| Part1 The relationship between plasma big endothelin-1 levels and future cardiovascular outcomes in patients with new onset stable coronary artery diseaseBackground and aim:It has been demonstrated in a large number of previous studies that big endothelin-1,derived from endothelium and smooth muscle cells,is associated with the formation as well as the progression of atherosclerosis and various cardiovascular diseases such as dysfunction of micro vessels,coronary artery calcification and myocardial infarction.Endothelin dysfunction,inflammation,stent thrombosis may be involved in the underlying mechanisms.The secondary prevention of new onset stable coronary artery disease(SCAD)is the most common type among the prevention and therapy of patients with coronary artery disease.The prognosis of patients with SCAD will be influenced by many factors,hence it is clinically important to explore new biomarkers correlated with the outcomes.However,until now the relationship between plasma big endothelin-1 levels and future cardiovascular outcomes in patients with SCAD has not been reported.Consequently,the aim of the present study was to explore whether baseline big endothelin-1 levels were correlated with future events in new onset SCAD patients.Methods:Between March 2011 and February 2014,a total of 3,154 patients definitely diagnosed with new onset SCAD were consecutively enrolled.The concentration of big endothelin-1 was measured using the method of enzyme-linked immunosorbent assays.The clinical and laboratory data of every enrolled patient were collected.The correlations of big endothelin-1 with clinical and laboratory factors were analyzed using Spearman method.Patients enrolled in the present study were followed up for 24 months.The events included all-cause death,non-fatal myocardial infarction,stroke and unplanned revascularization(percutaneous coronary intervention and coronary artery bypass grafting).Univariate and multivariate Cox proportional hazard regression analysis and Kaplan-Meier analysis were used to evaluate the prognostic value of big endothelin-1 on events.Results:The age of all SCAD patients were 58.5±10 years old.The proportions of male,hypertension and hyperlipidemia were high.The median of body mass index was over 25.The level of big endothelin-1 was 0.3(0.22-0.45)pmol/L.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).Patients in events group were older(60.39±10.67 vs.58.38±9.95,p=0.008),had higher prevalence of hypertension(75.66%vs.62.8%,p=0.001),higher big endothelin-1 levels and lower left ventricular ejection fraction.The Spearman analysis showed that big endothelin-1 was correlated with inflammatory factors,renal function and cardiovascular risk factors including age,hypertension,hyperlipidemia and smoking.After adjusting for potential confounding factors including age,gender,hypertension,diabetes mellitus,hyperlipidemia,current smoking,left ventricular ejection fraction,erythrocyte sedimentation rate,high sensitive C-reactive protein,fibrinogen and creatinine,multivariable Cox proportional hazard regression analysis showed that big endothelin-1 was positively and independently correlated with outcomes(Hazard Ratio:1.802,95%confidence interval:1.196-2.716,p=0.005).Additionally,the Kaplan-Meier analysis revealed that patients with higher levels of big endothelin-1(over the median)presented lower event-free survival rate(p=0.016).Conclusions:The present study with large sample size firstly found that baseline plasma big endothelin-1 levels were independently related to the prognosis of SCAD,which provided new information with respect to the clinical value of big endothelin-1 on patients with coronary artery disease.Part 2 The predictive value of big endothelin-1 on prognosis of patients with premature myocardial infarction younger than 35 years of ageBackground and aim: As we all know,the prevalence of myocardial infarction(MI)in our country was increasing in young individuals recent years.Based on the situation,it is clinically important to conduct studies on this special population.Endothelin-1,one of the most vasoconstrictive factors,was demonstrated to be associated with endothelial dysfunction,inflammation and thromboembolisms.Big endothelin-1,the precursor of endothelin-1,was reported to be associated with the presence and progression of ML However,to our knowledge,until now no attempts on the relationship between big endothelin-1 and prematxire MI have been made.The present study systematically analyzed data from MI patients younger than 35 years of age and aimed to explore the predictive value of big endothelin-1 on prognosis of premature MI patients.Methods: Among 61,863 consecutive patients with MI hospitalized in our hospital between February 2009 and May 2016,565 patients younger than 35 years of age undergoing coronary artery angiography were consecutively enrolled in the present study.The severity of coronary artery stenosis was calculated by tiie Gensini score system.The clinical and laboratory data were collected from every eligible patient.Concentrations of total cholesterol and triglyceride were measured using automatic biochemistry analyzer.Big endothelin-1 was measured using a highly sensitive and specific commercial sandwich enzyme immunoassay.Patients were followed up by clinic or using telephone.The events included all-cause death,non-fatal myocardial infarction,stroke,unplanned revascularization(percutaneous coronary intewention and coronaty artery bypass grafting),hospitalized for unstable angina and heart failure.Univariate and multivariate Cox proportional hazard regression analysis and Kaplan-Meier analysis were used to evaluate the prognostic value of big endothelin-1 on cardiovascular outcomes.The best cut-off value of big endothelin-1 for predicting events was analyzed by receiver operating characteristics(ROC)analysis.The area under ROC(area under the curve [AUC])was also conducted to show the predictive value of big endothelin-1 on events.Results: Patients were followed up for 37.8 ± 24.9 months.During follow-up,ninety-two events occurred: nine all-cause deatiis,eight nonfatal MI,forty-five revascularizations and thirty readmissions for severe mstable angina and heart failure.Patients were divided into two groups: events group(n=92)and non-events group(n=432).The proportion of hypertension was higher(42.39% vs.31.71%),and left ventricular ejection fraction was lower in events group when compared to non-events group.There were no significant differences among the two groups in terms of age,history of hyperlipidemia and diabetes mellitus,family history of coronary artery disease,lipid profiles including total cholesterol,triglyceride and low density lipoprotein cholesterol,inflammatory factors including erythrocyte sedimentation rate and high-sensitivity C-reactive protein and renal function.The concentration of big endothelin-1 was significantly higher in events group(0.44 vs.0.29 pmol/L, p<0.001).After adjustment for age,sex,hypertension,hyperlipidemia,diabetes mellitus,current smoke,ejection fraction,Gensini score and creatinine,big endothelin-1 was demonstrated to be independently correlated with events(odds ratio: 3.00;95% confidence interval: 1.92-4.68;p<0.001).The AUC was 0.67.A level of big endothelin-1 >0.30 pmol/L predicted the events witii 74% sensitivity and 62% specificity.Conclusions: The study firstly demonstrated that big endothelin-1 was independently correlated with cardiovascular outcomes in premature MI patients younger than 35 years of age,which indicated that big endothelin-1 might be an independent predictor for future outcomes in the special population. |
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