高敏C反应蛋白与急性冠状动脉综合征相关的临床证据

通过对近年有关高敏C反应蛋白与急性冠状动脉综合征关系临床证据的回顾,讨论测定高敏C反应蛋白对急性冠状动脉综合征患者进行心血管危险分层的重要性,探讨采用降低高敏C反应蛋白水平的方法来降低急性冠状动脉综合征患者总病死率的可行性.临床证据显示急性冠状动脉综合征患者中的高危人群,其血浆高敏C反应蛋白水平升高.血浆高敏C反应蛋白水平检测的临床应用有助于识别高危急性冠状动脉综合征患者,提高对血管和血管外活动性炎症反应的认识.炎症干预的临床证据同样也说明,早期使用他汀类药物,可能对高血浆高敏C反应蛋白水平的患者有效,即使低密度脂蛋白胆固醇在理想或接近理想水平.     

问：C反应蛋白与心血管疾病有何关系？

答：C反应蛋白（CRP）是在急性炎症时出现的一种非特异性急性期蛋白,一直用来检查和预测各种传染性、感染性和坏死性过程的结局,并评估这些过程的治疗效果。目前发现CRP可以预测健康个体将来发生冠脉事件以及估计急性冠脉综合征（ACS）患者的预后。CRP作为炎症标志物被认为是心血管事件危险最强有力的预测因子之一,已引起国内外学者极大兴趣和广泛关注。     

高敏C反应蛋白与急性冠状动脉综合征相关的临床证据

通过对近年有关高敏C反应蛋白与急性冠状动脉综合征关系临床证据的回顾，讨论测定高敏C反应蛋白对急性冠状动脉综合征患者进行心血管危险分层的重要性，探讨采用降低高敏C反应蛋白水平的方法来降低急性冠状动脉综合征患者总病死率的可行性。临床证据显示急性冠状动脉综合征患者中的高危人群，其血浆高敏C反应蛋白水平升高。血浆高敏C反应蛋白水平检测的临床应用有助于识别高危急性冠状动脉综合征患者，提高对血管和血管外活动性炎症反应的认识。炎症干预的临床证据同样也说明，早期使用他汀类药物，可能对高血浆高敏C反应蛋白水平的患者有效，即使低密度脂蛋白胆固醇在理想或接近理想水平。     

妊娠相关血浆蛋白-A和急性冠脉综合征的研究进展

妊娠相关血浆蛋白-A最先是从孕妇血清中分离出来的一种与妊娠相关联的大分子糖蛋白.近年来,发现妊娠相关血浆蛋白-A和急性冠脉综合征关系密切,是急性冠脉综合征新的标记物.在不稳定的粥样斑块中大量表达,代表斑块的稳定性,在急性冠脉综合征患者早期诊断、预后评估及危险分层中发挥重要作用.     

介入治疗对急性冠脉综合征患者血清IL6、MMP9及C反应蛋白的影响

目的：研究介入法治疗对急性冠脉综合征患者血清 IL 6、MMP 9及 C反应蛋白的影响,了解介入治疗对于血管内皮的损伤以及炎症反应的影响。方法选取急性冠脉综合征患者42例,分别在手术前及手术后1 d、1周后测IL 6、MMP 9及C反应蛋白。选取身体健康者42例,对于 IL 6、MMP 9及C反应蛋白进行测定,与患者血清含量进行对比。结果手术前,术后1 d,术后1周患者血清 IL 6、MMP 9及C反应蛋白出现先上升,后下降的趋势,实验结果具有统计学意义。患者三种测量值均高于健康者（P〈0.05）。结论急性冠脉综合征患者体内会产生炎症反应,介入法治疗后内皮损伤会造成炎症反应升高,经过一段时间之后,患者体内的炎症反应会下降。     

急性冠脉综合征白细胞计数升高:是否与炎症及血栓的基因突变有关

目前有证据表明急性冠脉综合征患者白细胞计数升高增加了疾病复发的风险及病死率 ,C反应蛋白的升高也与心脏病高病死率相关 ,而炎症可促使C反应蛋白升高 ,已发现前炎症因子白细胞介素 1和 6参与了冠心病的发生发展过程 ,因此 ,ConnieE .Byrne等人试图找出急性冠脉综合征病人前炎症因子白细胞介素 1和白细胞介素 6的基因突变与白细胞计数及C反应蛋白升高的相关性。入选者为胸痛发作 72h以内的急性冠脉综合征病人 ,除阿司匹林外还给予血小板糖蛋白Ⅱb/Ⅲa拮抗剂Orbofiban。一级终点包括急性心肌梗死、心肌缺血复发而再次住院、急诊冠脉血运…     

