Serum concentrations of high-sensitivity C-reactive protein predict progressively obstructive lesions rather than late restenosis in patients with unstable angina undergoing coronary artery stenting.

BACKGROUND: The present study tested the hypothesis that high-sensitivity C-reactive protein (hs-CRP) concentrations might show significant serial changes in patients with unstable angina (UAP), and that elevation of hs-CRP might indicate a progressively obstructive lesion, rather than late restenosis in such patients undergoing coronary stenting. METHODS AND RESULTS: Serum concentrations of hs-CRP in 168 patients with UAP undergoing coronary stenting for a new obstructive lesion were prospectively measured (pre-procedure, and on days 21, 90, and 180 post-procedure). The hs-CRP concentrations were also evaluated in 30 at-risk controls and 50 healthy volunteers. Moderately obstructive lesions of non-culprit vessels (defined as > or =50-69% stenosis) that were not treated by coronary angioplasty were found in 107 (63.7%) patients. The hs-CRP concentration was significantly higher at pre-procedure in the study patients than in the controls and healthy volunteers (all p-values <0.0001) and markedly declined after the procedure (p<0.0001). Pre-procedure (p=0.799) and post-procedure hs-CRP concentrations (all p-values >0.1) did not differ between restenotic and non-restenotic patients. However, at pre-procedure or on day 180, the concentration of hs-CRP was independently associated with progressively obstructive lesions of non-culprit vessels that required coronary angioplasty (both p-values <0.05). CONCLUSION: The hs-CRP concentration was significantly higher at pre-procedure and declined substantially thereafter in patients with UAP following coronary stenting. There was no evidence of a positive association between an elevated hs-CRP concentration and late restenosis. However, both the pre-procedure and day 180 concentrations of hs-CRP were strongly associated with the progression of moderately obstructive lesions in non-culprit vessels.     

Impact of clopidogrel on suppression of circulating levels of soluble CD40 ligand in patients with unstable angina undergoing coronary stenting

This study investigated whether a regimen that comprised a loading dose of 300 mg of clopidogrel followed by 75 mg/day could significantly suppress circulating levels of soluble CD40 ligand (sCD40L) in patients who had unstable angina and underwent coronary stenting. Study results showed that the clopidogrel loading dose substantially decreased the circulating level of sCD40L at 24 hours after stenting (p <0.0001). Combined with aspirin, 75 mg/day of clopidogrel continuously decreased sCD40L levels after coronary stenting.     

Circulating soluble CD40 ligand mediates the interaction between neutrophils and platelets in acute coronary syndrome

Following plaque rupture, activated platelet will induce subsequent inflammatory process including neutrophil recruitment. In vitro study demonstrated an interaction between neutrophils and platelets via a mechanism involving CD40-CD40 ligand. However, whether this mechanism exists in the clinical setting remains unknown. Fifty-four patients with acute myocardial infarction (AMI) and 25 with unstable angina of pain onset of ≤24 h were enrolled consecutively. Acute myocardial infarction was diagnosed from three diagnostic criteria, i.e., anginal pain, electrocardiogram ST-T changes, and cardiac enzyme elevation. Unstable angina was diagnosed in patients without elevated cardiac enzymes. Peripheral venous blood was drawn at admission for routine blood count and soluble CD40 ligand (sCD40L) measurement. Neutrophil count was determined by an automated blood cell counter. Circulating sCD40L was measured using a standard enzyme-linked immunosorbent assay. Neutrophil count was significantly higher in AMI as compared with unstable angina (P < 0.001), whereas circulating sCD40L did not significantly differ. Despite marked elevation, no correlation was observed between neutrophil count and circulating sCD40L in AMI. Interestingly, we observed a strong and positive significant correlation between neutrophil count and circulating sCD40L level (r = 0.607, P = 0.002) in unstable angina. Circulating sCD40L is associated with neutrophil count and may mediate interaction between neutrophils and platelets in acute coronary syndrome, particularly in unstable angina.     

