Predicting flow-mediated dilation of brachial artery in systemic lupus erythematosus patients by reproducible and operator-independent inflammatory and immunologic markers and development of a novel score

BackgroundEarly detection of endothelial dysfunction in patients with systemic lupus erythematosus (SLE) is important since they show accelerated atherosclerosis and an increased risk of cardiovascular mortality.AimThe aim of the study was to describe the correlation of flow-mediated dilation (FMD) with common inflammatory and immunological markers in patients with SLE. An attempt was made to predict a model of FMD with the help of these markers.Material and methodsThe study included 44 treatment-naive SLE patients as per American College of Rheumatology (ACR) criteria (1982) and 44 age- and sex-matched healthy controls. Each group consists of 42 females and 2 males. FMD of the brachial artery by B-mode ultrasonography was performed in both groups to compare the FMD value. Serum hsCRP, fibrinogen, uric acid, fasting insulin, serum ferritin, total cholesterol, triglyceride, VLDL, LDL, and HDL levels were measured as markers of inflammation in SLE patients to determine whether there was any correlation with FMD.ResultsThere were no significant differences in age and gender between the SLE and control groups. The mean FMD was 16.85 ± 10.64 and 21.89 ± 4.6 among cases and controls, respectively. FMD was significantly less among SLE patients (p = 0.005). The hsCRP, uric acid, fibrinogen, insulin resistance, and ferritin values were found to have significant correlations with FMD values among treatment-naive SLE patients. Multiple linear regression by the ENTER method was used to predict a model of FMD: FMD = 48.252 − 1.565 hsCRP − 0.143 fibrinogen − 0.217 uric acid + 0.001 ferritin + 7.658 IR.ConclusionInflammatory markers of SLE, such as hsCRP, fibrinogen, insulin resistance, and uric acid positively correlate with FMD values. FMD can be predicted from the value of these biochemical parameters.     

Determinants of atherosclerosis in an Egyptian cohort of systemic sclerosis: Relation to disease activity and severity

BackgroundSystemic sclerosis (SSc) is a rare multi-system autoimmune disease characterized by vascular abnormalities with an increased prevalence of macrovascular disease.Aim of the workTo evaluate macro-vascular disease (atherosclerosis) in SSc patients and determine its relation to the disease activity and severity.Patients and methodsTwenty-five SSc patients and 20 matched controls were included. The modified Rodnan skin score (mRss) and disease severity by Medsger’s severity score were assessed. Carotid intima-media thickness (IMT) and flow mediated vasodilatation (FMD) of the brachial artery were measured. Traditional vascular risk factors were assessed by thorough history taking and laboratory investigations.ResultsThe age of the patients ranged from 15 to 60 years and they were 22 females and 3 males. 15 had limited and 10 diffuse cutaneous SSc. All SSc patients had an increased IMT (1.24 ± 0.29 mm) which was normal in the control subjects (0.77 ± 0.09 mm) (p < 0.0001). SSc patients had significantly lower HDL, thickened IMT and lower FMD than controls (p = 0.005, p < 0.0001 and p < 0.0001 respectively). The younger age of disease onset was significantly associated with more FMD impairment (r = −0.4, p = 0.04) and Medsger’s severity score (r = 0.5, p = 0.009). The mRss and Medsger’s severity score significantly correlated with the IMT (r = 0.84, p = 0.01 and r = 0.56, p = 0.003 respectively). A significant negative correlation was found between FMD and IMT (r = −0.77, p < 0.0001). Medsger’s severity score significantly correlated with FMD (r = −0.44, p = 0.02).ConclusionSSc is associated with an increased risk of atherosclerosis when compared to age and sex-matched controls. Determinants of this include; younger age of disease onset and more sever disease and low levels of HDL.     

