Markers Of Endothelial Damage Research Articles

Vascular endothelium function among male carriers of BRCA 1&2 germline mutation.

Background: Breast cancer susceptibility genes 1&2 (BRCA1&2) mutations hinder DNA-repair. Germline mutations in these genes are known to cause cancer; however, they may have other consequences. In this study we evaluated for the first time, the effect of the BRCA mutations on the vascular endothelium of young healthy males. Results: The study included 82 participants (53 BRCA mutation positive-carriers and 29 negative-carriers). Subjects mean age was 40. There were no significant differences in the baseline characteristics of the two groups. BRCA-carriers had significantly higher levels of EPCs (fraction of CD34+/VEGF or CD133+/VEGF positive-cells) compared to non-carriers of the mutation (median 6.78[1.96,14.48]% vs. 1.46[0.65,6.18]%, p < 0.001, and median 7.17[1.70,16.69]% vs. 1.54[0.85,5.10]%, p < 0.001, respectively). This difference remained consistent after multivariate adjustment. We did not identify differences in endothelial function, endothelial damage markers and EPCs activity between the two groups.Methods: This was a prospective cohort study to test the association between BRCA status and possible endothelial alterations. The Study population included males, 18-50 years, with no cardiovascular morbidity, who were referred for BRCA screening. We tested the endothelial system by: Endothelial progenitor cells (EPC) production, endothelial function (EndoPAT2000), endothelial damage and related hormonal levels. We stratified the cohort by germline BRCA status and compared measurements between BRCA mutation positive- and negative-carriers. Conclusions: Male BRCA1&2 mutation positive-carriers had increased level of EPCs which may reflect a subclinical accumulative endothelial damage. These novel findings suggest that the effect of mutations in BRCA is not limited to increased cancer risk, but may affect the cardiovascular system.

The Potential Role of Circulating Endothelial Cells and Endothelial Progenitor Cells in the Prediction of Left Ventricular Hypertrophy in Hypertensive Patients.

BackgroundThe main aim of present study is to evaluate the potential role of circulating endothelial cells (CECs) and endothelial progenitor cells (CEPCs) – representing specific markers of endothelial damage, in the prediction of left ventricular hypertrophy (LVH) in hypertensive patients categorized into two groups; mild (MH) and resistant hypertension (RH).Materials and MethodsThirty patients with MH and 28 subjects with RH were involved in the study. In both groups, patients were divided into an LVH and non-LVH group. The control group included 33 age and sex-matched normotensive volunteers. Physical examination, laboratory tests and echocardiography were conducted.ResultsIn both the MH and RH group, patients with as well as without LVH demonstrated a higher number of CECs and a lower ratio of CEPCs/CECs as compared to the healthy control. Multiple linear regression analysis showed a positive association of CEPCs with left ventricular mass (LVM) and left ventricular mass index (LVMI), independently of other confounders.ConclusionOur results suggest that endothelial injury observed as an elevated CECs number and its impaired regeneration, reflected by a lowered CEPCs/CECs ratio, precede LVH occurrence and may play a significant role in LVH development regardless of the clinical severity of hypertension. Moreover, independent correlation of CEPCs with echocardiographic (ECG) incidences of LVH suggests their potential use as a screening biomarker to stratify the risk of LVH development.

Metabolic Systems Analysis of Shock-Induced Endotheliopathy (SHINE) in Trauma

Investigate the endothelial cell phenotype (s) that causes Shock-Induced Endotheliopathy in trauma. We have studied more than 2750 trauma patients and identified that patients with high circulating syndecan-1 (endothelial glycocalyx damage marker) in plasma have an increased mortality rate compared with patients with lower levels. Notably, we found that patients suffering from the same trauma severity could develop significantly different degrees of endothelial dysfunction as measured by syndecan-1. Prospective observational study of 20 trauma patients admitted to a Level 1 Trauma Centre and 20 healthy controls. Admission plasma syndecan-1 level and mass spectrometry were measured and analyzed by computational network analysis of our genome-scale metabolic model of the microvascular endothelial cell function. Trauma patients had a significantly different endothelial metabolic profile compared with controls. Among the patients, 4 phenotypes were identified. Three phenotypes were independent of syndecan-1 levels. We developed genome-scale metabolic models representative of the observed phenotypes. Within these phenotypes, we observed differences in the cell fluxes from glucose and palmitate to produce Acetyl-CoA, and secretion of heparan sulfate proteoglycan (component of syndecan-1). We confirm that trauma patients have a significantly different metabolic profile compared with controls. A minimum of 4 shock-induced endotheliopathy phenotypes were identified, which were independent of syndecan-1level (except 1 phenotype) verifying that the endothelial response to trauma is heterogeneous and most likely driven by a genetic component. Moreover, we introduced a new research tool in trauma by using metabolic systems biology, laying the foundation for personalized medicine.

