Anaemia in heart failure: a common interaction with renal insufficiency called the cardio-renal anaemia syndrome

BACKGROUND: Although many studies have found a high prevalence of anaemia in patients with congestive heart failure (CHF), few have carefully examined the relationship between the CHF and the prevalence of anaemia and chronic renal insufficiency (CRI). Patients with advanced renal failure, significant anaemia, diffuse atherosclerosis, respiratory disease and more elderly patients have been systematically excluded from the great majority of the randomised clinical trials. DISCUSSION: Both anaemia and renal insufficiency are very common associated diseases associated with increased mortality, morbidity and rate of hospitalisation in CHF patients. Impaired renal function is associated with adverse outcomes because it represents a marker of coexistent disease and more diffuse atherosclerosis. In patients with CHF, progressive renal dysfunction leads to a decrease in erythropoietin (EPO) levels with reduced erythrocyte production from bone marrow. This may explain the common association between CHF, anaemia and CRI in clinical practice. The normalisation of haemoglobin concentration by EPO in patients with CHF and CRI results in improved exercise capacity by increasing oxygen delivery and improving cardiac function. CONCLUSION: In this review, we describe the mechanisms linking anaemic status, CRI and CHF, the prognostic relevance of each disease, treatment implications, and potential benefit of EPO administration.     

Implications of the natriuretic peptide system in the pathogenesis of heart failure: diagnostic and therapeutic importance

The natriuretic peptide family consists of at least 3 structurally similar peptides: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Under normal conditions, ANP is synthesized by the atrium and released in response to atrial stretch. This peptide plays an important role in sodium and water homeostasis and is involved in cardiovascular function. In contrast, BNP is synthesized primarily by the ventricles, and its circulatory concentrations are significantly elevated in profound congestive heart failure (CHF). While both plasma levels of ANP and BNP have been found to be increased in patients with various heart diseases, the elevation in circulatory BNP correlates better than ANP with the severity of CHF. Therefore, plasma BNP has been suggested (and lately used) to aid in the accurate diagnosis of heart failure in patients admitted to the emergency room with symptoms of decompensated heart failure. Furthermore, circulatory BNP has been utilized as a prognostic marker in CHF as well as a hormone guide in the evaluation of the efficacy of the conventional treatment of this disease state. In light of the cardiovascular and renal effects of BNP, which most likely exceed those of ANP, the former has been used as a therapeutic agent for the treatment of patients with acute severe CHF. Intravenous infusion of BNP into patients with sustained ventricular dysfunction causes a balanced arterial and venous vasodilatation that has been shown to result in rapid reduction in ventricular filling pressure and reversal of heart failure symptoms, such as dyspnea and acute hemodynamic abnormalities. Thus, the goal of this article is to review the physiology and pathophysiology of natriuretic peptides and the potential use of their circulating levels for diagnosis and treatment of heart failure.     

促红细胞生成素对慢性充血性心力衰竭患者心肌细胞凋亡的影响——附31例检测分析

目的:探讨促红细胞生成素(EPO)对慢性充血性心力衰竭(CHF)患者心功能及心肌细胞凋亡的影响。方法:选择CHF患者62例,随机分为EPO治疗组与对照组各31例,两组患者均接受规范的CHF药物治疗,EPO治疗组在此基础上再接受每周2次重组人EPO 2 000 U皮下注射,疗程3个月。比较研究初始及结束时两组患者的血常规、脑钠肽、可溶性凋亡相关因子(sFas)、可溶性凋亡相关因子配体(sFasL)及心脏彩声多普勒超声结果;观察两组患者心血管事件发生率。结果:研究结束时,EPO治疗组患者血浆脑钠肽、sFas、sFasL水平及因心力衰竭再次住院率均明显低于对照组(P均﹤0.05);对照组患者血红蛋白水平较EPO治疗组略有降低,但两组比较差异无统计学意义;两组间LVEF比较差异无统计学意义(P>0.05)。两组治疗过程中均无出现明显不良反应。结论:在规范的CHF治疗基础上,对CHF患者加用小剂量EPO,可减少患者的贫血及心肌细胞凋亡发生率,改善心功能,并可减少再次因心力衰竭住院率,安全性高。     

