TF], thrombin–antithrombin [TAT] and D-dimer) in 47 patients with metabolic syndrome (21 with and 26 without overt IHD) versus 25 comparable healthy control subjects.ResultsSignificantly higher levels of sCD40L, IL-6, and thrombotic markers (TF, D-dimer and TAT) were found in patients with metabolic syndrome compared to healthy controls. The levels of IL-6 and sCD40 were highest in patients with overt IHD. Strong positive correlations existed between sCD40L and IL-6 (r = 0.67, p = 0.003), TF (r = 0.59, p = 0.008), and platelets count (r = 0.64, p = 0.005).ConclusionHigher levels of sCD40L, IL-6, and thrombotic markers exist in MetS patients, particularly those with IHD. The strong positive correlations between sCD40L and IL-6, TF, and platelets count support a link between the CD40–CD40L system and the underlying inflammatory and hypercoagulable state in MetS patients.     

Proinflammatory cytokines and cardiac abnormalities in uncomplicated obesity: relationship with abdominal fat deposition

Background and aimObesity can be considered a state of chronic, low-grade inflammation. Particularly, visceral adipose tissue (VAT) seems to be an active compartment in pro-inflammatory molecule secretion. The possible existence of a correlation between circulating cytokines, their soluble receptors, abdominal fat accumulation and echocardiographic abnormalities in uncomplicated obesity was investigated.Methods and resultsEchocardiographic parameters, C-reactive protein (CRP), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6-R), tumor necrosis factor-α (TNF-α) and soluble TNF receptor I (TNFR-I) were assessed in 27 normotensive obese women (age 33.3 ± 8.3 years; BMI 43.5 ± 4.8 kg/m²) and 15 normal-weight controls (age 36.8 ± 8.2 years; BMI 22.6 ± 1.7 kg/m²). VAT was assessed by CT. The obese patients had higher serum IL-6 (p < 0.01), sIL-6-R (p < 0.0001), sIL-6-R/IL-6 complex (p < 0.05), TNF-α (p < 0.02), sTNF-α-RI (p < 0.03) and CRP (p < 0.0001) levels than normal women. Moreover, end-diastolic septum thickness (SW), end-diastolic posterior wall thickness (PW), absolute and indexed left ventricular mass, deceleration time (DT), myocardial performance index (MPI) and isovolumetric relaxation time (IVRT) were correlated with sIL-6-R, sIL-6-R/IL-6 complex and CRP levels. Interestingly, sIL-6-R, sIL-6-R/IL-6 complex, CRP, SW, PW, DT and MPI were higher in patients with a VAT area >130 cm² than those with <130 cm².ConclusionIn normotensive obese women several pro-inflammatory molecules correlate with both echocardiographic abnormalities and the amount of intra-abdominal fat; these results may support a role for visceral fat in predisposing to cardiac dysfunction, possibly through a low-grade state of inflammation.     

Gender specific associations between matrix metalloproteinases and inflammatory markers in post myocardial infarction patients

ObjectiveAtherothrombotic disease in the coronary arteries leads to myocardial infarction (MI) through plaque rupture or erosion of the endothelium, the former mechanism predominating in men and the latter in women. Inflammation is a key feature of these processes, and the interplay between inflammation and matrix metalloproteinases (MMPs) in this context is not fully understood. In this study, we investigated the association between inflammatory markers and MMPs in men and women.MethodsBlood samples were drawn 3 months after a first MI in 387 patients and 387 sex- and age-matched controls (82% men). C-reactive protein (CRP), interleukin-6 (IL-6), IL-8, -18, tumour necrosis factor-α (TNF-α), macrophage chemoattractant protein-1 (MCP-1), MMP-1, -3 and -9 were measured. Coronary angiography was performed in 243 of the patients, and they were classified into 0-, 1-, 2- or 3-vessel disease groups.ResultsCRP, IL-6, -8, -18 and TNF-α were higher, and MMP-3 and -9 were lower, in patients than in controls. A greater proportion of women (49%) had 0-vessel disease than men (16%, p < 0.0001). A gender specific pattern of associations between inflammatory markers and MMPs was found as IL-6 (r_S = 0.29, p < 0.05), IL-18 (r_S = 0.34, p < 0.01) and MCP-1 (r_S = 0.35, p < 0.01) correlated with MMP-3 in female patients, whereas CRP (r_S = 0.23, p < 0.0001), IL-6 (r_S = 0.13, p < 0.05) and IL-8 (r_S = ?0.21, p < 0.01) correlated with MMP-9 in male patients.ConclusionsThe present study demonstrates different patterns of association between inflammatory markers and MMPs in men and women, strengthening the hypothesis of gender specific differences in pathophysiological mechanisms of MI.     