Isolated coronary artery ectasia debate: Inflammation versus atherosclerosis

BackgroundThe underlying pathogenesis of isolated coronary artery ectasia (CAE) is still unknown. The aim of this study was to shed light on the potential mechanisms underlying the development of isolated CAE and its relation to carotid intima media thickness (IMT) and certain inflammatory markers especially adhesion molecules and uric acid.MethodsThe study included 16 patients with isolated CAE, 16 patients with obstructive coronary artery disease (CAD) without CAE, and 10 gender and age matched subjects with normal coronary arteries as control group. All patients underwent diagnostic coronary angiography, B-mode ultrasonography to measure carotid IMT, and serum levels of soluble intercellular adhesion molecule (ICAM-1), E-selectin and uric acid.ResultsSerum ICAM-1 levels were found to be significantly higher in patients with isolated CAE compared to CAD and control subjects (p = 0.0001). E-selectin levels showed no difference between the three groups, while serum uric acid was significantly higher in patients with isolated CAE and patients with obstructive CAD compared to control group (p = 0.004). There were no difference in carotid IMT between isolated CAE and CAD. Univariate analysis showed that the carotid IMT, serum levels of ICAM-1, E-selectin, and uric acid were related with CAE. ICAM-1 was the independent variable most strongly associated with CAE by multiple linear regression analysis (p = 0.0001).ConclusionIsolated CAE reflects atherosclerosis associated with high grade vascular inflammation out of proportion to, atherosclerotic involvement. Serum levels of ICAM-1 were the most independent predictor of vascular inflammation.     

Serum sclerostin in acute kidney injury patients

BackgroundMany of the mineral metabolite abnormalities encountered in chronic kidney disease (CKD) patients were found also associated with acute kidney injury (AKI). In the last decade, sclerostin was found to intimately affect bone mineral metabolism in CKD patients. Nothing is known about sclerostin in AKI.ObjectiveWe looked for serum level of sclerostin in AKI patients in comparison to normal control subjects and if there is an impact on metabolic derangement, endothelial function or clinical outcome.Cases and methodsThis is a cross sectional case control observational study of 219 AKI cases (group I) beside 219 age matched normal control subjects (group II). All cases of group I were in the intensive care because of sepsis; 86 had acute on CKD (group Ib), while 133 had de novo AKI (group Ia). All studied subjects underwent estimation of serum sclerostin, parathyroid hormone (PTH), 25 hydroxy vitamin D (25 OH vit D), fibroblast growth factor 23 (FGF23), C-reactive protein (CRP), interleukin 6 (IL6), Homeostatic Model Assessment for Insulin Resistance (Homa IR), beside the routine CBC, kidney and liver function tests, serum calcium, and phosphorus, and flow mediated vasodilation of brachial artery (FMD). Follow-up of group I cases was done till they recovered or passed away.ResultsSerum sclerostin, PTH, FGF23, phosphorus, CRP, IL6, HOMA IR, creatinine, urea, uric acid, ALT, AST and white blood cell count (WBC) were significantly higher while serum calcium, 25 OH vit D, hemoglobin, platelet count and FMD were significantly lower in group I compared to group II (P < 0.001 in all). On the other hand, there was no significant difference in serum sclerostin, PTH, FGfF23, 25 OH vit D, CRP, IL6, Homa IR and FMD between group Ia and Ib. Survivors were younger in age (median 55.5 vs. 60 years, P < 0.04), had lower AST (30.5 vs. 58 units, P < 0.001), had higher platelet count (206 vs 162 × 10⁹/L, P < 0.001), otherwise, there was no significant difference in any of the other parameters between survivors and patients that were lost. Serum sclerostin had strong correlation with FGF23 in group I (r = 0.99, P < 0.001) and group II (r = 1, P < 0.001). Homa IR had positive correlation with serum sclerostin (r = 0.148, P = 0.014) and serum FGF23 (r = 0.142, P = 0.018) in group I.ConclusionSclerostin is intimately related to FGF23. Sclerostin level increases in AKI patients. Both sclerostin and FGF23 might increase insulin resistance but have no impact on FMD. Neither sclerostin nor FGF23 interfere with AKI outcome.     

Aortic velocity propagation: A novel echocardiographic method in predicting atherosclerotic coronary artery disease burden

