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目的:探讨普伐他汀对慢性心力衰竭(CHF)患者血浆C-反应蛋白(CRP)、N-末端脑钠素前体(NT-proBNP)水平和心功能的影响.方法:将90例CHF患者随机分为对照组(38例)和普伐他汀组(52例),对照组给予强心、利尿、扩血管治疗,普伐他汀组在此基础上加用普伐他汀10mg.d-1,疗程12周.采用改良Simpson法测定心衰患者治疗前后左心室舒张末内径(LVEDD)、左心室射血分数(LVEF).免疫比浊法测定血清C-反应蛋白(CRP)水平.采用酶联免疫法血浆NT-proBNP水平的变化.结果:两组患者治疗后LVEF和LVEDD水平较治疗前均明显改善(p<0.05);普伐他汀组LVEF由(36.2±3.5)%升至)45.6±4.8)%;血浆CRP浓度由(12.05+1.62)mg/L降至(6.43±1.35)mg/L;NT-proBNP浓度由(1198.7±312.2)fmol/ml降至(742.1±231.2)fmol/ml;TC由(5.60±0.63)mmol/L降至(4.03±0.41)mmol/L.与对照组比较差异均有统学意义(P<0.05).且患者血浆NT-proBNP水平与LVEDD呈正相关(r=0.52,P<0.05),而与LVEF存在负相关(r=-63,P<0.05).结论:CHF患者加用普伐他汀短期治疗可进一步改善心功能,降低CRP和NT-proBNP水平.  相似文献   

3.
目的:探讨老年男性慢性心衰患者在经过标准化抗心衰治疗后的血浆脑利钠肽水平的分布及其影响因素.方法:选取我院高干病房心内科65例老年男性慢性心衰患者,收集患者一般资料、入院后检查结果及药物治疗情况,包括:年龄、有无心衰相关性疾病(高血压、糖尿病、冠心病、肾功能不全)、入院时心率、血压,入院后血肌酐、电解质、胸片有无肺淤血、超声心动图指标(ESV,EDV,EF)、出院前血浆BNP水平以及住院期间的药物治疗情况(主要指β-受体阻滞剂,ACEI或者ARB,强心剂、利尿剂等).住院期间给予标准化抗心衰治疗并在出院前检测血浆BNP水平,按BNP水平将患者分成高BNP组(BNP>463 pg/ml)和正常BNP组(BNP≤ 463 pg/ml),比较两组间各研究因素分布有无差异,并对BNP水平与各因素之间的相关性进行统计分析.结果:经过标准化抗心衰治疗,出院时高BNP组患者44例(67.69%),这部分患者更多的伴有血压低、心率快、高肺动脉压、肺淤血的胸片表现.同时还发现高BNP组的患者中房颤及冠心病的发病率也偏高.对BNP的影响因素进行多元线性回归分析后得出房颤、低收缩压、肺淤血、高肌酐为出院时高BNP水平的影响因素.结论:在不同BNP分组中多个研究因素的分布有显著统计学差异,提示老年男性慢性心衰患者伴有低血压、房颤、高肌酐、肺淤血是出院时高血浆BNP的危险因素,需要给予密切的医疗关注和治疗.  相似文献   

4.
周熙琳  梁辉  陆英  黄耀  陈永刚 《生物磁学》2014,(8):1446-1448
目的:探讨老年慢性心力衰竭(CHF)肿瘤坏死因子α(TNF-α)以及脑利钠肽水平的变化,并对其进行相关性分析。方法:选择老年CHF患者59例,根据心功能分级,Ⅱ级19例,Ⅲ级25例,Ⅳ级15例;另选心功能正常的老年人36例。所有入选者予以血清BNP、TNF-α测定,并采用彩色多普勒超声测定左心室舒张末内径并计算左室射血分数(LVEF)。结果:与对照组比较,CHF组心功能Ⅲ、Ⅳ级患者TNF-α水平明显升高(P〈0.05),心功能Ⅱ、Ⅲ、Ⅳ级患者血BNP水平明显升高(P〈0.05),并随心功能分级加重而增加。血TNF-α水平与BNP呈正相关(r=0.57,P〈0.05)。CHF患者中血清TNF-α和BNP水平与LVEF比较均呈负相关(F-0.48,r=-0.64,P〈0.05)。结论:老年CHF患者血TNF-α显著升高,并与BNP及LVEF关系密切,是反应CHF患者心功能恶化的重要预测指标。  相似文献   

5.