Sepsis causes right ventricular myocardial inflammation independent of pulmonary hypertension in a porcine sepsis model.

IntroductionRight ventricular (RV) myocardial dysfunction is a common feature in septic shock. It can worsen outcome, but the etiology is poorly understood. Pulmonary artery hypertension (PAH) plays a part in the pathogenesis of the right heart dysfunction in sepsis but its importance is unknown. In pigs, PAH in sepsis is substantial and the translational value of porcine sepsis models therefore questioned. We hypothesized that porcine sepsis causes a myocardial inflammatory response which leads to myocardial dysfunction independent of PAH.Materials and methodsSepsis was induced by Escherichia coli-infusion in 10 pigs resulting in PAH and increased right ventricular pressure (RVP). The same degree of RVP was achieved by external pulmonary artery banding (PAB) in a consecutive series of 6 animals.ResultsSepsis, but not PAB, led to increase in endothelial damage marker PAI-1 and cytokines TNF and IL-6 (all p<0.05) in plasma. In myocardium, TNF and IL-6 were significantly elevated in sepsis, TNF in both ventricles and IL-6 mostly in RV, while IL-1β, IL-18 and C5a were significantly higher in RV compared to LV after PAB (all p<0.05). Myocardial mRNA levels of IL-1β, IL-6, IL-18, IP-10, E-selectin and PAI-1 were significantly elevated in RV and LV during sepsis compared to PAB, while Caspase-1 was decreased in septic compared to PAB animals (all p<0.05). Cathepsin L activity was increased in RV by PAB, while sepsis inhibited this response. Escherichia coli-induced sepsis caused myocardial inflammation independent of PAH.ConclusionProminent PAH should therefore not exclude porcine sepsis models to further our understanding of human sepsis.

High-intensity interval training followed by postexercise cold-water immersion does not alter angiogenic circulating cells, but increases circulating endothelial cells.

High-intensity interval training (HIIT) induces vascular adaptations that might be attenuated by postexercise cold-water immersion (CWI). Circulating angiogenic cells (CAC) participate in the vascular adaptations and circulating endothelial cells (CEC) indicate endothelial damage. CAC and CEC are involved in vascular adaptation. Therefore, the aim of the study was to investigate postexercise CWI during HIIT on CAC and CEC and on muscle angiogenesis-related molecules. Seventeen male subjects performed 13 HIIT sessions followed by 15 min of passive recovery (n = 9) or CWI at 10 °C (n = 8). HIIT comprised cycling (8-12 bouts, 90%-110% peak power). The first and the thirteenth sessions were similar (8 bouts at 90% of peak power). Venous blood was drawn before exercise (baseline) and after the recovery strategy (postrecovery) in the first (pretraining) and in the thirteenth (post-training) sessions. For CAC and CEC identification lymphocyte surface markers (CD133, CD34, and VEGFR2) were used. Vastus lateralis muscle biopsies were performed pre- and post-training for protein (p-eNOSser1177) and gene (VEGF and HIF-1) expression analysis related to angiogenesis. CAC was not affected by HIIT or postexercise CWI. Postexercise CWI increased acute and baseline CEC number. Angiogenic protein and genes were not differently modulated by post-CWI. HIIT followed by either recovery strategy did not alter CAC number. Postexercise CWI increased a marker of endothelial damage both acutely and chronically, suggesting that this postexercise recovery strategy might cause endothelial damage. Novelty HIIT followed by CWI did not alter CAC. HIIT followed by CWI increased CEC. Postexercise CWI might cause endothelial damage.

