Big Endothelin-1 Levels Research Articles

Prognostic value of plasma big endothelin-1 in patients with light chain cardiac amyloidosis

BackgroundLight chain cardiac amyloidosis (AL-CA) is associated with a high incidence of mortality. Big endothelin-1 (ET-1), the precursor of endothelial-vasoconstrictive ET-1, is closely related to the concentration of bioactive ET-1....

Gut Microbiota and Biomarkers of Endothelial Dysfunction in Cirrhosis.

Our aim was to study the association of endothelial dysfunction biomarkers with cirrhosis manifestations, bacterial translocation, and gut microbiota taxa. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of nitrite, big endothelin-1, asymmetric dimethylarginine (ADMA), presepsin, and claudin were measured as biomarkers of endothelial dysfunction, bacterial translocation, and intestinal barrier dysfunction. An echocardiography with simultaneous determination of blood pressure and heart rate was performed to evaluate hemodynamic parameters. Presepsin, claudin 3, nitrite, and ADMA levels were higher in cirrhosis patients than in controls. Elevated nitrite levels were associated with high levels of presepsin and claudin 3, the development of hemodynamic circulation, hypoalbuminemia, grade 2-3 ascites, overt hepatic encephalopathy, high mean pulmonary artery pressure, increased abundance of Proteobacteria and Erysipelatoclostridium, and decreased abundance of Oscillospiraceae, Subdoligranulum, Rikenellaceae, Acidaminococcaceae, Christensenellaceae, and Anaerovoracaceae. Elevated ADMA levels were associated with higher Child-Pugh scores, lower serum sodium levels, hypoalbuminemia, grade 2-3 ascites, milder esophageal varices, overt hepatic encephalopathy, lower mean pulmonary artery pressure, and low abundance of Erysipelotrichia and Erysipelatoclostridiaceae. High big endothelin-1 levels were associated with high levels of presepsin and sodium, low levels of fibrinogen and cholesterol, hypocoagulation, increased Bilophila and Coprobacillus abundances, and decreased Alloprevotella abundance.

Effects of PEAR1 gene polymorphism on big endothelin-1 levels in Chinese patients with acute myocardial infarction after percutaneous coronary intervention

Effects of <i>PEAR1</i> gene polymorphism on big endothelin-1 levels in Chinese patients with acute myocardial infarction after percutaneous coronary intervention

Prognostic Value of Endothelin-1 or Related Peptides in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis.

There is increasing evidence that endothelin-1 (ET-1) or related peptides play a prognostic value in coronary artery disease (CAD). The objective of this systematic review and meta-analysis was to evaluate the predictive role of ET-1 or related peptides in CAD patients. We comprehensively searched PubMed and Embase databases until January 15, 2023. Studies examining the association of ET-1, big ET-1, or C-terminal proendothelin-1 (CT-proET-1) level with all-cause mortality or major adverse cardiovascular events (MACEs) in CAD patients were included. Fourteen studies with 30,181 patients were identified. Comparison of the top and the lowest ET-1 level, the pooled risk ratio (RR) of all-cause mortality was 3.77 (95% confidence interval [CI] 1.59-8.94) for ET-1 and 1.65 (95% CI 1.25-2.18) for big ET-1. The pooled RR of MACEs was 2.24 (95% CI 1.85-2.72) for ET-1, 1.49 (95% CI 1.10-2.03) for big ET-1, and 3.55 (95% CI 2.12-5.96) for CT-proET-1, respectively. Subgroup analysis indicated that elevated ET-1 level was associated with 2.66-fold and 2.09-fold higher risk of in-hospital/30-day and long-term MACEs. Elevated ET-1, big ET-1, or CT-proET-1 may be independently associated with higher risk of all-cause mortality and MACEs in patients with CAD.

Association between Plasma Big Endothelin-1 Level and The Severity of Coronary Artery Disease in Patients with Non-ST Segment-Elevated Myocardial Infarction.