BackgroundThe major burden of cardiovascular disease mortality around the globe is due to atherosclerosis and its complications. Hence its early detection and management with easily accessible and noninvasive methods are valuable. Aortic velocity propagation (AVP) through color M-mode of the proximal descending aorta determines aortic stiffness, reflecting atherosclerosis. The aim of this study was to find the utility of AVP in predicting coronary artery disease (CAD) burden assessed through SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) score and compared with carotid intima-media thickness (CIMT), which is an established surrogate marker of atherosclerosis.MethodsIn this cross-sectional comparative study, we measured AVP by color M-mode and CIMT by using Philips QLAB-IMT software in 100 patients, who underwent conventional coronary angiogram (CAG) between May 2013 and November 2014. Coronary artery disease is considered significant if >50% diameter stenosis is present in any epicardial coronary artery and insignificant if otherwise.ResultsInitially, to know the normal range we measured AVP and CIMT in 50 patients without any major risk factors for CAD but CAG was not done. Aortic velocity propagation ranged from 46 cm/s to 76 cm/s (mean = 58.62 ± 6.46 cm/s), CIMT ranged from 0.50 mm to 0.64 mm (mean = 0.55 ± 0.03 mm). Among 100 patients who underwent CAG we found 69% had significant CAD, 13% had insignificant CAD, and 18% had normal coronaries. Those with significant CAD had significantly lower AVP (41.65 ± 4.94 cm/s) [F (2,97) = 44.05, p < 0.0001] and significantly higher CIMT (0.86 ± 0.11 mm) [F (2,97) =35.78, p < 0.0001]. AVP had significant strong negative correlation with CIMT (r = −0.836, p < 0.0001, n = 100) and SYNTAX score (r = –0.803, p < 0.0001, n = 69), while CIMT was positively correlated with SYNTAX score significantly (r = 0.828, p < 0.0001, n = 69).ConclusionsAVP and CIMT can predict CAD burden in a robust way. AVP may emerge as an exquisite bedside tool to predict atherosclerotic burden and guide in implementing preventive therapy for cardiovascular disease.     

Plasminogen activator inhibitor-1 (PAI-1) in children and adolescents With Type 1 Diabetes Mellitus: relation to diabetic micro-vascular complications and carotid intima media thickness

BackgroundPlasminogen activator inhibitor-1 (PAI-1) is a fast-acting inhibitor of fibrinolysis that has been linked to increase risk of thrombosis. We determined PAI-1 levels in 80 children and adolescents with type 1 diabetes (T1DM) compared with 40 healthy controls as a potential marker for micro-vascular complications and assessed the relation to carotid intima media thickness (CIMT) as a synergistic risk factor for development of atherosclerosis.MethodsPatients were divided into 2 groups according to micro-vascular complications. Hemoglobin A1c (HbA1c), urinary albumin excretion, fasting serum lipid profile and PAI-1 levels were measured. CIMT of the common carotid artery was assessed using high resolution ultrasonography.ResultsPAI-1 levels were significantly elevated in the group with diabetes compared with control group (p < 0.001). PAI-1 levels were also increased in patients with micro-vascular complications compared with those without (p < 0.001). CIMT was significantly higher in patients, particularly those with micro-vascular complications than patients without complications or controls (p < 0.001). Positive correlations were found between PAI-1 levels and random blood glucose, HbA1c, triglycerides, total cholesterol and CIMT (p < 0.05).ConclusionsIncreased plasma PAI-1 may be involved in the state of hypofibrinolysis in patients with T1DM leading to the occurrence of micro-vascular complications and increased risk of atherosclerosis.     

Insulin resistance as a risk factor for subclinical atherosclerosis in rheumatoid arthritis

BackgroundInsulin resistance (IR) is strongly associated with systemic inflammation. Insulin resistance is known to be increased in patients with rheumatoid arthritis (RA) and has been shown to be a risk factor for both clinical cardiovascular disease and subclinical atherosclerosis.Aim of the workTo study the relationship between insulin resistance, disease activity and subclinical atherosclerosis in RA patients.Patients and methodsForty RA patients and twenty age and sex matched healthy individuals as controls were included. Patients with diabetes mellitus, obesity and hypertension were excluded. Fasting plasma sugar and serum insulin were done, RA disease activity was assessed using the disease activity score (DAS28) and IR was evaluated by the homeostasis model assessment (HOMA2). Carotid artery intima media thickness (IMT) was evaluated using ultrasound.ResultsRA patients had significantly higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) positivity, fasting plasma sugar and fasting serum insulin, HOMA2-IR levels than the controls. IR was present in 33 (82.5%) RA patients while it was present in only one (10%) of the controls (p = 0.001). RA patients with IR had significantly longer disease duration (p = 0.003), higher disease activity (p = 0.000), greater carotid IMT (p = 0.000), and more carotid plaques (p = 0.043) than those without insulin resistance. RA patients with increased IMT had significantly longer disease duration (p = 0.002), higher DAS28 score (p = 0.000) and higher HOMA2-IR (p = 0.000) than those with normal IMT.ConclusionsIn RA patients, IR significantly correlated with both disease activity and disease duration. Our study pointed out a significant association between IR and subclinical atherosclerosis in RA.     