Decreased sEng plasma levels in hypertensive patients with endothelial dysfunction under chronic treatment with Perindopril.

Purpose: Endoglin is a transmembrane glycoprotein which plays an important role in maintaining cardiovascular homeostasis. One of its forms, soluble endoglin (sEng), a molecule with antiangiogenic properties, has been found overexpressed in patients suffering from hypercholesterolemia, diabetes mellitus and hypertension, and is proposed as a marker of endothelial damage. Accordingly, we aimed to quantify the efficacy of various antihypertensive regimens on sEng levels, in hypertensive patients with endothelial dysfunction.Patients and methods: 323 patients were enrolled, and there were 99 patients with normal blood pressure values, 106 hypertensive patients under chronic treatment with different types of antihypertensive molecules (beta blockers, calcium channel blockers, and diuretics) in monotherapy, and 118 hypertensive patients under chronic treatment with perindopril. sEng plasma levels were quantified and were correlated with classical methods of assessing the endothelial damage.Results: Patients under chronic treatment with perindopril had lower sEng plasma levels compared with the other group of hypertensive patients under different regimens of antihypertensive treatment (sEng: 4.73±1.39 versus 5.63±2.33, p<0.01).Conclusion: Decreased sEng plasma levels were found in patients under chronic treatment with perindopril, when compared with other antihypertensive regimens of treatment (beta blockers, calcium channel blockers, and/or diuretics).

Design of a study to investigate the mechanisms of obstructive sleep apnoea by means of drug-induced sleep endoscopy.

Background Obstructive sleep apnoea (OSA) is an independent risk factor of hypertension and cardiovascular diseases. Recurrent episodes of upper airways collapse during sleep causing blood oxygen desaturation, hypercapnia, and micro-arousals, are known to activate the sympathetic nervous system (SNS). However, whether changes in the renin-angiotensin-aldosterone system and endothelial activation also occur remains contentious. Methods Based on routine use of drug-induced sleep endoscopy (DISE) for the work-up of OSA patients in our centre, we designed a prospective study to investigate the haemodynamic and humoral changes occurring during the apnoeic episodes reproduced in vivo in the course of DISE. Specifically, plasma aldosterone concentration and renin activity, C-terminal fragment of proendothelin-1, as a marker of endothelial damage, and free plasma catecholamines, will be measured at fixed times during DISE. The activity of catechol-O-methyltransferase (COMT), a key catecholamine-inactivating enzyme that has been scantly investigated thus far owing to the lack of commercially available kits, will be also determined by a newly developed high performance liquid chromatography method, which is herein described. Results and conclusions The aim of this study is to provide novel information on the haemodynamic, hormonal, and SNS changes, and also on COMT activity modification concomitantly occurring during apnoea, thus contributing substantively to the understanding of the pathophysiology of OSA.

Relationship among HbA1c and Some Markers of Endothelial Damage in Type 2 Diabetes Mellitus

Background: A number of processes regulating the thrombolytic balance are impaired in diabetic patients as a result of dysfunction of endothelial cells leading to a hypercoagulative state. Von Willebrand factor (VWF) is an important marker of endothelial dysfunction. Plasminogen activator inhibitor-1 antigen (PAI-1-Ag), the major physiological inhibitor of tissue plasminogen activator (tPA), is mainly produced by endothelium. The aim of this study is to measure plasma levels of von Willebrand factor, Plasminogen activator inhibitor-1 antigen in type 2 diabetes mellitus patients and to correlate with glycated haemoglobin (HbA1c).&#x0D; Study Design: This prospective cohort study was conducted on 30 diagnosed type 2 DM patients who were about to start treatment.&#x0D; Place and Duration of Study: Medical outpatient (MOP) clinic of Enugu State University of Science and Technology Teaching Hospital (ESUTTH), between January and December 2016.&#x0D; Methodology: We included 30 patients (13 men, 17 women; age range 40-80 years) with type 2 diabetes mellitus. Blood samples were drawn from the patients before they commenced treatment, six months into the treatment and at twelve months of the treatment. Blood samples were also drawn from 25 age matched non diabetic patients. Plasma von Willebrand factor and Plasminogen activator inhibitor-1 antigen levels were determined by Enzyme linked immunosorbent assay. Glycated haemoglobin (HbA1c) and fasting blood sugar (FBS) levels were also evaluated along with them.&#x0D; Results: This study was conducted on 30 type 2 DM patients consisting of 13 males and 17 females. At treatment naïve, mean levels of vWF were significantly increased (45.48 +/- 6.46) in male type 2 Diabetic patients compared to the control (20.45 +/- 0.26). Six months into treatment mean levels of vWF were significantly increased (48.18 +/- 4.99) in female type 2 Diabetic patients compared to the control (37.64 +/- 7.93). The plasma levels of vWF were significantly and positively correlated with HbA1c at six months into treatment in male type 2 DM patients. The plasma levels of vWF were also significantly and positively correlated with PAI-1 at six and twelve months into treatment in both genders.&#x0D; Conclusion: There was strong significant positive correlation between plasma levels of vWF and PAI-1 in type 2 diabetes mellitus patients.