Early risk stratification with simple biomarkers is essential in patients with non-ST segment-elevation myocardial infarction (NSTEMI). This study aimed to evaluate the association between plasma big endothelin-1 (ET-1) level and the SYNTAX score (SS) in patients with NSTEMI. A total of 766 patients with NSTEMI undergoing coronary angiography were recruited. Patients were divided into three groups: low SS (≤22), intermediate SS (23-32), and high SS (>32). Spearman correlation, smooth curve fitting, logistic regression, and receiver operating characteristic (ROC) curve analysis were performed to evaluate the association between plasma big ET-1 level and the SS. A p-value <0.05 was considered statistically significant. There was a significant correlation between the big ET-1 and the SS (r=0.378, p<0.001). The smoothing curve indicated a positive correlation between the plasma big ET-1 level and the SS. The ROC curve analysis showed that the area under the curve was 0.695 (0.661-0.727) and the optimal cutoff of plasma big ET-1 level was 0.35pmol/l. Logistic regression showed that elevated big ET-1 was an independent predictor of intermediate-high SS in patients with NSTEMI, whether entered as a continuous variable [OR (95% CI): 1.110 (1.053-1.170), p<0.001] or as a categorical variable [OR (95% CI): 2.962 (2.073-4.233), p<0.001]. In patients with NSTEMI, the plasma big ET-1 level was significantly correlated with the SS. Elevated plasma big ET-1 level was an independent predictor for intermediate-high SS.

Renin-angiotensin and endothelin systems in patients post takotsubo syndrome

Abstract Background We investigate if renin-angiotensin and endothelin-1 response pathways follow the same pattern of recovery as left ventricular ejection fraction in patients with takotsubo syndrome. Purpose To provide better insight into the pathophysiology underlying this condition. Methods Ninety takotsubo syndrome patients [n=30 in each of “acute”, “convalescent” (3–5 months) and “recovered” (&amp;gt;1 year) groups] who were on minimal or no medication and were free of any significant cardiac/metabolic co-morbidities, and 30 healthy controls were studied. Serum concentrations of renin, angiotensin converting enzyme, angiotensin II, big endothelin-1, endothelin-1 were measured using commercially available ELISA, and BNP was measured using an immunoassay. Results Left ventricular ejection fraction was 38±1.6% in acute, 63±2.0% in convalescent and 64±2.6% in recovered takotsubo syndrome patients. As shown in Figure 1, serum renin concentrations are persistently elevated after a takotsubo episode (p=0.03 vs controls). Angiotensin converting enzyme levels are significantly depressed during the acute phase compared to convalescent (p=0.004), recovered takotsubo (p=0.02) or controls (p=0.03). Angiotensin II is increased in takotsubo patients (p&amp;lt;0.001 vs controls) remaining persistently elevated long-term in the recovered group (p=0.03 vs controls). B-type natriuretic peptide concentrations remain elevated after a Takotsubo episode compared to controls (p=0.003). Big endothelin-1 levels are unchanged, but endothelin-1 is significantly lower after takotsubo syndrome compared to controls (p=0.03). Conclusions Despite “normalisation” of the left ventricular ejection fraction, there is long-term maladaptive activation of renin-angiotensin system in takotsubo syndrome patients. This suggests therapy aimed at modulating this pathway may be beneficial in the long-term. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): British Heart Foundation

Renin-Angiotensin and Endothelin Systems in Patients Post-Takotsubo Cardiomyopathy.