C-反应蛋白与心脑血管疾病的研究进展

C-反应蛋白(C-reactive protein,CRP)是由肝细胞合成的一种五聚体,属急性期蛋白,长期以来被看作急性炎症的一个指标。随着对炎症过程及炎症介质认识的不断深入,人们发现在心脑血管疾病的发展过程中炎症也有重要作用,血管壁损伤伴随对损伤的炎症反应是动脉粥样硬化的主要原因之一[1]。CRP是反映周身低度炎症的非特异性标志,当血管发生病变时,特别是动脉粥样斑块破裂即急性冠脉综合征时,血浆CRP水平明显升高。1CRP与冠心病徐会圃等[2]研究发现,急性冠脉综合征组的血清CRP水平明显高于稳定型心绞痛组和对照组,且急性冠脉综合症组血浆高…     

C-反应蛋白与急性冠脉综合征及其干预研究进展

炎症在急性冠脉综合征的发病机制中发挥重要作用,C-反应蛋白不仅是冠状动脉事件的标志物,也是冠状动脉事件的独立致病因素,因此有效的降低血浆C-反应蛋白浓度将是急性冠脉综合征治疗与预防的又一手段。     

急性冠脉综合征患者炎症反应、他汀治疗和脑卒中危险的关系:阿托伐他汀治疗急性冠脉综合征的一个随机对照试验

急性冠脉综合征（ACS）患者易发生脑卒中。在阿托伐他汀治疗急性冠脉综合征的一个随机对照试验（MIRACL）中，测定炎症反应指标，探讨炎症反应与脑卒中的相关性。测定2926例ACS患者的基础C反应蛋白（CRP），血清淀粉样A蛋白（SAA）和白介素6（IL-6）水平。发现基础炎症反应指标与16周后卒中危险高度相关。     

妊娠相关血浆蛋白-A与心血管疾病的关系

实验研究及临床观察发现心血管疾病,特别是急性冠脉综合征（ACS）的发病机制与炎症反应之间的关系越来越密切。本文重点介绍妊娠相关血浆蛋白-A在心血管疾病特别是ACS诊断和预后方面的研究进展。     

Inflammation,atherosclerosis and acute coronary syndromes

Inflammatory mechanisms play a pivotal role in the atherosclerotic process. At the base of atherogenesis there are complex interactions between macrophages, T lymphocytes and smooth muscle cells. A growing body of experimental evidences suggest that inflammation is involved in the pathogenesis of acute coronary syndromes (ACS) and influences their clinical evolution. In fact, in patients with ACS, coronary atherosclerotic plaques are characterized by an abundant inflammatory infiltrate. Moreover, in these patients systemic signs of inflammatory reaction can be observed: activated circulating inflammatory cells (neutrophil, monocytes and lymphocytes) and increased concentrations of pro-inflammatory cytokines, such as interleukin (IL)-1 and 6, and of acute phase reactants, in particular C-reactive protein (CRP). Recent data demonstrate that CRP is a strong independent predictor of adverse cardiac events and death in patients with ACS, but also in patients with stable ischemic heart disease and in apparently healthy men and women. Furthermore, CRP is an important prognostic index, for early and late outcome, in patients undergoing percutaneous coronary interventions, and may be useful in choosing the therapeutic management of the patient. Although the causes of inflammation in patients with ACS are not yet clear, this new line of research may open the way to a different clinical approach for these patients.     

Dynamics of changes of blood inflammatory-oxidative biomarkers in acute coronary syndrome

Some inflammatory cytokines and parameters of low density lipoproteins (LDL) oxidative modification were studied in blood of 250 acute coronary syndrome (ACS) patients--Siberian inhabitants, men and women with myocardial infarction (MI) or unstable angina on first, tenth and thirtieth days of disease. The inflammatory biomarkers in men and women with MI are: increased concentrations of interleukin (IL)-6, IL-8 and C-reactive protein (CRP), especially on the first day of disease. The most significant inflammatory biomarker of ACS is increased CRP level, especially in women. Oxidative biomarkers in men with ACS are increased basal level of LDL lipid peroxidation (LPO) products and decreased LDL resistance to oxidation. Inflammatory-oxidative biomarkers IL-6, IL-8, CRP and basal level of LDL LPO products are correlated and independently associated with MI.     