Pre-operative methylprednisolone decreased early vascular endothelial injury after total knee arthroplasty

Objective To investigate the effect of methylprednisolone on markers of early vascular endothelial activation and damage after total knee arthroplasty. Methods We randomly selected 88 patients undergoing unilateral total knee arthroplasty. The patients were divided into two groups by a completely random grouping method(n=44), they were given either pre-operative intravenous methylprednisolone 120 mg (number of patients for methylprednisolone group) or isotonic saline (number of patients for control group). All operations were performed under lumbar spinal and epidural anesthesia. Blood samples were collected at 2, 6, 12 h and 24 h pre- and post-operation, respectively. By enzyme-linked immunosorbent assay(ELISA), we analyzed concentrations of Syndecan-1, plasma soluble thrombomodulin (sTM), E-selectin, vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) at different time points. Results There was no significant difference in age, gender, body mass index (BMI), operation time and ropivacaine dose between patients in two groups (P>0.05). Syndecan-1、E-selectin and CRP were significantly decreased at 2, 6, 12 h and 24 h in methylprednisolone group, sTM and VEGF were significantly decreased at 6, 12 h and 24 h in methylprednisolone group (P<0.05) . Compared with preoperative, the level of Syndican-1 and E-selectin at 2, 6, 12 h and 24 h were significantly decreased, the level of CRP was significantly increased (P<0.05) , the level of sTM and VEGF were significantly decreased at 6, 12 h and 24 h in methylprednisolone group (P<0.05) . Conclusions Pre-operative administration of methylprednisolone 120 mg could reduce markers of endothelial activation, reduce the level of damage markers and reduce the systemic inflammatory response after total knee arthroplasty. Key words: Total knee arthroplasty; Syndecan-1; Soluble thrombomodulin; E-selectin; Vascular endothelial growth factor; C-reactive protein

SAT-055 The Aldosterone-Renin Ratio Predicts Cardiometabolic Disorders in Subjects without Classic Primary Aldosteronism

Background: Aldosterone has been linked with obesity, metabolic syndrome (MetS), pro-inflammatory and pro-thrombotic states. However, most of these studies relate to patients with evident primary aldosteronism (PA). Objective: To determine whether aldosterone, renin or the plasma aldosterone/renin ratio (ARR) are associated with metabolic disorders and inflammatory/vascular biomarkers in a no-PA population. Methods: We studied 275 patients including adolescents and adults of both genders and measured aldosterone in plasma and urine and determined the plasma renin activity (PRA). In all subjects, the presence of MetS was determined according to Adult Treatment Panel III. Renal, vascular, inflammatory and mineralocorticoid activity biomarkers were evaluated. Results: The ARR correlated with the number of variables of MetS (r=0.191, p=0.002), BMI (r=0.136, p=0.026), SBP (r=0.183, p=0.002), DBP (r=0.1917, p=0.0014), potassium excreted fraction (r=0.174, p=0.004), LDL (r=0.156, p=0.01), PAI-1 (r=0.158, p=0.009), microalbuminuria (r=0.136, p=0.029), and leptin (r=0.142, p=0.019). In a linear regression model adjusted by age, BMI and gender, only the ARR was significant (r= 0.108, p= 0.05). In a logistic regression analysis, the ARR predicted MetS index (OR 1.07 [CI 1.011- 1.131] p= 0.02) even after adjusting for age, BMI and gender. On the other hand, aldosterone showed no association with MetS nor inflammatory markers. Conclusion: These results suggest a continuum of cardiometabolic risk beyond the classic PA threshold screening. We believe that the ARR seems to be a more sensitive marker of obesity, MetS and endothelial damage in non-PA patients than aldosterone or renin alone. More prospective studies are needed to develop future screening values.