Background We investigate if renin-angiotensin and endothelin-1 response pathways follow the same pattern of recovery as left ventricular ejection fraction in patients with takotsubo cardiomyopathy. Methods and Results Ninety patients with takotsubo cardiomyopathy (n=30 in each of "acute," "convalescent" [3-5 months] and "recovered" [>1 year] groups) who were on minimal or no medication and were free of any significant cardiac/metabolic comorbidities, and 30 controls were studied. Serum concentrations of renin, angiotensin-converting enzyme, angiotensin II, big endothelin-1, endothelin-1 were measured using commercially available ELISA, and B-type natriuretic peptide was measured using an immunoassay. Mean left ventricular ejection fraction was <40% during the acute phase in all groups, but recovered to 63% in convalescent and 64% in the recovered groups, respectively. Serum renin concentrations remain persistently elevated after a episode of takotsubo cardiomyopathy (P=0.03 versus controls). Angiotensin converting enzyme levels are significantly depressed during the acute phase compared with convalescent (P=0.004), recovered takotsubo cardiomyopathy (P=0.02) or controls (P=0.03). Angiotensin II is increased in patients with takotsubo cardiomyopathy (P<0.001 versus controls) remaining persistently elevated in the chronically recovered group alone (P=0.03 versus controls). Big endothelin-1 levels are unchanged, but endothelin-1 is significantly lower after takotsubo cardiomyopathy compared with controls (P=0.03). Conclusions Despite "normalization" of the left ventricular ejection fraction, there is long-term maladaptive activation of renin-angiotensin system in patients with takotsubo cardiomyopathy. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02897739, NCT02989454.

Predictive Value of Plasma Big Endothelin-1 in Adverse Events of Patients With Coronary Artery Restenosis and Diabetes Mellitus: Beyond Traditional and Angiographic Risk Factors.

BackgroundPatients with diabetes are a high-risk group for coronary in-stent restenosis (ISR), so it would be valuable to identify biomarkers to predict their prognosis. The plasma big endothelin-1 (big ET-1) level is closely related to cardiovascular adverse events; however, for patients with ISR and diabetes who undergo percutaneous coronary intervention (PCI), whether big ET-1 is independently correlated with prognosis is still uncertain.MethodsPatients with drug-eluting stent (DES) restenosis who underwent successful re-PCI from January 2017 to December 2018 at the Chinese Academy of Medical Sciences Fuwai Hospital were enrolled and followed up for 3 years. The patients were divided into the tertiles of baseline big ET-1. The primary end points were major adverse cardiovascular events (MACEs): cardiac death, non-fatal myocardial infarction (MI), target lesion revascularization (TLR), and stroke. A Cox multivariate proportional hazard model and the C-statistic were used to evaluate the potential predictive value of big ET-1 beyond traditional and angiographic risk factors.ResultsA total of 1,574 patients with ISR were included in this study, of whom 795 were diabetic. In patients with ISR and diabetes, after an average follow-up of 2.96 ± 0.56 years, with the first tertile of big ET-1 as a reference, the hazard ratio [HR] (95% CI) of MACEs after adjustment for traditional and angiographic risk factors was 1.24 (0.51–3.05) for the second tertile and 2.60 (1.16–5.81) for the third. Big ET-1 improved the predictive value for MACEs over traditional risk factors (C-statistic: 0.64 vs. 0.60, p = 0.03). Big ET-1 was not significantly associated with the risk of MACEs in patients without diabetes.ConclusionIncreased plasma big ET-1 was associated with a higher risk of adverse cardiovascular prognosis independent of traditional and angiographic risk factors, and therefore, it might be used as a predictive biomarker, in patients with ISR and diabetes.

Plasma Big Endothelin-1 Levels and Long-Term Outcomes in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Undergoing Percutaneous Coronary Intervention.

