C反应蛋白与急性冠脉综合征

动脉粥样硬化是一种炎症性病变,急性冠脉综合征的发生、发展更与炎症密切相关。C反应蛋白是一种典型的炎症急性相反应蛋白,其血浆水平的高低可直接反映冠状动脉粥样硬化斑块的炎症状态及稳定程度。目前,把血浆C反应蛋白作为急性冠脉综合征患者危险分层和预后判定指标的临床价值已逐渐得到认同,但最新研究发现,新蝶呤和脑利钠肽等对急性冠脉综合征患者的预后评估可能较C反应蛋白更为特异而敏感。     

T cells and cytokines in atherogenesis

Recent findings suggest that inflammation plays a key role in atherosclerosis from the earliest stage of lesion initiation, to the ultimate complication of thrombosis. In patients who died because of acute coronary syndromes (ACS), coronary atherosclerotic plaques are characterized by the presence of macrophages, and to a lesser extent T-lymphocytes, at the immediate site of either plaque rupture or superficial erosion. The rupture-related inflammatory cells are activated, indicating ongoing inflammation. ACS patients are also characterized by activated circulating lymphocytes, monocytes and neutrophils, and by increased concentrations of proinflammatory cytokines and of the highly sensitive acute phase reactant C-reactive protein. Interestingly, an unusual subset of T cells, CD4+ CD28null T cells, involved in vascular complication of rheumatoid arthritis because of their functional profile predisposing for vascular injury, are expanded in the peripheral blood and infiltrate the coronary lesions of ACS patients. The presence of activated T lymphocytes implies antigenic stimulation, but the nature of such antigen(s) remains to be investigated. Several autoantigens expressed in the atherosclerotic plaque, including oxidized LDL and heat shock proteins, and infectious agents are able to elicit an immune response. The inflammatory component is not localized to the 'culprit' plaque, but it is diffused to the entire coronary vascular bed, and involves also the myocardium.     

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.     

Inflammation and acute coronary syndromes

The presence of inflammatory infiltrates in unstable coronary plaques suggests that inflammatory processes may contribute to the pathogenesis of these syndromes. In patients with unstable angina, coronary atherosclerotic plaques are characterized by the presence of macrophages, and to a lesser extent, T-lymphocytes, at the immediate site of either plaque rupture or superficial erosion; moreover, the rupture-related inflammatory cells are activated, indicating ongoing inflammation at the site of plaque disruption. These observations are confirmed by clinical studies demonstrating activated circulating neutrophils, lymphocytes and monocytes, and increased concentrations of pro-inflammatory cytokines, such as interleukin (IL) 1 and 6, and of acute phase reactants in patients with unstable angina and myocardial infarction. In particular elevated levels of C-reactive protein are associated with an increased risk of in-hospital and 1 to 2 years new coronary events in patients with unstable angina, but are also associated with an increased long-term risk of death and myocardial infarction in apparently normal subjects. Thus, accumulating evidence suggests that inflammation may cause local endothelial activation and, possibly, plaque fissure, leading to unstable angina and infarction. Although no information is yet available on the causes of inflammation and on its localization, these novel lines of research may open the way to a different approach to the patient with acute coronary syndromes.     

Can carotid plaque histology selectively predict the risk of an acute coronary syndrome?

The aim of this study was to assess whether carotid plaque morphology is an independent predictive factor of stroke and, innovatively, of acute coronary syndrome (ACS). We analyzed morphological aspects of carotid atherosclerotic plaque associated with an increased risk of ACS and stroke. We examined 72 carotid endarterectomy (CEA) specimens obtained between January 2005 and February 2009. All patients underwent follow-up for 12 months after the revascularization treatment to assess the occurrence of ACS and stroke. Data obtained showed that in patients with a previous ACS and in those who had developed an ACS during follow-up after CEA, the degree of carotid plaque calcification was more severe than in patients who did not develop an ACS, either before CEA or during follow-up. However, plaques of patients with ACS were mostly devoid of a significant inflammatory component, whereas a rich infiltrate, mainly consisting of monocytes-macrophages and lymphocytes, was present in plaques of subjects who did not develop an ACS. This element was particularly important since strokes occurred only in the latter group of patients (62% versus 0%). Therefore, we deduced that inflammation, from the histological point of view, is more correlated with cerebral circulation disorders than with coronary disease. In conclusion, while the finding of a soft plaque with a large necrotic core and a marked inflammatory component, often characterized by acute complications, may be predictive of an increased risk of cerebro-vascular events, a heavily calcified plaque may be indicative of a high risk of coronary events.     

