摘要
研究背景：射血分数正常心力衰竭(HFNEF)是一组具有心力衰竭的症状和/或体征,以左心室射血分数(LVEF)正常而舒张功能异常为特征的临床综合征。流行病学研究表明,在心力衰竭发病人群中,HFNEF所占比例超过50%,且其预后与射血分数下降心力衰竭(HFREF)相似。脂联素(Adiponectin, APN)是由脂肪细胞合成并分泌的一种血浆蛋白,在能量代谢、胰岛素抵抗、炎症反应及动脉粥样硬化的形成等生理病理过程中发挥重要的调节作用。大量研究显示,血浆APN水平在HFREF患者明显升高,但APN在HFNEF患者血浆水平的变化却少见报道。
目的：观察HFNEF和HFREF患者在一般资料、病因、APN、实验室常规检查指标、超声心动图指标等方面存在的异同点；观察HFNEF患者中APN与各实验室检查指标的相关性；随访HFNEF和HFREF患者的预后情况,探讨APN与HFNEF预后的关系。
方法：选取2009年2月至2010年9月天津医科大学总医院心血管病中心慢性充血性心力衰竭(CHF)的住院患者190例,及同时期入院的无心力衰竭患者(因冠心病、高血压、糖尿病、高脂血症、心律失常等入院)80例作为对照组,入院后第二日取肘静脉血测定患者血浆APN、氨基末端脑钠肽前体(N-terminal pro-brain natriuretic peptide, NT-proBNP)、及常规实验室检查指标,行多普勒超声心动图检查,根据《2007年ESC心力衰竭和超声协会对诊断左室射血分数正常心力衰竭的共识》将心力衰竭患者分为HFNEF组(n=70)、HFREF组(n=120)。所有患者经过病史询问、体格检查、实验室检查和超声心动图检查排除先天性心脏病,心包疾病,慢性呼吸系统疾病,心脏瓣膜病,自身免疫性疾病,恶性肿瘤及严重肝肾功能不全者。电话随访患者出院后因心力衰竭加重导致死亡或再入院的时间和例数。根据三组患者一般资料、病因、实验室检查等结果进行分析,观察各指标在两种心力衰竭患者中的异同点,APN与各指标的相关性,比较两种心力衰竭患者的预后情况及APN与预后的关系。
结果：1.所有CHF患者中,HFNEF患者比例为37%,与HFREF患者比较, HFNEF患者体重指数(BMI)更高,女性及高血压患者比例更高；2.HFNEF患者APN水平低于HFREF患者,但二者均高于无心力衰竭对照组(8.13±2.48μg/ml vs 12.34±4.78μg/ml vs 5.45±1.34μg/ml,均P<0.01); HFNEF患者NT-proBNP水平低于HFREF患者,但二者均高于无心力衰竭对照组(1987±748pg/ml vs 2507±985pg/ml vs 80±23pg/ml,均P<0.01)；两组心力衰竭患者高敏C反应蛋白(hs-CRP)水平均高于对照组(8.62±13.3mg/l vs 8.79±6.96mg/l vs 1.92±2.31mg/l, P<0.01); HFNEF组左室舒末径(LVDD)和左室质量指数(LVMI)低于HFREF组(45.3±8.5mm vs 55.26±7.74mm, P<0.01; 117±74g/m2 vs 132±64g/m2, P<0.01),室间隔厚度(IVST)、左室后壁厚度(LVPWT)高于HFREF组(11.8±2.5mm vs 10.3±3.2mm, P<0.01; 11.1±3.1mm vs 9.6±4.3mm, P<0.01); 3.HFNEF组中,APN水平与NYHA分级、hs-CRP、NT-proBNP、LVMI呈正相关(R=0.484,P=0.001；R=0.312, P=0.038; R=0.868, P=0.000; R=0.350, P=0.000); 4.HFNEF患者APN、NT-proBNP水平随NYHA(?)心功能级别的增加而上升(P<0.05)；5.随访16个月后,HFNEF和HFREF组因心力衰竭死亡或再入院的比例分别为44.29%和48.33%,差异无统计学意义(P=0.193)；两组患者死亡率分别为20.00%和21.43%,差异无统计学意义(P=0.248)；6.随访期间,HFNEF和HFREF两组发生心脏事件的患者中血浆APN和NT-proBNP水平显著高于无心脏事件患者,差异有统计学意义(P=0.034,P=0.021；P=0.006,P=0.000)；以是否发生终点事件为因变量,以HFNEF患者的年龄、性别、BMI、病因、实验室检查指标及超声心动图检查指标为协变量使用比例危险率回归模型进行Cox回归分析,提示NYHA分级、hs-CRP、NT-proBNP和APN为评价HFNEF患者预后的危险因素(P=0.045；P=0.043：P=0.001；P=0.020)。
结论：1.所有CHF患者中,HFNEF患者比例为37%,与HFREF患者比较,HFNEF患者BMI更高,女性及高血压患者比例更高；2.与对照组相比,心力衰竭患者血浆hs-CRP、NT-proBNP、APN水平显著升高(P<0.01)；并且,NT-proBNP、APN水平在HFREF患者水平高于HFNEF患者。HFNEF患者NT-proBNP、APN水平随着NYHA分级的升高而升高。3. HFNEF患者血浆APN水平与NT-proBNP具有良好的相关性。4.HFNEF患者预后与HFREF患者相似；NYHA分级、hs-CRP、NT-proBNP和APN为评价HFNEF患者预后的危险因素。
Background Heart failure with normal ejection fraction (HFNEF) constitutes nearly half of all HF patients and is associated with high morbidity and mortality. The prognosis of patients with HFNEF was similar to those with systolic dysfunction. Desipite the high prevalence of this syndrome, very little information is known regarding its mortality and morbidity, or the efficacy of drugs. Adiponectin, a recently discovered adipocyte-derived peptide, is involved in the regulation of insulin sensitivity and lipid oxidation and, purportedly, in the development of atherosclerosis and coronary heart disease in humans. Several prospective studies have assessed the association between adiponectin levels and HF. High levels are associated with increased mortality and severity in patients with HFREF, very little information is known regarding the patients with HFNEF.