Gender differences in short-term effects of atorvastatin on lipid profile, fibrinolytic parameters, and endothelial function

Background and aimLittle is known about the impact of gender on short-term effects of atorvastatin. We investigated the gender differences in the short-term lipid-lowering and pleiotropic effects of atorvastatin therapy.Methods and resultsSeventy-two consecutive patients including 48 women with primary hypercholesterolemia, were assigned prospectively to treatment with atorvastatin (10 mg/day) for 3 months. We measured fasting lipid concentrations, thiobarbituric acid reactive substances (TBARS) as marker of lipid peroxide, fibrinolytic parameters, and endothelial function by flow-mediated vasodilation of the brachial artery (FMD), at baseline and after 3 months of therapy. We assessed the impact of gender on temporal differences in these parameters.In men, atorvastatin decreased total, low-density lipoprotein (LDL), and small, dense LDL-cholesterol concentrations, and increased FMD after 3 months. In women, atorvastatin decreased TBARS, triglyceride, and total, LDL, small, dense LDL, and remnant-like lipoprotein particle-cholesterol concentrations, and increased FMD after 3 months. Fibrinolytic parameters did not change significantly in either men or women. With respect to the percent change in those parameters after 3 months, TBARS (−17.6 ± 12.4 vs. −0.4 ± 18.8%, p < 0.01) and small, dense LDL-cholesterol (−96.7 ± 8.3 vs. −68.6 ± 29.7%, p < 0.01) decreased to a greater degree in women, although the relative changes in other parameters were similar between men and women.ConclusionsWe found gender differences in some of the lipid altering changes, including TBARS and small, dense LDL-cholesterol concentrations, after short-term atorvastatin therapy, which were greater in women. However, short-term atorvastatin therapy may be beneficial in improving endothelial function equally in both men and women.     

Children with familial hypercholesterolemia are characterized by an inflammatory imbalance between the tumor necrosis factor α system and interleukin-10

ObjectiveFamilial hypercholesterolemia (FH) is associated with increased risk of premature atherosclerosis. Increasing evidence supports involvement of inflammation in atherogenesis. The inflammatory cytokine tumor necrosis factor (TNF)α has been regarded as a key mediator in the development of atherosclerosis due to its involvement in several stages in this process. We hypothesized that children with FH, as a model of early atherosclerosis, have different serum levels of inflammation markers than healthy control children.MethodsWe measured serum levels of TNFα, as well as its endogenous inhibitors (i.e., soluble TNF receptors [sTNFR] 1 and 2) and the anti-inflammatory cytokine interleukin (IL)-10 in healthy children (7–20 years) with (n = 102) and without (n = 48) heterozygote FH as well as adult FH subjects (n = 20) and healthy adult controls (n = 16).ResultsThe main findings were: Compared to control children, FH children had higher serum levels of TNFα, accompanied by lower sTNFRs levels, resulting in an increased TNFα/sTNFRs ratio (P < 0.05), potentially reflecting enhanced TNFα activity. In contrast to the increased TNFα levels, FH children had decreased serum levels of IL-10 (P < 0.01) resulting in an increased TNFα/IL-10 ratio (P < 0.01). We did not observe any difference in the same parameters between adult subjects with and without FH.ConclusionsFH children are characterized by an inflammatory imbalance between TNFα and IL-10, potentially contributing to the accelerated atherosclerotic process in these individuals.     