炎性因子CD40配体在急性冠脉综合征患者中的作用

目的探讨急性冠脉综合征（ACS）患者血清可溶性CD40配体（sCD40L）和超敏C反应蛋白（hs-CRP）的水平及临床意义。方法按照诊断标准入选研究对象137例,分为两组：冠状动脉造影无异常者为对照组,21例,ACS组116例,男86例,30例,年龄35～77（56.9±12.6）岁,包括不稳定型心绞痛88例,急性心肌梗死28例。采集患者空腹肘静脉血,采用酶联免疫吸附（ELISA）方法测定血清sCD40L浓度和hs-CRP浓度。所有患者入院第2～4天行冠状动脉造影检查,用直径法测定冠状动脉狭窄的程度,用Gensini评分系统进行评分,累计积分。结果 ACS组sCD40L与hs-CRP水平均高于对照组（P＜0.05）。sCD40L水平与Gensini积分呈正相关关系（r＝0.328,P＝0.000）,hs-CRP水平与Gensini积分呈正相关关系（r＝0.748,P＝0.000）,sCD40L与hs-CRP之间呈正相关关系（r＝0.192,P＝0.039）。结论 ACS患者外周血清sCD40L和hs-CRP水平明显升高,提示CD40/CD40L系统与ACS的发生有关。     

蛋白芯片法联检急性冠状动脉综合征患者血中细胞因子的意义

目的 探讨急性冠状动脉综合征(ACS)患者血中炎性细胞因子、炎性细胞相关因子及心肌损伤因子浓度的变化及临床意义.方法 运用蛋白芯片技术同步联检经冠状动脉造影及临床表现证实为ACS患者104例及对照者50例血清或血浆中10种细胞因子水平;同时对不稳定性心绞痛(UA)患者按Braunwald分级进行分析.结果 急性心肌梗死(AMI)组和UA组血清中C反应蛋白(CRP)、白介素(IL)-6、可溶性CD40L(sCD40L)、基质金属蛋白酶(MMP)-9、心脏型脂肪酸结合蛋白(H-FABP)、肌钙蛋白Ⅰ(cTnⅠ)及血浆中的IL-8、内皮素(ET)-1、可溶性血管细胞黏附分子(sVCAM)-1、氨基酸N末端脑钠肽原(NT-proBNP)浓度高于对照组,差异有统计学意义(P＜0.01);AMI组cTnⅠ[(11.08±10.49) μg/L]和H-FABP[(19.80±4.60)μg/L]浓度高于UA组[cTnⅠ:(0.69±0.18)μg/L,H-FABP:(4.12±2.45)μg/L,P＜0.01],而CRP、IL-6、MMP-9、sCD40L及ET-1浓度,两组比较差异无统计学意义;UA组MMP-9、sCD40L及H-FABP的浓度与Braunwald分级存在显著正相关(分别r=0.653,r=0.745,r=0.933,均P＜0.01).随着心绞痛严重程度的增加,MMP-9、sCD40L及H-FABP水平明显升高,心绞痛Ⅰ级＜心绞痛Ⅱ级＜心绞痛Ⅲ级(P＜0.01).结论 ACS患者血中存在多种细胞因子浓度异常,其中MMP-9、sCD40L、H-FASP的浓度与UA患者心绞痛严重程度存在良好的相关性.提示上述细胞因子参与和促使了ACS的发生、发展,为ACS的危险分层、预后判断提供了可能的分子标志物依据.     

术前sCD40L预测冠脉支架后再狭窄的临床价值研究

目的探讨冠心病患者支架植入术前sCD40L对再狭窄的诊断预测价值。方法选择成功接受普通支架置入术的稳定型心绞痛和不稳定型心绞痛患者共92例,分别于支架术前,术后第1、5、15天和180天取外周静脉血测定血清sCD40L。所有患者随访6个月。结果支架内再狭窄率23.9%(22/92)。再狭窄患者支架术前和术后血清sCD40L浓度均显著高于无再狭窄患者术前sCD40L浓度;再狭窄患者支架术后高水平sCD40L持续至术后6个月,而无再狭窄患者术后5天恢复至正常。根据受试者工作特征曲线确定术前血清sCD40L>3.96μg/L为截断值,计算术前sCD40L诊断再狭窄的敏感性、特异性、阳性预测值(PPV)、阴性预测值(NPV)、准确度和阳性似然比分别为72.7%、90%、69.6%、91.3%、85.9%和7.27。多变量Logistic回归分析发现,在校正混杂因素后,术前sCD40L是术后再狭窄独立预测因子,OR1.92(95%CI1.39～2.64,P=0.013)。结论再狭窄患者支架术前、术后血清sCD40L水平增加提示可能与支架内再狭窄有关。支架术前血清sCD40L是术后再狭窄的独立预测因子,术前sCD40L有...     