Uric acid as a potential mediator of cardiovascular morbidity in obstructive sleep apnea syndrome

Background and aimsObstructive sleep apnea (OSA) is now considered as an independent risk factor for cardiovascular (CV) disease. Although uric acid is increasingly being implicated in CV morbidity and mortality, no study attempted to determine independent role of uric acid in CV morbidity of OSA patients. We aimed to assess the role of serum uric acid as a potential mechanism of CV morbidity in a nonselected cohort of OSA patients.MethodsThis was a cohort study in which patients who had undergone a formal sleep study for diagnosis of OSA were recruited. Included patients were grouped according to apnea–hypopnea index (AHI) as mild, moderate and severe OSA. Patients with AHI < 5 served as control group. Patients were interrogated as to cardiovascular morbid conditions which included prior history and an established diagnosis of coronary artery disease, cerebrovascular accident, congestive heart failure due to coronary artery disease and arrhythmias.Results436 OSA patients included (72 controls, 97 with mild, 75 with moderate, and 192 with severe OSA). The severe group also had higher serum uric acid level compared with the control and other OSA groups. Linear regression showed that the Ln uric acid was positively associated with Ln AHI score. In unadjusted logistic regression, severe OSA was associated with higher odds of a cardiovascular event, OR = 2.81 (1.307–6.041), p = 0.0081 while the other categories of sleep apnea were not. However, severe OSA was no longer significant after adjusting for age, gender, diabetes mellitus status, hypertension status, BMI, and smoking, OR = 1.882 (0.826–4.287), p = 0.1322. Uric acid was significantly higher in those who had a cardiovascular event even in the mild, moderate and severe OSA groups.ConclusionHyperuricemia is strongly associated with cardiovascular disease in OSA patients. This strong relationship persists even after controlling for well-known traditional risk factors for cardiovascular disease.     

The association between increased carotid intima–media thickness and SYNTAX Score in coronary artery disease: A single center study

BackgroundCarotid artery lesions frequently coexist with coronary arterial disease (CAD). The aim of this study was to investigate the relation between carotid intima-media thickness (CIMT) and the extent of CAD and whether CIMT could be predictive of severity of coronary atherosclerosis.MethodsCoronary angiography and carotid ultrasound evaluations of 100 consecutive patients with CAD who had undergone elective coronary angiography were reviewed. IMT was measured at both carotid arteries. CIMT and severity of CAD relationship based on SYNTAX score was assessed. The relation between CIMT and cardiovascular risk factors was determined.ResultsMean overall SYNTAX score was 15.76 + 4.82. Mean right CIMT was 0.86 ± 0.29 and mean left CIMT was 0.83 ± 0.24. There were no significant correlation between the SYNTAX score and CIMT (r: 10, P: 30). There was significant relationship between hypertension,diabetes and CIMT (P: 0.01).Conclusionwe found no relationship between CIMT and SYNTAX score in patients who underwent coronary angiography. Diabetes mellitus and hypertension are related to increased carotid intima-media thickness.     

Sex and age interaction with genetic association of atherogenic uric acid concentrations

BackgroundHigh serum uric acid levels are associated with gout, atherosclerosis and cardiovascular disease. Three genes (SLC2A9, ABCG2, and SLC17A3) were reported to be involved in the regulation of uric acid levels.ResearchDesign and Methods: SNPs rs2231142 (ABCG2) and rs1165205 (SLC17A3) were genotyped in three cohorts (n = 4492) and combined with previously genotyped SNPs within SLC2A9 (rs6855911, rs7442295, rs6449213, rs12510549).ResultsEach copy of the minor allele decreased uric acid levels by 0.30–0.38 mg/dL for SLC2A9 (p values: 10^?20–10^?36) and increased levels by 0.34 mg/dL for ABCG2 (p = 1.1 × 10^?16). SLC17A3 influenced uric acid levels only modestly. Together the SNPs showed graded associations with uric acid levels of 0.111 mg/dL per risk allele (p = 3.8 × 10^?42). In addition, we observed a sex-specific interaction of age with the association of SLC2A9 SNPs with uric acid levels, where increasing age strengthened the association of SNPs in women and decreased the association in men.ConclusionsGenetic variants within SLC2A9, ABCG2 and SLC17A3 show highly significant associations with uric acid levels, and for SNPs within SLC2A9 this association is strongly modified by age and sex.     