Association of asymptomatic hyperuricemia and endothelial dysfunction in psoriatic arthritis

IntroductionCardiovascular disease is an increasingly recognized contributor to excess morbidity and mortality in psoriatic arthritis (PsA). Traditional cardiovascular risk factors do not adequately account for the extent of cardiovascular disease in PsA.Aim of the workTo examine the prevalence of subclinical atherosclerosis in patients with PsA to emphasize the potential role of serum uric acid on endothelial dysfunction, as an early predictor for atherosclerosis in PsA patients.Patients and methodsThis study included 60 PsA patients as well as 60 age and sex matched healthy controls. Assay of serum uric acid, interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1) was done for all patients and controls. Patients were subjected to psoriasis area severity index (PASI) and assessment of disease activity. Patients and controls underwent brachial flow-mediated dilatation (FMD) assessment by color duplex sonography to determine endothelial dysfunction as well as extracranial carotid arteries assessment by high-resolution B-mode ultrasound to measure the common carotid intima-media thickness (CIMT) and the detection of atheromatous plaques.ResultsPsA patients have a high significant difference in CIMT, FMD of the brachial artery and mean levels of serum uric acid compared to healthy controls (p < 0.001). PsA patients with hyperuricemia have a high significant difference in CIMT and FMD of the brachial artery than those with normal serum uric acid. Serum uric acid levels showed a high significant positive correlation with each of CIMT, disease duration, markers of inflammation (ESR, CRP, IL-6, sICAM-1), disease activity score in 28 joints (DAS 28) and PASI (r = 0.71, 0.893, 0.956, 0.858, 0.853, 0.877, 0.907, 0.847, respectively, as p < 0.001). A high significant negative correlation was found between serum uric acid levels and FMD of the brachial artery as r = ?0.634, p < 0.001.ConclusionPatients with PsA have a high prevalence of subclinical atherosclerosis dependent on serum uric acid, suggesting that chronic systemic inflammation and endothelial dysfunction appear to be the link between asymptomatic hyperuricemia and atherosclerosis. Therefore, proper control of serum uric acid may play a preventive role in the development of atherosclerosis in PsA patients.     

Homocysteine and endothelial markers are increased in patients with chronic liver diseases

BackgroundHyperhomocysteinaemia is a disorder of methionine metabolism, in which a liver plays a role. It may be frequently due to nutritional deficiencies, particularly low folate status. The aim of the study was to evaluate the serum concentration of homocysteine (Hcy) in patients with chronic liver diseases (CLD), and to assess the relation between Hcy, folate levels, and endothelial markers.MethodsSeventy-one patients with CLD and 51 healthy subjects of similar sex and age were investigated. There were 19 patients with steatosis and 52 patients with fibrosis/cirrhosis, classified by the Child–Pugh score as groups A, B and C. Fasting serum Hcy and folate levels were measured by the IMx diagnostic system (ABBOTT, USA). Plasma thrombomodulin (TM) and von Willebrand factor (vWF) as markers of endothelial dysfunction/damage were determined by ELISA methods.ResultsA significant increase of Hcy in all groups of patients with CLD was found: steatosis (P = 0.0036), fibrosis/cirrhosis — groups A, B and C (P = 0.0067, P < 0.0001, P = 0.0005, respectively). No significant changes of serum folate in CLD patients were observed, but there was an inverse correlation between Hcy and folate concentrations (r² = 0.1076, P = 0.0003). A significant increase of endothelial markers in CLD patients was found: TM in steatosis (P = 0.029), fibrosis/cirrhosis — group A (P = 0.0010), groups B and C (P < 0.0001, respectively), vWF in fibrosis/cirrhosis — group A (P = 0.0003), groups B and C (P < 0.0001, respectively). No significant correlation between serum Hcy and endothelial markers was observed.ConclusionHyperhomocysteinaemia and abnormalities of endothelial function are demonstrated in CLD patients. The impairment of liver metabolism and local changes in vessel integrity are supposed to play a main role.     