Use of Phosphodiesterase Inhibition During Ex-Vivo Lung Perfusion of Donor Lungs Unsuitable for Transplantation

Purpose Primary Graft Dysfunction after lung transplantation is characterised by inflammatory cascade activation, vascular leak and pulmonary oedema. Nitric oxide signalling plays a critical role in pulmonary vascular homeostasis. Reduced cyclic guanosine monophosphate (cGMP) following ex-vivo lung perfusion (EVLP) is associated with increased microvascular permeability. Phosphodiesterase-5 inhibitors e.g. Sildenafil prevent cGMP breakdown causing pulmonary vasodilation and reduced pulmonary vascular resistance (PVR). We investigated the effects of Sildenafil during EVLP on physiology, inflammatory status and endothelial activation markers. Methods Five human, clinically unused donor lungs, underwent acellular EVLP with 40% predicted cardiac output and a closed left atrium. Following 30 minutes of stable EVLP, a 10mg Sildenafil (Revatio; Pfizer) bolus was administered. Haemodynamic data was continuously monitored and perfusate sampled at intervals and evaluated via a MSD pro-inflammatory panel.Physiological data was compared using ANOVA method. Inflammatory protein concentrations were compared with DEVELOP-UK historical control data and analysed by multiple unpaired t-tests. Results Following Sildenafil administration, rapid development of alveolar oedema was observed. No measured effects on pulmonary haemodynamics including flow, PAP, PVR and oxygenation were seen. The overall trends for the pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α) were similar in both groups. Significance was observed at the final 120-minute time-point; with higher levels of IL-8 and TNF-α following Sildenafil. The treatment group had significantly decreased expression of soluble tight junctional proteins (VE-cadherin, thrombomodulin and VWF) compared to the control group. Conclusion Sildenafil didn't improve pulmonary physiology as expected and appeared to promote the development of alveolar oedema. While the mechanism for this remains unclear, we observed significantly lower concentrations of the endothelial damage markers in the Sildenafil group. This difference may be confounded by the control group being a historical cohort which used a different EVLP protocol, limiting comparison. We conclude that Sildenafil failed to have the hypothesised therapeutic effects and is detrimental to lungs undergoing EVLP.

Abstract P019: Albuminuria in Mid-Life and Older-Age and Risk of Dementia: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Dementia is increasingly appreciated to have important vascular disease contributions. Albuminuria and decreased estimated glomerular filtration rate (eGFR) define chronic kidney disease (CKD) and are related to the risk of its consequences as well as microvascular disease and endothelial damage across multiple vascular beds. We extend previous studies by examining albuminuria and eGFR measured at both mid-life and older age as risk factors for dementia. Methods: We studied 10,876 adult participants in the Atherosclerosis Risk in Communities (ARIC) Study excluding participants with end-stage renal disease, stroke and incident dementia at baseline. We analyzed the adjusted relative hazard of incident dementia as a function of eGFR (linear spine with a knot at 60 ml/min per 1.73m 2 ) and log urinary albumin-creatinine-ratio (UACR) adjusting for age, sex, race, education level, Apolipoprotein E4 level, smoking, alcohol consumption, body mass index, diabetes and hypertension. We used two different baseline visits: (1) Starting in 1996-1999 (Visit 4, age 54-74 years); (2) Starting 2011-2013 (Visit 5, age 70-90 years) with follow-up to 2017. Results: We observed 2,001 dementia cases over 16 years of follow-up (446 after Visit 5). Risk of dementia increased with higher levels of albuminuria with a stronger magnitude at older-age than in midlife ( see table ). Estimated GFR was more weakly associated with dementia (p&gt;0.05 at both baselines). The albuminuria association was consistent across sex and race (p-interaction&gt;0.05). Conclusion: Albuminuria, a marker of kidney disease and endothelial damage, is strongly related to dementia incidence. Albuminuria’s association with dementia is stronger in late-life unlike other vascular risk factors, where the association is weaker at older age.