促红细胞生成素对慢性心力衰竭伴贫血患者脑钠肽和心功能的影响

【目的】探讨促红细胞生成素（EPO）对慢性心力衰竭（CHF）4#贫血患者脑钠肽（BNP）和心功能的影响。【方法】176例CHF伴贫血患者,随机分为治疗组和对照组,两组患者均给予常规抗心衰治疗,治疗组加用EPO注射及铁剂口服治疗,随访6个月,比较两组在BNP及心功能等指标上的差别。【结果】治疗组治疗前后BNP、运动耐力、贫血指标及心功能指标的改善均优于对照组（P〈0．05）。【结论】使用EPO治疗CHF伴贫血,可显著改善患者的临床症状及心功能。     

Pathogenetic mechanisms of chronicity in liver diseases in patients with circulatory failure

Patients with chronic heart failure (CHF) can often develop such diseases as hepatitis of viral etiology, alcoholic hepatitis, drug affection of the liver and other diseases masked as congestive liver. In most cases CHF concomitant liver diseases have an atypical course with a tendency to a chronic course. CHF is one of the important pathogenetic mechanisms lying in the basis of chronicity of concomitant liver diseases. Refractory CHF, inconsistency of the hemodynamic indices of persistent hepatomegaly must lead a physician to the detection of probable independent liver diseases complicating the syndrome of heart failure. CHF is a factor causing an enhanced fibrosing liver reaction. An important diagnostic test of fibrinogenesis lying in the basis of chronicity of liver diseases, is the determination of enzymatic markers reflecting synthesis and catabolism of the main substance of connective tissue. Change in the levels of haptoglobin, ceruloplasmin and glutamic acid dehydrogenase is an indirect sign of damage of the liver parenchymal endoplasmic reticulum. These indices can serve as differential criteria of the prevalence of cardiovascular disorders in the liver or concomitant independent liver diseases.     

Increased erythropoietin synthesis in patients with COLD or left heart failure is related to alterations in renal haemodynamics

The mechanisms controlling erythropoietin (EPO) synthesis by the kidney in patients with chronic obstructive lung disease (COLD) or congestive left heart failure (CLHF) remain incompletely understood. Renal dysfunction occurs as a consequence of decreased renal blood flow (RBF) in these diseases. Because alterations in renal haemodynamics may affect EPO synthesis and red blood cell production, we investigated the potential relationships between renal function and plasma EPO synthesis in patients with COLD or CLHF. Thirty-two patients with COLD and 13 with CLHF underwent determination of renal physiology parameters, plasma EPO levels and haemoglobin levels. Plasma EPO concentrations were increased in patients with COLD or CLHF as compared to normal subjects, and were inversely correlated to haemoglobin concentrations. In patients with COLD or CLHF, plasma EPO was negatively correlated with both RBF and renal oxygen delivery (ROD) and positively correlated with filtration fraction. Plasma EPO was not correlated with glomerular filtration rate, fractional excretion of sodium, PO2 or PCO2. Among the patients with COLD, those with polycythemia (haemoglobin > 150 g L-1) had lower plasma EPO and higher RBF and ROD values than those with normocythemia (haemoglobin < or = 150 g L-1). Taken together, our data suggest that in patients with COLD or CLHF the critical determinant for EPO production is impairment of renal haemodynamics.     

慢性心衰-心肾综合征及生物标志物

慢性心衰不仅是一种疾病诊断,更是一种复杂的临床综合征,在合并慢性肾病尤其是终末期肾病患者中,心衰发病率增加是死亡的主要原因。心脏和肾脏之间存在密切而复杂的关系(即所谓"心肾综合征"),心衰患者一旦合并慢性肾病或肾损伤均显示预后不良。因而,对于这类高风险患者应予以早期诊断并积极干预治疗。一些标志物已被证明在心血管疾病的诊断和预后评价中具有新的、重要的作用,由于其与慢性心衰-心肾综合征具有密切关系而备受关注,具有高度敏感性和特异性的生物标志物成为近年来研究的热点。     

The case for statin therapy in chronic heart failure

Both primary and secondary prevention studies have provided a wealth of evidence that statin therapy effectively reduces cardiovascular events. However, this general statement on the efficacy and safety of statin treatment has not been validated in patients with chronic heart failure (CHF). Recently, numerous statin trials have reported analysis on CHF parameters and numerous CHF trials have performed analysis on baseline statin use. In this article, we will review the currently available evidence from a pathophysiological as well as clinical perspective, building a case for and against the use of statins in CHF. From a pathophysiological perspective, we will discuss the known association of cholesterol and mortality, the ubiquinone, and the endotoxin–lipoprotein hypothesis. From a clinical perspective, we will discuss the observational studies, subgroup analysis of large randomized controlled trials, prospective randomized trials in CHF patients, and the future perspectives of the large European statin studies focussing on the statin therapy in CHF.     