Systemic and vascular markers of inflammation in relation to metabolic syndrome and insulin resistance in adults with elevated atherosclerosis risk

ObjectiveIn recent years high sensitive C-reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1) were recognized as risk factors for cardiovascular disease (CVD). The aim of the present study was to investigate the relationship between these vascular and systemic markers of low-grade inflammation and traditional risk factors, the metabolic syndrome (MetS) or insulin resistance (IR).Methods and resultsIn 137 adults (41–78 years) with at least 2 risk factors for atherosclerosis the following parameters were determined: hsCRP, sVCAM-1, sICAM-1, PAI-1, fibrinogen, waist circumference (WC), blood pressure, Body Mass Index (BMI), fasting serum glucose (FSG), insulin, triglycerides (TG), total cholesterol (TC), LDL, and HDL. The presence or absence of MetS according to the AHA/NHLBI Scientific Statement criteria was assessed. IR was defined using the homeostasis model (HOMA-IR). Subjects with MetS had significantly higher values of hsCRP, sICAM-1, sVCAM-1, PAI-1, fibrinogen (each P < 0.05) and lower HDL-levels (P < 0.05) compared with subjects without MetS. Similar results were found using HOMA-IR-quartiles. Subjects in the bottom quartile (HOMA-IR ≤ 1.32) had significantly lower levels of hsCRP, sVCAM-1, sICAM-1, and PAI-1 (each P < 0.05) than subjects in the top quartile (HOMA-IR ≥ 5.03). HDL was significantly higher (P < 0.05) in subjects in the lowest quartile versus those in the highest quartile. Incidentally we found no significant differences in total and LDL cholesterol among MetS, HOMA, and traditional CVD risk factor groups, respectively.ConclusionSystemic and vascular markers of inflammation showed significant associations with IR and the MetS and may be incorporated into traditional CVD risk prediction models. Such models should be established and validated in forthcoming large scale prospective studies on CVD risk.     

Associations between alcohol consumption and selected cytokines in a Swiss population-based sample (CoLaus study)

ObjectiveTo assess the associations between alcohol consumption and cytokine levels (interleukin-1beta – IL-1β; interleukin-6 – IL-6 and tumor necrosis factor-α – TNF-α) in a Caucasian population.MethodsPopulation sample of 2884 men and 3201 women aged 35–75. Alcohol consumption was categorized as nondrinkers, low (1–6 drinks/week), moderate (7–13/week) and high (14+/week).ResultsNo difference in IL-1β levels was found between alcohol consumption categories. Low and moderate alcohol consumption led to lower IL-6 levels: median (interquartile range) 1.47 (0.70–3.51), 1.41 (0.70–3.32), 1.42 (0.66–3.19) and 1.70 (0.83–4.39) pg/ml for nondrinkers, low, moderate and high drinkers, respectively, p < 0.01, but this association was no longer significant after multivariate adjustment. Compared to nondrinkers, moderate drinkers had the lowest odds (Odds ratio = 0.86 (0.71–1.03)) of being in the highest quartile of IL-6, with a significant (p < 0.05) quadratic trend. Low and moderate alcohol consumption led to lower TNF-α levels: 2.92 (1.79–4.63), 2.83 (1.84–4.48), 2.82 (1.76–4.34) and 3.15 (1.91–4.73) pg/ml for nondrinkers, low, moderate and high drinkers, respectively, p < 0.02, and this difference remained borderline significant (p = 0.06) after multivariate adjustment. Moderate drinkers had a lower odds (0.81 [0.68–0.98]) of being in the highest quartile of TNF-α. No specific alcoholic beverage (wine, beer or spirits) effect was found.ConclusionsModerate alcohol consumption is associated with lower levels of IL-6 and (to a lesser degree) of TNF-α, irrespective of the type of alcohol consumed. No association was found between IL-1β levels and alcohol consumption.     

