Background-NADPH oxidase is believed to modulate arterial tone, but its role in humans is still unclear. The objective of this study was to evaluate whether NADPH oxidase is involved in flow-mediated arterial dilation (FMD). Methods and Results-Twenty-five patients with hereditary deficiency of gp91 phox , the catalytic core of NADPH oxidase, (X-CGD), 25 healthy subjects, and 25 obese patients matched for sex and age were recruited. FMD, platelet gp91 phox , serum levels of nitrite and nitrate as markers of nitric oxide generation, oxidized low-density lipoprotein, and urinary excretion of isoprostanes as markers of oxidative stress were determined. Platelet gp91 phox expression was downregulated in X-CGD patients (1.0Ϯ0.8 mean fluorescence; PϽ0.001) and upregulated in obese patients (4.1Ϯ2.2 mean fluorescence; Pϭ0.01) compared with healthy subjects (2.9Ϯ1.7 mean fluorescence). Urinary excretion of isoprostanes was reduced in X-CGD patients (41.7Ϯ33.3 pg/mg creatinine; Pϭ0.04) and increased in obese patients (154.4Ϯ91 pg/mg creatinine; PϽ0.001) compared with healthy subjects (69.5Ϯ52.4 pg/mg creatinine). Obese patients had higher serum oxidized low-density lipoprotein than healthy subjects (35.3Ϯ6.7 versus 24.8Ϯ9.8 U/L; PϽ0.001) and X-CGD patients (28.5Ϯ7.2 U/L; PϽ0.001). X-CGD patients had significantly higher FMD (14.7Ϯ5.9%) compared with healthy subjects (7.9Ϯ2.5%; PϽ0.001); obese patients had lower FMD (5.3Ϯ3.0%; Pϭ0.028) compared with healthy subjects. Serum nitrite and nitrate levels were significantly higher in patients with X-CGD (36.0Ϯ10.8 mol/L; Pϭ0.016) and lower in obese patients (9.3Ϯ11.0 mol/L; Pϭ0.001) compared with healthy subjects (27.1Ϯ19.1 mol/L). Serum nitrite and nitrate levels significantly correlated with FMD (R s ϭ0.403, PϽ0.001) and platelet gp91 phox (R s ϭϪ0.515, PϽ0.001). FMD inversely correlated with platelet gp91 phox (R s ϭϪ0.502, PϽ0.001) and isoprostanes (R s ϭϪ0.513, PϽ0.001). Conclusion-This study provides the first evidence that, in humans, gp91 phox is implicated in the modulation of arterial tone.

Objective: The association between hyperuricemia, metabolic syndrome (MS), and atherosclerotic vascular disease has been reported in adults, but very little is known about this association in children. The aims of our study were to ascertain the correlates of uric acid (UA) in a sample of obese children, and to investigate whether UA is associated with carotid intima-media thickness (IMT) independently from classical risk factors including MS. Methods: We analyzed carotid IMT along with serum triglycerides, total and high-density lipoprotein cholesterol, glucose, insulin, insulin resistance index (as homeostasis model assessment of insulin resistance), alanine aminotransferase, g-glutamyltransferase, creatinine, and UA in 120 obese children and 50 healthy control children. Results: UA concentrations were significantly higher in obese children compared with controls; moreover, they correlated with the most established cardiovascular risk factors. In the group of obese children, after adjustment for age, sex, pubertal stage, and creatinine, an independent association between UA levels and the presence of MS syndrome was observed (unstandardized coefficient, 0.044 (95% confidence intervals (CI) 0.015-0.072); P!0.01). Carotid IMT significantly increased in the fourth quartile of UA compared with that in the first, second, and third quartile (0.49 (0.46-0.53), 0.53 (0.49-0.56), and 0.55 (0.52-0.59) vs 0.61 (95% CI, 0.58-0.64); P!0.01). When multivariate analysis was performed after adjusting for age, gender, pubertal stage, creatinine, and MS (considered as a single clinical entity), or the individual components of MS simultaneously included, the association between UA and carotid IMT was significant (P!0.01). Conclusions: In obese children and adolescents, increased UA levels are associated with carotid atherosclerosis.

