Surrogate Marker Of Endothelial Dysfunction Research Articles

Circulating Serum Cystatin C as an Independent Risk Biomarker for Vascular Endothelial Dysfunction in Patients with COVID-19-Associated Multisystem Inflammatory Syndrome in Children (MIS-C): A Prospective Observational Study.

Multisystem inflammatory syndrome in children (MIS-C) is a new clinical entity that has emerged in the context of the COVID-19 pandemic. Despite the less severe course of the disease, varying degrees of cardiovascular events may occur in MIS-C; however, data on vascular changes occurring in MIS-C are still lacking. Endothelial dysfunction (ED) is thought to be one of the key risk factors contributing to MIS-C. We conducted a prospective observational study. We investigated possible manifestations of cardiac and endothelial involvement in MIS-C after the treatment of the acute stage and potential predictive biomarkers in patients with MIS-C. Twenty-seven consecutive pediatric subjects (≥9 years), at least three months post-treated MIS-C of varying severity, in a stable condition, and twenty-three age- and sex-matched healthy individuals (HI), were enrolled. A combined non-invasive diagnostic approach was used to assess endothelial function as well as markers of organ damage using cardiac examination and measurement of the reactive hyperemia index (RHI), by recording the post- to pre-occlusion pulsatile volume changes and biomarkers related to ED and cardiac disease. MIS-C patients exhibited a significantly lower RHI (indicative of more severe ED) than those in HI (1.32 vs. 1.80; p = 0.001). The cutoff of RHI ≤ 1.4 was independently associated with a higher cardiovascular risk. Age and biomarkers significantly correlated with RHI, while serum cystatin C (Cys C) levels were independently associated with a diminished RHI, suggesting Cys C as a surrogate marker of ED in MIS-C. Patients after MIS-C display evidence of ED, as shown by a diminished RHI and altered endothelial biomarkers. Cys C was identified as an independent indicator for the development of cardiovascular disease. The combination of these factors has the potential to better predict the cardiovascular consequences of MIS-C. Our study suggests that ED may be implicated in the pathophysiology of this disease.

The penile duplex ultrasound: How and when to perform it?

Because it is a superficial structure, the penis is ideally suited to ultrasound imaging. A number of disease processes, including Peyronie's disease, penile fractures and tumors, are clearly visualized with ultrasound. Baseline and dynamic assessment of cavernosal arterial changes after pharmaco-stimulation with alprostadil allows standardized diagnosis of arterial and venogenic causes of erectile dysfunction (ED). To illustrate how to correctly perform flaccid and dynamic penile duplex ultrasound (D-PDU) and in which patients to recommend it. An extensive search of the literature was carried out on Pubmed with the insertion of the following Medical Subjects Headings (MeSH) terms and keywords "penile color Doppler ultrasound" "peak systolic velocity" "end-diastolic velocity", "acceleration time", "resistance index". In our experience, arterial erectile dysfunction is identified after standardized intracavernous injection (ICI) of alprostadil (10mcg) when values of peak systolic velocity (PSV) are <35cm/s and, in the most severe forms, for values <25cm/s. Arterial insufficiency can also be identified by increased acceleration time (AT) values (>110ms) and/or by a lack of visualization of helicine arteries at power Doppler mode along with incomplete achievement of penile rigidity. The veno-occlusive incompetence is determined when end-diastolic velocity (EDV) values are >4.5-5cm/s or in the case of resistance index (RI) values <0.75. The assessment of additional surrogate markers of endothelial dysfunction, that is, intima-media thickness, mean platelet volume (MPV), endothelial progenitor cells (EPC), endothelial cell specific molecule-1(endocan) are also useful in assessing the patient's cardiovascular risk but are still considered investigational in the interpretation of D-PDU results. D-PDU scan after ICI with vasoactive drugs is a safe procedure and represents the gold standard for the diagnostics of penile pathologies and should be performed in men with ED not responding to oral conventional therapies and/or in those requiring accurate stratification of cardiovascular risk.