Volociximab in cancer

Importance of the field: Despite the advances in the cardiovascular field, cardiovascular diseases remain an important health problem with a high mortality rate. Novel therapeutic attempts that target myocardial ischemia and heart failure offer attractive adjuncts and/or alternatives to commonly employed regimens. The development of novel laboratory technologies over the last decade has led to substantial progress in bringing new therapies to the bedside.

Areas covered in this review: Current experimental and clinical trials in the use of erythropoietin (EPO) in cardiovascular diseases are reviewed.

What the reader will gain: This review will widen knowledge of the therapeutic potential of EPO's non-erythropoietic beneficial effects in a clinical cardiovascular setting.

Take home message: Results from preclinical trials regarding the non-erythropoietic effects of erythropoietin are really encouraging. Further clinical studies are warranted to define the beneficial role of EPO in the clinical setting of coronary artery disease, heart failure and peripheral artery disease.     

Upcoming therapies for heart failure

Treatment of maladaptive neurohormonal activation in congestive heart failure (CHF) has been successful because basic cardiovascular science findings have been confirmed or dismissed through the use of well-controlled, large-scale clinical trials. It should be no surprise that this exciting approach is evolving toward novel agents and devices directed toward other pathways involved in CHF neurohormonal/cytokine activation. Several of these are in advanced clinical development and are likely to play prominent roles in CHF therapy in the near future.     

Differential diagnosis of acute dyspnea: the value of B natriuretic peptides in the emergency department

Congestive heart failure (CHF) is the main cause of acute dyspnea in patients presenting to an emergency department (ED) and is associated with high morbidity and mortality. B-type natriuretic peptide (BNP) is a polypeptide, released by ventricular myocytes in direct proportion to wall tension, which lowers renin-angiotensin-aldosterone activation. For the diagnosis of CHF, both BNP and the biologically inactive NT-proBNP have similar accuracy. Threshold values are higher in an elderly population, and in patients with renal dysfunction. They might also have a prognostic value. Studies have demonstrated that the use of BNP or NT-proBNP in dyspneic patients early following admission to the ED, reduced the time to discharge and total treatment cost. BNP and NT-proBNP should be available in every ED 24 h a day, because the literature strongly suggests the beneficial impact of an early appropriate diagnosis and treatment in dyspneic patients. The purpose of this review is to indicate recent developments in biomarkers of heart failure and to evaluate their impact on clinical use in the emergency setting.     

Natriuretic peptides and NGAL in heart failure: Does a link exist?

In recent years there has been growing interest in the development of new diagnostic tools and particularly in laboratory tests for the identification of heart failure (HF) patients. Because of the rise in HF occurrence, it is necessary to use simple and reliable method to recognize those patients at risk before the onset of the clinical symptoms. To date HF diagnosis remains difficult: its symptoms and signs are often non specific as well as being poor sensitive indicators for HF severity. Throughout the last 10years published literature has highlighted a boom in the use of biomarkers for HF. Both B-type and N-terminal pro-B-type natriuretic peptides have demonstrated specific role in heart failure diagnosis, as well as risk assessment. A single determination of BNP at any time during the development of chronic heart failure (CHF) provides a clinically useful tool to establish the outcome. Renal dysfunction is often associated with heart failure and predicts adverse clinical outcomes. Many studies have recently suggested the clinical use of serum neutrophil gelatinase-associated lipocalin (NGAL) levels in patients admitted to the hospital for acute HF can be used to estimate the risk of early worsening renal function. This could be potentially applied in clinical practice for early identification of renal dysfunction development in patients with HF. NGAL levels appear also to predict renal dysfunction in patients with chronic HF and preserved renal function. For all these reasons, BNP and NGAL are two emerging tools useful for diagnosis and prognosis in HF. The combination of two laboratory biomarkers could potentially identify patients with more elevated risks of both cardiac hemodynamic impairment and kidney dysfunction.     

