Plasma Big Endothelin-1 Levels Research Articles

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.

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.

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

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.

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...

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.

Plasma big endothelin-1 predicts new-onset atrial fibrillation after surgical septal myectomy in patients with hypertrophic cardiomyopathy

BackgroundPostoperative atrial fibrillation (POAF) is a common complication in patients with obstructive hypertrophic cardiomyopathy (HOCM) who undergo surgical myectomy. POAF is associated with poor outcome. The role of plasma big endothelin-1 level in predicting atrial fibrillation after surgical septal myectomy in HOCM patients has not well been studied.MethodsA total of 118 patients with HOCM who underwent surgical septal myectomy were recruited in this study. Plasma big endothelin-1 level was measured. The heart rhythm was continuously monitored during hospital stay. Preoperative, intraoperative, and postoperative variables were collected.ResultsPOAF developed among 26 of the 118 patients (22%) in this study. Compared with those without POAF, patients with POAF were significantly older (53.5 ± 10.6 vs. 47.3 ± 13.6 years, P = 0.033), more likely to undergo mitral valve surgery (38.5% vs. 18.5%, P = 0.032), and had higher plasma big endothelin-1 levels (0.41 ± 0.19 vs. 0.27 ± 0.14 pmol/l, P = 0.001), longer hospital stay (9.1 ± 3.7 vs. 7.5 ± 2.8 days, P = 0.022), larger preoperative left atria (48.0 ± 5.2 vs. 44.1 ± 5.9 mm; P = 0.003). In the receiver operating characteristic curve analysis, the area under the curve for big endothelin-1 was 0.734 (95% CI, 0.634 to 0.834, P<0.001). In multivariate logistic regression analysis, preoperative big endothelin-1 level (OR 100.7, 95%CI: 5.0–2020.0, P = 0.003) and left atrial diameter (OR 1.106, 95%CI: 1.015–1.205, P = 0.022) were independent predictors of POAF.ConclusionElevated preoperative plasma big endothelin-1 level is an independent predictor of POAF in HOCM patients undergoing surgical septal myectomy.

Prognostic Value of Plasma Big Endothelin-1 Level among Patients with Three-Vessel Disease: A Cohort Study.

Aim: To evaluate the prognostic value of plasma big endothelin-1 level in the context of three-vessel disease (TVD) with heavy atherosclerotic burden.Methods: A total of 6,150 patients with TVD and available big endothelin-1 data were included in the study. Participants were divided into two groups according to the optimal cutoff value of big endothelin-1 for mortality prediction. The primary endpoint was all-cause death. C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to evaluate the added prognostic value of plasma big endothelin-1 level beyond the SYNTAX score II.Results: On the basis of the optimal cutoff value of 0.79 pmol/L, 1,984 patients were assigned to the high big endothelin-1 group. During a median follow-up of 6.8 years, 818 patients experienced all-cause death. Plasma big endothelin-1 level was significantly higher in patients who died than in patients who survived. Multivariable analysis found that high big endothelin-1 level was independently associated with an increased risk of mortality (hazard ratio: 1.36, 95% confidence interval: 1.18–1.57, P < 0.001). The association of big endothelin-1 with all-cause death was relatively consistent across subgroups with no significant interactions. The predictive ability of the SYNTAX score II was significantly enhanced by addition of plasma big endothelin-1 level (C-index: 0.723 vs. 0.715, P = 0.029; NRI: 0.304, P < 0.001; IDI: 0.009, P < 0.001).Conclusions: Plasma big endothelin-1 level is an independent predictor of long-term mortality in patients with TVD. It can improve the discrimination and reclassification of the SYNTAX score II for mortality prediction.

GW29-e0012 The Association between Plasma Big Endothelin-1 Levels at Admission and Long-term Outcomes in Patients with Atrial Fibrillation

Big endothelin-1 (ET-1) has been identified as a risk marker in a variety of cardiovascular diseases, while its prognostic role in atrial fibrillation (AF) is unclear. A total of 716 AF patients were enrolled and divided into high plasma levels of big ET-1 group and low plasma levels of big ET-1

The association between plasma big endothelin-1 levels at admission and long-term outcomes in patients with atrial fibrillation