Association between coronary artery disease severity and videocapillaroscopic findings of nail fold capillary circulation

Aim: Endothelial dysfunction plays a significant role in the etiology of coronary artery disease (CAD), which develops due to atherosclerosis, and is a major cause of morbidity and mortality. Nail fold videocapillaroscopy (NVC) assessment is a surrogate marker of endothelial dysfunction. To the best of our knowledge, the relationship between the microcirculation features on NVC and the severity of coronary atherosclerosis has not previously been investigated. In this study, we aimed to investigate the relationship between severity of coronary atherosclerosis (shown by SYNTAX and Gensini scores) and NVC findings which is an indirect indicator of systemic endothelial damage.Methods: The study was designed as a retrospective cohort. One-hundred consecutive patients who underwent coronary angiography (CAG) and had at least one lesion in the epicardial coronary arteries, narrowing the lumen by more than 50%, were included. Coronary angiographic images of the patients were evaluated by two experienced interventional cardiologists and SYNTAX and Gensini scores were calculated. Patients were divided into three groups according to the SYNTAX scores (SYNTAX score ≤22, between 23-32, and ≥33) and two groups according to Gensini scores (Gensini score ≥30 and ˂30). The NVC examinations were performed by a rheumatologist who was experienced in this field, and the reduction in capillary density, presence of dilated capillaries, giant capillary, microhemorrhage, branching, disorganization, tortuosity, avascular area, extravasation, and neoangiogenesis were investigated.Results: Dilated capillary vessels were more common in diabetic patients (85%) than in non-diabetics (66.7%) (P=0.041). Besides, there was no significant difference in NVC parameters between patients with and without diabetes mellitus (P>0.05 for all), with and without hypertension (P>0.05 for all). There was no significant difference between the SYNTAX groups in terms of NVC findings (P>0.05 for all). The NVC findings were similar between Gensini groups (P>0.05 for all). Conclusion: The severity of atherosclerosis surrogated by SYNTAX and Gensini scores was not related to the NVC findings. Therefore, NVC is inappropriate for determining the severity of CAD.

P0848PROSPECTIVE OPEN-LABEL EXPLORATIVE RANDOMISED SINGLE-CENTRE COMPARATIVE STUDY TO DETERMINE THE EFFECTS OF VARIOUS INTRAVENOUS IRON PREPARATIONS ON MARKERS OF OXIDATIVE STRESS AND KIDNEY INJURY IN CHRONIC KIDNEY DISEASE (IRON-CKD)

Abstract Background and Aims Iron deficiency is commonly treated with intravenous (IV) iron where oral iron is insufficient or cannot be tolerated. While IV iron is considered efficient and effective, safety concerns exist regarding the potential effect of IV iron on oxidative stress, inflammation and endothelial function. Transferrin is unable to saturate all the iron administered. Consequently, evidence has suggested differential generation of “free” or catalytic labile iron, depending on iron preparation. Labile iron stimulates lipid oxidation and free radical generation which can lead to increased oxidative stress, inflammation and endothelial dysfunction. The comparative risk of IV iron preparations has not been previ-ously extensively assessed. The possibility of IV iron leading to changes in oxidative stress, inflammation and endothelial function is assessed in this study. The potential interplay of IV iron changes with signaling pathways may lead to renal damage depending on the iron formulation used. This may lead to tubular and glomerular injury manifested as raised Neutrophil gelatinase-associated lipocalin (NGAL) levels in patients with chronic kidney disease (CKD). Method IRON-CKD is a prospective open-label explorative randomized, single-centre study assessing comparative safety and efficacy of three parenteral iron preparations. Patients with established CKD stages 3-5 and serum ferritin (SF) &amp;lt; 200microg/L and/or transferrin saturation (TS) &amp;lt;20% were recruited and randomized in a 1:1:1:1 ratio. The groups received a single infusion of 200mg Iron Dextran (Cosmofer ®), 200 mg Iron Sucrose (Venofer ®), and Iron Isomaltoside (Monofer ®) either as low (200mg) or high dose (1000mg). The patients were followed-up after IV iron at 2 hours and then at 1 day, 1 week, 1 month and 3 month intervals. Oxidative stress markers (Thiobarbituric acid reactive substances (TBARS)), inflammatory markers (Interleukin-1b, Interleukin-6, Interleukin-8, Interleukin-10) and surrogate markers of endothelial dysfunction (E-selectin, P-selectin) were measured. NGAL levels for establishment of potential acute kidney insult were measured. Free catalytic iron generation was also measured using the FeROS™ as-say. Data are presented as means and standard error of the mean (SEM). Statistical analysis was carried out using ANOVA. A p value of &amp;lt;0.05 was statistically significant. Results Forty patients were recruited and randomised with 10 per group. The mean age was 58.8 (±2.2) years and 23 (58%) were male. Free labile iron and TBARS increased within 2 hours of infusion (1.4 ΔFU/min (±0.5) to 7.4 ΔFU/min (±2.4)) (1083.0 nM (± 117.1) to 1552.6 nM (±156.0)) respectively with complete recovery within one week. TBARS and free labile iron were more pronounced within one day in the group receiving high dose Monofer® (TBARS: pre-infusion: 846.0 nM (±108.9) to 1865.0 nM (±203.2); Free labile iron: pre infusion: 0.3 ΔFU/min (±0.2) to 19.6 ΔFU/min (±7.1)). These were statistically significant with p &amp;lt; 0.001. These returned to pre-dosage levels and did not translate to any detriment in markers of inflammation or endothelial function (E-selectin or P-selectin). There was a non-statistically significant increase in Interleukin-10 (an anti-inflammatory cytokine) 2-hours post-infusion which was transient. Intravenous iron cumulatively and comparatively did not lead to a significant increase in NGAL (pre-infusion 570.5 ng/ml (±52.8); post-infusion 547.8 ng/ml (SEM: ±50.5); 3 months interval 534.8 ng/ml (±52.8)) at any given time point. Conclusion High dose of IV iron leads to a transient increased generation of free iron which disappears within one week. Iron therapy, at least in the short term, does not adversely affect markers of acute kidney injury, endothelial function, inflammation and oxidative stress status. This mechanistic data indicates that IV iron at both low and high doses is safe in patients with chronic kidney disease.

