Int J Cardiol ：贫血可预测心衰患者健康相关生活质量

贫血是心力衰竭患者常见的合并症之一。临床实践中，有些心衰患者轻度贫血的化验结果似乎千篇一律，患者的临床表现也好似不脱巢臼，以至进一步诊断常常被忽视

这种对贫血的认识不足在几年前一项观察性研究中展现地淋漓尽致。在3.5年的随访后，研究的2000多名患有心衰的门诊病人中，有29%患者出现贫血，其中仅11%心衰患者的贫血由内科医生诊断出，而心脏医生只诊断出了4.4%。此外，这些患者中只有6%得到了进一步诊断检查。

这种忽视也许可以用人们对心力衰竭的病理生理学逻辑和临床预期来解释。确实，液体潴留也许可以解释血液稀释和运动耐量降低，且呼吸困难和疲乏显然是心力衰竭的主要症状，这些都会掩盖贫血的类似症状。甚至血液变稀带来的流力学改善也可能减轻衰弱心脏的负担。虽然如此，欧洲和美国心脏学领域的心衰相关指南直至近些年才对贫血进行详细介绍，这点依然让人费解。直到2000年后，Donald Silverberg发表了几篇里程碑性的文章，阐明了贫血在心衰中的临床和流行病的联系，此后，人们才对心衰中的贫血有了新的临床认识，并对其开始更加全面的病理生理学和流行病学检查。因此，关于贫血在心力衰竭中预后及临床意义的大量证据主要源自于近十年来该领域如火如荼的研究结果。这些研究结果证实，贫血是急性、慢性以及射血分数正常或减小的心力衰竭的一种严重并发症，可能预示着死亡率和发病率的提高。

在最近一期的《国际心脏病学杂志》上，Kraai及其同事发表了一篇关于贫血对住院心衰患者健康相关生活质量（HR-QoL）影响的文章。他们发现贫血程度和HR-QoL的关键组分之间存在逐步联系。其中，贫血程度与患者体能、躯体功能及患者对自身整体健康和幸福水平的自我认知之间的相关性格外显著。他们证实并推广了一幅新兴图景：贫血是心力衰竭带来的一个相关问题，并会加重患者的心衰症状。有趣的是，HR-QoL的普适评价工具（如RAND 36条健康量表1.0和“坎特里尔生活阶梯”）可以显示贫血的这种临床影响，但专用于心衰患者的明尼苏达生活质量分数（MLHFQ）却无法检测到。两种评价方法结果不一致的原因尚未阐明，但这却让我们不由质疑，虽然MLHFQ评价方法在其他方面已经验证有效，但它在Kraai及其同事研究的这类患者人群中的灵敏度和适用性究竟如何？此外，心力衰竭和贫血在临床症状上的部分重叠可能掩盖了贫血给心衰患者带来的附加效应。

这项研究结果让人们对血红蛋白水平应用范围的争论进一步升级，目前血红蛋白水平界限主要用于对贫血的诊断。根据WHO的定义，女性血红蛋白水平低于12g/dl、男性血红蛋白水平低于13g/dl，即可诊断为贫血。不同的研究在定义贫血时，往往采用不同的临界值和诊断标准（如红细胞比容），这样可能会造成不同HF人群非疾病相关因素引起的贫血发病率的大幅波动（9%-61%）。不过我们应该认识到，WHO专家在发布原报告（贫血诊断标准）时，并没有打算像如今这样在一个广泛的临床背景下研究贫血问题。WHO科研组1968年发表的技术报告旨在描述营养缺陷（特别是在发展中国家的环境中）引起的贫血。作者很清楚，准确定义“正常值”几乎是不可能的，因此，临界值被认为是比超过95%的正常人略高一点的血红蛋白水平（如：正常）。这一定义中，贫血的病理生理学主导机制是炎症激活和功能性缺铁。因此，显然这一定义并不是为诸如心衰患者的这一类临床患者人群设定的，并且设定的血红蛋白水平的临床预后和症状预测能力也从未经过验证。而如今，任何被提名作为临床诊断或预后指标的新型生物标志物都需要研究验证。从这几个方面出发考虑，也许现在是解决如下问题的最好时机：1）对正常人群（一级预防）、特定人群（如运动员或老年人）和不同健康状况的病人的贫血进行区别对待是否更为合适？2）针对疾病特异的血红蛋白水平临界值是否能提供有用的信息？

Kraai及其同事进行的这项研究另一个卖点在于，研究重心从心力衰竭转向功能状态和“软性”临床终点（如幸福感和躯体功能）。过去20年间，心衰治疗的新概念主要要求证明：治疗对死亡率和住院时间或频率等“硬性可计量”临床终点的效果。相比而言，治疗对体能、症状改善和整体幸福感之类效果的研究较少。文中特别值得注意的是，研究已表明，缺铁和缺铁性贫血都是改善运动耐量、灵活性和生活质量的很有前景的治疗靶点。对这一方面的研究（如Kraai及其同事的工作）将会加强人们对症状和生活质量作为决定性的重要临床终点的认识。

与贫血相关的拓展阅读：

• MNT：阿片类药物对镰状细胞贫血患者的影响
• Blood：地中海贫血临床研究获进展
• GASTROINTEST ENDOSC：缺铁性贫血病人的微型肠道胶囊内镜检查
• PLoS ONE：感染幽门螺杆菌A型血者更易贫血
• IBD患者贫血的治疗
• 2012~2013版肿瘤相关性贫血临床实践指南
更多信息请点击：有关贫血更多资讯

Anaemia predicts health related quality of life in heart failure patients.
Anaemia is a very common comorbidity in patients with heart failure. In fact, lab results showing some mild anaemia in a patient with heart failure seemed such a regular observation and well within the expected picture of clinical presentation that further diagnostic workup was often overlooked.