C-reactive protein as an independent marker of prognosis in acute coronary syndrome: comparison with troponin T

BACKGROUND: It has been suggested that inflammatory processes play a role in the pathogenesis of acute coronary syndromes (ACS). C-reactive protein (CRP) is a classic acute phase protein. It is yet unclear whether, in addition to established markers as troponin T (TnT), determination of CRP in patients admitted for ACS contributes significantly to the diagnosis and prognosis of ACS. PATIENTS AND METHODS: We investigated 50 patients with ACS (59.4 SD 13.9 years) in the first hour after admission and 4-24 h later with respect to TnT (Elecsys, Roche Diagnostics) and CRP (biokit, modified Quantex CRP plus, analytical sensitivity 0.02 mg/dL). Fifty percent of the patients were classified as having unstable angina retrospectively. All patients were followed in the 6 weeks post discharge regarding death and recurrent ACS. RESULTS: The cumulative event rate at 6 weeks after discharge was 62.5% for patients being CRP and TnT positive compared to 35.3% in TnT positive and CRP negative patients. In TnT negative patients a positive CRP test predicted 33.3% of events and 28.8% of patients negative for CRP and TnT had events at 42 days post discharge. Logistic regression analysis regarding the primary endpoint including TnT and CRP (4-24 h values), age, gender and diagnosis resulted in independent prediction of ACS or death by TnT (cutoff 0.1 microgram/L, p = 0.048, odds ratio = 7.5) and CRP (cutoff 0.862 mg/dL, p = 0.026, odds ratio = 5.3). Sensitivity/specificity for AMI diagnosis were 69.6%/75% for TnT and 12%/72% for CRP in the first hour and 91.3%/68.2% for TnT and 68%/72% for CRP 4-24 h later. CONCLUSIONS: Besides TnT, high sensitivity CRP determination has no additional value for early AMI diagnosis. The prognosis of these patients during the first 24 hours is significantly and independently predicted by CRP measurements in addition to troponin T.     

Relation of C-reactive protein to extent and complexity of coronary narrowing in patients with non-ST elevation acute coronary syndromes. A prospective cohort study

BACKGROUND: Inflammatory markers have been associated with adverse clinical outcome in patients with acute coronary syndromes (ACS). In addition, angiographic plaque morphology and extension of coronary artery disease has been related to worse prognosis in this group of patients. The aim of the present study was to determine if the clinical prognostic value of C-reactive protein (CRP), an inflammatory marker, can by associated with the angiographic findings in patients with non-ST elevation ACS. METHODS: This prospective multicenter cohort study included 1253 patients with non-ST elevation ACS. CRP, which was considered positive (+) if >/=3 mg/l, was measured at a median of 9 h from symptoms onset and were kept blinded until the end of the study. Coronary angiography was performed in 633 patients (50%). The presence of complex coronary lesions (CCLs) was defined as the presence of any of the following: thrombus (+), Thrombolysis In Myocardial Infarction (TIMI) flow 相似文献   

Acute-phase proteins and Chlamydia pneumoniae infection: which one is more important in acute coronary syndrome?

Elevated levels of acute-phase proteins, a systemic marker for inflammation, predict coronary events; Chlamydia pneumoniae (C. pneumoniae) infection is associated with coronary atherosclerosis. The present study investigated whether inflammation or infection is involved in the pathogenesis of acute coronary syndrome (ACS) and which one has the more important role. The study group comprised 49 patients with angiographically diagnosed ACS, 48 cases of chronic coronary heart disease (CCHD), and 44 subjects with a normal coronary profile. The levels of serum C-reactive protein (CRP), fibrinogen and anti-C. pneumoniae IgG antibody were measured. The IgG antibody against C. pneumoniae was higher in the ACS and CCHD groups compared with the control group after adjusting for age and gender. The levels of CRP and fibrinogen were significantly increased in patients with ACS compared with controls and CCHD patients. Multiple stepwise logistic regression analysis revealed that C. pneumoniae IgG antibody is an independent risk factor for both ACS and CCHD (odds ratio 2.3 and 2.1, respectively), but the CRP level is a risk factor only for ACS (odds ratio 6.9). The inflammatory response, as indicated by acute-phase proteins, especially CRP, rather than C. pneumoniae infection, may contribute more to the clinical course of ACS.     