Study of carotid intima media thickness as surrogate marker of endothelial dysfunction in early chronic kidney disease patients

Background: Micro-albuminuria has been extensively regarded as a marker of generalized vascular endothelial impairment. Endothelial dysfunction is an early marker for atherosclerosis and can be detected before structural changes to the vessel wall.Methods: This case control study was carried out in the Department of Medicine, MGM Medical College and MY Hospital, Indore, India, from December 2017 to February 2019, with sample size of 100 including 50 cases and 50 controls.Results: In our study, mean CIMT of cases and controls was 0.83±0.10mm and 0.63±0.14mm in right respectively. Mean CIMT of cases and controls was 0.83±0.10 and 0.64±0.07mm in left side respectively. These results are suggestive that mean CIMT are significantly higher (p values &lt;0.05 in each) in cases than controls. 90% of cases were in stage II of CKD and their mean CIMT was 0.83±0.09mm and 10% of cases were in stage I of CKD and their mean CIMT was 0.80±0.09mm and there were no significant difference in mean CIMT between CKD stage I and CKD stage II in cases. There were significant positive correlation between Mean CIMT and Age of cases (Pearson correlation=0.382, p-value 0.006).Conclusions: Increased CIMT was found in all the cases as compare to controls so, increased CIMT can be used as an early marker of atherosclerosis in early CKD patients. Further study in large number of subjects may help to confirm or exclude the findings.

Effect of treatment with testosterone on endothelial function in hypogonadal men: a systematic review and meta-analysis.

Despite several studies showing an inverse correlation of total testosterone with endothelial damage, the effect of testosterone replacement therapy (TTh) on endothelial function has been scarcely investigated. In order to systematically assess the relationship between endothelial dysfunction and TTh, we performed a review and meta-analysis of available prospective and cross-sectional studies. A thorough research was performed on MEDLINE for hypogonadism and endothelial dysfunction. We retrieved 28 papers, among which 23 were excluded for different reasons: five papers accounting for six studies (two crossover randomized clinical trial (RCT), three observational, one placebo controlled RCT) were therefore included in analysis. Overall, 86 patients with hypogonadism were included in analysis (mean age 49.57 ± 8.85 years). Baseline total testosterone serum levels were 8.11 ± 2.42 nmol/L and significantly increased while undergoing TTh (standard mean difference (SMD) 2.93 nmol/L, 95% confidence interval (CI) 1.89:3.97, p < 0.001). Due to the paucity of studies available, flow-mediated dilation (FMD) was chosen as the best surrogate marker of endothelial dysfunction. FMD did not significantly change after testosterone administration (SMD -0.22, 95% CI -1.29:0.84, I2 = 90%); acute testosterone administration was associated with an increase in FMD, whereas a reduction in FMD emerged following chronic treatment, but statistical significance was not reached for both effects. This is the first meta-analysis study assessing the influence of TTh on endothelial function; however, results are far from conclusive, as proven by the high heterogeneity.