Background and aimsThe prognostic role of big endothelin-1 (ET-1) in atrial fibrillation (AF) is unclear. We aimed to assess its predictive value in patients with AF. MethodsA total of 716 AF patients were enrolled and divided into two groups based on the optimal cut-off value of big ET-1 in predicting all-cause mortality. The primary outcomes were all-cause mortality and major adverse events (MAEs). Cox regression analysis and net reclassification improvement (NRI) analysis were performed to assess the predictive value of big ET-1 on outcomes. ResultsWith the optimal cut-off value of 0.55 pmol/L, 326 patients were classified into the high big ET-1 levels group. Cardiac dysfunction and left atrial dilation were factors related to high big ET-1 levels. During a median follow-up of 3 years, patients with big ET-1 ≥ 0.55 pmol/L had notably higher risk of all-cause death (44.8% vs. 11.5%, p < 0.001), MAEs (51.8% vs. 17.4%, p < 0.001), cardiovascular death, major bleeding, and tended to have higher thromboembolic risk. After adjusting for confounding factors, high big ET-1 level was an independent predictor of all-cause mortality (hazard ratio (HR) 2.11, 95% confidence interval (CI) 1.46–3.05; p < 0.001), MAEs (HR 2.05, 95% CI 1.50–2.80; p = 0.001), and cardiovascular death (HR 2.44, 95% CI 1.52–3.93; p < 0.001). NRI analysis showed that big ET-1 allowed a significant improvement of 0.32 in the accuracy of predicting the risk of both all-cause mortality and MAEs. ConclusionsElevated big ET-1 levels is an independent predictor of long-term all-cause mortality, MAEs, and cardiovascular death in patients with AF.

Plasma big endothelin-1 and stent thrombosis: An observational study in patients undergoing percutaneous coronary intervention in China

IntroductionStent thrombosis (ST) is a rare but catastrophic complication of percutaneous coronary intervention, leading to poor prognosis. Endothelin-1 (ET-1) plays an important role in endothelial dysfunction and thrombogenesis. However, the impact of big ET-1 level on ST in patients with coronary stenting is unknown. We aimed to evaluate big ET-1 level as a potential predictor of ST in patients undergoing percutaneous coronary intervention. Materials and methodsFrom January 2013 to December 2013, 8106 consecutive patients underwent successful coronary stent implantation and were prospectively enrolled in this study. Patients were stratified into three groups based on plasma big ET-1 level at admission. ResultsThe incidence of definite and probable ST at 2years postoperatively was 0.84%; ST incidence was lowest in the low big ET-1 group (0.56%), highest in the high big ET-1 group (1.48%), and intermediate in the medium big ET-1 group (0.74%, log-rank p=0.001). Compared with the low big ET-1 group, the multivariate-adjusted hazard ratio (HR) for ST in the high big ET-1 group was 2.06 (95% confidence interval (CI) 1.14–3.73, p=0.017). In subgroup analyses, high big ET-1 level was independently associated with ST in patients with acute coronary syndrome (HR 2.29, 95% CI 1.03–5.06, p=0.041), but not in those with stable coronary artery disease (p=0.331), and tended to be associated with older age. ConclusionsPlasma big ET-1 level is a valuable independent predictor of ST in patients with coronary stents, especially in the acute coronary syndrome population.

Plasma level of big endothelin-1 predicts the prognosis in patients with hypertrophic cardiomyopathy

BackgroundCardiac remodeling is one of major pathological process in hypertrophic cardiomyopathy (HCM). Endothelin-1 has been linked to cardiac remodeling. Big endothelin-1 is the precursor of endothelin-1. MethodsA total of 245 patients with HCM were enrolled from 1999 to 2011 and partitioned to low, middle and high level groups according to their plasma big endothelin-1 levels. ResultsAt baseline, significant associations were found between high level of big endothelin-1 and left atrium size, heart function and atrial fibrillation. Big endothelin-1 was positively correlated with N-terminal B-type natriuretic peptide (r=0.291, p<0.001) and late gadolinium enhancement (LGE) on magnetic resonance imaging (r=0.222, p=0.016). During a follow-up of 3 (range, 2–5) years, big endothelin-1 level was positively associated with the risks of all-cause mortality, cardiovascular death and progression to NYHA class 3 or 4 (p=0.020, 0.044 and 0.032, respectively). The rate of above events in the highest tertile were 18.1%, 15.7%, 24.2%, respectively. After adjusting for multiple factors related to survival and cardiac function, the significance remained in the association of big endothelin-1 with the risk of all-cause mortality (hazard ratio (HR)=4.94, 95% confidence interval (CI) 1.07–22.88; p=0.041) and progression to NYHA class 3 or 4 (HR=4.10, 95%CI 1.32–12.75, p=0.015). ConclusionOur study showed that high level of plasma big endothelin-1 predicted prognosis for patients with HCM and it can be added to the marker panel in stratifying HCM patients for giving treatment priority to those at high risk.