A Study to derive distribution of carotid intima media thickness and to determine its COrrelation with cardiovascular Risk factors in asymptomatic nationwidE Indian population (SCORE-India)

BackgroundThere is presently no data to describe normal distribution of carotid intima-media thickness (CIMT), an established measure of subclinical atherosclerosis, in Indian subjects.MethodsIn this multi-centric study, 1229 subjects with age ≥30 years and no previous cardiovascular disease (CVD) underwent CVD risk factor assessment and CIMT measurement. Mean far wall common carotid artery IMT was measured on both sides and averaged.ResultsMean age of the subjects was 48.0 ± 12.0 years and 54.2% were men. CIMT measurement was feasible in 1157 subjects. Mean, median and 75th percentile values of CIMT for different age-groups were derived for men and women separately. There was a progressive increase in CIMT with increasing age (P < 0.001) and men had higher CIMT values than women (0.608 ± 0.12 mm vs. 0.579 ± 0.11 mm, P < 0.001). The CIMT values were also higher in diabetics (0.635 ± 0.10 mm) and hypertensives (0.624 ± 0.10 mm) as compared to non-diabetics (0.589 ± 0.12 mm, P < 0.001) and non-hypertensives (0.592 ± 0.12, P 0.02) respectively. Among continuous variables, age, systolic blood pressure and fasting blood glucose had strong to modest correlation with CIMT (Pearson's r 0.524, 0.282 and 0.192 respectively, all P values <0.001), whereas body mass index, diastolic blood pressure and serum triglycerides exhibited weak but still statistically significant relationship (Pearson's r 0.069, P 0.019; Pearson's r 0.065, P 0.026; and Pearson's r 0.094, P 0.001, respectively).ConclusionsThis is the first study to provide age- and gender-specific distribution of CIMT in Indian subjects free from CVD. This information should help facilitate further research and clinical work involving CIMT in India.     

The relationship between retinal nerve fiber layer thickness and carotid intima media thickness in patients with type 2 diabetes mellitus

AimsThe aim of the present study was to investigate retinal nerve fiber layer (RNFL) thickness in patients with type 2 diabetes mellitus (T2D) using spectral-domain optical coherence tomography and to evaluate the relationship between RNFL thickness and carotid intima media thickness (CIMT).MethodsThis study included 171 patients with T2D (53.2 ± 8.8 years) and age matched 61 healthy controls (51.9 ± 8.1 years). We evaluated anthropometric and metabolic parameters as well as RNFL and CIMT measurements in patients with T2D and controls. The Mann–Whitney U test was used to compare the continuous variables and the Chi-square test was used to compare categorical variables. Spearmanʼs rank correlation test was used for calculation of associations between variables.ResultsThe average RNFL thickness was 84.82 ± 11.22 μm in patients with T2D and 92.35 ± 8.45 μm in healthy controls (p < 0.001). Mean CIMT values were higher in patients with T2D (0.80 ± 0.1 mm) than the healthy subjects (0.72 ± 0.1 mm) (p < 0.001). A significant negative correlation was found between age and all quadrants of RNFL. There was a negative correlation between average RNFL thickness and HbA1c (r = −0.176), uric acid (r = −0.145), CIMT (r = −0.190) and presence of carotid plaque (r = −0.193). The superior RNFL thickness was negatively associated with HbA1c (r = −0.175), CIMT (r = −0.207) and carotid plaque (r = −0.176). There was also an inverse correlation between the inferior RNFL thickness and HbA1c (r = −0.187) and carotid plaque (r = −0.157).ConclusionThinning of RNFL might be associated with atherosclerosis in patients with T2D.     

Endothelial function and cardiovascular risk in active inflammatory bowel diseases

BackgroundEndothelial dysfunction has been already reported in inflammatory bowel diseases (IBD). However, case series so far examined were rather heterogeneous as for disease severity and subsets investigated.ObjectiveWe evaluated endothelial dysfunction by brachial artery flow-mediated vasodilatation (FMD), and subclinical atherosclerosis by assessment of common carotid intima-media thickness (CCA-IMT) in a cohort of patients with Crohn's disease (CD) or Ulcerative colitis (UC) in active phase compared to healthy control subjects.MethodsForty-nine patients (mean age 41 ± 16 years), 25 with CD and 23 with UC, and forty controls (mean age 45 ± 15 years) were enrolled. Diagnosis was based on the standard clinical, endoscopic and histological criteria. Disease activity was assessed by Crohn's Disease Activity Index or Disease Activity Index. All patients, were under medical treatment as appropriate.ResultsFMD values were lower in IBD patients than controls (6.1 ± 3.0 vs 8.2 ± 3.4. p = 0.003); no difference was seen between UC/CD groups (5.9 ± 3.5 vs 6.3 ± 2.6, p = 0.67). No changes in statistical differences occurred after adjustment for age, gender, body mass index and family history of cardiovascular disease. Finally, no differences in IMT values were seen between IBD patients and controls. Disease duration and medical treatment did not affect endothelial function.ConclusionsOur study showed a lower FMD in IBD patients. Inflammation and immune response could explain endothelial dysfunction, which is the earliest stage of atherosclerotic process. IBD patients in active phase might therefore be at higher risk for atherosclerosis progression.     