Association of low serum Meteorin like (Metrnl) concentrations with worsening of glucose tolerance, impaired endothelial function and atherosclerosis

ObjectiveMeteorin-like (Metrnl) is a novel secreted protein that has a beneficial effect on glucose homeostasis with anti-inflammatory properties. Our goal is to determine whether low serum Metrnl levels are associated with worsening of glucose tolerance, impaired endothelial function, and atherosclerosis. MethodsThis study included 260 adults, 89 of whom had normal oral glucose tolerance (nOGT), 77 with glucose tolerance impairment (GTI) and 94 with type 2 diabetes (T2DM). Insulin resistance was assessed by evaluating the homeostasis model assessment of insulin resistance (HOMA-IR). Serum Metrnl level, proinflammatory, biochemical, endothelial and atherosclerosis parameters were measured. ResultsSerum Metrnl levels decreased significantly in patients with T2DM versus subjects with nOGT (P < 0.001). Metrnl levels were negatively correlated with fasting blood glucose, 2-h postload glucose (2 h-PLG), fasting insulin, HOMA-IR, HbA1c, high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), Carotid intima media thickness (CIMT), brachial-ankle pulse wave velocity (baPWV), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. High serum Metrnl level was significantly correlated with reduced risk of T2DM as revealed by multivariate logistic regression analysis after control of potential risk factors for diabetes. Furthermore, the association remains significant after further adjustment for IL-6, TNF-α, hs-CRP, CIMT, baPWV, ICAM-1, VCAM-1 and E-selectin. ConclusionsLow Serum Metrnl may be associated with worsening of glucose tolerance, impaired endothelial function and atherosclerosis. It may also be considered a possible surrogate marker of endothelial dysfunction, and atherosclerosis and an independent risk factor of T2DM.

Visceral adiposity index and triglyceride/high-density lipoprotein cholesterol ratio in hypogonadism.

Cardiometabolic risk is high in patients with hypogonadism. Visceral adiposity index (VAI) and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio are the practical markers of atherosclerosis and insulin resistance and independent predictors of cardiaovascular risk. To date, no study has evaluated VAI levels and TG/HDL-C ratio in hypogonadism. A total of 112 patients with congenital hypogonadotrophic hypogonadism (CHH) (mean age, 21.7 ± 2.06 years) and 124 healthy subjects (mean age, 21.5 ± 1.27 years) were enrolled. The demographic parameters, VAI, TG/HDL-C ratio, asymmetric dimethylarginine (ADMA), high-sensitivity C-reactive protein (hs-CRP), and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured for all participants. The patients had higher total cholesterol (p = 0.04), waist circumference, triglycerides, insulin, and HOMA-IR levels (p = 0.001 for all) than the healthy subjects. VAI and ADMA and TG/HDL-C levels were also higher in patients than in healthy subjects (p < 0.001 for all). VAI was weakly correlated with ADMA (r = 0.27, p = 0.015), HOMA-IR (r = 0.22, p = 0.006), hs-CRP (r = 0.19, p = 0.04), and total testosterone (r = -0.21, p = 0.009) levels, whereas TG/HDL-C ratio was weakly correlated weakly with ADMA (r = 0.30, p = 0.003), HOMA-IR (r = 0.22, p = 0.006), and total testosterone (r = -0.16, p = 0.03) levels. Neither VAI nor TG/HDL-C ratio determined ADMA, HOMA-IR, and hs-CRP levels. The results of this study demonstrate that patients with hypogonadism have elevated VAI and TG/HDL-C ratio. These values are significantly correlated with the surrogate markers of endothelial dysfunction, inflammation, and insulin resistance. However, the predictive roles of VAI and TG/HDL-C ratio are not significant. Prospective follow-up studies are warranted to clarify the role of VAI and TG/HDL-C ratio in predicting cardiometabolic risk in patients with hypogonadism.

Endothelial Microparticles From Acute Coronary Syndrome Patients Induce Premature Coronary Artery Endothelial Cell Aging and Thrombogenicity: Role of the Ang II/AT1 Receptor/NADPH Oxidase-Mediated Activation of MAPKs and PI3-Kinase Pathways.