BackgroundThis study aimed to evaluate the association between plasma big ET-1 levels and long-term outcomes in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI).MethodsA total of 930 patients were enrolled and followed up for a median duration of 2.3 years. According to the optimal cutoff of big ET-1 for predicting all-cause death, these patients were divided into two groups. The primary endpoints were all-cause death and net adverse clinical events (NACE). The secondary endpoints included cardiovascular death, major adverse cardiovascular events (MACE), BARC class ≥ 3 bleeding, and BARC class ≥ 2 bleeding. Cox regressions were performed to evaluate the association between big ET-1 and outcomes.ResultsBased on the optimal cutoff of 0.54 pmol/l, 309 patients (33.2%) had high big ET-1 levels at baseline. Compared to the low big ET-1 group, patients in the high big ET-1 group tended to have more comorbidities, impaired cardiac function, elevated inflammatory levels, and worse prognosis. Univariable and multivariable Cox regressions indicated that big ET-1 ≥ 0.54 pmol/l was associated with increased incidences of all-cause death [HR (95%CI):1.73 (1.10–2.71), p = 0.018], NACE [HR (95%CI):1.63 (1.23–2.16), p = 0.001], cardiovascular death [HR (95%CI):1.72 (1.01–2.92), p = 0.046], MACE [HR (95%CI):1.60 (1.19–2.16), p = 0.002], BARC class ≥ 3 [HR (95%CI):2.21 (1.16–4.22), p = 0.016], and BARC class ≥ 2 bleeding [HR (95%CI):1.91 (1.36–2.70), p < 0.001]. Subgroup analysis indicated consistent relationships between the big ET-1 ≥ 0.54 pmol/l and the primary endpoints.ConclusionElevated plasma big ET-1 levels were independently associated with increased risk of all-cause death, NACE, cardiovascular death, MACE, BARC class ≥ 3 bleeding, and BARC class ≥ 2 bleeding in patients with AF and ACS or undergoing PCI.

Plasma Big Endothelin-1 Level Predicted 5-Year Major Adverse Cardiovascular Events in Patients With Coronary Artery Ectasia.

Background: Coronary artery ectasia (CAE) is found in about 1% of coronary angiography and is associated with poor clinical outcomes. The prognostic value of plasma big Endothelin-1 (ET-1) in CAE remains unknown.Methods: Patients with angiographically confirmed CAE from 2009 to 2015, who had big ET-1 data available were included. The primary outcome was 5-year major adverse cardiovascular events (MACE), defined as a component of cardiovascular death and non-fatal myocardial infarction (MI). Patients were divided into high or low big ET-1 groups using a cut-off value of 0.58 pmol/L, according to the receiver operating characteristic curve. Kaplan-Meier method, propensity score method, and Cox regression were used to assess the clinical outcomes in the 2 groups.Results: A total of 992 patients were included, with 260 in the high big ET-1 group and 732 in the low big ET-1 group. At 5-year follow-up, 57 MACEs were observed. Kaplan-Meier analysis and univariable Cox regression showed that patients with high big ET-1 levels were at increased risk of MACE (9.87 vs. 4.50%; HR 2.23, 95% CI 1.32–3.78, P = 0.003), cardiovascular death (4.01 vs. 1.69%; HR 2.37, 95% CI 1.02–5.48, P = 0.044), and non-fatal MI (6.09 vs. 2.84%; HR 2.17, 95% CI 1.11–4.24, P = 0.023). A higher risk of MACE in the high big ET-1 group was consistent in the propensity score matched cohort and propensity score weighted analysis. In multivariable analysis, a high plasma big ET-1 level was still an independent predictor of MACE (HR 1.82, 95% CI 1.02–3.25, P = 0.043). A combination of high plasma big ET-1 concentrate and diffuse dilation, when used to predict 5-year MACE risk, yielded a C-statistic of 0.67 (95% CI 0.59–0.74).Conclusion: Among patients with CAE, high plasma big ET-1 level was associated with increased risk of MACE, a finding that could improve risk stratification.

Circulating Levels of Endothelin-1 and Big Endothelin-1 in Patients with Essential Hypertension.