The role of flow-mediated dilatation and high sensitive C-reactive protein in paroxysmal atrial fibrillation

BackgroundAtrial fibrillation (AF) is the most common type of arrhythmia and recognized as a risk factor for thromboembolism. Endothelial damage or dysfunction may contribute to increase the risk of thromboembolism via the mediation of a prothrombotic or hypercoagulable state.ObjectivesThe aim of the current study is to investigate endothelial dysfunction (represented by brachial flow-mediated dilatation “FMD”) and inflammation (represented by hs-CRP) in patients with paroxysmal atrial fibrillation.Subjects and methodsForty-two patients with AF taken from the Cardiology Department and Outpatients Clinic, Specialized Medical Hospital, Mansoura University, in the period between February 2011 and May 2011 were enrolled in our study, the patients were then subsequently divided according to the clinical type of AF into Group I: comprised 20 patients with paroxysmal AF (PAF) with mean age 57.35y. Group II: comprised 22 patients with chronic AF (CAF) with mean age 57.68y. Twenty control subjects without AF were enrolled in this study (Group III). Patients and control groups were subjected to clinical evaluation, electrocardiography (ECG), echocardiography and brachial FMD (using external brachial ultrasonography. Serum level of hs-CRP was assessed in all subjects. The diameter change induced by FMD was expressed as the percent change relative to that at the initial scan (FMD%) according to the following equation:$\text{FMD}\%=\frac{\text{Maximum diameter}-\text{baseline diameter}}{\text{Baseline diameter}}\times 100\text{.}$ResultsLeft atrial diameter was significantly increased when compared either GI or GII with control group (3.96 ± 0.27; 4.7 ± 0.48 vs 3.05 ± 0.35 cm) (P < 0.001). Brachial flow-mediated dilatation difference and percentage change of FMD were significantly lower in groups I and II in comparison to group III (0.09 ± 0.05; 0.09 ± 0.04 vs 0.79 ± 0.07 mm) and (1.96 ± 0.98; 1.99 ± 0.89 vs 18.3 ± 3.26) (P < 0.001). High sensitive CRP was significantly higher when compared either group I or group II with control group. Also hs-CRP has significantly increased when compared GII with group I (8.35 ± 1.55; 10.58 ± 1.75 vs 3.61 ± 0.61 mg/L) (P < 0.001).ConclusionPatients with PAF are comparable in the degree of endothelial dysfunction (reflected as impaired brachial artery FMD) and inflammatory element (reflected as a higher serum hs-CRP) to CAF. This may explain why the risk of thromboembolism in PAF is comparable with that in CAF patients.     

Disfunción endotelial en niños con enfermedad renal crónica

Background and objectiveCardiovascular disease is the main cause of death in children with chronic kidney disease. Inflammation and endothelial dysfunction are found in the majority of these patients and are factors associated to cardiovascular disease. Flow mediated dilatation (FMD) is a surrogate marker validated for evaluating endothelial dysfunction. Our objective was to identify risk factors associated to endothelial dysfunction in children with chronic kidney disease.Materials and methodsChildren 2-16 years of age were studied. Clinical information and biochemical variables were gathered, including intact parathyroid hormone (iPTH), interleukins 6 and 1β, high sensitivity C reactive protein (hsCRP), reduced glutathione, nitric oxide, malondialdehyde and homocysteine. FMD was measured, and considered altered if < 7%.ResultsIncluded were 129 patients aged 13.1 ± 2.6 years. FMD < 7% was found in 69 (52.7%). Patients with altered FMD had higher levels of triglycerides and hsCRP than those with normal FMD (145.5 vs. 120.0 mg/dL, P = .042, and 1.24 vs. 0.55 U/L, P = .007, respectively), as well as higher frequency of low iPTH (19.1 vs. 4.9%, P = .036). Levels of hsCRP correlated significantly with FMD (Rho = −0.28, P = .003). Patients with low iPTH (OR 4.41, 95% CI 1.13-17.27, P = .033) and increased hsCRP (OR 2.89, 95% CI 1.16-7.17, P = .022) had higher adjusted risk of having FMD < 7%.ConclusionsHypertriglyceridemia, inflammation and low iPTH associated significantly with altered FMD. They are frequent, treatable risk factors for cardiovascular disease.     