Plasma Dimethylarginine Levels and Carotid Intima-Media Thickness are related to Atrial Fibrillation in Patients with Embolic Stroke.

A relevant part of embolic strokes of undetermined source (ESUS) is assumed to be due to non-detected atrial fibrillation (AF). In this study, we aimed to investigate if markers of endothelial dysfunction and damage may indicate AF risk in embolic stroke. Eighty-eight patients with ischemic stroke confirmed by imaging were assigned to one of three groups: ESUS, AF, or micro-/macroangiopathy. ESUS patients underwent prolonged Holter electrocardiography scheduled for three days. The National Institutes of Health Stroke Scale (NIHSS), the CHA2DS2VASC score, and the carotid intima–media thickness (CIMT) were obtained. Markers of endothelial (dys)function (L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA)) were measured at day seven after stroke. ESUS patients were younger and had fewer cardiovascular risk factors than patients with determined stroke etiology. Compared with AF patients, ESUS patients showed significantly lower values of SDMA (p = 0.004) and higher values of L-arginine (p = 0.031), L-arginine/ADMA ratio (p = 0.006), L-arginine/SDMA ratio (p = 0.002), and ADMA/SDMA ratio (p = 0.013). Concordant differences could be observed comparing ESUS patients with those with newly diagnosed AF (p = 0.026; p = 0.03; p = 0.009; p = 0.004; and p = 0.046, respectively). CIMT was significantly larger in AF than in ESUS patients (p < 0.001), and was identified as an AF risk factor independent from CHA2DS2VASC in the regression analysis (p = 0.014). These findings may support future stratification for AF risk in patients who have suffered embolic stroke.

The Aldosterone/Renin Ratio Predicts Cardiometabolic Disorders in Subjects Without Classic Primary Aldosteronism.

Aldosterone has been linked with obesity, metabolic syndrome (MetS), pro-inflammatory, and prothrombotic states; however, most studies relate these indicators with primary aldosteronism (PA), excluding non-PA patients. To determine whether aldosterone, renin, or the plasma aldosterone/renin ratio (ARR) are associated with metabolic disorders and inflammatory/vascular biomarkers in a non-PA population. We studied 275 patients including adolescents and adults of both genders and measured plasma and urinary aldosterone and determined the plasma renin activity. In all subjects, the presence of MetS was determined according to Adult Treatment Panel III. Renal, vascular, inflammatory, and mineralocorticoid activity biomarkers were evaluated. The ARR correlated with the number of variables of MetS (r = 0.191, P = 0.002), body mass index (BMI; r = 0.136, P = 0.026), systolic blood pressure (r = 0.183, P = 0.002), diastolic blood pressure (r = 0.1917, P = 0.0014), potassium excreted fraction (r = 0.174, P = 0.004), low-density lipoprotein (r = 0.156, P = 0.01), plasminogen activator inhibitor type 1 (r = 0.158, P = 0.009), microalbuminuria (r = 0.136, P = 0.029), and leptin (r = 0.142, P = 0.019). In a linear regression model adjusted by age, BMI, and gender, only the ARR was still significant (r = 0.108, P = 0.05). In a logistic regression analysis, the ARR predicted MetS index (odds ratio (OR) = 1.07 [95% confidence interval (CI) = 1.011-1.131], P= 0.02) even after adjusting for age, BMI, and gender. On the other hand, aldosterone showed no association with MetS or inflammatory markers. These results suggest a continuum of cardiometabolic risk beyond the classic PA threshold screening. The ARR could be a more sensitive marker of obesity, MetS, and endothelial damage in non-PA patients than aldosterone or renin alone. Prospective studies are needed to develop future screening cutoff values.

Ascophyllum nodosum and Fucus vesiculosus on glycemic status and on endothelial damage markers in dysglicemic patients.