血浆高敏C反应蛋白对冠状动脉介入术后早期并发症及再狭窄的预测价值

目的　探讨心绞痛患者行经皮冠状动脉介入治疗 (PCI)前 ,高敏C 反应蛋白 (hs CRP)水平对早期并发症及术后再狭窄的预测价值。方法　对 12 0例心绞痛的患者 (5 2例稳定型心绞痛 ,6 8例不稳定型心绞痛 )入院时测定血浆hs CRP水平 ,然后行单支血管的经皮冠状动脉腔内成形术(PTCA) ,随访 1年 ,观察早期并发症及晚期再狭窄发生率 ,对其进行分析。结果　 12 0例患者中 ,血浆hs CRP升高者 6 8人 ,早期并发症均发生在高hs CRP水平者。再狭窄发生率为 4 6 % ,其中血浆hs CRP正常者 14例 ,占 2 7% ;血浆hs CRP升高者 37例 ,占 6 3% (P <0 0 0 1)。经多因素回归分析显示 ,术前CRP水平增高 (r=11 7,P <0 0 0 1)、高血压 (r=4 3,P =0 0 3)、女性 (r=4 1,P =0 0 13)是预测早期并发症的独立危险因素 ,而高CRP(r=6 7,P <0 0 0 1)及术后残余狭窄 (r=3 2 ,P =0 0 0 7)是预测再狭窄的独立危险因素。结论　血浆hs CRP水平可作为炎症标志物反映冠状动脉炎症情况 ,对PTCA早期并发症及术后再狭窄有一定的预测价值。     

Usefulness of preprocedural soluble CD40 ligand for predicting restenosis after percutaneous coronary intervention in patients with stable coronary artery disease

CD40-CD40 ligand interaction is involved in the inflammatory pathogenesis of atherosclerosis but clinical data about its role in stent restenosis are still limited. We investigated the effect of preprocedural CD40 ligand (sCD40L) on stent restenosis. We enrolled 36 patients (mean age 61.4 +/- 8.5 years) with stable angina who underwent successful stent implantation. Control angiograms were performed in all patients after 6 months. Plasma sCD40L and high-sensitive C-reactive protein levels were measured before stent implantation and at 1 and 6 months after the procedure. Angiographically proven restenosis rate was 27.8%. Plasma sCD40L levels were significantly higher (preprocedural 0.74 +/- 0.79) and more prolonged in patients with stent restenosis compared with patients without stent restenosis (0.02 +/- 0.22 ng/ml, p < 0.001). According to receiver-operator characteristic analysis, sCD40L > 0.41 ng/ml was the best distinguished parameter between patients with and without restenosis. At the multivariate logistic regression analysis, preprocedural sCD40L was an independent predictor (RR 39.4, 95% confidence interval 4.05 to 383.8, p = 0.002) of stent restenosis after adjusting for confounding variables, including diabetes, reference vessel diameter, lesion length, stent diameter, stent length, and baseline high-sensitive C-reactive protein. Sensitivity, specificity, and positive and negative predictive values and likelihood ratio of preprocedural sCD40L levels in stent restenosis were 78%, 92%, 78%, 92%, and 9.37%, respectively. In conclusion, enhanced inflammation of plaque (increased sCD40L) before percutaneous coronary intervention may increase the rate of stent restenosis. Increased preprocedural sCD40L level is an independent predictor of stent restenosis. We can use this marker for the assessment of risk stratification before planning stent implantation.     

Local release of C-reactive protein from vulnerable plaque or coronary arterial wall injured by stenting

OBJECTIVES: The purpose of this study was to assess local release of C-reactive protein (CRP) from atherosclerotic plaques or the vessel wall injured by stenting. BACKGROUND: Recent research has focused on the local production of CRP, especially in inflammatory atherosclerotic plaques. METHODS: The study consisted of two separate protocols. In protocol 1, we measured serum high-sensitivity-CRP (hs-CRP) levels in coronary arterial blood sampled just distal and proximal to the culprit lesions in 36 patients with stable angina and 13 patients with unstable angina. In protocol 2, we measured serial serum hs-CRP levels and activated Mac-1 on the surface of neutrophils in both coronary sinus and peripheral blood in 20 patients undergoing coronary stenting. RESULTS: In protocol 1, CRP was higher in distal blood than proximal blood in both stable (p < 0.05) and unstable angina (p < 0.01). The translesional CRP gradient (distal CRP minus proximal CRP, p < 0.05) as well as the proximal CRP (p < 0.05) and distal CRP (p < 0.05) was higher in unstable angina than in stable angina. In protocol 2, the transcardiac CRP gradient (coronary sinus minus peripheral blood) and activated Mac-1 increased gradually after stenting, reaching a maximum at 48 h (p < 0.001 vs. baseline for both). There was a positive correlation between the transcardiac CRP gradient and activated Mac-1 at 48 h (r = 0.45, p < 0.01). CONCLUSIONS: C-reactive protein is an excellent marker for plaque instability or poststent inflammatory status, and its source might be the inflammation site of the plaque or the coronary arterial wall injured by stenting.     