Background

Metabolic syndrome has been shown to be associated with lower levels of plasma N-terminal pro-B-type natriuretic peptide (Nt-proBNP) in the general population. We sought to elucidate the relationship between Nt-proBNP and components of metabolic syndrome in patients with congestive heart failure (CHF).

Methods

Fasting blood samples were obtained from 93 patients in our institution. Plasma levels of Nt-proBNP and other biochemical data were measured. The New York Heart Association (NYHA) classification system (I-IV) was used to define the functional capacity of CHF. Metabolic syndrome and its components were defined using diagnostic criteria from the International Diabetes Federation.

Results

Forty-nine patients (52.7%) had CHF. There was a positive correlation between plasma Nt-proBNP levels and NYHA functional capacity in CHF patients. Plasma Nt-proBNP levels increased significantly with each increasing NYHA class of the disease. The prevalence of metabolic syndrome in CHF patients was higher than that in patients without CHF. Most importantly, we found that plasma Nt-proBNP levels were lower in CHF patients with metabolic syndrome attributable to inverse relationships between plasma Nt-proBNP and body mass index (β = −0.297), plasma triglyceride (β = −0.286) and homeostasis model assessment of insulin resistance (HOMA-IR; β = −0.346). Fasting glucose to insulin ratio (FGIR, an insulin sensitivity index) was positively associated with plasma Nt-proBNP levels (β = 0.491), and was the independent predictor of plasma Nt-proBNP levels in CHF patients.

Conclusions

Plasma Nt-proBNP levels are inversely associated with metabolic syndrome in CHF patients. Reduced plasma Nt-proBNP levels in CHF patients may lead to impaired lipolysis and metabolic function, and may contribute to the development of metabolic syndrome in CHF patients.  相似文献   

6.
目的:探讨慢性心力衰竭(CHF)患者N端脑钠肽前体(NT-proBNP)、脑钠肽(BNP)与患者心脏超声参数及炎症因子的关系。方法:选取2015年3月~2018年2月期间我院收治的CHF患者135例为研究组。根据纽约心脏病学协会(NYHA)心功能分级将研究组分为Ⅰ级组26例,Ⅱ级组34例,Ⅲ级组42例,IV级组33例。另选取同期于我院体检的健康志愿者30例为对照组。检测并比较对照组与研究组、不同NYHA心功能分级的血清标志物、炎症因子、心功能超声参数,采用Pearson相关性分析NT-proBNP、BNP与炎症因子、心功能超声参数的相关性。结果:研究组血清BNP、NT-proBNP、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、超敏C反应蛋白(hs-CRP)水平及左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)均显著高于对照组,左心室射血分数(LVEF)则低于对照组(P0.05)。BNP、NT-proBNP、IL-6、TNF-α、hs-CRP水平及LVEDD、LVESD随心功能分级的升高而升高,LVEF随心功能分级的升高而降低(P0.05)。经Pearson相关性分析显示,CHF患者BNP、NT-proBNP与IL-6、TNF-α、hs-CRP、LVEDD、LVESD呈正相关,而与LVEF呈负相关(P0.05)。结论:血清NT-proBNP、BNP与CHF患者的心脏超声参数及炎症因子密切相关,可考虑将其作为临床诊断CHF的生物学指标。  相似文献   

7.
摘要目的:探讨老年慢性心力衰竭(CHF)肿瘤坏死因子琢(TNF-α)以及脑利钠肽水平的变化,并对其进行相关性分析。方法:选 择老年CHF患者59 例,根据心功能分级,Ⅱ级19 例,Ⅲ级25 例,Ⅳ级15 例;另选心功能正常的老年人36例。所有入选者予以血 清BNP、TNF-α测定,并采用彩色多普勒超声测定左心室舒张末内径并计算左室射血分数(LVEF)。结果:与对照组比较,CHF组 心功能Ⅲ、Ⅳ级患者TNα-琢水平明显升高(P<0.05),心功能Ⅱ、Ⅲ、Ⅳ级患者血BNP水平明显升高(P<0.05),并随心功能分级加 重而增加。血TNF-α水平与BNP 呈正相关(r=0.57,P<0.05)。CHF患者中血清TNF-α和BNP 水平与LVEF比较均呈负相关 (r=-0.48, r=-0.64, P<0.05)。结论:老年CHF患者血TNF-α显著升高,并与BNP及LVEF关系密切,是反应CHF患者心功能恶化 的重要预测指标。  相似文献   