The aim of this study was to evaluate a nutraceutical combination containing polyphenols extracted from Ascophyllum nodosum and Fucus vesiculosus and chromium picolinate on glyemic status; secondary outcomes were considered the changes on endothelial markers. We randomized 65 dysglycemic patients to placebo or the nutraceutical agent for 6months. We evaluated fasting plasma glucose (FPG), postprandial plasma glucose (PPG), HbA1c , fasting plasma insulin, homeostatic model assessment (HOMA) index, high sensitivity C-reactive protein (Hs-CRP), tumor necrosis factor-α (TNF-α), and adhesion molecules. At baseline and at 3 and 6months, all patients underwent an oral glucose tolerance test. We recorded a reduction of HbA1c , FPG, PPG, and HOMA-IR compared with placebo (p<0.05). After 6months, 18.2% of patients retuned to a normal glycemic status in the nutraceutical group versus 0 patients in placebo group (p<0.05); 69.7% were classified as impaired fasting glycemia and 12.1% as impaired glucose tolerance in the nutraceutical group versus 17.2% and 82.8 in placebo group (p<0.01) for both. A reduction of Hs-CRP and TNF-α was recorded with the nutraceutical. The administration of a nutraceutical combination containing A.nodosum and F.vesiculosus can be helpful in improving insulin sensitivity and glycemic status. Larger randomized studies are required to confirm the positive effects of these agents.

Plasma Thrombomodulin Levels are Associated with Endothelial Injury in Patients with Bacterial Infections.

Endothelial injury is the key to the occurrence and development of bacterial infections. The aim of this study was to discuss the relationship between the molecular marker of endothelial damage, thrombomodulin (TM), and infectious disease severity, and prognosis. From January 2017 to April 2018, 296 patients with bacterial infections and 163 controls were recruited from our hospital. The concentrations of thrombomodulin and other routine coagulation and inflammatory factors were quantified. Plasma levels of thrombomodulin were obviously increased in infection group compared with control group (8.30 (7.23 - 9.68) vs. 15.83 (10.60 - 22.20) TU/mL, p < 0.001) and logistic regression analysis showed that the thrombomodulin was an independent risk factor for bacterial infection (OR, 1.189 (1.079 - 1.311)). In the infection group, patients with elevated thrombomodulin levels (> 75th percentile of its distribution, n = 71) experienced a higher level of coagulation factors (p < 0.05) and inflammatory factors (p < 0.05) than patients with levels below this cutoff. Multiple linear regression analysis showed that there was a positive correlation among the plasma thrombomodulin and D-dimer, white blood cells, and procalcitonin (β coefficient = 0.590, 0.220, and 0.208, p = 0.004, 0.027, and 0.025, respectively). With the increase of severity of disease, thrombomodulin levels gradually rose (13.58 ± 0.47 TU/mL vs. 25.07 ± 2.01 TU/mL vs. 31.34 ± 2.56 TU/mL, respectively, p < 0.001). Furthermore, there was an abnormal increase of plasma thrombomodulin in patients with bacterial infections and poor prognosis (p < 0.05). The area under curve of thrombomodulin as diagnosis for organ failure and non-survivor was 0.867 and 0.778, respectively. Plasmatic level of thrombomodulin could be considered as a diagnostic tool for bacterial infections. An increase in thrombomodulin plasmatic level was associated with poor outcome.

244. Predicting maternal morbidity in hypertension in pregnancy with the ‘shrunken pore syndrome’ ratio for optimal timing of delivery

Introduction Hypertension in pregnancy is still associated with a considerable risk of severe maternal morbidity due to difficulties in appropriately timing delivery. Timing based on gestational age alone or already manifest progression of maternal disease has proven to be too blunt an instrument to prevent maternal morbidity. Objectives Our aim was to evaluate a previously described marker of glomerular endothelial damage, the “shrunken pore syndrome ratio”, to determine whether women with hypertensive disorders of pregnancy should be considered low-risk or high-risk for developing maternal complications if delivery is delayed. Methods Women admitted to the perinatal ward at the Skane University Hospital in Lund during the year of 2016-09-01–2017-08-31 under the diagnosis of hypertension in pregnancy were invited to join the study. After delivery and discharge from the hospital all registered measures of renal function were analysed. A cut-off of 0.60 was used to distinguish high-risk women from low-risk women. A ”shrunken pore syndrome ratio”, SPS-ratio, of 0.60 or less was considered to define high risk for maternal complications, since this ratio reflects a reduction in the glomerular pore size, previously associated with endothelial damage. Results We included 61 patients in the study, of which two were excluded due to chronic hypertension, and one due to delivery before samples were taken. Of the remaining 58 patients 13 were defined as low-risk women according to the SPS-ratio of which only one (7.7%) developed severe maternal disease. Among the 45 high-risk women 18 women (40%) developed serious disease whereas 27 (60%) could avoid complications. Discussion The SPS-ratio seems promising as a predictive marker for maternal morbidity and its performance as a tool in the monitoring of progressing disease should be evaluated further for an improved management. With delivery before the SPS-ratio decreases to or below 0.60 maternal complications might be avoided.

