背景:炎症和氧化应激与冠心病患者的充血性心力衰竭有关。
目的:慢性充血性心力衰竭是冠状动脉疾病的严重阶段,主要是65岁以上老年人的疾病。老年心力衰竭患者以心肌缺血为特征,和缺血后心肌功能障碍。氧化应激,炎症,免疫反应在心力衰竭的发生发展中起重要作用。我们试图检查氧化应激(丙二醛)的相互触发,炎性细胞因子(肿瘤坏死因子-α和可溶性肿瘤坏死因子受体-1/2),免疫反应(toll样受体2,3,4),和高敏C反应蛋白在老年患者冠状动脉支架置入后复发性充血性心力衰竭中的表达,并研究这些变化的相互作用对老年患者冠状动脉支架置入后复发性充血性心力衰竭的发生和进展的影响。
方法:本研究共纳入726例患者。我们确定了丙二醛(MDA)的水平,高敏C反应蛋白(hs-CRP),肿瘤坏死因子-α(TNF-α),可溶性肿瘤坏死因子受体1和2(sTNFR-1/2)和toll样受体2,3,4(TLR2/3/4)在老年患者冠状动脉支架植入术后复发性充血性心力衰竭中的应用。
结果:MDA水平,hs-CRP,TNF-α,sTNFR-1、sTNFR-2、TLR2、TLR3和TLR4在老年患者冠状动脉支架置入后显著升高(p<0.01)。结果表明,这些标志物彼此密切相关,并表明这些标志物与纽约心脏协会功能分类增加和左心室射血分数低有关。进一步分析证实复发性充血性心力衰竭的独立临床危险因素为MDA,hs-CRP,TNF-α,sTNFR-1、sTNFR-2、TLR2、TLR3和TLR4。氧化应激的相互作用,炎性细胞因子和Toll样受体,hs-CRP表达水平是影响老年患者冠状动脉支架置入术后再发充血性心力衰竭的重要因素。
结论:高水平的MDA,hs-CRP,TNF-α,sTNFR-1,sTNFR-2,TLR2,TLR3和TLR4对纽约心脏协会功能分级增加和左心室射血分数低的复发性心力衰竭具有重要意义。这八个因素相互放大了它们的积极作用,这种相互作用可能是它们在复发性心力衰竭中作用的关键因素。八个危险因素是相互依赖的,同时发生,并产生有害影响,形成恶性循环。MDA可能引发促炎危险因素(hs-CRP,TNF-α,sTNFR-1,sTNFR-2)通过激活TLRs作为导致心肌线粒体功能障碍的危险因素(TLR2,TLR3和TLR4),心肌细胞肥大,适应不良的心肌重塑,心肌间质纤维化,心脏收缩减少和复发性心力衰竭。这八个危险因素是复发性心力衰竭机制的基础。因此,氧化应激的相互触发,炎症和toll样受体信号通路,hs-CRP的表达在老年患者冠状动脉支架置入术后复发性充血性心力衰竭的发生发展中起关键作用。
BACKGROUND: Inflammation and oxidative stress are related to congestive heart failure in patients with coronary heart disease.
OBJECTIVE: Chronic congestive heart failure is a serious stage of coronary artery disease and is mainly a disease of elderly people over the age of 65. Elderly heart failure patients are characterized by myocardial ischemia, and post-ischemic myocardial dysfunction. Oxidative Stress, inflammation, and immune response play important roles in the development of heart failure. We tried to examine the mutual triggering of oxidative stress (malondialdehyde), inflammatory cytokines (tumor necrosis factor-α and soluble tumor necrosis factor receptor-1/2), immune response (toll-like receptors 2,3,4), and high sensitivity C-reactive protein expression in elderly patients with recurrent congestive heart failure after coronary stenting and investigated the effect of interplay of these changes on onset and progression of recurrent congestive heart failure in elderly patients underwent coronary stent implantation.
METHODS: A total of 726 patients were enrolled in this study. We determined the levels of malondialdehyde (MDA), high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF- α), soluble tumor necrosis factor receptor-1 and 2 (sTNFR-1/2) and toll-like receptor 2,3,4 (TLR2/3/4) in elderly patients with recurrent congestive heart failure after coronary artery stent implantation.
RESULTS: Levels of MDA, hs-CRP, TNF-α, sTNFR-1, sTNFR-2, TLR2, TLR3 and TLR4 were remarkably increased (p<0.01) in elderly patients with recurrent congestive heart failure after coronary artery stenting. The results indicated that these markers were closely correlated to each other and showed that these markers were associated with increased New York Heart Association functional classification and low left ventricular ejection fractions. Further analysis confirmed that the independent clinical risk factors for recurrent congestive heart failure were MDA, hs-CRP, TNF-α, sTNFR-1, sTNFR-2, TLR2, TLR3 and TLR4. The interplay of oxidative stress, inflammatory cytokines and toll-like receptors, and hs-CRP expression levels was an important factor involved in recurrent congestive heart failure of elderly patients after coronary stenting.
CONCLUSIONS: High levels of MDA, hs-CRP, TNF-α, sTNFR-1, sTNFR-2, TLR2, TLR3 and TLR4 had an important implication for recurrent heart failure with increased New York Heart Association functional classification and low left ventricular ejection fractions. These eight factors amplified each other\'s positive effects and this interaction may be a key element of their roles in recurrent heart failure. The eight risk factors were inter-dependent and occurred simultaneously, and exerted detrimental effects forming a vicious circle. MDA may trigger the over-expressions of pro-inflammatory risk factors (hs-CRP, TNF-α, sTNFR-1, sTNFR-2) through the activation of TLRs as risk factors (TLR2, TLR3 and TLR4) contributing to the dysfunction of myocardial mitochondria, cardiomyocyte hypertrophy, maladaptive myocardial remodeling, myocardial interstitial fibrosis, cardiac systolic decrease and recurrent heart failure. These eight risk factors were the basis of the mechanisms of recurrent heart failure. Therefore, the mutual triggering of oxidative stress, inflammatory and toll-like receptor signaling pathways, and hs-CRP expression could play key roles in the development of recurrent congestive heart failure in elderly patients after coronary stenting.