8.
彭欣辉  彭建强 《生物磁学》2011,(15):2907-2909
目的:了解美托洛尔联合普伐他汀对慢性心力衰竭(CHF)患者血浆N-末端脑钠素前体(NT-proBNP)与C-反应蛋白(CRP)两分子水平及其心功能的影响。方法:156例CHF患者随机分为美托洛尔治疗组、普伐他汀治疗组与美托洛尔联用普伐他汀治疗组,每组患者52例。三组患者均予常规抗心衰治疗的基础上分别加入一定剂量的上述药物,疗程16周。用彩超测定患者治疗前后左心室射血分数、左心室舒张末内径;用ELISA法测定血浆N2末端脑钠肽前体州T—proBNP)水平的变化、用散射比浊法测定血浆中c反应蛋O(CRP)水平的变化。结果:治疗16周后,三组患者的左心室射血分数与左心室舒张末内径均得到明显的改善(P〈0.05);三组患者血浆中NT-proBNP与CRP分子水平均呈现一定程度的下降(P〈0.05);其中效果最明显者为美托洛尔联用普伐他汀组。且三组患者血浆中NT-proBNP分子水平与LVEF、CRP分子水平与LVEF增加均呈负相关的趋势。结论:美托洛尔联合普伐他汀对慢性心力衰竭时可显著降低患者血浆中NT-proBNP和CRP分子水平,疗效明显,值得借鉴。  相似文献   

9.
目的:了解美托洛尔联合普伐他汀对慢性心力衰竭(CHF)患者血浆N-末端脑钠素前体(NT-proBNP)与C-反应蛋白(CRP)两分子水平及其心功能的影响。方法:156例CHF患者随机分为美托洛尔治疗组、普伐他汀治疗组与美托洛尔联用普伐他汀治疗组,每组患者52例。三组患者均予常规抗心衰治疗的基础上分别加入一定剂量的上述药物,疗程16周。用彩超测定患者治疗前后左心室射血分数、左心室舒张末内径;用ELISA法测定血浆N2末端脑钠肽前体(NT-proBNP)水平的变化、用散射比浊法测定血浆中C反应蛋白(CRP)水平的变化。结果:治疗16周后,三组患者的左心室射血分数与左心室舒张末内径均得到明显的改善(P<0.05);三组患者血浆中NT-proBNP与CRP分子水平均呈现一定程度的下降(P<0.05);其中效果最明显者为美托洛尔联用普伐他汀组。且三组患者血浆中NT-p roBNP分子水平与LVEF、CRP分子水平与LVEF增加均呈负相关的趋势。结论:美托洛尔联合普伐他汀对慢性心力衰竭时可显著降低患者血浆中NT-proBNP和CRP分子水平,疗效明显,值得借鉴。  相似文献   

10.
目的:评价脑钠肽在慢性心功能不全过程中的诊治效果,探讨其临床适用性。方法:选择从2012年3月至2013年3月于我院就诊的82例心功能不全患者作为实验组,另选择同期的80例健康体检者作为对照组,分析实验组和对照组人员的脑钠肽的浓度,以及实验组患者经过治疗后的脑钠肽浓度变化情况,所有人员同时给予超声心动并观察实验组血浆脑钠肽浓度与左室射血分数及心功能分级之间的关系。结果:实验组患者的血浆脑钠肽浓度明显高于对照组人员,差异有统计学意义(P〈0.05);实验组患者治疗前后血浆脑钠肽浓度有明显改变,差异也有统计学意义(P〈0.05);心功能和左室射血分数不同分级之间的血浆脑钠肽浓度也不同,各级差异有明显统计学意义(P〈0.05);脑钠肽浓度的不同参考值测定的灵敏度和特异性也不同。结论:脑钠肽在慢性心功能不全的诊治过程中有重要价值,为临床心功能的判断可以提供较为敏感的指示,适合临床长期推广应用。  相似文献   