The role of endothelin-1 (ET-1) in the pathogenesis of hypertension (HTN) is not clearly established. There is evidence that its circulating levels are elevated in some forms of experimental and human HTN, but this was not a consistent finding. Based on these controversial data, we tested serum levels of ET-1 and Big ET-1 (the precursor of ET-1) in patients with essential HTN, comparing the results with those of healthy normotensive controls. The levels of ET-1 and Big ET-1 were measured by ELISA. Our results in patients with essential HTN showed that the mean levels of ET-1 (5.01 ± 2.1 pg/mL) were significantly higher (F = 6.34, p = 0.0144) than the mean levels in the control group (3.2 ± 1.0 pg/mL). The levels of Big ET-1 in patients with essential HTN (0.377 ± 0.1 pmol/L) were similar to those in the control group (0.378 ± 0.07 pmol/L) and did not differ significantly (F = 0.00, p = 0.9531). These data suggest that ET-1, but not Big ET-1, may play an important role in the pathogenesis of primary HTN.

Association between plasma big endothelin-1 level and the severity of coronary artery disease in patients with non-ST segment-elevated myocardial infarction

Abstract Background This study aimed to evaluate the association between plasma big endothelin-1 (ET-1) level and the severity of coronary artery disease assessed by the SYNTAX score (SS) in patient with non-ST segment-elevated myocardial infarction (NSTEMI). Methods A total of 766 patients with NSTEMI undergoing coronary angiography were recruited. Patients were divided into divided into three groups: low SS (SS ≤22), intermediate SS (23–32) and high SS group (SS &amp;gt;32). Spearman correlation, smooth curve fitting, logistic regression and Receiver operating characteristic (ROC) curve analysis were performed to evaluated the association between plasma big ET-1 level and the SS. Results There was a significant correlation between the big ET-1 and the SS (r=0.378, p&amp;lt;0.001). Smoothing curve indicated a positive correlation between plasma big ET-1 level and the SS, after adjustment for potential confounders. The ROC curve analysis showed that the area under the curve was 0.695 (0.661–0.727) and the optimal cutoff of plasma big ET-1 level were 0.35pmol/l, with a sensitivity of 68.9% and a specificity of 62.9%. Logistic regression showed that elevated big ET-1 was an independent predictor of intermediate-high SS in patients with NSTEMI, no matter entered as a continuous variable [OR (95% CI): 1.110 (1.053–1.170), p&amp;lt;0.001] or as a categorical variable [OR (95% CI): 2.873 (2.016–4.094), p&amp;lt;0.001]. The association between big ET-1 and intermediate-high SS was consistent across subgroups without significant interactions. Conclusion In patients presenting with NSTEMI, plasma big ET-1 level was significantly correlated with the SS. Elevated plasma big ET-1 level was an independent predictor for intermediate-high SS. Funding Acknowledgement Type of funding sources: None. ROC of big ET-1 for high SYNTAX score

Plasma Levels of Big Endothelin-1 Are Associated with Renal Insufficiency and In-Hospital Mortality of Immune Thrombotic Thrombocytopenic Purpura.

Immune thrombotic thrombocytopenic purpura (iTTP) is caused by severe deficiency of plasma ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity. Despite advances in early diagnosis and management, the mortality rate of acute iTTP remains high in a large part of world where access to some of the most novel therapies is limited. To determine the role of plasma big endothelin-1 (bigET-1) or its bioactive product ET-1 as a biomarker and/or a pathogenic factor in acute iTTP, plasma levels of bigET-1 were determined using an immunoassay in patients with iTTP on admission and during remission, as well as in healthy controls; moreover, the biological effect of ET-1 in thrombus formation was determined by a microfluidic assay. We show that plasma levels of bigET-1 were dramatically increased in patients with acute iTTP on admission, which was significantly decreased during clinical response/remission; elevated admission levels of plasma bigET-1 were associated with low estimated glomerular filtration rate, the need for intensive care unit admission or intubation, and in-hospital mortality. Moreover, an addition of a bioactive product ET-1 to cultured endothelial cells in a microfluidic channel significantly accelerated the rate of thrombus formation under arterial flow. Our results demonstrate for the first time a potential role of measuring plasma bigET-1 in patients with acute iTTP in assessing the disease severity and risk of in-hospital mortality, which may help stratify patients for a more aggressive monitoring and therapeutic strategy; also, the bioactive ET-1, derived from bigET-1, may result in acute renal injury in TTP patient, likely through its vasoconstriction and prothrombotic properties.

