磷酸肌酸治疗老年慢性心力衰竭的临床疗效及其对心力衰竭标志物的影响研究

Clinical Efficacy of Exogenous Phosphocreatine in the Treatment of Elderly Patients with Chronic Heart Failure and Its Impact on Heart Failure Markers

背景近年来,半乳糖凝集素3(Galectin-3)、ST2蛋白、和肽素(Copeptin)等新型生物学标志物对心力衰竭预后的评估价值逐渐得到认可,而外源性磷酸肌酸可促进三磷酸腺苷的转运及利用,改善心肌能量代谢,但其对老年慢性心力衰竭的作用尚不完全清楚。目的观察外源性磷酸肌酸治疗老年慢性心力衰竭的临床疗效及其对心力衰竭标志物的影响。方法选取2014年3月—2016年6月在山东大学齐鲁医院老年心血管内科、心内科、急诊心内科住院治疗的老年慢性心力衰竭患者80例,根据住院编号并采用随机数字表余数法分为对照组和磷酸肌酸组,每组40例。磷酸肌酸组中2例患者治疗期间因个人原因退出试验。对照组患者给予慢性心力衰竭标准药物治疗方案,磷酸肌酸组患者在对照组基础上给予磷酸肌酸治疗;两组患者均连续治疗7 d。比较两组患者临床疗效、治疗前后血清心力衰竭标志物〔包括N末端脑钠肽前体(NT-proBNP)、Galectin-3、ST2蛋白及Copeptin〕水平差值,并比较不同纽约心脏病协会(NYHA)分级患者血清心力衰竭标志物水平;心力衰竭标志物与老年慢性心力衰竭患者NYHA分级的相关性分析采用Spearman秩相关分析。结果磷酸肌酸组患者临床疗效优于对照组(P<0.05)。磷酸肌酸组患者治疗前后血清NT-proBNP、Galectin-3、ST2蛋白、Copeptin水平差值大于对照组(P<0.05);不同NYHA分级患者治疗前血清NT-proBNP水平比较,差异无统计学意义(P>0.05);NYHA分级Ⅳ级患者血清Galectin-3、ST2蛋白、Copeptin水平高于Ⅲ级(P<0.05)。Spearman秩相关分析结果显示,治疗前血清Galectin-3(rs=0.775)、ST2蛋白(rs=0.347)、Copeptin(rs=0.278)水平与老年慢性心力衰竭患者NYHA分级呈正相关(P<0.05),而治疗前血清NT-proBNP水平与老年慢性心力衰竭患者NYHA分级无直线相关关系(rs=0.062,P>0.05)。两组患者治疗期间不良反应发生率比较,差异无统计学意义(P>0.05)。结论外源性磷酸肌酸治疗老年慢性心力衰竭患者的临床疗效确切,可有效降低血清NT-proBNP、Galectin-3、ST2蛋白、Copeptin水平,改善患者心功能,且安全性较高。

Background Novel biomarkers such as Galectin-3,ST2 protein and Copeptin got the nod in the evaluation of prognosis of heart failure in recent years,however exogenous phosphocreatine can promote the transshipment and utilization of ATP as well as improve the myocardial energy metabolism,but its mechanism of action on chronic heart failure is not completely clear in the aged.Objective To observe the clinical efficacy of exogenous phosphocreatine in the treatment of elderly patients with chronic heart failure and its impact on heart failure markers.Methods From March 2014 to June 2016,a total of 80 elderly patients with chronic heart failure were selected in the Department of Cardiovascular Diseases,Department of Cardiology and Department of Emergency Cardiology in Qilu Hospital of Shandong University,and they were divided into control group and phosphocreatine group according to the inpatient number and the method of random number table remainder,with 40 cases in each group.Two patients in the phosphocreatine group withdrew from the trial due to personal reasons.The patients in the control group were given the standard drug treatment plan for chronic heart failure,and the patients in the phosphocreatine group were given the phosphocreatine on the basis of the control group;both groups were continuously treated for 7 days.The clinical effect and difference value of serum levels of heart failure markers(including NT-proBNP,Galectin-3,ST2 protein and Copeptin)before and after treatment were compared between the two groups,as well as the serum levels of heart failure markers was compared in patients with different NYHA grades,correlation of NYHA grades with heart failure markers in elderly patients with chronic heart failure was analyzed by Spearman rank correlation.Results Clinical effect in phosphocreatine group was statistically significantly better than that in control group(P<0.05).The difference value of serum levels of NT-proBNP,Galectin-3,ST2 protein or Copeptin before and after treatment in phosphocreatine group was statistically significantly higher than that in control group(P<0.05);before treatment,no statistically significant difference of serum NT-proBNP level in patients with different NYHA grades(P>0.05);while the serum levels of Galectin-3,Copeptin and ST2 protein in patients with NYHA gradeⅣwas statistically significantly higher than that in patients with NYHA gradeⅢ(P<0.05).Spearman rank correlation analysis showed that,before treatment serum levels of Galectin-3(rs=0.775),ST2 protein(rs=0.347)and Copeptin(rs=0.278)were positively correlated with NYHA grade in elderly patients with chronic heart failure(P<0.05),while serum NT-proBNP level was not linearly correlated with NYHA grade of elderly patients with chronic heart failure(rs=0.062,P>0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion The clinical effect of exogenous phosphocreatine in the treatment of elderly patients with chronic heart failure is definite,can effectively reduce the serum levels of NT-proBNP,Galectin-3,ST2 protein and Copeptin,improve heart function,with relatively high safety.