Nonalcoholic fatty liver disease (NAFLD) has been consistently found to be associated with features of the metabolic syndrome (MS), a condition carrying a high risk of cardiovascular events. The present study aimed to determine whether, in children and adolescents, NAFLD is atherogenic beyond its association with MS and its components. We assessed both flowmediated dilation of the brachial artery (FMD) and carotid intima-media thickness (cIMT), along with lipid profile, glucose, insulin, insulin resistance, and high-sensitivity C-reactive protein (CRPHS), in 250 obese children, 100 with and 150 without NAFLD, and 150 healthy normal-weight children. NAFLD was diagnosed by ultrasound examination and persistently elevated alanine aminotransferase, after exclusion of infectious and metabolic disorders. Compared to controls and children without liver involvement, those with ultrasounddiagnosed NAFLD (and elevated alanine aminotransferase) demonstrated significantly impaired FMD and increased cIMT. Patients with NAFLD had more features of MS and elevated CRPHS levels. In addition, percent FMD was remarkably reduced, whereas cIMT was increased in obese children with MS compared to those without MS. Using logistic regression analysis, the presence of NAFLD was found to be an independent predictor of low percent FMD (odds ratio, 2.25 [95% confidence interval, 1.29 to 3.92]; P 5 0.004) as well as of increased cIMT (1.98 [1.16 to 3.36]; P 5 0.031), after adjustment for age, gender, Tanner stage, and presence of MS. When we analyzed the relations between cIMT and measures of FMD in patients with NAFLD, the disease was associated with increased cIMT in children with impaired FMD status. Conclusion: The presence of liver disease entails more severe functional and anatomic changes in the arterial wall. Its detection may help identify individuals with increased cardiometabolic risk.

Novel lipid-lowering agents have potential to improve the performance of LA, but more evidence is needed. The Multidisciplinary International Group for Hemapheresis TherapY and Metabolic DIsturbances Contrast scientific society aims to establish an international registry of clinical experience on LA combination therapy to expand the evidence on this treatment in individuals at high cardiovascular disease risk.

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Summary. Background: Dark chocolate is reported to decrease platelet activation but the underlying mechanism is still undefined. Dark chocolate is rich in polyphenols that could exert an antiplatelet action via inhibition of oxidative stress. The aim of the present study was to assess if dark chocolate inhibits platelet reactive oxidant species (ROS) formation and platelet activation. Methods: Twenty healthy subjects (HS) and 20 smokers were randomly allocated to receive 40 g of dark (cocoa > 85%) or milk chocolate (cocoa < 35%) in a cross-over, single-blind study. There was an interval of 7 days between the two phases of the study. At baseline and 2 h after chocolate ingestion, platelet recruitment (PR), platelet ROS, platelet isoprostane 8-ISO-prostaglandin F2a (8-iso-PGF2a), Thromboxane (TxA2) and platelet activation of NOX2, the catalytic sub-unit of NADPH oxidase, and serum epicatechin were measured. Results: Compared with HS, smokers showed enhanced PR, platelet formation of ROS and eicosanoids and NOX2 activation. After dark chocolate, platelet ROS ()48%, P < 0.001), 8-iso-PGF2a ()10%, P < 0.001) and NOX2 activation ()22%, P < 0.001) significantly decreased; dark chocolate did not affect platelet variables in HS. No effect of milk chocolate was detected in both groups. Serum epicatechin increased after dark chocolate in HS (from 0.454 ± 0.3 nM to 118.3 ± 53.7 nM) and smokers (from 0.5 ± 0.28 nM to 120.9 ± 54.2 nM). Platelet incubation with 0.1-10 lM catechin significantly reduced PR, platelet 8-iso-PGF2a and ROS formation and NOX2 activation only in platelets from smokers. Conclusions: Dark chocolate inhibits platelet function by lowering oxidative stress only in smokers; this effect seems to be dependent on its polyphenolic content.

Dyslipidemia and obesity are considered strong risk factors for premature atherosclerotic cardiovascular disease and increased morbidity and mortality and may have a negative impact on myocardial function.Our purpose was to assess the presence of early myocardial deformation abnormalities in dyslipidemic children free from other cardiovascular risk factors, using 2-dimensional speckle tracking echocardiography (2DSTE) and 3-dimensional speckle tracking echocardiography (3DSTE).We studied 80 consecutive nonselected patients (6–18 years of age) with hypercholesterolemia (low-density lipoprotein [LDL] cholesterol levels >95th percentile for age and sex). Forty of them had normal weight and 40 were obese (body mass index >95th percentile for age and sex). Forty healthy age-matched children were selected as controls. Left ventricular (LV) global longitudinal, circumferential, and radial strains were calculated by 2DSTE and 3DSTE. Global area strain (GAS) was calculated by 3DSTE as percentage of variation in surface area defined by the longitudinal and circumferential strain vectors. Right ventricular (RV) global and free-wall longitudinal strain and LV and RV diastolic strain rate parameters were obtained. Data analysis was performed offline.LV global longitudinal strain and GAS were lower in normal-weight and obese dyslipidemic children compared with normal controls and reduced in obese patients compared with normal-weight dyslipidemic children. LV early diastolic strain rate was lower compared with normals. RV global and free-wall longitudinal strain was significantly reduced in obese patients when compared with the control group. A significant inverse correlation was found between LV strain, LDL cholesterol levels, and body mass index.2DSTE and 3DSTE show LV longitudinal strain and GAS changes in dyslipidemic children and adolescents free from other cardiovascular risk factors or structural cardiac abnormalities. Obesity causes an additive adverse effect on LV strain parameters and RV strain impairment.