11.
老年人心力衰竭(heart failure,简称心衰)的临床表现具有隐匿性、复杂性,且并发症多等特点,诊断及鉴别困难,越来越多的研究表明,B型脑钠肤(brain natriuretic peptide,BNP)在老年心衰的诊断及鉴别中发挥了越来越重要的作用.  相似文献   

12.
目的:观察慢性心力衰竭患者外周血B型利钠肽(BNP)、C反应蛋白(CRP)浓度的变化,探讨丹参酮ⅡA磺酸钠注射液增加心肌供血,改善心功能的机制.方法:采用美国BIOSITE公司的trige分析仪检测外周血BNP的浓度,免疫浊度法测定CRP的浓度,研究正常对照组(20人),心脏病心功能正常组(33人),慢性心力衰竭组(61人)BNP、CRP浓度变化与慢性心衰患者心功能的相关性.并将CHF患者分为治疗组(33人)和对照组(28人),两组在同等的抗心衰治疗基础上,治疗组加用丹参酮ⅡA磺酸钠注射液60毫克,1个疗程(15天)结束后评定治疗前后两组的疗效及血浆BNP、CRP水平的变化.结果:与正常对照组和心脏病心功能正常组相比较,慢性心衰组BNP、CRP浓度均明显升高.治疗后慢性心力衰竭治疗组总有效率87.9%,对照组总有效率75%(P<0.05).结论:慢性心力衰竭患者存在非特异炎症反应,血浆BNP、CRP水平与患者心功能密切相关.丹参酮ⅡA磺酸钠注射液可改善CHF患者的心功能,其机制可能是通过增加心肌供血,抑制炎症反应而实现的.  相似文献   

13.
Myocardium viability in ischemic heart failure (HF) may affect the effect of cardiac resynchronization therapy (CRT). We hypothesized that longitudinal strain of 2D-STE, which reflects myocardium viability, can predict the response to CRT in patients with ischemic HF. 2D-STE was performed in 42 patients with HF, 1 week before and 1 year after CRT. GLS, RLS, and the LV synchrony index (SI), defined as the difference in timing to peak radial strain between LV anterior septal and posterior wall in LV short axis view, were calculated. A decrease in the LV end-systolic volume (LVESV) value of ≥15 % 1 year after CRT was defined as response to CRT. Twenty-nine patients responded to CRT (CRT-R group), while 13 patients did not respond and were assigned as CRT-NR group. Pre-CRT RLS and GLS were higher, while SI is lower, in CRT-R patients compared with CRT-NR group (p < 0.001). The ROC curve revealed that RLS of ?11.5 % predicted response to CRT with sensitivity of 80.0 % and specificity of 77.9 % (AUC = 0.84, p < 0.001). Further, GLS of ?13 % predicted response to CRT with sensitivity of 73.0 % and specificity of 73.4 % (AUC = 0.79, p < 0.001). In conclusion, LV dyssynchrony, GLS, and RLS calculated by 2D-STE can predict long-term response to CRT in patients with ischemic HF.  相似文献   

14.
目的:探讨冠心病(CHD)患者血浆大内皮素(Bigendothelin-1,Big ET-1)与N末端脑钠肽(NT-pro BNP)的水平及其与心功能的关系。方法:选择本院2014年1月-2014年5月收治的60例CHD患者为观察组,及同期接受体检的60例健康志愿者作为对照组,测定并比较两组的血浆大内皮素与N末端脑钠肽水平以及不同心功能分级CHD患者的血浆大内皮素与N末端脑钠肽水平的差异,分析血浆大内皮素与N末端脑钠肽水平与CHD患者心功能的关系。结果:观察组患者血浆Big ET-1和NT-pro BNP的水平均显著高于对照组,差异具有统计学意义(P0.05)。随着CHD患者的心功能分级的增加,其血浆Big ET-1和NT-pro BNP的水平逐渐升高,且各组之间比较差异均具有统计学意义(P0.05)。血浆Big ET-1、NT-pro BNP水平与CHD患者的心功能之间存在明显的正相关性(P0.05)。结论:CHD患者的血浆Big ET-1与NT-pro BNP水平均异常升高,且与患者的心功能呈正相关,监测其水平对判断CHD的病情及心功能可能具有重要的临床参考价值。  相似文献   

15.