Microparticles (MPs) have emerged as a surrogate marker of endothelial dysfunction and cardiovascular risk. This study examined the potential of MPs from senescent endothelial cells (ECs) or from patients with acute coronary syndrome (ACS) to promote premature EC aging and thrombogenicity. Primary porcine coronary ECs were isolated from the left circumflex coronary artery. MPs were prepared from ECs and venous blood from patients with ACS (n=30) and from healthy volunteers (n=4) by sequential centrifugation. The level of endothelial senescence was assessed as senescence-associated β-galactosidase activity using flow cytometry, oxidative stress using the redox-sensitive probe dihydroethidium, tissue factor activity using an enzymatic Tenase assay, the level of target protein expression by Western blot analysis, platelet aggregation using an aggregometer, and shear stress using a cone-and-plate viscometer. Senescence, as assessed by senescence-associated β-galactosidase activity, was induced by the passaging of porcine coronary artery ECs from passage P1 to P4, and was associated with a progressive shedding of procoagulant MPs. Exposure of P1 ECs to MPs shed from senescent P3 cells or circulating MPs from ACS patients induced increased senescence-associated β-galactosidase activity, oxidative stress, early phosphorylation of mitogen-activated protein kinases and Akt, and upregulation of p53, p21, and p16. Ex vivo, the prosenescent effect of circulating MPs from ACS patients was evidenced only under conditions of low shear stress. Depletion of endothelial-derived MPs from ACS patients reduced the induction of senescence. Prosenescent MPs promoted EC thrombogenicity through tissue factor upregulation, shedding of procoagulant MPs, endothelial nitric oxide synthase downregulation, and reduced nitric oxide-mediated inhibition of platelet aggregation. These MPs exhibited angiotensin-converting enzyme activity and upregulated AT1 receptors and angiotensin-converting enzyme in P1 ECs. Losartan, an AT1 receptor antagonist, and inhibitors of either mitogen-activated protein kinases or phosphoinositide 3-kinase prevented the MP-induced endothelial senescence. These findings indicate that endothelial-derived MPs from ACS patients induce premature endothelial senescence under atheroprone low shear stress and thrombogenicity through angiotensin II-induced redox-sensitive activation of mitogen-activated protein kinases and phosphoinositide 3-kinase/Akt. They further suggest that targeting endothelial-derived MP shedding and their bioactivity may be a promising therapeutic strategy to limit the development of an endothelial dysfunction post-ACS.

Potential marker of endothelial dysfunction in patients with various grade of cardiovascular risk

Aim. As the endothelial glycocalix (EG) — gel-like layer on the surface of endothelium, participates in normal endothelial functioning maintenance, search for markers that characterize its condition, is of high scientific interest. Aim of the study — to evaluate clinical and diagnostic opportunities for novel EG marker, related to thickness and plasticity of EG, represented as perfused boundary region (PBR, μm) of erythrocytes. Material and methods. Totally, 208 patients included (123 men, 85 women) at the age 40-65 y.o., with various level of cardiovascular risk by SCORE, and coronary heart disease (CHD). EG of microvessels was charterized via PBR, that was measured with dark field capillaroscope with diod light of green spectrum. Results. With the values of PBR >2 μm there is worsening of morphofunctional state of arteries of different localizations, and microcirculatory vessels, level of apolipoprotein A1 decreases, as structure protein of high density lipoproteins, and prevalence of carotid atherosclerosis increases two times, of CHD — 2,5 times (p 2 μm, is associated with worsening of microcirculatory vessel condition, and of large arteries, prevalence of stenosing atherosclerosis of carotid arteries and CHD, that points on its properties of surrogate marker of endothelial dysfunction and further opportunities for its implementation with diagnostical aims.