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.     

Elevation of C-reactive protein in "active" coronary artery disease

Unstable angina occurs most commonly in the setting of atherosclerotic coronary artery disease (CAD), but there is little information concerning the mechanisms responsible for the transition from clinically stable to unstable coronary atherosclerotic plaque. Recently, increased focal infiltration of inflammatory cells into the adventitia of coronary arteries of patients dying suddenly from CAD and activation of circulating neutrophils in patients with unstable angina have been observed. To characterize the presence of inflammation in "active" atherosclerotic lesions, the acute phase reactant C-reactive protein (CRP) was measured in 37 patients admitted to the coronary care unit with unstable angina, 30 patients admitted to the coronary care unit with nonischemic illnesses and 32 patients with stable CAD. CRP levels were significantly elevated (normal less than 0.6 mg/dl) in 90% of the unstable angina group compared to 20% of the coronary care unit group and 13% of the stable angina group. The average CRP values were significantly different (p = 0.001) for the unstable angina group (2.2 +/- 2.9 mg/dl) compared to the coronary care (0.9 +/- 0.7 mg/dl) and stable angina (0.7 +/- 0.2 mg/dl) groups. There was a trend for unstable angina patients with ischemic ST-T-wave abnormalities to have higher CRP values (2.6 +/- 3.4) than those without electrocardiographic changes (1.3 +/- 0.9, p = 0.1). The data demonstrate increased levels of an acute phase reactant in unstable angina. These findings suggest that an inflammatory component in "active" angina may contribute to the susceptibility of these patients to vasospasm and thrombosis.     

辛伐他汀调脂干预治疗急性冠脉综合征病人血浆CRP及NO水平的影响

目的探讨辛伐他汀对急性冠状动脉综合征(ACS)病人血浆C-反应蛋白(CRP)及血脂干预的作用。方法符合ACS诊断标准的病人73例,随机分成辛伐他汀组(治疗组)和常规组(对照组),分别在治疗前和治疗28d后,清晨空腹抽静脉血5mL,应用速率散射免疫比浊法测定血浆CRP,同时测定血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)、一氧化氮(NO)等水平。结果治疗组CRP,LDL,TC,TG较对照组明显下降(P<0.05或P<0.01),而NO水平明显升高(P<0.01)。结论辛伐他汀调脂干预治疗,能够降低ACS应激反应,减轻冠状动脉粥样硬化的炎症反应和脂质过氧化损伤,改善冠状动脉内皮细胞功能。     

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   

The role of C-reactive protein in cardiovascular disease risk

The genesis of an atherosclerotic plaque depends on interplay of cellular components of the immune system such as monocytes, cytokines, and cell adhesion molecules with lipids, platelets and endothelial cells. Thus, inflammation may play a pivotal role in the propagation of coronary artery disease. Several reports have linked inflammation and cardiovascular risk, particularly a novel acute inflammatory peptide, C-reactive protein (CRP), with future risk of coronary events independent of the traditional coronary artery disease risk factors. To this end, many studies suggest that CRP may be used as a marker of sub-clinical atherosclerosis and cardiovascular risk. Specifically, CRP has been positively linked to future cardiovascular events in healthy women, healthy men, elderly patients, and high-risk individuals. In addition, reports have shown associations between CRP and peripheral vascular disease and stroke. Furthermore, preliminary data suggest that the relative efficacy of secondary preventive therapies such as statin drugs and aspirin may depend on the individual patient's baseline CRP level.     