Background and Objective

Several studies on diagnostic accuracy of pleural N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) for effusions from congestive heart failure (CHF) conclude that pleural NT-pro-BNP is a useful biomarker with high diagnostic accuracy for distinguishing CHF effusions. However, its applicability in critical care settings remains uncertain and requires further investigations.

Methods

NT-proBNP was measured in pleural fluid samples of a prospective cohort of intensive care unit patients with pleural effusions. Receiver operating characteristic curve analysis was performed to determine diagnostic accuracy of pleural NT-proBNP for prediction of CHF effusions.

Results

One hundred forty-seven critically ill patients were evaluated, 38 (26%) with CHF effusions and 109 (74%) with non-CHF effusions of various causes. Pleural NT-proBNP levels were significantly elevated in patients with CHF effusions. Pleural NT-pro-BNP demonstrated the area under the curve of 0.87 for diagnosing effusions due to CHF. With a cutoff of 2200 pg/mL, pleural NT-proBNP displayed high sensitivity (89%) but moderate specificity (73%). Notably, 29 (27%) of 109 patients with non-CHF effusions had pleural NT-proBNP levels >2200 pg/mL and these patients were more likely to experience septic shock (18/29 vs. 10/80, P<0.001) or acute kidney injury (19/29 vs. 9/80, P<0.001).

Conclusions

Among critically ill patients, pleural NT-proBNP measurements remain a useful diagnostic aid in evaluation of pleural effusions. However, patients with non-CHF effusions may exhibit high pleural NT-proBNP concentrations if they suffer from septic shock or acute kidney injury. Accordingly, it is suggested that clinical context should be taken into account when interpreting pleural NT-proBNP values in critical care settings.  相似文献   

16.
目的:探讨BNP和D二聚体对老年心功能不全严重程度的关系及预后的影响。方法:以2010年1月-2012年12月来我院就诊的慢性心功能不全患者为观察对象,根据心功能不全程度分为无症状组、心功能不全II级、III级、IV级3,另取健康体检者为对照,比较各组间BNP、D二聚体水平及相关性分析。结果:各患者组BNP和D二聚体水平与对照组相比明显增加(P〈0.05);BNP与心功能不全分级、LVEDD、LAD呈直线正相关关系(P〈0.05),与LVEF呈直线负相关关系(P〈0.05);D二聚体与心功能不全分级、LVEDD呈直线正相关关系(P〈0.05),与LVEF呈呈直线负相关关系(P〈0.05),与LAD直线关系无统计学意义(P〉0.05);BNP水平1000pg/mL以下治疗有效率80.2%,疗效优于1000pg/mL以上者(Riditz=15.245,P=0.000),D二聚体5μg/mL以下者治疗有效率85.4%,疗效优于5μg/mL以上者(Riditz=26.354,P=0.000)。结论:BNP和D二聚体与老年心功能不全严重程度和超声心动图指标密切相关,可以作为疾病预后预测。  相似文献   

17.
Abstract

In dogs, it has been reported that acute ischemia or severe and terminal heart failure results in a selective reduction of myocardial α3 isoform of Na, K-ATPase activity. The aim of this study was to evaluate if a similar change in the two canine digitalis receptor isoforms occurs following 4 weeks of rapid ventricular pacing-induced heart failure without profound necrosis. Heart failure was induced in dogs by rapid ventricular pacing (240 beats × min-1). Digitalis receptors were quantitated by [3H]-ouabain binding with isolated microsomal membranes from sham-operated (n = 3) and heart failure dogs (n = 4) and by Western blot analysis using specific α1 and α3 polyclonal antibodies. In kinetic studies, similar dissociation rates of 19 to 22 × 10-4 s-1 and 1.3 to 2.4 10-4 s-1 corresponding to high and low affinity sites respectively, were found in sham-operated and CHF dogs. Immunoblotting showed similar abundance of α1 isoform in the two groups; however, levels of α3 were increased by at least 50% in pacing-induced heart failure animals. In conclusion, heart failure selectively modulates the expression of cardiac α3 isoform in dogs.  相似文献   