Fibroblast growth factor 23 is associated with left ventricular hypertrophy, not with uremic vasculopathy in peritoneal dialysis patients

Cardiovascular (CV) events are the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD), including those patients on peritoneal dialysis (PD). Fibroblast growth factor 23 (FGF23) has been associated with left ventricular hypertrophy (LVH) and mortality in patients with CKD. However, the role of FGF23 in uremic vasculopathy remains unclear. In this study, we aimed to assess the relationship between FGF23 and LVH, endothelial dysfunction, vascular calcification, and arterial stiffness in 48 stable PD patients. Left ventricular mass index (LVMI) was assessed using 2-D echocardiography. Intact FGF23 blood levels were evaluated using an ELISA kit (Immutopics, Inc., San Clemente, CA, USA). Reactive hyperemia index (RHI) is a surrogate marker of endothelial dysfunction and the augmentation index (AI) is a surrogate marker of arterial stiffness. Both were assessed using peripheral arterial tonometry (EndoPAT 2000). Vascular calcification (VC) was assessed using the Adragão score. In unadjusted analysis; FGF23 was positively correlated with serum Pi (r = 0.487, p < 0.001), serum urea (r = 0.351, p = 0.015), serum creatinine (r = 0.535, p < 0.001), dialysis vintage (r = 0.309, p = 0.033), and LVMI (r = 0.369, p = 0.027) and was negatively correlated with age (r = -0.343, p = 0.017), residual renal function (r = -0.359, p < 0.012), and AI (r = -0.304, p = 0.038). In multivariate adjusted analysis, FGF23 was associated with LVMI (β = 0.298, p = 0.041), serum Pi (β = 0.345, p = 0.018), and age (β = -0.372, p = 0.007) independent of dialysis vintage, gender, residual renal function (RRF), albumin, C-reactive protein and systolic blood pressure. There were no associations found between FGF23 and RHI, AI, or VC in multivariable- adjusted models. Our results show that FGF23 is associated with LVH but not with endothelial dysfunction, arterial stiffness, or vascular calcification in PD patients.

The relationship of exposure to air pollutants in pregnancy with surrogate markers of endothelial dysfunction in umbilical cord

BackgroundThis study aims to investigate the association of exposure to ambient air pollution during pregnancy with cord blood concentrations of surrogate markers of endothelial dysfunction. MethodsThis population-based cohort was conducted from March 2014 to March 2015 among 250 mother-neonate pairs in urban areas of Isfahan, the second large and air-polluted city in Iran. We analyzed the association between the ambient carbon monoxide (CO), ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), particular matter 10 (PM10), and air quality index (AQI) with cord blood levels of endothelin-1, vascular adhesion molecule (VCAM), and intercellular adhesion molecule (ICAM). Multiple regression analysis was conducted after adjustment for potential confounding factors and covariates. The regression coefficient (beta), standard error of the estimate (SE), and 95% confidence intervals for each regression coefficient (95% CI) are reported. ResultsData of 233 mother-neonate pairs were complete, and included in the analysis. Multiple regression analyses showed that AQI, CO and O3 had significant correlation with cord blood ICAM-1 [Beta (SE), 95%CI: 2.93 (0.72), 1.33,5.54; 2.28(1.44), 1.56,5.12; and 2.02(0.01), 1.03,2.04, respectively] as well as with VCAM-1 [2.78(0.91), 1.69,4.57; 2.47(1.47), 1.43,5.37; and 2.01(0.01),1.07,2.04, respectively]. AQI, PM10, and SO2 were significantly associated with Endothelin-1 concentrations [Beta (SE), 95%CI: 10.16(5.08),7.61,14.28; 9.70(3.46), 2.88,16.52; and 1.07(0.02), 1.03,2.11, respectively]. ConclusionsThe significant associations of air pollutants with markers of endothelial dysfunction during fetal period may provide another evidence on the adverse health effects of air pollutants on early stages of atherosclerosis from fetal period. Our findings underscore the importance of considering environmental factors in primordial prevention of chronic diseases.

THU-295 - Growth Differentiation Factor 15 (GDF-15) A Surrogate Marker of Endothelial Dysfunction Correlates with Severity and Predicts Short-Term Survival of Patients with Alcoholic Hepatitis

THU-295 - Growth Differentiation Factor 15 (GDF-15) A Surrogate Marker of Endothelial Dysfunction Correlates with Severity and Predicts Short-Term Survival of Patients with Alcoholic Hepatitis

Gadolinium chloride modulates bradykinin-induced pulmonary vasoconstriction and hypoxic pulmonary vasoconstriction during polymicrobial abdominal sepsis in rats