Relationship between C-reactive protein and the electrocardiographic pattern on admission in patients with acute coronary syndrome

BACKGROUND: In patients with acute coronary syndrome (ACS), the prevalence of a primary inflammatory pathogenic component of coronary instability, as detectable by elevated C-reactive protein (CRP), varies considerably. The aim of the present study was to assess the prevalence of inflammation in patients with ACS according to the different electrocardiographic (ECG) patterns on admission. METHODS: Hundred and thirty-six consecutive patients with the diagnosis of acute myocardial infarction were divided in three groups according to the ECG pattern on admission. Group 1 included 59 patients with ST segment elevation, group 2 included 50 patients with ST depression and/or T wave inversion and group 3 included 27 patients with no ECG changes. CRP was measured on admission in all patients. For the prevalence of inflammation analysis, we used a cutoff value of 3 mg/l. RESULTS: CRP was above cutpoint significantly more often in patients with ST depression and/or T wave inversion (44.1% in group 1, 70% in group 2 and 40.7% in group 3; p=0.009). Patients with similar ECG pattern and CRP levels above the cutpoint presented a poorer outcome (coronary death, myocardial infarction and recurrence of instability) at one-year follow-up: 54 versus 27% for group 1, 74 versus 27% for group 2 and 45 versus 31% for group 3. CONCLUSIONS: Patients with ST depression and/or T wave inversion on admission exhibit a higher prevalence of elevated CRP than those with ST elevation or no ECG changes, suggesting an important heterogeneity of the role of inflammatory triggers of the clinical syndromes of coronary instability.     

急性冠状动脉综合征患者血清基质金属蛋白酶-2与C-反应蛋白水平

目的:在血清学水平上探讨C反应蛋白(CRP)、基质金属蛋白酶2(MMP2)与冠状动脉粥样硬化斑块破裂的关系,评价CRP、MMP2水平作为粥样硬化斑块破裂的血清学指标的意义。方法:分别利用酶联免疫吸附法及散射比浊法对40例急性冠状动脉综合征(ACS)组、40例稳定型心绞痛(SAP)组、40例非冠心病者(正常对照组)外周血血清CRP、MMP2水平进行测定。结果:ACS组、SAP组血清CRP、MMP2水平明显高于正常对照组,差异具有统计学意义(P<0.01),ACS组血清CRP、MMP2水平明显高于SAP组,差异具有统计学意义(P<0.01);经相关性检验血清CRP和MMP2水平呈明显正相关(P<0.01)。结论:血清CRP、MMP2水平可反映斑块稳定性,可作为检测斑块破裂的血清学指标。     

Monocyte chemoattractant protein-1/CCL2 as a biomarker in acute coronary syndromes

The CC chemokine monocyte chemoattractant protein (MCP)-1/CCL2 is involved in the formation, progression, and destabilization of atheromatous plaques and plays an essential role in postinfarction remodeling. These properties generated significant interest in the potential significance of MCP-1 as a biomarker in acute coronary syndromes (ACS). Emerging evidence suggests that MCP-1 plasma levels have prognostic value in the acute and chronic phase following ACS, providing information independent of standard clinical variables. The mechanisms responsible for adverse prognosis in patients with elevated plasma MCP-1 following ACS remain unknown. High plasma MCP-1 levels may reflect a higher burden of atherosclerotic disease, may exert prothrombotic effects resulting in recurrent coronary events, or may identify patients who mount a more intense cardiac inflammatory reaction following a coronary event, resulting in enhanced adverse remodeling. Beyond its prognostic significance, the MCP-1 axis may be an attractive target for therapy in patients with ACS.     

C-reactive protein as a marker for active coronary artery disease in patients with chest pain in the emergency room

BACKGROUND: Markers of inflammation, such as C-reactive protein (CRP), were found to be related to risk for cardiovascular disease (CVD) events in patients with angina pectoris. In addition, recent studies have shown that, in the case of atherosclerosis, increased CRP concentration reflects the inflammatory condition of the vascular wall. HYPOTHESIS: The study was undertaken to determine whether CRP levels in individuals with chest pain attending the emergency room (ER) may be used as a marker of active CVD. METHODS: Serum CRP level was measured in 226 of 326 consecutive patients (128 men, 98 women; mean age 61.3 +/- 5.9 years; range 19-87 years) referred to the ER with chest pain. The decision whether to admit orrelease the subjects was determined without taking the CRP level into account. Follow-up was then performed for 1 year. RESULTS: Eighty-four patients were admitted to the hospital. Of these, 9 with acute coronary syndrome (ACS) had very high levels of CRP (25-40 mg/l), 35 had had an acute coronary event within the preceding 3 months, with levels of CRP 14-20 mg/l. Only eight patients with nonsignificant CVD had elevated CRP levels. Twenty-eight subjects who were released from the ER had elevated CRP levels (7-14 mg/l); 8 of these, in addition to 4 subjects with normal CRP levels, had a late coronary event. CONCLUSION: This study indicates that in patients referred to the ER with chest pain and no other indication for hospitalization, a normal level of CRP suggests safe release. Most hospitalized patients with normal CRP will not have acute coronary syndrome. Patients who will develop early coronary events have very high CRP levels. High serum CRP level, after excluding other inflammatory sources, was proven to be a sensitive diagnostic and prognostic marker for significant coronary disease.     