Albuminuria and Microalbuminuria as Predictors of Cognitive Performance in a General Population: An 11-Year Follow-Up Study

Microalbuminuria, defined as urine albumin-to-creatinine ratio (UACR)>3.0 mg/mmol and ≤ 30 mg/mmol, is an early marker of endothelial damage of the renal glomeruli. Recent research suggests an association among microalbuminuria, albuminuria (UACR > 3.0 mg/mmol), and cognitive impairment. Previous studies on microalbuminuria, albuminuria, and cognition in the middle-aged have not provided repeated cognitive testing at different time-points. We hypothesized that albuminuria (micro- plus macroalbuminuria) and microalbuminuria would predict cognitive decline independently of previously reported risk factors for cognitive decline, including cardiovascular risk factors. In addition, we hypothesized that UACR levels even below the cut-off for microalbuminuria might be associated with cognitive functioning. These hypotheses were tested in the Finnish nationwide, population-based Health 2000 Survey (n = 5,921, mean age 52.6, 55.0% women), and its follow-up, Health 2011 (n = 3,687, mean age at baseline 49.3, 55.6% women). Linear regression analysis was used to determine the associations between measures of albuminuria and cognitive performance. Cognitive functions were assessed with verbal fluency, word-list learning, word-list delayed recall (at baseline and at follow-up), and with simple and visual choice reaction time tests (at baseline only). Here, we show that micro- plus macroalbuminuria associated with poorer word-list learning and a slower reaction time at baseline, with poorer word-list learning at follow-up, and with a steeper decline in word-list learning during 11 years after multivariate adjustments. Also, higher continuous UACR consistently associated with poorer verbal fluency at levels below microalbuminuria. These results suggest that UACR might have value in evaluating the risk for cognitive decline.

Does administration of eicosapentaenoic acid increase soluble thrombomodulin level in statin-treated patients with stable coronary artery disease?

Interventions targeting the serum eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio could be useful for the prevention of coronary artery disease (CAD). Few data exist regarding the effects of administration of EPA on the serum levels of soluble thrombomodulin (sTM) as a marker of endothelial damage, or on the relationship between the sTM and EPA/AA ratio in patients with CAD receiving statin treatment. We assigned stable CAD patients already receiving statin therapy to an EPA group (1800mg/day: n = 50) or control group (n = 50). A significant increase of the sTM level was observed in the EPA group as compared to that in the control group 0.40 (0.10/0.70) FU/mL vs. 0.20 (0/0.40) FU/mL, p = 0.004 at the 6-month follow-up examination. Multivariate regression analysis after adjustments for coronary risk factors and changes of the serum lipid levels identified an increased EPA/AA ratio as an independent predictor of increased serum sTM level (β = 0.244, p = 0.02). The results suggest that an increased sTM level caused by additional administration of EPA to statin might be associated with an increased EPA/AA ratio. The increase of the serum sTM after administration of EPA might reflect an increase of the TM expression on the endothelial surface rather than endothelial damage in CAD patients under statin treatment.Clinical Trial Registration Information UMIN ( http://www.umin.ac.jp/ ), Study ID: UMIN000010452.

Impact of different doses of rosuvastatin therapy on functional and structural markers of endothelium damage in hypertensive patients determined by smoking status

Aim: To compare the effects of different doses of rosuvastatin on early markers of vascular endothelial further damage (flow-mediated vasodilatation, %FMD and carotid intima-media thickness, cITM,) in hypertensive patients according their smoking status.