Understanding B-type natriuretic peptide and its role in diagnosing and monitoring congestive heart failure

Congestive heart failure (CHF) is a complex clinical syndrome characterized by dysfunction of the left, right, or both ventricles, which results in the impairment of the heart's ability to circulate blood at a rate sufficient to maintain the metabolic needs of peripheral tissues and various organs. Owing to the drastic increase in cardiovascular risk factors such as obesity, diabetes, and improved survival rate after acute myocardial infarction and subsequent development of CHF in the last quarter of a century, CHF has become a major and increasing cause of death and disability in the United States. Unfortunately, the signs and symptoms are nonspecific for CHF Also, routine laboratory values, electrocardiograms, and X-rays are not always accurate enough to make the appropriate diagnosis. Recently, the US Food and Drug Administration approved a new biomarker, B-type natriuretic peptide (BNP), for the purpose of diagnosing and assessing severity of CHE BNP is synthesized, stored, and released primarily by the ventricular myocardium in response to volume expansion and pressure overload. The use of SNP, along with other diagnostic tools, can enable care providers to facilitate and optimize care of heart failure patients in a variety of clinical settings. Emerging clinical data will help further refine biomarker-guided therapeutic and monitoring strategies involving BNP.     

Coenzyme Q10 and cardiovascular disease: a review

This article provides a comprehensive review of 30 years of research on the use of coenzyme Q10 in prevention and treatment of cardiovascular disease. This endogenous antioxidant has potential for use in prevention and treatment of cardiovascular disease, particularly hypertension, hyperlipidemia, coronary artery disease, and heart failure. It appears that levels of coenzyme Q10 are decreased during therapy with HMG-CoA reductase inhibitors, gemfibrozil, Adriamycin, and certain beta blockers. Further clinical trials are warranted, but because of its low toxicity it may be appropriate to recommend coenzyme Q10 to select patients as an adjunct to conventional treatment.     

充血性心力衰竭患者血清CA125和NT-proBNP水平测定及其临床意义

【目的】探讨慢性充血性心力衰竭（CHF）患者血清糖类抗原125（CAl25）及N末端B型钠尿肽原（NTproBNP）水平与患者心功能及其相关因素之间的关系。【方法】180例CHF患者通过超声测定左室内径及左室射血分数（LVEF）,以电化学发光法（ECLIA）测定其血清CAl25和NT—proBNP水平,所有患者根据纽约心功能分级标准分为Ⅱ、Ⅲ、Ⅳ级组。另随机抽取40例有心血管疾病但无CHF的患者作为非CHF组。【结果】①CHF组血清CAl25及NTproBNP水平高于非CHF组,Ⅳ级心功能组水平明显高于Ⅲ级组,且Ⅲ级组明显高于Ⅱ级组;②血清CAl25及NT-proBNP水平均与LVEF呈负相关,而与导致CHF的原发病种类不相关。[结论]CHF患者血清CAl25及NT-proBNP水平升高,并且其水平与LVEF有关,而与导致CHF的原发病种类无关。     

BNP等指标在心血管疾病诊疗中的临床意义

目的探讨脑钠肽(BNP)、尿酸(UA)、乳酸脱氢酶(LDH)和肌钙蛋白T(TnT)检查指标在心血管疾病诊断及预后观察中的作用。方法选取心血管疾病患者271例和非心血管疾病患者271例分别作为心血管疾病组和对照组,并将心血管疾病组按照民族类型进一步分为维吾尔族心血管疾病组和汉族心血管疾病组,检测所有研究对象BNP、LDH、UA和TnT水平,对检测结果进行统计分析。结果心血管疾病组BNP、UA、LDH和TnT水平明显高于对照组,差异有统计学意义(P0.05);维吾尔族心血管疾病组LDH、TnT水平高于汉族心血管疾病组,汉族心血管疾病组BNP、UA水平高于维吾尔族心血管疾病组,差异均无统计学意义(P0.05);心力衰竭、冠心病患者治疗1周后BNP水平下降最明显,且与治疗前比较差异有统计学意义(P0.05);心力衰竭患者治疗1周后UA水平与治疗前比较差异有统计学意义(P0.05)。结论 BNP、UA、LDH和TnT联合检测在心血管疾病的早期诊断、治疗及预后观察中有重大临床意义。     

Current perspectives on protective roles of erythropoietin in cardiovascular system: erythropoietin receptor as a novel therapeutic target