Aspirin adherence, aspirin dosage, and C-reactive protein in the first 3 months after acute coronary syndrome

Persistent elevation of inflammatory markers such as C-reactive protein (CRP) has been associated with an increased risk of recurrent cardiac events after acute coronary syndromes (ACS). Conflicting evidence is available regarding whether aspirin can reduce CRP after ACS. We investigated whether the dosage and adherence to aspirin was associated with the CRP level 3 months after ACS. Adherence to aspirin was monitored for 3 months in a cohort of 105 patients enrolled within 1 week of an ACS using an electronic chip stored in the pill bottle cap. The CRP level was measured at baseline and 3 months. Logistic regression analysis was used to test whether poor adherence to aspirin and a lower aspirin dosage were associated with increased CRP levels, controlling for age, ACS type, disease co-morbidity, baseline CRP level, use of clopidogrel and statins, depressive symptoms, smoking, and adherence to other medications. Aspirin adherence was inversely correlated with the CRP level at 3 months (Spearman's r = -0.36, p < 0.001). In the adjusted model, every 10% decrease in aspirin adherence was associated with a 1.7 increased risk (95% confidence interval 1.2 to 2.4) of a CRP level of ≥ 3.0 mg/L at 3 months. Low-dose aspirin was associated with a 7.1 increased risk (95% confidence interval 1.5 to 33.3) of a CRP level of ≥ 3.0 mg/L. The Charlson co-morbidity index, depressive symptoms, and baseline CRP level were also predictive of a CRP level of ≥ 3.0 mg/L at 3 months. The association between aspirin adherence and CRP level was not attenuated by controlling for other risk-reducing behaviors. In conclusion, a strong association was found between aspirin adherence and the CRP level after an ACS.     

C-reactive protein increase in unstable coronary disease cause or effect?

A crucial point in understanding the clinical and pathophysiologic meaning of C-reactive protein (CRP) elevation in acute coronary syndromes (ACS) is whether CRP release is predominantly a response to even small amounts of myocardial necrosis, for which troponin is a sensitive and specific marker, or is an independent indicator of the inflammatory process occurring in that clinical condition. Whereas troponin is a good predictor of both mortality and myocardial infarction (MI), although the highest values are associated with a decreased probability of MI, CRP predicts mortality but has no relation with the early or late occurrence of MI. The large variability of CRP values in ACS may depend on the different response of this inflammation marker to various stimuli, some patients being particularly hyperresponsive, especially those with elevated CRP values at baseline. We hypothesize that myonecrosis, as detected by troponin increases, would represent the strongest stimulus for CRP increase in ACS, causing in some patients, especially those with already-elevated CRP values at baseline, a disproportionate increase of this marker. Accordingly, the highest CRP values during ACS are likely to be observed in patients with already-elevated CRP values at baseline (which would increase the probability of having death and MI in the follow-up) and the highest troponin values (which would increase the probability of death in the follow-up, but not of subsequent MI). This hypothesis would explain why high CRP levels in unstable coronary disease are good predictors of death, but not of MI.     