Levels and values of inflammatory markers in patients with angina pectoris

Inflammation plays an important pathogenic role in the initiation and progression of atherosclerotic plaque lesions. C-reactive protein (CRP), which directly participates in plaque inflammation, induces vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells. However, the levels and values of high-sensitivity (hs)-CRP, white blood cell (WBC) count, and VCAM-1 in both stable and unstable angina pectoris (AP) have not been fully investigated. This study examines the levels and values of these inflammatory markers in patients with stable or unstable AP. From March 2003 to December 2003, a prospective cohort study was conducted in 128 consecutive patients, including unstable AP patients (class I: n = 59; combined class II and III: n = 16) and stable AP patients (n = 53) undergoing elective coronary stenting. Blood samples for hs-CRP, WBC count, and VCAM-1 were obtained in the catheterization laboratory before coronary angiography. The circulating levels of hs-CRP and VCAM-1 were also evaluated in 40 healthy volunteers. The circulating levels of these three inflammatory markers were substantially higher in patients than in healthy volunteers (all P values < 0.0001). Additionally, circulating levels of hs-CRP and the WBC count were significantly higher in patients with unstable AP than in patients with stable AP (all P value < 0.0001). However, only those patients with class II and III unstable AP had significantly higher circulating levels of VCAM-1 than patients with stable AP (P < 0.0001). On the other hand, the circulating levels of VCAM-1 did not differ between patients with class I unstable AP and patients with stable AP (P = 0.782). Multiple stepwise logistic regression analysis showed that only hs-CRP level was independently associated with unstable AP (P = 0.0002). In conclusion, circulating levels of hs-CRP, WBC count, and VCAM-1 were significantly increased in patients with AP. The circulating level of hs-CRP was strongly associated with the clinical setting of unstable AP.     

The presence of metabolic syndrome is independently associated with elevated serum CD40 ligand and disease severity in patients with symptomatic coronary artery disease

Nontraditional atherosclerotic risk factors have become the focus of attention in recent years. In addition, metabolic syndrome is gaining recognition as another multiplex cardiovascular risk factor. However, to date, no studies have investigated the effect of metabolic syndrome on circulating soluble CD40 ligand (sCD40L), monocyte chemoattractant protein 1, cellular adhesion molecules, and disease severity in patients with symptomatic coronary artery diseases. This study was conducted to address this issue. Patients with stable angina who received percutaneous coronary interventions for significant (> or = 70% diameter stenosis) de novo lesions between January 1999 and January 2004 and had preprocedural serum samples were enrolled. Metabolic syndrome was defined by the National Cholesterol Education Program criteria with waist criterion modified into body mass index of more than 25 kg/m2. The serum samples were thawed and analyzed for circulating sCD40L, monocyte chemoattractant protein 1, adhesion molecules, and high sensitivity C-reactive protein (hs-CRP). Coronary severity was assessed by a modified version of Gensini scoring system. A total of 313 patients, 248 males and 65 females, were studied. Among them, 222 (70.9%, 170 males and 52 females) had metabolic syndrome. Patients with metabolic syndrome had higher serum creatinine level and lower low-density lipoprotein cholesterol despite higher triglyceride concentration. In multivariate analysis, patients with metabolic syndrome had higher sCD40L (6057 +/- 275 vs. 5051 +/- 423 pg/mL, P = .037) and more hs-CRP in higher tertiles (P = .005) than patients without, but similar levels of intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and P selectin. Metabolic syndrome was also significantly associated with multiple coronary vessel involvements with 70% or higher diameter stenosis (36.5% double-vessel and 14% triple-vessel diseases vs 30.8% double-vessel and 5.5% triple-vessel diseases, P = .026) and multiple coronary segment involvements with 50% or higher diameter stenosis (P = .014) in multivariate analysis. In conclusion, the presence of metabolic syndrome is independently associated with elevated sCD40L, hs-CRP, and coronary disease severity in patients with coronary artery disease requiring interventional treatment of stable angina.     