Asociación del nivel de ácido úrico en suero con los beneficios del control intensivo de la presión arterial

Introduction and objectivesIntensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether the serum uric acid concentration at baseline alters the benefits of intensive SBP control is unknown.MethodsThe STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to < 130 mmHg) and standard (SBP target of 130 to < 150 mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. This post hoc analysis was performed to examine whether the effects of intensive SBP intervention differed by the baseline uric acid concentration using 2 models: restricted cubic spline curves and subgroup analyses, both based on the Fine-Gray subdistribution hazard model in the analysis of the primary outcome and secondary outcomes (excluding all-cause death). In the analysis of all-cause death, the Cox regression model was used. We also examined the change in the follow-up uric acid concentrations.ResultsOverall, the risk of the primary outcome rose as the cumulative uric acid concentration increased in both the intensive and standard treatment groups. Patients with intensive treatment had a lower multivariable-adjusted subdistribution hazard ratio for the primary outcome, but with a wide overlap of 95%CI. Next, we stratified patients according to their baseline uric acid concentration (tertile 1 [T1], < 303.0 μmol/L; tertile 2 [T2], 303.0 to < 375.8 μmol/L; and tertile 3 [T3], ≥375.8 μmol/L). Subgroup analyses using tertiles provided HRs and 95%CI in T1 (HR, 0.55; 95%CI, 0.36–0.86; P = .008), T2 (HR, 0.80; 95%CI, 0.56–1.14; P = .22) and T3 (HR, 0.86; 95%CI, 0.60–1.21; P = .39), with an interaction P value of .29. The results for most of the secondary outcomes followed the same trends.ConclusionsThere was no evidence that the benefit of the intensive SBP control differed by baseline uric acid concentrations. This trial was registered at ClinicalTrial.gov (Identifier: NCT03015311).     

Serum Uric Acid concentration is associated with insulin resistance and impaired insulin secretion in adults at risk for Type 2 Diabetes

AimsInsulin resistance (IR) predisposes to type 2 diabetes mellitus (T2DM). Although previous studies have associated serum uric acid concentration with IR in T2DM, its association with impaired insulin secretion and beta-cell dysfunction in subjects at risk for developing T2DM remains uncertain. Thus, we aimed to analyze the association of serum uric acid concentration with IR using surrogate insulin resistance/secretion and beta-cell function indices in subjects at risk for developing T2DM.MethodsThis is a cross-sectional study that included 354 subjects who underwent an oral glucose tolerance test who had at least two risk factors for T2DM without any chronic disease.ResultsParticipants were 51 ± 8 years old, 72.2% were women, had a mean body mass index of 29.9 ± 6.5 kg/m² and mean serum uric acid concentration of 5.7 ± 1.3 mg/dL. HOMA-IR, first-phase insulin secretion (S1Ph_OGTT), second-phase insulin secretion (S2Ph_OGTT), Matsuda and disposition indices were significantly correlated with serum uric acid concentrations (r = 0.239, r = 0.225, r = 0.201, r = ?0.287, r = ?0.208; respectively). After multiple linear regression analysis, serum uric acid concentration was independently associated with HOMA-IR (β = 0.283), HOMA-B (β = 0.185), S1Ph_OGTT (β = 0.203), S2Ph_OGTT (β = 0.186), and Matsuda Index (β = ?0.322). A serum uric acid concentration of 5.5 mg/dL had the best sensitivity/sensibility to identify subjects with IR (HOMA-IR ≥2.5).ConclusionsSerum uric acid concentration is significantly associated with IR and impaired insulin secretion, but not with beta-cell dysfunction, in subjects at risk for developing T2DM.     