经皮冠状动脉介入治疗术后炎症指标对急性冠脉综合征患者预后影响

目的 前瞻性观察接受经皮冠状动脉介入治疗（percutaneous coronary intervention,PCI）的急性冠脉综合征患者PCI术后中性粒细胞/淋巴细胞比值（neutrophil to lymphocyte ratio,NLR）、血小板/淋巴细胞比值（platelet to lymphocyte ratio,PLR）、C反应蛋白（ C-reactive protein?,CRP）、降钙素原（procalcitonin,PCT）、白细胞介素-6（interleukin-6,IL-6）等炎症指标水平对近期预后的影响。方法　214例急性冠脉综合征患者行PCI治疗手术后次日清晨,抽取外周肘静脉血行全血细胞测定（计算NLR和PLR）和 CRP、PCT、IL-6等炎症因子检测。应用二分类Logistic 多因素回归模型分析急性冠脉综合征PCI术后主要心脏不良事件 (?major adverse cardiac events,MACE)?发生的影响因素;ROC曲线评估上述炎症指标对急性冠脉综合征患者PCI术后MACE发生的预测价值。结果　214例急性冠脉综合征患者,平均随访12月（中位数）,共累计33例患者（15.4%）出现MACE事件。应用二分类Logistic 多因素回归模型分析,发现NLR[（odds ratio,OR值）2.98,P<0.001]和急性冠脉综合征类型（OR=0.29,P=0.048）是PCI术后MACE发生的独立影响因素。ROC曲线评估分析发现,NLR、PLR、CRP、PCT、IL-6均有预测PCI术后MACE发生的价值（P<0.01）,但是NLR预测MACE发生的ROC曲线下面积最大（0.898）,NLR预测PCI术后MACE事件发生最佳切点为3.94。结论 PCI术后NLR、PLR、CRP、PCT、IL-6等炎症指标均具有预测PCI术后MACE发生的价值,而NLR的预测价值最高。PCI术后过高的NLR和急性ST段抬高型心肌梗死是急性冠脉综合症患者PCI术后MACE发生的独立影响因素。     

CRP, interleukin-6, secretory phospholipase A2 group IIA, and intercellular adhesion molecule-1 during the early phase of acute coronary syndromes and long-term follow-up

OBJECTIVES: The objectives of this study were to examine the time course of the inflammatory response in acute coronary syndromes (ACS) and to assess the markers of inflammation and their relation to disease severity. METHODS: We prospectively studied 134 patients with ACS who survived for at least 30 months. The patients were divided into four groups: acute myocardial infarction (MI) with (n=54) or without (n=46) ST-segment elevation and unstable angina with (n=14) or without (n=20) increased risk. Plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), secretory phospholipase A2 group IIA (sPLA2-IIA), and intercellular adhesion molecule-1 (ICAM-1) were measured on days 1 and 4 and after 3 and 30 months. RESULTS: The highest levels of CRP and sPLA2-IIA were seen on day 4 but for IL-6 on day 1. These three markers, but not ICAM-1, were significantly related to disease severity, CKMB, and ejection fraction. Patients in Killip class II-IV had higher levels than those in Killip class I. The individual acute-phase responses correlated with marker levels at 3 and 30 months. ICAM-1 correlated with the development of congestive heart failure. CONCLUSIONS: In ACS there seems to be an individual predisposition to inflammatory response. Plasma IL-6 is the first marker to rise, while sPLA2-IIA and CRP peak later. All three markers, especially CRP, may discriminate between MI and non-MI. ICAM-1 seems to reflect other aspects of the inflammatory processes than the other markers. The results emphasize the complexity of the inflammatory response in ACS and stress the need for further studies involving multiple markers.     

Rofecoxib, a COX-2 inhibitor, lowers C-reactive protein and interleukin-6 levels in patients with acute coronary syndromes

BACKGROUND: Patients with acute coronary syndromes (ACS) have high levels of inflammatory mediators such as C-reactive protein (CRP) and interleukin (IL)-6. AIM: To evaluate whether patients with ACS treated with rofecoxib, a COX-2 inhibitor, will have reduced CRP, IL-6, and soluble tumor necrotic factor receptor-1 (sTNF-R1) levels and improved endothelial function. METHODS AND RESULTS: Thirty-four patients hospitalized with ACS were randomized to receive rofecoxib, 25 mg/d plus aspirin 100 mg/d, or placebo plus aspirin, 100 mg/d, for a period of 3 months. Blood samples for CRP, IL-6, and sTNF-R1 levels were drawn prior to randomization, and after 1 month and 3 months. CRP levels in the rofecoxib group (n = 18) were significantly lower both at 1 month and 3 months compared to the baseline levels (p < 0.02). IL-6 levels were significantly lower at 1 month (p < 0.02) in the rofecoxib group, but not at 3 months. There was no change in endothelial function or sTNF-R1 levels. CONCLUSION: Patients recovering from ACS had lower levels of CRP and IL-6 at 1 month and lower CRP levels at 3 months when treated with rofecoxib plus aspirin. Suppression of inflammatory processes may lead to retardation of coronary atherosclerosis and coronary events.