Relation between local temperature and C-reactive protein levels in patients with coronary artery disease: effects of atorvastatin treatment

Although previous studies have shown systemic inflammatory activation the relation with the local plaque inflammatory activation has not been extensively studied. The present study investigated the relation between local and systemic inflammatory activation in patients with coronary artery disease and the impact of atorvastatin treatment. We included 215 patients undergoing percutaneous coronary intervention; of them 140 were treated with atorvastatin. Patients with stable angina (SA) and acute coronary syndromes (ACS) were included. Systemic inflammation was assessed by serum C-reactive protein (CRP), soluble adhesion molecules levels and local plaque inflammatory activation by coronary thermography. Temperature difference (DeltaT) was assigned as the difference between the proximal vessel wall temperature from the maximal temperature at the culprit plaque. Patients with ACS (n=78) had increased DeltaT compared to patients with SA (n=137) (0.16+/-0.10 degrees C versus 0.08+/-0.07 degrees C, P<0.001). Patients treated with atorvastatin had lower DeltaT compared to untreated patients (0.10+/-0.07 degrees C versus 0.15+/-0.10 degrees C, P<0.01). DeltaT was less in the treated group compared to the untreated group in patients with SA and ACS (ACS: 0.13+/-0.08 degrees C versus 0.20+/-0.11 degrees C, P<0.01, SA: 0.08+/-0.06 degrees C versus 0.13+/-0.08 degrees C, P=0.03). Although a correlation was found between CRP levels and DeltaT (R=0.29, P<0.01), in certain groups a discrepancy between CRP levels and DeltaT was observed. In 25% of patients with low DeltaT CRP levels were >1mg/dl and in 35.5% of patients with high DeltaT CRP was <2mg/dl. The correlation between soluble adhesion molecules and DeltaT did not reach statistical significance. Although there is a correlation between widespread and local inflammatory activation in patients with coronary artery disease, a discrepancy between culprit plaque and systemic inflammatory activation is observed. Atorvastatin has a parallel effect on systemic and local inflammatory process in patients with coronary artery disease.     

急性冠状动脉综合征患者B7∶CD28/CTLA4共刺激分子的表达

目的:探讨急性冠状动脉综合征(ACS)患者外周血中单核细胞共刺激分子CD28、细胞毒T淋巴细胞抗原(CTLA)4、CD80(B7-1)的变化,探讨这些分子在发病中的意义。方法:采用直接荧光标记流式细胞仪测定23例ACS患者(ACS组)和31例稳定型心绞痛(SA)患者(SA组)入院时外周血CD4 ,CD8 T淋巴细胞CD28、CTLA4、B7-1分子的表达,同时选健康人群15例作为对照(对照组)。结果:与对照组相比,SA组及ACS组发病时CD4 ,CD8 T淋巴细胞表面共刺激分子CD28均显著升高(均P<0.01);SA组与ACS组比较差异无统计学意义。与对照组相比,SA组CD4 ,CD8 T淋巴细胞表面CTLA4表达均显著升高(P<0.01);而ACS组CD4 ,CD8 T淋巴细胞表面CTLA4表达均显著下降(P<0.01)。各组B7-1的表达差异无统计学意义。结论:①共刺激分子B7-1:CD28/CTLA4途径参与了冠心病的发病过程;②ACS的强烈的炎症反应与CT-LA4的低表达有关。     

Acute phase proteins in patients with acute coronary syndrome: Correlations with diagnosis, clinical features, and angiographic findings

