The Circulating Plasma Copeptin In Patients With Coronary Heart Disease And Its Clinical Implication

Background:Coronary heart disease (CHD) is a common disease and a principal cause of death in adults, it's morbility and mortality rates are increasing year by year. Biomarkers have emerged as a useful tool for predicting prognosis in patients with coronary heart disease. Very recently, a large clinical research found that copeptin has been shown to be an independent predictor of death in patients with AMI, especially in those with an elevated NTproBNP. Copeptin, the C-terminal part of the vasopressin prohormone, is secreted stoichiometrically with vasopressin from the neurohypophysis. However, AVP is unstable in isolated plasma and AVP measurement is cumbersome. While copeptin is very stable in vitro, and can be quickly and easily measured. There are some researches found that the copeptin assay may be a useful alternative to direct measurement of AVP concentration. AVP plays a crucial role in the regulation of the hypothalamo-pituitary–adrenal axis, reflecting the individual stress response. As the presence and the extent of myocardial ischemia strongly predicts mortality in CHD ,we hypothesized that copeptin and the AVP system may be involved in the response to myocardial ischemia. Also the results from the PASSAT study supported this hypothesis. They found, that levels of AVP increased immediately after percutaneous coronary intervention in patients with acute myocardial infarction,suggesting also that myocardial ischemia may induce AVP secretion. The present findings suggest that the AVP system is another candidate neurohormonal pathway, in addition to the renin-angiotensin and sympathetic nervous systems, that may be associated with poor outcome after AMI. However, the role of copeptin in coronary heart disease remains to be established, especially the association of copeptin with the severity of coronary atherosclerosis.Objective : To see whether plasma copeptin correlates with coronary heart disease(CHD),severity of coronary atherosclerosis and other established cardiovascular risk factors.Methods:Coronary angiography (CAG) was performed in 180 hospitalized patients who were suspected as having coronary heart disease (CHD). The severity of pathological changes of the coronary artery was assessed by the number of diseased coronary branches and Gensini's score. According to the results of CAG, the 180 patients were divided into two groups: CHD group (n=101) and non-CHD group as control (n=79). The CHD patients were further divided into subgroups according to the number of diseased coronary branches and Gensini's score. Plasma copeptin, lipids, fasting plasma glucose ,blood pressure, body mass index were measured, and age, sex and prior medical histories including hypertension, diabetes mellitus and smoking status were obtained before CAG in all patients. Copeptin were compared statistically between the subgroups, and correlation coefficient of copeptin and other conventional risk factors for CHD was calculated. Measurement data which follows the normal distribution were described with mean±std and T-test was used to compare the difference between two groups and the difference among three or more groups were compared with ANOVA. In addition, the Pearson method was also employed for the correlation analysis. The data which do not follows the normal distribution(BMI) were described with median and quartile and compared with Wilcoxon rank sum test and Kruskal-Wallis H test. The difference between enumeration data were compared with Chi-square test and the Spearman method was used for the correlation analysis. All the data were analyzed by SAS9.1.3 and P<0.05 was supposed to be statistically significant.Results:1) Plasma copeptin in CHD patients was significantly higher than that in controls (0.9536±0.0986ng/ml vs 0.9244±0.0649ng/ml,P<0.05); 2) Plasma copeptin in double diseased coronary branches subgroup and three diseased coronary branches subgroup was respective significantly higher than that in controls and single diseased coronary branche subgroup(P<0.05), but plasma copeptin in double diseased coronary branches subgroup and three diseased coronary branches subgroup have no significant statistical difference(P>0.05).Plasma copeptin in 20≤Gensini's score<40 subgroup and Gensini's score≥40 subgroup was respective significantly higher than that in controls and 00.05);3) Plasma copeptin was not correlated with age, body mass index, blood pressure,smoking status, hypertension, diabetes mellitus,TC ,TG, LDL-C;HDL-C, and FPG.Conclusion: 1) Plasma copeptin level is significantly increased in patients with coronary heart disease, especially in double diseased coronary branches subgroup, three diseased coronary branches subgroup, 20≤Gensini's score<40 subgroup and Gensini's score≥40 subgroup, which indicate that plasma copeptin level can be used as a parameter to predict pathological severity of coronary atherosclerosis. 2) Plasma copeptin is not correlated with age, body mass index, blood pressure,smoking status, hypertension, diabetes mellitus,TC ,TG, LDL-C;HDL-C, and FPG.