Elevated Plasma Big Endothelin-1 at Admission Is Associated With Poor Short-Term Outcomes in Patients With Acute Decompensated Heart Failure.

Objective: We aimed to evaluate the association between plasma big endothelin-1 (ET-1) at admission and short-term outcomes in acute decompensated heart failure (ADHF) patients.Methods: In this single-center, retrospective study, a total of 746 ADHF patients were enrolled and divided into three groups according to baseline plasma big ET-1 levels: tertile 1 (<0.43 pmol/L, n = 250), tertile 2 (between 0.43 and 0.97 pmol/L, n = 252), and tertile 3 (>0.97 pmol/L, n = 244). The primary outcomes were all-cause death, cardiac arrest, or utilization of mechanical support devices during hospitalization. Logistic regression analysis and net reclassification improvement approach were applied to assess the predictive power of big ET-1 on short-term outcomes.Results: During hospitalization, 92 (12.3%) adverse events occurred. Etiology, arterial pH, lactic acid, total bilirubin, serum creatine, serum uric acid, presence of atrial fibrillation and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were positively correlated with plasma big ET-1 level, whereas systolic blood pressure, serum sodium, hemoglobin, albumin, and estimated glomerular filtration rate were negatively correlated. In multivariate logistic regression, tertile 3 compared with tertile 1 had a 3.68-fold increased risk of adverse outcomes [odds ratio (OR) = 3.681, 95% confidence interval (CI) 1.410–9.606, p = 0.008]. However, such adverse effect did not exist between tertile 2 and tertile 1 (OR = 0.953, 95% CI 0.314–2.986, p = 0.932). As a continuous variable, big ET-1 level was significantly associated with primary outcome (OR = 1.756, 95% CI 1.413–2.183, p < 0.001). The C statistic of baseline big ET-1 was 0.66 (95% CI 0.601–0.720, p < 0.001). Net reclassification index (NRI) analysis showed that big ET-1 provided additional predictive power when combining it to NT-proBNP (NRI = 0.593, p < 0.001).Conclusion: Elevated baseline big ET-1 is an independent predictor of short-term adverse events in ADHF patients and may provide valuable information for risk stratification.

Cardioprotective Effects of Mebudipine in a Rat Model of Doxorubicin-Induced Heart Failure.

Background: Mebudipine, a dihydropyridine calcium-channel blocker (CCB), shows greater time- and voltage-dependent inhibitory effects than nifedipine. Its significant negative chronotropic effects without having considerable negative inotropic properties may make it a suitable candidate for the pharmacotherapy of heart failure (HF). This study aimed to investigate the possible beneficial action of mebudipine in a rat model of HF. Methods:The present study carried out in the Department of Pharmacology at the Iran University of Medical Sciences during the years of 2009-2011. An experimental model of HF was induced in male Wistar rats using doxorubicin (DOX). The rats were divided into five groups with seven animals in each group: normal control group, DOX-induced HF control groups, and treatment groups. The animals were administered DOX for 15 days. A consistent deterioration occurred after a four-week rest period. The animals were then treated with intraperitoneal mebudipine (0.5 mg/kg) and intraperitoneal amlodipine (0.35 mg/kg), as well as an equal volume of distilled water for 15 days. The plasma levels of big endothelin-1 (BET-1), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), as well as the clinical status (heart rate and blood pressure), were assessed before and after treatment. Statistical analysis was performed with SPSS software using parametric and nonparametric ANOVA.Results: Mebudipine and amlodipine reversed the increased plasma BET-1 values in the treated animals when compared with the HF control group (0.103 and 0.112 vs 0.231 pg/mL, respectively). The increased plasma levels of AST, ALT, CK-MB, and LDH were also reversed in the HF animals that received mebudipine or amlodipine.Conclusion: The administration of mebudipine to HF animals, akin to amlodipine, palliated the clinical and biochemical signs of the disease in the present study. The abstract was presented in the Iranian Congress of Physiology and Pharmacology as a poster and published in the Scientific Information Database as a supplement (2015; Vol 22).