BACKGROUND: C-reactive protein (CRP) plasma levels increase in patients with acute coronary syndrome (ACS). The role and implications of increased plasma concentrations of other acute phase proteins (APPs), such as alpha-1-antitrypsin (A1AT), alpha-1 glycoprotein (A1GP), haptoglobin (HG), ceruloplasmin (CP), and C3c and C4 complement fraction, in patients with ACS are still not completely defined. METHODS: A total of 218 consecutive patients with ACS were included in the study, 185 with acute myocardial infarction (AMI) and 33 with unstable angina (UA). In all patients, A1AT, A1GP, HG, CP, C3c and C4 complement fraction, and CRP were evaluated within 12 h after the onset of symptoms. Sixty-two patients with AMI underwent coronary angiography. RESULTS: APPs showed a significant correlation with CRP concentrations. Patients with AMI had higher concentrations of A1AT and HG than UA patients. Cholesterol levels were correlated with APPs in patients with AMI. Patients with three coronary vessel disease or LAD disease had significantly higher C3c concentrations. Coronary collateral flow was associated with higher A1GP and CP concentrations, and total coronary occlusion with A1AT and CP. CONCLUSIONS: APPs were correlated with CRP concentrations in subjects with ACS. The increase in APPs in patients with ACS seems to be linked to the entity of myocardial damage and coronary atherosclerotic burden.     

Pathological Changes in Acute Coronary Syndromes: The Role of Statin Therapy in the Modulation of Inflammation,Endothelial Function and Coagulation

Considerable progress has been made in our understanding of the pathophysiology of coronary artery disease (CAD), their acute presentations as acute coronary syndromes (ACS) and the role of LDL cholesterol. In particular there is clear evidence that atherosclerosis is far from being a process that leads to an amorphous flow limiting lesion on an angiogram, but rather involves a complex interplay between the endothelium, inflammatory cells and the coagulation cascade occurring throughout the coronary vascular bed. While a culprit flow limiting lesion may be effectively treated by a drug eluting stent or coronary bypass surgery, this will have little impact on the global molecular processes that determine recurrent plaque instability at non-culprit sites. The search for systemic long term therapy, which is safe and effective and reduces the changes in inflammation, endothelial function and thrombosis that are the hallmark of ACS, has pushed statins to the forefront. A number of recent clinical trials have shown the benefits of early statin therapy in the treatment of ACS. In addition to their effects on LDL cholesterol, statins have a number of properties collectively referred to as pleiotropic effects, which enable them to modulate the adverse biological changes that are associated with ACS. The purpose of this review is to acquaint the reader with the biological changes that accompany ACS, highlight how these pathways may be modulated for clinical benefit by statins and identify potential novel targets for future therapy.Abbreviated abstract. Acute coronary syndromes are associated with pathological changes in inflammation, endothelial function, and coagulation, and many of these are attenuate by statins in a lipid independent manner. In light of recent clinical trials showing the early benefit of statin therapy in ACS, this review discusses how the pleiotropic effects of statins may result in early clinical benefit.     

急性冠状动脉综合征患者血清炎性细胞因子水平及临床意义

目的通过对急性冠状动脉综合征患者血清炎性细胞因子水平的测定及比较,分析炎症及细胞因子在急性冠状动脉综合征发生发展过程中的作用及临床意义。方法选择急性心肌梗死(AMI)患者44例(AMI组),不稳定性心绞痛(UAP)患者44例(UAP组),稳定性心绞痛(SAP)患者43例(SAP组),无冠心病患者35例(对照组),分别检测各组患者血清白细胞介素6(IL-6)、白细胞介素8(IL-8)、白细胞介素10(IL-10)、TNF-α、C反应蛋白(CRP)和基质金属蛋白酶9(MMP-9)浓度并进行比较。结果 AMI组患者血清IL-6、IL-8、IL-10、TNF-α、CRP和MMP-9水平均明显高于SAP组和对照组(P<0.01);AMI组患者血清IL-10、TNF-α、CRP、MMP-9水平明显高于UAP组(P<0.05);UAP组患者血清IL-6、IL-8、IL-10水平明显高于SAP组和对照组;MMP-9和CRP与IL-6呈正相关(r=0.308,r=0.384,P<0.01)。结论冠心痛与炎性反应密切相关,多种细胞因子参与了动脉粥样硬化斑块的形成和进程,血清炎性细胞因子水平的升高是冠状动脉粥样硬化斑块不稳定的标志。