Apolipoprotein B-48 as a determinant of endothelial function in obese subjects with type 2 diabetes mellitus: effect of fenofibrate treatment

ObjectiveElevated triglyceride-rich lipoproteins may contribute to endothelial dysfunction in obese diabetic subjects. We investigated the association between plasma concentrations of chylomicron-related particles and endothelial function, and the corresponding responses to fenofibrate treatment.MethodsPlasma apolipoprotein (apo) B-48 and remnant-like particle (RLP)-cholesterol concentrations were measured in 28 obese subjects with T2DM. Flow-mediated endothelium-dependent dilation (FMD) and glyceryl-trinitrate mediated dilatation (GTNMD) in the brachial artery during reactive hyperaemia were examined by high-resolution ultrasound technique.ResultsIn univariate analysis, plasma apoB-48 and RLP-cholesterol concentrations were inversely associated with brachial artery FMD (r = ?0.425 and ?0.423, respectively, P < 0.05), but not with GTNMD. In regression models including BMI and HOMA score, plasma apoB-48 was an independent predictors (P < 0.05) of brachial artery FMD (β coefficient = ?0.384). Replacing HOMA-IR score with plasma triglyceride, adiponectin or CRP concentrations did not alter the findings. The subjects were then randomized to a 12-week treatment period of either 200 mg micronized fenofibrate or matching placebo. Compared with the placebo group, fenofibrate treatment (200 mg daily for 12 weeks) achieved significant increase in FMD (+34%) and reduction in plasma triglyceride (?42%), apoB-48 (?52%) and RLP-cholesterol (?51%) concentrations. The increase in FMD with fenofibrate was significantly associated with the corresponding decrease in plasma apoB-48 (r = ?0.644, P < 0.02) concentrations.ConclusionsOur findings demonstrate an association between changes in lipid metabolism and improvement in endothelial function in patients with diabetic dyslipidaemia treated with fenofibrate that may involve the effect of apoB-48 on endothelium-dependent vasodilator function.     

Plasma levels of soluble receptor for advanced glycation end products (sRAGE) and proinflammatory ligand for RAGE (EN-RAGE) are associated with carotid atherosclerosis in patients with peritoneal dialysis

ObjectivesThe soluble receptor for advanced glycation end products (sRAGE) exerts a protective effect on the development of atherosclerotic vascular complications by inhibiting RAGE-mediated inflammatory response. In contrast, extracellular newly identified RAGE-binding protein (EN-RAGE) contributes to increased atherosclerosis as a pro-inflammatory ligand for RAGE. We determined the levels of sRAGE and EN-RAGE in peritoneal dialysis (PD) patients and evaluated their relationship with carotid atherosclerosis.MethodsA cross-sectional study was performed in 91 PD patients and 29 control subjects. Carotid IMT (cIMT) and abdominal aortic vascular calcification score (VCS) were evaluated using high-resolution B-mode ultrasonography and plain radiographic film of the lateral abdomen.ResultsPlasma sRAGE and EN-RAGE levels were more than twice as higher in PD patients compared to controls. EN-RAGE showed a strong positive correlation with serum high-sensitivity CRP (p = 0.007) and IL-6 (p = 0.002), whereas sRAGE was negatively associated with those inflammatory markers (p = 0.001, p = 0.031). Even after adjustments for traditional cardiovascular risk factors, both sRAGE and EN-RAGE were independently associated with cIMT (β = ?0.230, p = 0.037, β = 0.155, p = 0.045) and VCS (β = ?0.205, p = 0.049, β = 0.197, p = 0.156). Multivariate logistic analysis revealed that old age (OR 1.14, 95% CI 1.03–1.25, p = 0.009), presence of diabetes (OR 13.4, 95% CI: 1.20–150.18, p = 0.035) and elevated plasma EN-RAGE (OR 2.26, 95% CI: 1.05–5.11, p = 0.048) were significant predictors for the occurrence of carotid atherosclerosis (cIMT > 1.0 mm and/or plaque formation).ConclusionsOur findings suggest that elevated plasma EN-RAGE and decreased sRAGE level could play a crucial role in systemic inflammation and carotid atherosclerosis in PD patients.     