Prognostic value of plasma big endothelin-1 in left ventricular non-compaction cardiomyopathy

ObjectiveTo determine the prognostic role of big endothelin-1 (ET-1) in left ventricular non-compaction cardiomyopathy (LVNC).MethodsWe prospectively enrolled patients whose LVNC was diagnosed by cardiac MRI and who had big ET-1...

Metformin prevents the development of monocrotaline-induced pulmonary hypertension by decreasing serum levels of big endothelin-1.

Pulmonary hypertension (PH) is a disease with poor prognosis, and it is characterized by the progressive elevation of pulmonary vascular resistance and pressure. Various factors are associated with the pathology of PH, including AMP-activated protein kinase (AMPK) deficiency. The present study aimed to evaluate the therapeutic effect of metformin, an AMPK activator, in a monocrotaline (MCT)-induced PH rat model. Rats were randomly divided into the following three groups: i) Saline-injected group (sham group); ii) monocrotaline (MCT)-injected group (PH group); iii) MCT-injected and metformin-treated group (MT group). Four weeks following MCT injection, cardiac ultrasonography, invasive hemodynamic measurements, measurement of serum levels of big endothelin-1 (big ET-1) and histological analysis were performed to evaluate the effect of metformin treatment in PH. Pulmonary arterial pressure and serum big ET-1 concentrations were reduced in the MT group compared with the PH group. Medial wall thickness and wall area of the pulmonary arterioles in the MT group were decreased compared with the PH group. Comparing the right heart functional parameters among groups revealed that the acceleration time/ejection time ratio improved in the MT group compared with the PH group. Thus, the present study demonstrated the efficacy of metformin in an MCT-induced PH rat model and suggested that metformin may be a valuable, potential novel therapeutic for the treatment of PH.

Plasma big endothelin-1 is an effective predictor for ventricular arrythmias and end-stage events in primary prevention implantable cardioverter- defibrillator indication patients.

ObjectiveTo investigate whether plasma big endothelin-1 (ET-1) predicts ventricular arrythmias (VAs) and end-stage events in primary prevention implantable cardioverter-defibrillator (ICD) indication patigents.MethodsIn total, 207 patients fulfilling the inclusion criteria from Fuwai Hospital between January 2013 and December 2015 were retrospectively analyzed. The cohort was divided into three groups according to baseline plasma big ET-1 tertiles: tertile 1 (< 0.38 pmol/L, n = 68), tertile 2 (0.38–0.7 pmol/L, n = 69), and tertile 3 (> 0.7 pmol/L, n = 70). The primary endpoints were VAs. The secondary endpoints were end-stage events comprising all-cause mortality and heart transplantation.ResultsDuring a mean follow-up period of 25.6 ± 13.9 months, 38 (18.4%) VAs and 78 (37.7%) end-stage events occurred. Big ET-1 was positively correlated with NYHA class (r = 0.165, P = 0.018), serum creatinine concentration (Scr; r = 0.147, P = 0.034), high-sensitivity C-reactive protein (hs-CRP; r = 0.217, P = 0.002), Lg NT-pro BNP (r = 0.463, P < 0.001), left ventricular end diastolic diameter (LVEDD; r = 0.234, P = 0.039) and negatively correlated with left ventricular ejection fraction (LVEF; r = −0.181, P = 0.032). Kaplan-Meier analysis showed that elevated big ET-1 was associated with increased risk of VAs and end-stage events (P < 0.05). In multivariate Cox regression models, big ET-1 was an independent risk factor for VAs (hazard ratio (HR) = 3.477, 95% confidence interval (CI): 1.352–8.940, P = 0.010, tertile 2 vs. tertile 1; HR = 4.112, 95% CI: 1.604–10.540, P = 0.003, tertile 3 vs. tertile 1) and end-stage events (HR = 2.804, 95% CI: 1.354–5.806, P = 0.005, tertile 2 vs. tertile 1; HR = 4.652, 95% CI: 2.288–9.459, P < 0.001, tertile 3 vs. tertile 1).ConclusionsIn primary prevention ICD indication patients, plasma big ET-1 levels can predict VAs and end-stage events and may facilitate ICD-implantation risk stratification.