This lack of recognition was impressively illustrated some years ago from an observational study in more than 2000 ambulatory patients with heart failure. During a 3.5year follow up, 29% of the patients developed anaemia, yet anaemia was diagnosed in only 11% of the patients by internists and in a mere 4.4% of the cases by cardiologists [1]. Moreover, only 6% of these patients received further diagnostic workup.

Pathophysiologic reasoning and clinical expectations in heart failure may to some degree explain this unawareness. Indeed, fluid retention may be accepted to explain haemodilution and exercise limitation, dyspnoea and fatigue are of course cardinal symptoms of heart failure and may easily overlie similar symptoms from anaemia. Even some beneficial effects due to improved rheology of the thinner blood was discussed to alleviate the strain of the weaker heart. It is nevertheless surprising that anaemia was not addressed in more detail in the relevant guidelines for heart failure of the European or American cardiac societies until the early years of this millennium. Clinical awareness and a more thorough pathophysiologic and epidemiologic workup of anaemia in heart failure only begun after the year 2000 after several landmark publications on the clinical and epidemiologic relevance of anaemia in heart failure by Donald Silverberg [2]. Hence, the substantial body of evidence on prognostic and clinical implications of anaemia in heart failure results from the last decade of intensified investigations into the subject. From these studies it has clearly been established that anaemia is a serious complication in acute and chronic heart failure as well as in heart failure with preserved or reduced ejection fraction that indicates increased mortality and morbidity [3], [4], [5], [6], [7].

In a recent issue of the Journal, Kraai et al. report on the impact of anaemia on health-related quality of life (HR-QoL) in hospitalised patients with heart failure. They find a stepwise association of the degree of anaemia with key domains of health-related quality of life, particularly addressing the physical capacity and functioning and self-perception of general health and well-being [8]. They confirm and extend the emerging picture of anaemia as a relevant problem in heart failure that adds to the symptomatic status of the patients. Interestingly, this clinical impact of anaemia was shown with generic instruments for assessment of HR-QoL such as the RAND 36-item Health Survey 1.0 and the Cantril Ladder of Life. By contrast, the heart failure specific Minnesota Living with Heart Failure Questionnaire (MLHFQ) was unable to detect this additional impact of anaemia. The reasons for this unexpected discrepancy are not clear but raise the question of the sensitivity and applicability of the otherwise validated MLHFQ in the context of a patient population as studied by Kraai et al. It seems that the overlap of clinical symptoms of heart failure and of anaemia may mask the additional effect attributable to anaemia.

The results of this study also fuel the ongoing discussion on applicability of the limits for haemoglobin levels currently used to identify anaemia. According to the definition of the World Health Organisation (WHO) haemoglobin levels below 12g/dl for women and below 13g/dl for men define the presence of anaemia [9]. Different cut off levels but also different criteria such as the haematocrit have been used in various studies to define anaemia and this may, beside truly disease related factors, contribute to the wide variation in the prevalence of anaemia in different HF populations ranging from 9 to 61% [10]. It should be recognised that the original report from the WHO experts was not intended to address the issue of anaemia in this wide clinical context as applied today. The aim of the technical report from the WHO scientific group in 1968 was to describe anaemia due to nutritional deficits particularly in the environment of developing countries. While the authors recognise that it may be impossible to define normality precisely, the cut-off levels were considered to identify more than 95% of normal individuals with higher (i.e. normal) haemoglobin levels. It is obvious that neither the clinical setting of patient populations such as heart failure patients was the target for this definition where inflammatory activation and functional iron deficiency are dominant in the underlying pathophysiology of anaemia [11]. Nor have these haemoglobin levels been validated for their prognostic or symptomatic predictive power. The latter would be expected from any novel biomarker proposed today for clinical application as diagnostic or prognostic marker. In view of these points it may be timely to address the question if a more differentiating perspective on anaemia in normal populations (primary prevention), specific populations such as athletes [12] or elderly subjects [13], and in patients of varying conditions may be more appropriate, and if disease specific cut-off levels would provide even stronger information.

Another point of interest in the study by Kraai et al. is the shifting focus in heart failure research towards functional conditions and “soft” endpoints such as well-being and physical functioning. In the last 2 decades novel treatment concepts in heart failure were predominantly required to demonstrate effects on mortality and length or frequency of hospitalisation as hard and countable endpoints. Beneficial effects on physical capacity, symptomatic improvement and global well-being were, in comparison, pursued with less intensity. Noteworthy in this context, in particular iron deficiency and iron deficient anaemia have been shown to be promising treatment targets to improve functional capacity, mobility and quality of life [14]. Investigations such as the current study by Kraai et al. will help to increase the recognition of symptomatic conditions and quality of life as the decisive and relevant endpoints that they are.