Endothelial function and arterial stiffness in normotensive normoglycemic first-degree relatives of diabetic patients are independent of the metabolic syndrome

Background and aimThe aim of the present study was to investigate endothelial function and arterial stiffness in normotensive normoglycemic first-degree relatives (offspring) of diabetic subjects and to explore the relationship with the metabolic syndrome and its components.Methods and resultsForty-five healthy normotensive normoglycemic subjects (aged 18–42 years), 29 first-degree relatives of diabetic subjects (FDR) and 16 with no parental history of type 2 diabetes mellitus were studied. Endothelial function was measured as flow-mediated dilation of the brachial artery (FMD) and arterial stiffness as carotid-femoral pulse wave velocity (PWV). Insulin resistance was calculated by homeostasis model assessment (HOMA). Plasma levels of inflammation markers (hsCRP, TNF-α, IL-1β, CD40L, VCAM, and ICAM) were evaluated.Normotensive normoglycemic FDR presented a 33% lower flow-mediated dilation than the control group (9.8 ± 5.2 vs. 16.2 ± 7.6%, p < 0.01). FMD was reduced in FDR, with or without insulin resistance, whereas arterial stiffness was significantly increased only in FDR with insulin resistance. To investigate the role of FDR status independently of altered components of the metabolic syndrome, subjects with no altered components of the metabolic syndrome were compared according to their FDR status: FDR subjects with no altered components of the metabolic syndrome presented a blunted endothelial function (lower FMD: 11.2 ± 1.6 vs. 16.8 ± 2.0%, p < 0.05) and stiffer large arteries (higher PWV: 9.6 ± 0.3 vs. 8.8 ± 0.3 m/s, p < 0.05) than controls.ConclusionNormoglycemic first-degree relatives of diabetic subjects have blunted endothelial function and increased stiffness of the large arteries. These alterations are already present at a very young age, before any alteration in glycemic control or blood pressure values can be detected, and are independent of the presence of the metabolic syndrome and its altered components.     

Inflammatory cytokines in insulin-treated patients with type 2 diabetes

ObjectiveAn association between type 2 diabetes mellitus and inflammation has been described in several studies. The aim of this study was to search for the presence of low-grade inflammation in a special group of insulin-treated patients with type 2 diabetes, and to investigate a possible correlation between inflammation and obesity, glucose homeostasis and insulin requirement (IU insulin/kg body weight, BW).MethodsWe studied 85 subjects with type 2 diabetes that were receiving insulin treatment (group A) and 32 receiving sulfonylurea treatment (group B), and 57 subjects without diabetes (group C). Interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and the soluble TNF-α receptors sTNFR-60 and sTNFR-80 were measured in serum samples taken from all patients.ResultsThe mean serum cytokine levels in group A vs. group B were: IL-6, 8.54 ± 11 vs. 2.71 ± 1.9 pg/ml (p = 0.000); TNF-α, 14.33 ± 24 vs. 5.12 ± 15 pg/ml (p = 0.016); sTNFR60, 3.9 ± 2.8 vs. 2.36 ± 1.4 ng/ml (p = 0.000); and sTNFR80, 11.9 ± 7 vs. 9.4 ± 6 ng/ml (p = 0.080). The mean serum cytokine levels in group A vs. group C were: IL-6, 8.54 ± 11 vs. 4.74 ± 7 pg/ml (p = 0.017); TNF-α, 14.33 ± 24 vs. 5.94 ± 3.4 pg/ml (p = 0.003); sTNFR60, 3.9 ± 2.8 vs. 2.54 ± 1.4 ng/ml (p = 0.000); and sTNFR80, 11.9 ± 7 vs. 10.85 ± 8 ng/ml (p = 0.470). A positive association between waist circumference and IL-6 (r = 0.165, p = 0.030) and sTNFR-60 (r = 0.276, p = 0.000) was detected. A significant correlation coefficient was observed between haemoglobin A1c (HbA1c) and both IL-6 (r = 0.278, p = 0.000) and sTNFR-60 (r = 0.293, p = 0.000), when the groups were studied as one. No correlation between inflammation and units of insulin/kg BW was found. In conclusion, low-grade chronic inflammation, as estimated by the relative levels of inflammatory cytokines, was present in patients with type 2 diabetes that were receiving insulin treatment, with significantly higher cytokine levels recorded compared to sulfonylurea-treated patients. In addition, an association between inflammation and both obesity and glucose homeostasis was detected.     