Big endothelin-1 level as a predictive marker for the presence of isolated coronary artery ectasia in patients presented with chest pain

Abstract Background Coronary artery ectasia (CAE) is a common finding of coronary angiography, therefore, to find a biomarker to discriminate isolated coronary artery ectasia ICAE from obstructive coronary artery disease CAD may be important for clinical implication. Objectives The aim is to study the relationship between big ET-1 level and isolated CAE in patients presented with chest pain, undergoing coronary angiogram. Methods This study was conducted on 55 patients. They were presented by cardiac symptoms (chest pain, dyspnea, unstable and stable angina). They were subjected to coronary angiography. According to its findings, patients were classified into four different groups (ICAE; n = 15), (CAE &amp; CAD; n = 15), (CAD; n = 15), and (Normal; n = 10). The level of big ET-1 was found to be significantly higher in the patients with ICAE compared with the other three groups (ICAE; 261±176 ng/ml, CAD + CAE; 132±29 ng/ml, CAD; 107±16 ng/ml and Normal; 109±17 ng/ml, p &amp;lt; 0.001, respectively). Also we found that the percentage of hypertension was significantly higher in patients with CAD group compared with ICAE group and normal coronary angiography group. Conclusion In conclusion, in our study, our data suggested that the big ET-1 level was higher in isolated CAE patients and was an independent predictor for isolated CAE. Recognizing big ET-1 as an independent predictor of isolated CAE requires multivariate analysis which was not done in our study.

Association between big endothelin-1 and CHADS2/CHA2DS2-VASc scores in non-valvular atrial fibrillation.

BackgroundEndothelial function, as measured by big endothelin-1 (ET-1), has been demonstrated to be useful in predicting adverse long-term events in patients with cardiovascular disease. Nevertheless, there are little data about the association between big ET-1 and thromboembolism risk in atrial fibrillation (AF). We aimed to investigate the relationship between big ET-1 and CHADS2/CHA2DS2-VASc scores used for evaluating thromboembolic risk in patients with non-valvular AF.MethodsThe study population consisted of 238 consecutive AF patients (67.6% with paroxysmal AF and 32.4% with persistent AF). The patients were divided into two groups (high- or low-intermediate risk group) based on CHADS2 and CHA2DS2-VASc scores (score ≥ 2 or < 2, respectively). Clinical, laboratory, and echocardiographic parameters were evaluated, and the CHADS2/CHA2DS2-VASc scores were compared between groups. The association between big ET-1 levels and CHADS2/CHA2DS2-VASc score was assessed. Multivariate logistic regression analysis was performed to identify independent predictors of CHADS2/CHA2DS2-VASc scores.ResultsThe high CHADS2/CHA2DS2-VASc score group had older age, higher big ET-1 levels, and enlarged left atrial diameter than the low CHADS2/CHA2DS2-VASc score group (P < 0.05). Multiple logistic regression analysis revealed that big ET-1 level was an independent determinant of high CHADS2/CHA2DS2-VASc scores [odds ratio (OR) = 2.545 and OR = 3.816; both P < 0.05].ConclusionsOur study indicates that in non-valvular AF, big ET-1 was significantly correlated with CHADS2/CHA2DS2-VASc scores and an independent predictor of high CHADS2/CHA2DS2-VASc scores. Big ET-1 may serve as a useful marker for risk stratification in this setting.