Herrmann Wolfgang, Herrmann Markus, Joseph Jacob, Tyagi Suresh C
Department of Clinical Chemistry and Laboratory Medicine/Central Laboratory, University Hospital, Saarland University, Homburg/Saar, Germany.
Clin Chem Lab Med. 2007;45(12):1633-44. doi: 10.1515/CCLM.2007.360.
Chronic heart failure (CHF) is a major public health problem causing considerable morbidity and mortality. Recently, plasma homocysteine (HCY) has been suggested to be significantly increased in CHF patients. This article reviews the relation between hyperhomocysteinemia (HHCY) and CHF. Clinical data indicate that HHCY is associated with an increased incidence, as well as severity, of CHF. In addition, HCY correlates with brain natriuretic peptide (BNP), a modern biochemical marker of CHF, which is used for diagnosis, treatment guidance and risk assessment. Animal studies showed that experimental HHCY induces systolic and diastolic dysfunction, as well as an increased BNP expression. Moreover, hyperhomocysteinemic animals exhibit an adverse cardiac remodeling characterized by accumulation of interstitial and perivascular collagen. In vitro superfusion experiments with increasing concentrations of HCY in the superfusion medium stimulated myocardial BNP release independent from myocardial wall stress. Thus, clinical and experimental data underline a correlation between HHCY and BNP supporting the role of HHCY as a causal factor for CHF. The mechanisms leading from an elevated HCY level to reduced pump function and adverse cardiac remodeling are a matter of speculation. Existing data indicate that direct effects of HCY on the myocardium, as well as nitric oxide independent vascular effects, are involved. Preliminary data from small intervention trials have initiated the speculation that HCY lowering therapy by micronutrients may improve clinical as well as laboratory markers of CHF. In conclusion, HHCY might be a potential etiological factor in CHF. Future studies need to explore the pathomechanisms of HHCY in CHF. Moreover, larger intervention trials are needed to clarify whether modification of plasma HCY by B-vitamin supplementation improves the clinical outcome in CHF patients.
慢性心力衰竭（CHF）是一个重大的公共卫生问题，会导致相当高的发病率和死亡率。最近，有研究表明慢性心力衰竭患者的血浆同型半胱氨酸（HCY）水平显著升高。本文综述了高同型半胱氨酸血症（HHCY）与慢性心力衰竭之间的关系。临床数据表明，高同型半胱氨酸血症与慢性心力衰竭的发病率增加以及病情严重程度相关。此外，同型半胱氨酸与脑钠肽（BNP）相关，脑钠肽是慢性心力衰竭的一种现代生化标志物，用于诊断、治疗指导和风险评估。动物研究表明，实验性高同型半胱氨酸血症会导致收缩和舒张功能障碍，以及脑钠肽表达增加。此外，高同型半胱氨酸血症动物表现出以间质和血管周围胶原积累为特征的不良心脏重塑。在体外灌注实验中，随着灌注培养基中同型半胱氨酸浓度的增加，刺激心肌脑钠肽释放，且与心肌壁应力无关。因此，临床和实验数据强调了高同型半胱氨酸血症与脑钠肽之间的相关性，支持高同型半胱氨酸血症作为慢性心力衰竭病因的作用。从同型半胱氨酸水平升高到泵功能降低和不良心脏重塑的机制尚属推测。现有数据表明，同型半胱氨酸对心肌的直接作用以及一氧化氮非依赖性血管作用都与之有关。小型干预试验的初步数据引发了这样的推测，即通过微量营养素降低同型半胱氨酸水平的疗法可能会改善慢性心力衰竭的临床和实验室指标。总之，高同型半胱氨酸血症可能是慢性心力衰竭的一个潜在病因。未来的研究需要探索高同型半胱氨酸血症在慢性心力衰竭中的发病机制。此外，还需要更大规模的干预试验来阐明补充B族维生素对血浆同型半胱氨酸的调节是否能改善慢性心力衰竭患者的临床结局。