Risk factors of mild cognitive impairment in middle aged patients with type 2 diabetes: a cross-section study

The aim of this study was to evaluate the risk factors of mild cognitive impairment (MCI) in middle-aged patients with type 2 diabetes (T2DM).MethodsMontreal Cognitive Assessment (MoCA) was applied as cognition assessment implement. One hundred and fifty-seven middle-aged type 2 diabetic patients were enrolled in this cross-section study (age 40～69, mean age 55 ± 7). There were 93 patients with MCI (MoCA score < 26) in MCI group and 64 with normal cognitive function (MoCA score ≥ 26) in control group. Information of history of disease, family history, data of BMI, WHR, HbA1c, FINS, C-Peptide (C-P), SBP, DBP, blood lipid (TG, TC, LDL-C, HDL-C and carotid ultrasound (carotid IMT, carotid resistance index [RI]) was collected.ResultsThere were significant differences in the rate of patients with hypertension ([40.63 vs. 58.06%], P = 0.026), duration of diabetes mellitus ([3.09 ± 4.04 y vs. 4.80 ± 4.94 y], P = 0.024), C-P ([2.79 ± 1.09 ng/ml vs. 2.26 ± 1.00 ng/ml], P = 0.008), Max C-IMT ([0.81 ± 0.15 mm vs. 0.91 ± 0.15 mm], P < 0.001), Min C-RI (0.71 ± 0.06 vs. 0.68 ± 0.06, P < 0.05), and no significant differences in the duration of hypertension and hyperlipidemia, BMI, WHR, HbA1c, SBP, DBP and blood lipid between control group and MCI group. MoCA scores were positively correlated with C-P (r = 0.252, P = 0.005), and negatively correlated with the history of hypertension (r = ?0.244, P = 0.002), duration of DM (r = ?0.161, P = 0.044), Max C-IMT (r = ?0.253, P = 0.005) and Min C-RI (r = ?0.183, P = 0.023). Multiple regression analysis showed that history of hypertension (Beta = ?0.267, P = 0.002), C-P (Beta = 0.281, P = 0.001) and Min C-RI (Beta = ?0.221, P = 0.011) were significantly independent determinants for the MoCA scores.ConclusionsThe longer duration of diabetes, history of hypertension, lower serum C-P levels, thickened C-IMT and higher C-RI could be risk factors of MCI in type 2 diabetic patients. This finding could have an important impact on the management of cognitive decline in diabetic patients.     

Is excessive daytime sleepiness a predictor of carotid atherosclerosis in sleep apnea?