ABSTRACTBackground: Macrophages importantly contribute to sepsis-induced lung injury. As their impact on pulmonary endothelial injury and dysregulation of hypoxic pulmonary vasoconstriction (HPV) remains unclear, we assessed pulmonary endothelial dysfunction and HPV by macrophage inhibition via gadolinium chloride (GC) pre-treatment in rats with peritonitis (cecal ligation and puncture [CLP]). Methods: The following four study groups were made: Group I: SHAM and group II: SHAM + GC (pre-treatment with NaCl 0.9% or GC 14 mg/kg body weight (b.w.) intravenously 24 hours prior to sham laparotomy); group III: CLP and group IV: CLP + GC (pre-treatment with NaCl 0.9% or GC 14 mg/kg b.w. 24 hours prior to induction of peritonitis). Exhaled nitric oxide (exNO), bradykinin-induced pulmonary vasoconstriction (=surrogate marker of endothelial dysfunction) and HPV were investigated in isolated and perfused lungs (n = 40). Using the same protocol wet to dry lung weight ratio and myeloperoxidase (MPO) activity were investigated in separate rats (n = 28). In additional rats (n = 12) of groups III and IV nitrite levels in alveolar macrophages (AM) were measured. Results: In sepsis, GC pre-treatment significantly attenuated exNO levels, AM-derived nitrite levels, lung MPO activity, and restored blunted HPV, but severely enhanced endothelial dysfunction in healthy and septic animals. Conclusion: Macrophages exhibit a controversial role in sepsis-induced lung injury. The GC-induced restoration of inflammation parameters to sham levels is clearly limited by the negative impact on CLP-induced endothelial injury in this setting. The exact link between the GC-associated modulation of the NO pathway demonstrated and septic lung injury needs to be determined in future studies.

Effect of vitamin C on endothelial function of children with chronic renal failure: An experimental study.

Background:It is well established that improvement of endothelial dysfunction (ED) could prevent or delay the occurrence of cardiovascular disease (CVD) and its related morbidity and mortality in patients with chronic kidney disease (CKD). In this study we investigated whether administration of vitamin C could be effective by improving brachial artery flow-mediated dilation (FMD) and intima media thickness (IMT), two surrogate markers of ED, in children with CKD or chronic renal failure (CRF).Materials and Methods:In this analytic-experimental study children aged 3-18 years with a diagnosis of CRF and a group of healthy children were enrolled. Vitamin C (250 mg/day) administrated for the two studied groups for 1 month. Endothelial function was evaluated by FMD and IMT measurement using vascular Doppler ultrasonography, before and after trial.Results:In this study 18 patients with CRF and 19 normal children as the control group were studied. At baseline mean of IMT and FMD was not different in the two studied groups (P > 0.05). After vitamin C administration IMT decreased significantly in the two studied groups (P < 0.05). FMD increased in the two studied groups but the difference was significant in the control group (P < 0.05).Conclusion:The findings of this interventional trial have demonstrated that vitamin C could have protective effect on ED of patients with CRF possibly in those with severe form of the disease but for obtaining more conclusive results larger sample size is needed.

Symmetric Dimethylarginine Is Not Associated with Cumulative Inflammatory Load or Classical Cardiovascular Risk Factors in Rheumatoid Arthritis: A 6-Year Follow-Up Study.

Symmetric dimethylarginine (SDMA) indirectly inhibits nitric oxide (NO) synthesis and predicts cardiovascular and all-cause mortality in high-risk patients. The aim of our study was to investigate the associations of cumulative inflammatory burden (assessed by serial measurements of inflammatory markers) and classical cardiovascular (CV) disease risk factors with SDMA in RA patients. 201 RA patients (155 females, median age 67 (59–73)) were assessed at baseline (2006). Classical CV disease risk factors were recorded and systemic inflammation was determined by the measurement of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). At follow-up (2012) SDMA levels were measured by enzyme-linked immunosorbent assay. Mean SDMA levels in RA population were 0.40 (0.40–0.53) μmol/L. No significant association between SDMA and cumulative inflammatory load was established in the analysis. SDMA levels were not found to be significantly related to CV disease risk factors. We explored the potential relationship between SDMA and cumulative inflammatory burden in patients with RA and obtained negative results. SDMA did not relate to CV disease risk factors in our population and its clinical significance as a surrogate marker of endothelial dysfunction in patients with RA remains to be determined.