Objectives:The purpose of this study was to compare the clinical characteristic and prognosis among consecutively hospitalized patients with CHF and preserved ejection fraction versus reduced ejection fraction; and to determine concentrations of adiponectin(APN) in heart failure with normal ejection fraction(HFNEF) patients and heart failure with reduced ejection fraction(HFREF)patients, determine its predictive value on outcome in patients with HFNEF, and to find out the prognostic indicators in HFNEF.
Methods:The study sample included 190 patients with CHF and 80 control patients without heart failure who were hospitalized during the past 2-year period. The CHF patients were classified into 2 groups according to "ESC 2007 Association consensus for the diagnosis of heart failure with normal ejection" :HFNEF group(n=70), HFREF(n=120) group and control group(n=80). All the selected patients were asked the medical history, paysical examination, laboratory tests and echocardigraphic examinations. Excluded congenital cardiovascular disease, pericardial disease, chronic respiratory disease, valvular heart disease, autoimmune disease, malignant tumor and renal insufficiency. Compare the clinical characteristic and prognosis between the two groups. Serum and clinical data were obtained for patients with HFNEF group、HFREF group and non-HF control group. Serum concentrations of APN, N-terminal pro-brain natriuretic peptide (NT-proBNP) were determined, doppler echocardiography were measured after admission. Following-up the death and readmission of time and number of each group by telephone.
Result:1.In all patients with chronic heart failure, the proportion of HFNEF is 37%. HFNEF patients were more often women, had a higher level of BMI and a higher prevalence of hypertention.2.Concentrations of APN in patients with HFNEF were significantly lower than patients with HFREF, both HFNEF and HFREF group are higher than control group(8.13±2.48μg/ml vs 12.34±4.78μg/ml vs 5.45±1.34μg/ml, P<0.01). Also, Concentrations of NT-proBNP in patients with HFNEF were significantly lower than patients with HFREF, but higher than control group (1987±748 pg/ml vs 2507±985 pg/ml vs 80±23 pg/ml, P<0.01); Concentrations of hs-CRP in heart failure patients were higher than control group(8.62±13.3 mg/l vs 8.79±6.96 mg/l vs 1.92±2.31 mg/l, P<0.01).3.Plasma APN concentration in HFNEF is positively correlated with NYHA classification, hs-CRP, NT-proBNP concentration and LVMI(R=0.484, P=0.001;R=0.312, P=0.038;R=0.868, P=0.000;R=0.350, P=0.000); 4.Concentrations of APN and NT-proBNP in patients with HFNEF were elevated with the elevation of NYHA classification; 5.The occurrence of cardiovascular events in HFNEF group is 44.29% and 48.33% in HFREF group (P=0.193); no difference was found between the 2 group in the mortality rate(P=0.248), and readmission rates(P=0.893).6.The results of a multivariate analysis using a Cox proportional hazards model to identify predictors of the prognosis of heart failure revealed NYHA classification、hs-CRP、NT-proBNP and APN were identified as independent predictors of cardiovascular events rate in HFNEF (P=0.045;P=0.043; P=0.001; P=0.020).
Conclusion:1.In all patients with chronic heart failure, the proportion of HFNEF is 37%. HFNEF patients were more often women, had a higher level of BMI and a higher prevalence of hypertention.2. Concentrations of APN in patients with HFNEF were significantly lower than patients with HFREF(P<0.01); both of the groups were higher than control group(P<0.01); and concentrations of APN and NT-proBNP in patients with HFNEF were elevated with the elevation of NYHA classification; 3. Plasma APN concentration in HFNEF is positively correlated with NT-proBNP concentration.4. The prognosis of HFNEF was similar to those with HFREF. NYHA classification、hs-CRP、NT-proBNP and APN are independent predictors of cardiovascular events rate in HFNEF.
引文
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