Plasma big endothelin-1 levels at admission and future cardiovascular outcomes: A cohort study in patients with stable coronary artery disease

BackgroundBig endothelin-1 (ET-1) has been proposed as a novel prognostic indicator of acute coronary syndrome, while its predicting role of cardiovascular outcomes in patients with stable coronary artery disease (CAD) is unclear. Methods and resultsA total of 3154 consecutive patients with stable CAD were enrolled and followed up for 24months. The outcomes included all-cause death, non-fatal myocardial infarction, stroke and unplanned revascularization (percutaneous coronary intervention and coronary artery bypass grafting). Baseline big ET-1 was measured using sandwich enzyme immunoassay method. Cox proportional hazard regression analysis and Kaplan–Meier analysis were used to evaluate the prognostic value of big ET-1 on cardiovascular outcomes. One hundred and eighty-nine (5.99%) events occurred during follow-up. Patients were divided into two groups: events group (n=189) and non-events group (n=2965). The results indicated that the events group had higher levels of big ET-1 compared to non-events group. Multivariable Cox proportional hazard regression analysis showed that big ET-1 was positively and statistically correlated with clinical outcomes (Hazard Ratio: 1.656, 95% confidence interval: 1.099–2.496, p=0.016). Additionally, the Kaplan–Meier analysis revealed that patients with higher big ET-1 presented lower event-free survival (p=0.016). ConclusionsThe present study firstly suggests that big ET-1 is an independent risk marker of cardiovascular outcomes in patients with stable CAD. And more studies are needed to confirm our findings.

GW27-e0858 Plasma big endothelin-1 levels at admission and future cardiovascular outcomes: a cohort study in patients with stable coronary artery disease

GW27-e0858 Plasma big endothelin-1 levels at admission and future cardiovascular outcomes: a cohort study in patients with stable coronary artery disease

Associations of big endothelin-1 and C-reactive protein in atrial fibrillation.

BackgroundAtrial fibrillation (AF) is associated with inflammation and endothelial dysfunction. However, the association between inflammation (as indexed by high-sensitivity C-reactive protein, hs-CRP) and endothelial function [as indexed by big endothelin-1 (ET-1)] in AF patients remains unclear.MethodsWe enrolled 128 patients with lone AF, among which 83 had paroxysmal AF, and 45 had persistent AF. Eighty-two age- and gender-matched controls of paroxysmal supraventricular tachycardia without AF history were evaluated. Plasma hs-CRP, big ET-1 levels and other clinical characteristics were compared among the groups.ResultsPatients with persistent AF had higher hs-CRP concentrations than those with paroxysmal AF (P < 0.05), both groups had higher hs-CRP level than controls (P < 0.05). Patients with persistent AF had higher big ET-1 level than those with paroxysmal AF, although the difference did not reach the statistical significance (P > 0.05), and both groups had higher big ET-1 levels than controls (P < 0.05). Multiple regression analyses revealed hs-CRP as an independent determinant of AF (P < 0.001). Further adjusted for big ET-1, both big ET-1 and hs-CRP were independent predictors for AF (P < 0.001), but the odds ratio for hs-CRP in predicting AF attenuated from 8.043 to 3.241. There was a positive relation between hs-CRP level and big ET-1 level in paroxysmal AF patients (r = 0.563, P < 0.05), however, the relationship in persistent AF patients was poor (r = 0.094, P < 0.05).ConclusionsBoth plasma hs-CRP and big ET-1 levels are elevated in lone AF patients, and are associated with AF. In paroxysmal lone AF patients, there were significant positive correlations between plasma hs-CRP level and big ET-1 level.

Association of Big Endothelin-1 with Coronary Artery Calcification.