AB0363 Assymetric Dimethylarginine is Associated with Cumulative Inflammatory Burden in Rheumatoid Arthritis

BackgroundRheumatoid arthritis (RA) is associated with premature cardiovascular (CV) morbidity and mortality. Inflammatory processes in the rheumatoid synovium and atherosclerotic plaques are remarkably similar, suggesting that RA disease-related inflammation may...

THU0490 Mthfr C677T Polymorphism but not DDAH Gene Variants Are Associated with Asymmetric Dimethylarginine in Patients with Rheumatoid Arthritis

BackgroundEndothelial dysfunction is highly prevalent in patients with Rheumatoid Arthritis (RA) contributing to the excess cardiovascular (CV) risk observed in this population. Assymetric dimethylarginine (ADMA) is an endogenous inhibitor of...

Masked Hypertension as an Unrecognized Destructive Condition

We have read the article “Masked Hypertension Defined by Home Blood Pressure Monitoring Is Associated With Impaired Flow-Mediated Vasodilatation in Patients With Cardiovascular Risk Factors” written by Kabutoya and colleagues1 with great interest. They speculated that home blood pressure (BP) and masked hypertension defined by home BP would be associated with integrated flow-mediated dilatation (FMD) response in patients with a cardiovascular risk factor. The study concluded that home systolic BP was associated with a decrease in FMD. This finding may likely contribute to an increased incidence of cardiovascular events in this group. The subject is important in terms of daily practice and the study justifies emphasis with its successful design and documentation. Ambulatory and home BP measurement have been shown to be superior to conventional measurement of BP in terms of reproducibility, relationship to the impact of high BP on target organs, and the prediction of cardiovascular events.2 Masked hypertension is defined as a clinical condition in which a patient's office BP is <140/90 mm Hg and home BP is ≥135 mm Hg and/or 85 mm Hg.3 Reactivity to daily life stressors and behavioral factors such as smoking, alcohol use, contraceptive use in women, and sedentary habits can influence masked hypertension. Masked hypertension should also be investigated in individuals who are at increased risk for cardiovascular complications, including patients with kidney disease.4 Masked hypertension defined by 24-hour ambulatory BP is associated with an increased serum glucose level and urinary albumin-creatinine ratio.5 For this reason, if the authors gave information about kidney function tests and lifestyle of patients, the results of the present study may be useful and different. Patients with masked hypertension have been demonstrated to have a greater-than-normal prevalence of organ damage, particularly with higher prevalence of metabolic risk factors, left ventricular mass index, carotid intima-media thickness, and impaired large artery distensibility compared with patients with a truly normal BP level. Masked hypertension is a predictor of cardiovascular disease, and FMD may measure the endothelial dysfunction and accelerated atherogenesis associated with masked hypertension. FMD measurement is a gold standard method for endothelial function; however, it may be associated with many conditions that are related to inflammation or endothelial impairment. Therefore, researchers who use this method should pay attention to inflammatory diseases or related conditions. Obstructive sleep apnea syndrome (OSAS) and nonalcoholic fatty liver disease (NAFLD) are common in clinical practice. Cardiovascular complications, which are also common in patients with OSAS, have been linked to morbidity and mortality in these patients based on endothelial dysfunction. In addition, the presence and degree of NAFLD are associated with higher inflammatory parameters. Additionally, common pathways involved in the pathogenesis of NAFLD include hepatic insulin resistance, subclinical inflammation, and atherosclerosis.6 Because NAFLD and OSAS are associated with inflammatory status and insulin resistance, if the authors had mentioned these factors, it would be stronger. Inflammatory status can also be affected by many conditions including inflammatory disease such as psoriasis,7 cardiac syndrome X, and infection.8 In the present study, the authors did not mention some of these possible contributing factors. It would have been better if the authors gave information about these factors. In conclusion, FMD itself without other inflammatory indicators may not provide information to clinicians about masked hypertension. For this reason, we think that it should be evaluated together with other serum inflammatory markers in routine clinical practice.9 We believe that these findings will act as a guide for further studies that will assess inflammatory status as a surrogate marker of endothelial dysfunction and its relationship with masked hypertension. There are no conflict of interests.

G233 Aortic Wall Stiffness Studies in Children with Kawasaki Disease Without Coronary Artery Abnormalities – a Follow-Up Study from North India

IntroductionThe main focus of concern in Kawasaki disease (KD) hitherto has been on children who develop coronary artery abnormalities (CAA). There is emerging evidence to suggest that several long term...