ObjectiveTo elucidate the relationship between excessive daytime sleepiness (EDS) in obstructive sleep apnea (OSA) and carotid atherosclerosis determined by ultrasonography and serum surrogate markers.MethodsOne hundred and forty-seven patients (102 males) with snoring and sleep-disordered breathing were investigated. Carotid atherosclerosis was evaluated by serum analysis of high-sensitivity C-reactive protein and fibrinogen and four sonographic indices: intima media thickness (IMT) of the common carotid artery (CCA), IMT from the bulb to the internal carotid artery (ICA), combined IMT measurements from all segments and a plaque score. EDS was assessed by the Epworth Sleepiness Scale (ESS). Pearson correlation analysis, intergroup comparison (ANOVA) and two multiple regression models explored associations between confounders, surrogate markers and EDS.ResultsForty-four patients had no OSA (apnea–hypopnea index AHI < 5 h^?1), 27 mild (5–15), 25 moderate (15–30) and 51 severe OSA (>30). The ESS significantly distinguished severe OSA from non-OSA patients (p = 0.003). It showed significant correlations with the BMI, HbA1c, systolic RR, the AHI, sleep time spent with an oxygen saturation <90%, the respiratory arousal index, IMT of the CCA and combined IMT measurements, but no correlation with serum markers. The ESS was found to be an independent predictor of CCA-IMT in the pre-polysomnographic multiple regression model (p = 0.008), but not in the post-polysomnographic model after including respiratory variables.ConclusionEDS is associated with obesity, diabetes and all respiratory variables in OSA patients and may serve as an independent predictor of carotid atherosclerosis before polysomnography.     

Ketamine does not inhibit interleukin-6 synthesis in hepatic resections requiring a temporary porto-arterial occlusion (Pringle manoeuvre): a controlled, prospective, randomized, double-blinded study

IntroductionPrevious studies have shown that interleukin-6 (IL-6) levels correlated with mortality in critically ill patients.GoalTo determine the effect of ketamine on IL-6 levels in liver resections patients with a temporary porto-arterial occlusion (Pringle manoeuvre).Materials and methodsControlled, prospective, randomized, double-blinded study. One group (n = 21) received ketamine whereas the other group (n = 17) received placebo. IL-6 levels were obtained at baseline, 4, 12, 24 h, 3 and 5 days.ResultsThere were no significant differences in IL-6 levels between the groups (basal P = 089, 4 h P = 0.83, 12 h P = 0.39, 24 h, P = 0.55, 3 days P = 0.80 and 5 days P = 0.45). Both groups had elevated IL-6 levels that became almost undetectable by day 5. There was no major morbidity and no mortality in either group.ConclusionsKetamine does not seem to have an effect on plasma levels of IL-6. This could be interpreted as a potential finding associated with outcome as we did not encounter any deaths or major complications. Further studies will likely be needed to determine the range of IL-6 levels associated with survival and mortality, and whether it could be a predictor of survival.     

Objectively-measured and self-reported physical activity and fitness in relation to inflammatory markers in European adolescents: the HELENA Study

ObjectiveAtherogenesis involves an inflammatory process that occurs early in life even though clinical symptoms are not observed until adulthood. Two important protective factors for low-grade inflammation may be physical activity (PA) and fitness. We examined the independent associations of objective and subjective measurements of PA and fitness with low-grade inflammation in European adolescents.MethodsA total of 1045 adolescents, aged from 12.5 to 17.5 years old from 10 European cities, were selected from the HELENA-Cross-Sectional Study. Objectively-measured and self-reported PA variables were obtained by accelerometry and the International PA Questionnaire for Adolescents, respectively. Overall, cardiorespiratory, muscular and motor fitness variables were assessed by standardized field-based fitness tests and the International Fitness Scale. C-reactive protein (CRP), complement factors 3 (C3) and 4 (C4), interleukin-6 and TNF-α inflammatory markers were measured.ResultsObjectively-measured vigorous PA was inversely associated with C3 (β = ?0.094, P = 0.021) but it did not remain significant after any objective fitness indicator was included in the model. Other objectively measured or self-reported assessments of PA were not significantly associated with inflammatory markers. All objective measures of fitness were inversely associated with CRP, C3 and C4, whereas only self-reported motor fitness remained significantly associated with C3, C4 and TNF-α. All these observations were independent of age, sex, city and body mass index or waist circumference.ConclusionHigh PA in adolescence may play an indirect role on lessening low-grade inflammation through improvements in fitness.