18.
刘裕英  黄澄  吕艳  陈永烨  李胜玲 《生物磁学》2013,(36):7025-7027
目的:探讨血清肌钙蛋白I(cTnI)、N端前体脑钠肽(NT-proBNP)和高敏c反应蛋白(hs—CRP)水平在充血性心力衰竭(CHF)中的临床意义。方法:选取2010年1月-2012年12月在我院诊治的CHF患者210例(CHF组),心功能按纽约心脏病协会(NYHA)分级:Ⅱ级88例、Ⅲ级96例和Ⅳ级26例。同时选取同期在我院行健康体检的自愿者30例为健康对照组。观察和比较两组血清hs.CRP、cTnI和NT.proBNP水平的差异及其与CHF患者心功能的心功能分级的相关系。结果:CHF组患者的血清hs-CRP.cTnI和NT.proBNP水平均较对照组明显增高,差异均有统计学意义(P〈0.0t),且CHF患者的血清hs—CRP、cTnI和NT—proBNP水平随着心功能分级的增加而升高,差异有统计学意义(P〈0.01)。血浆hs—cI冲(F0.694,P〈0.01)水平,cTnI(r=0.782,P〈0.01)水平均与NT—proBNP水平呈显著正相关,血浆hs.CRP和cTnI水平也呈显著正相关(r==0.649,P〈0.01)。结论:CHF患者的血清hs—CRP、cTnI和NT-proBNP水平与其心功能分级显著相关,有助于评估CHF患者心功能不全的严重程度,可能与CHF患者的预后相关。  相似文献   

19.
We demonstrated in previous works that the circadian rhythms of blood pressure (BP) and atrial natriuretic peptide (ANP) are antiphasic in normal subjects and in essential hypertension. The aim of the present study was to assess the circadian rhythms of BP and ANP in 20 patients with stable congestive heart failure (CHF), divided into two groups of 10 according to their New York Heart Association functional class. A matched control group of 10 normal volunteers was also studied. Noninvasive BP monitoring at 15-min intervals was performed for 24 h. Peripheral blood samples were also obtained at 4-h intervals starting from 08:OO h. The mean (±SEM) circadian mesors of ANP plasma levels were 13.4 ± 1.7 pmol/L in the control group, 28.6 ± 2.4 pmol/L in the group of 10 patients in class 11, and 81.5 ± 12 pmol/L in the group of 10 patients in class 111-IV. In normal subjects, plasma ANP concentration was highest at 04:OO h (21.5 ± 2.7 pmol/L) and lowest at 16:OO h (8.8 ± 2.4 pmol/L; p < 0.01). Both groups of patients with CHF showed no significant circadian change in the plasma levels of ANP and also a significantly blunted circadian rhythm of BP. Cosinor analysis confirmed the loss of the circadian rhythms of ANP and BP in CHF patients. Our findings support the existence of a causal relationship between the circadian rhythms of ANP and BP.  相似文献   

20.

Objective

Although the plasma B-type natriuretic peptide (BNP) level is a marker of heart failure, it is unclear whether BNP per se plays a pivotal role for pathogenic mechanisms underlying the development of ischemic heart disease (IHD). In this study, we retrospectively examined the plasma BNP levels in stable patients with IHD and compared to stable patients with cardiovascular diseases other than IHD.

Methods

The study population was 2088 patients (1698 males and 390 females) who were admitted to our hospital due to IHD (n = 1,661) and non-IHD (n = 427) and underwent cardiac catheterization. Measurements of the hemodynamic parameters and blood sampling were performed.

Results

The plasma BNP levels were significantly lower in the IHD group than in the non-IHD group (p<0.001). The multiple regression analysis examining the logBNP values showed that age, a male gender, low left ventricular ejection fraction, low body mass index, serum creatinine, atrial fibrillation and IHD per se were significant explanatory variables. When the total study population was divided according to gender, the plasma BNP levels were found to be significantly lower in the IHD group than in the non-IHD group among males (p<0.001), but not females (p = NS). Furthermore, a multiple logistic regression analysis of IHD showed the logBNP value to be a significant explanatory variable in males (regression coefficient: −0.669, p<0.001), but not females (p = NS).

Conclusions

The plasma BNP levels were relatively low in stable patients with IHD compared with those observed in stable patients with non-IHD; this tendency was evident in males. Perhaps, the low reactivity of BNP is causally associated with IHD in males. We hope that this study will serve as a test of future prospective studies.  相似文献   

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