Uric acid and high sensitive C-reactive protein are associated with subclinical thoracic aortic atherosclerosis

Background and purposeThe detection of atherosclerotic lesions in the aorta by transesophageal echocardiography (TEE) is a marker of diffuse atherosclerotic disease. Hyperuricemia is a well-recognized risk factor for cardiovascular diseases. However, no data are available concerning the relationship between serum uric acid (UA) and subclinical thoracic aortic atherosclerosis. We aimed to investigate the association between thoracic aortic atherosclerosis and serum UA level.MethodsWe studied 181 patients (mean age 46.3 ± 8 years) who underwent TEE for various indications. Four different grades were determined according to intima–media thickness (IMT) of thoracic aorta. UA and other biochemical markers were measured with an automated chemistry analyzer.ResultsTEE evaluation characterized thoracic aortic intimal morphology as Grade 1 in 69 patients, Grade 2 in 52 patients, Grade 3 in 31 patients, and Grade 4 in 29 patients. The highest UA level was observed in patients with Grade 4 IMT when compared with Grade 1 and 2 IMT groups (p < 0.001 and p = 0.014, respectively). UA levels in patients with Grade 3 and Grade 2 IMT were also higher than patients with Grade 1 IMT group (p < 0.001, for all). In multiple linear regression analysis, IMT was independently associated with UA level (β = 0.350, p < 0.001), age (β = 0.219, p = 0.001), total cholesterol (β = ?0.212, p = 0.031), low-density lipoprotein cholesterol (β = 0.350, p = 0.001), and high sensitivity C-reactive protein (hsCRP) levels (β = 0.148, p = 0.014).ConclusionUric acid and hsCRP levels are independently and positively associated with subclinical thoracic atherosclerosis.     

Correlation of metabolic syndrome severity with cardiovascular health markers in adolescents

Background and ObjectivesThe presence of metabolic syndrome (MetS) in childhood is a significant risk factor for later cardiovascular disease (CVD). Recent data showed temporal decreases in a sex- and race/ethnicity-specific MetS severity z-score among U.S. adolescents. Our goal was to characterize the relationship of this MetS z-score with other CVD risk indicators and assess their temporal trends and lifestyle influences.MethodsWe analyzed 4837 participants aged 12–20 years from the National Health and Nutrition Examination Survey by 2-year waves from 1999 to 2012. We used linear regression to compare MetS z-score and dietary factors with serum levels of low-density lipoprotein (LDL), apolipoprotein-B (ApoB), high-sensitivity C-reactive protein (hsCRP) and uric acid.ResultsMetS severity z-score was positively correlated with LDL, ApoB, hsCRP, and uric acid measurements (p < 0.0001 for all). These correlations held true among individual racial/ethnic groups. LDL, ApoB, and hsCRP measurements decreased over time among U.S. adolescents (p = 0.002, p < 0.0001, and p = 0.024, respectively). Saturated fat consumption was positively correlated with LDL (p = 0.005) and ApoB (p = 0.012) and inversely related to serum uric acid (p = 0.001). Total caloric intake was inversely related to LDL (p = 0.003) and serum uric acid (p = 0.003). Unsaturated fat, carbohydrate, and protein consumption were not related to LDL, ApoB, hsCRP, or serum uric acid.ConclusionsThere is a positive correlation between MetS severity and all four CVD risk indicators studied. LDL, ApoB, and hsCRP showed favorable temporal trends, which could be related to similar trends in MetS z-score. These data support the importance of considering multiple inter-related factors in clinical CVD risk assessment.     

Association between serum uric acid (SUA) levels and metabolic syndrome (MetS) components in personnel of Shahroud University of Medical Sciences

AimsSerum uric acid level has been suggested to be associated with metabolic syndrome risk factors. However, the association between metabolic syndrome and serum uric acid is still controversial and challenging. This study was aimed to investigate the association between serum uric acid levels and metabolic syndrome components in personnel of the Shahroud University of Medical Sciences.Material and methodsThis case–control study was conducted on 499 personnel aged 30–60 years old who were working in Shahroud University of Medical Sciences, in 2015. MetS was defined according to the National Cholesterol Education Program (NCEP) criteria. The relationship between serum UA level and the number of metabolic components was determined by linear regression analysis.ResultIn this study, the mean concentration of serum uric acid in men with the syndrome was higher than that in women. Mean serum UA level increased as the number of metabolic factors increased. The mean serum uric acid levels was 4.98 ± 1.64 in patients with metabolic syndrome and 4.5 ± 1.28 in non-patients (p = 0.005). Subject with abnormal uric acid were almost 2.62 times more likely than other subject to develop the syndrome.ConclusionsThe results of this study showed that only hypertriglyceridemia is a component which increases the risk of hyperuricemia. In addition, hyperuricemia increases the risk of metabolic syndrome by more than two fold. It seems that high uric acid can be considered as a predisposing factor for metabolic syndrome; thus, it is recommended to measure serum uric acid in routine tests.