BackgroundThe coronary artery calcification (CAC) is clinically considered as one of the important predictors of atherosclerosis. Several studies have confirmed that endothelin-1(ET-1) plays an important role in the process of atherosclerosis formation. The aim of this study was to investigate whether big ET-1 is associated with CAC.Methods and ResultsA total of 510 consecutively admitted patients from February 2011 to May 2012 in Fu Wai Hospital were analyzed. All patients had received coronary computed tomography angiography and then divided into two groups based on the results of coronary artery calcium score (CACS). The clinical characteristics including traditional and calcification-related risk factors were collected and plasma big ET-1 level was measured by ELISA. Patients with CAC had significantly elevated big ET-1 level compared with those without CAC (0.5±0.4 vs. 0.2±0.2, P<0.001). In the multivariate analysis, big ET-1 (Tertile 2, HR = 3.09, 95% CI 1.66–5.74, P <0.001, Tertile3 HR = 10.42, 95% CI 3.62–29.99, P<0.001) appeared as an independent predictive factor of the presence of CAC. There was a positive correlation of the big ET-1 level with CACS (r = 0.567, p<0.001). The 10-year Framingham risk (%) was higher in the group with CACS>0 and the highest tertile of big ET-1 (P<0.01). The area under the receiver operating characteristic curve for the big ET-1 level in predicting CAC was 0.83 (95% CI 0.79–0.87, p<0.001), with a sensitivity of 70.6% and specificity of 87.7%.ConclusionsThe data firstly demonstrated that the plasma big ET-1 level was a valuable independent predictor for CAC in our study.

Circulating levels of endothelin-1 (ET-1) and its precursor (Big ET-1) in breast cancer early diagnosis

Deregulation of the endothelin system, comprised of endothelin-1 (ET-1), its isoforms (ET-2 and ET-3) and their receptors (ET(A)R and ET(B)R), is under investigation in various types of human cancer. ET-1 has been suggested to participate in breast cancer development and progression, while Big ET-1, its biological precursor, has also been found elevated in breast cancer patients. In the present study, we investigated plasma ET-1 and Big ET-1 levels in patients with suspicious mammographic lesions, in order to assess their potential application as diagnostic biomarkers in the early estimation of breast disease. The study consisted of 94 patients (Group A to 30 patients with invasive ductal carcinoma: Group B, 30 with ductal carcinoma in situ; and group C, 34 with papilloma or ductal hyperplasia), who underwent an image-guided vacuum-assisted breast biopsy, and 30 healthy controls (group D). ET-1 and Big ET-1 plasma levels were measured with enzyme-linked immunosorbent assay. ET-1 levels did not exhibit significant differences between patients and healthy controls (Group A to 0.92 fmol/mL; Group B: 0.90 fmol/mL; Group C: 0.66 fmol/mL; and Group D: 0.86 fmol/mL). In contrast, Big ET-1 levels were significantly higher in patients with invasive or in situ carcinoma compared to healthy controls (Group A: 0.69 fmol/mL; Group B, 0.62 fmol/mL; and group D: 0.39 fmol/mL; p < 0.001 and p < 0.01). Plasma Big ET-1 may provide a useful tool for the early detection of invasive or noninvasive ductal breast cancer. The utilization of such a diagnostic tool would greatly assist in the modern management of breast cancer.

Elevated levels of plasma Big endothelin-1 and its relation to hypertension and skin lesions in individuals exposed to arsenic

Chronic arsenic (As) exposure affects the endothelial system causing several diseases. Big endothelin-1 (Big ET-1), the biological precursor of endothelin-1 (ET-1) is a more accurate indicator of the degree of activation of the endothelial system. Effect of As exposure on the plasma Big ET-1 levels and its physiological implications have not yet been documented. We evaluated plasma Big ET-1 levels and their relation to hypertension and skin lesions in As exposed individuals in Bangladesh. A total of 304 study subjects from the As-endemic and non-endemic areas in Bangladesh were recruited for this study. As concentrations in water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The plasma Big ET-1 levels were measured using a one-step sandwich enzyme immunoassay kit. Significant increase in Big ET-1 levels were observed with the increasing concentrations of As in drinking water, hair and nails. Further, before and after adjusting with different covariates, plasma Big ET-1 levels were found to be significantly associated with the water, hair and nail As concentrations of the study subjects. Big ET-1 levels were also higher in the higher exposure groups compared to the lowest (reference) group. Interestingly, we observed that Big ET-1 levels were significantly higher in the hypertensive and skin lesion groups compared to the normotensive and without skin lesion counterpart, respectively of the study subjects in As-endemic areas. Thus, this study demonstrated a novel dose–response relationship between As exposure and plasma Big ET-1 levels indicating the possible involvement of plasma Big ET-1 levels in As-induced hypertension and skin lesions.