Erythropoietin (EPO) is a principal regulator that promotes proliferation and terminal differentiation of erythroid progenitor cells. EPO receptors are expressed not only in hematopoietic lineage cells but also in the cardiovascular system. We performed animal experiments using transgene-rescued EPO receptor null mutant mice (EpoR-/- rescued) that express the EPO receptor exclusively in the hematopoietic cells. The results of these experiments suggest that endogenous EPO/EPO receptor system in the heart exerts cardioprotective effects against myocardial injury induced by ischemia followed by reperfusion and pressure-overload induced left ventricular dysfunction. Many animal experiments have shown that the administration of recombinant human EPO also elicits cardioprotective effects against myocardial injury induced by ischemia and reperfusion. In contrast to the promising results of these animal experiments, recent clinical trials failed to demonstrate the reduction in infarct size or improvement of cardiac function by the administration of recombinant human EPO in patients with acute myocardial infarction who underwent primary percutaneous coronary intervention. It should be tested in future clinical studies whether a relatively low dose of recombinant human EPO or its derivatives that have no erythropoietic action reduces infarct size and ameliorates cardiac dysfunction in patients with acute myocardial infarction. In this article, we review implications of anemia associated with chronic heart failure, roles of the endogenous EPO/EPO receptor system, and the effects of the administration of erythropoiesis-stimulating agents in pathologic conditions of the heart by focusing on the EPO receptor as a potential candidate of novel therapeutic targets in cardiovascular diseases.     

Diagnosis the state of the proximal renal tubular epithelium in patients with coronary heart disease and chronic heart failure

Renal dysfunction is a common complication of chronic heart failure (CHF). Renal filtration capacity has been evaluated in numerous studies, but there are studies dealing with renal tubular function in patients with coronary heart disease (CHD) concurrent with CHF, which became the subject of the present study. Seventy-nine patients with CHD with different stages of CHF (OCCH, 2002) and 12 healthy individuals were examined. The urinary activity of neutral maltase and L-alanine aminopeptidase was evaluated. The renal tubular dysfunction evaluated by the blood levels on the enzymes was found to increase with the greater severity of CHF.     

Endothelin receptor antagonists

Endothelin receptor antagonists (ERAs) have been developed to block the effects of endothelin-1 (ET-1) in a variety of cardiovascular conditions. ET-1 is a powerful vasoconstrictor with mitogenic or co-mitogenic properties, which acts through the stimulation of 2 subtypes of receptors [endothelin receptor subtype A (ETA) and endothelin receptor subtype B (ETB) receptors]. Endogenous ET-1 is involved in a variety of conditions including systemic and pulmonary hypertension (PH), congestive heart failure (CHF), vascular remodeling (restenosis, atherosclerosis), renal failure, cancer, and cerebrovascular disease. The first dual ETA/ETB receptor blocker, bosentan, has already been approved by the Food and Drug Administration for the treatment of pulmonary arterial hypertension (PAH). Trials of endothelin receptor antagonists in heart failure have been completed with mixed results so far. Studies are ongoing on the effects of selective ETA antagonists or dual ETA/ETB antagonists in lung fibrosis, cancer, and subarachnoid hemorrhage. While non-peptidic ET-1 receptor antagonists suitable for oral intake with excellent bioavailability have become available, proven efficacy is limited to pulmonary hypertension, but it is possible that these agents might find a place in the treatment of several cardiovascular and non-cardiovascular diseases in the coming future.     

充血性心力衰竭患者检测HCYBNPCAl25的临床意义

目的探讨同型半胱氨酸（HCY）、B型脑钠肽（BNP）和癌抗原125（CAl25）水平与充血性心力衰竭（CHF）患者心功能及相互之间的关系。方法对60例CHF患者和有心血管疾病但无心力衰竭患者60例（对照组）检测血清HCY浓度、BNP浓度、CAl25浓度,应用多普勒超声心动图仪测量左室射血分数（LVEF）,比较HCY、BNP、CAl25、心功能分级（根据纽约心功能分级标准分为Ⅱ、Ⅲ、Ⅳ级）及LVEF差异。结果CHF组血清HCY、BNP及CAl25水平高于非CHF组,Ⅳ级心功能组水平明显高于Ⅲ级组,且Ⅲ级组明显高于Ⅱ级组;血清HCY、BNP及CAl25水平均与LVEF呈负相关,而与导致CHF的原发病种类无相关性。结论联合检测HCY、BNP及CAl25水平对判断CHF患者心功能严重程度和影响更有意义。