Re-elevation of high-sensitivity C-reactive protein but not the von Willebrand Factor after withdrawing atorvastatin therapy in patients with unstable angina undergoing coronary artery stenting

Statins are known to reduce high-sensitivity C-reactive protein (hs-CRP) concentrations and improve endothelial function. However, whether statin withdrawal causes re-elevated concentrations of hs-CRP and von Willebrand Factor (vWF) (a marker of endothelial damage) remains unknown. We hypothesized that the concentrations of hs-CRP and vWF are substantially increased in patients with unstable angina pectoris (UAP) and noticeably decreased following coronary stenting along with atorvastatin therapy. However, re-elevations of these biomarker concentrations occurred once again after withdrawing atorvastatin therapy. We serially examined the plasma concentrations of hs-CRP and vWF in 51 patients with UAP before (day 0) and after (days 21, 90, 180, 270) performing coronary artery stenting. The concentrations of these 2 biomarkers were also measured in 30 healthy control subjects. Patients were treated with atorvastatin (40 mg/day orally) for 180 days, after which the therapy was withdrawn. The hs-CRP and vWF concentrations were significantly higher in the patients than in the healthy control subjects before the procedure (both P values < 0.001). The hs-CRP concentration decreased significantly on day 21 (P < 0.001), and further to a substantially lower level on day 180 (P < 0.0001). However, the hs-CRP level significantly increased again on day 270, as compared with that on day 180 (P < 0.001). The vWF plasma concentration decreased gradually to a significantly lower level on day 180. The concentration of this biomarker did not differ between days 180 and 270. In conclusion, although hs-CRP concentrations decreased markedly following combined stenting and atorvastatin therapy, re-elevation after atorvastatin therapy was withdrawn in UAP patients undergoing coronary stenting was not observed. Conversely, restoration of endothelial function was slow and persistent in these patients.     

老年人冠状动脉介入治疗术后氯吡格雷抵抗与炎性因子的关系

目的 观察冠状动脉支架植入后发牛氯吡格霄抵抗的老年冠心病患者术前、术后血清炎症因子的变化,并探讨其临床意义. 方法 选择因冠心病不稳定心绞痛住院并成功接受冠状动脉支架植入术的老年患者93例,分别于术前和术后24 h、7 d、1个月抽取外周血,比浊法检测二磷酸腺苷诱导的血小板聚集率,氯吡格雷抵抗33例(抵抗组)和正常反应60例(非抵抗组).酶联免疫法测定C反应蛋白质(CRP)、可溶性CD40配体(sCD40L)和P-选择素(P-selectin),分析氯吡格雷抵抗与炎症因子的关系. 结果 冠状动脉介入术后24 h、7 d、30 d时氯吡格雷抵抗的发生率为35.5%(33例)、26.9%(25例)、20.4%(19例),抵抗组患者术后24 h、7 d时血CRP水平[(8.8±2.5)mg/L、(5.3±2.5)mg/L]与术前(2.1±1.0)mg/L和非抵抗组[(8.1±2.3)mg/L和(2.5±1.4)mg/L]比较,差异有统计学意义(均P<0.05),30 d时有增高趋势,但差异无统计学意义,术后不同时间点P-selectin水平均较非抵抗组增高(P<0.05).术后24 hsCD40L水平较术前升高(P<0.05).相关分析结果显示,P-selectin水平、吸烟与术后30 d时氯吡格雷抵抗呈正相关(r=1.334,r=1.053,均P<0.05). 结论 冠状动脉支架术后对氯吡格雷具有不同反应性的老年患者血CRP、sCD40L、P-selectin表达存在差异,可能与氯吡格雷抵抗有关,P-selectin水平和吸烟是老年人冠状动脉支架植入术后30 d时氯吡格雷抵抗发生的预测因素.     

Increased circulating monocyte activation in patients with unstable coronary syndromes.

OBJECTIVES: The primary objective of this research was to assess the activation level of circulating monocytes in patients with unstable angina. BACKGROUND: Markers of systemic inflammatory responses are increased in patients with unstable coronary syndromes, but the activation state and invasive capacity of circulating monocytes have not been directly assessed. METHODS: Peripheral blood mononuclear cell (MC) activation in blood samples isolated from patients with stable and unstable coronary artery disease was measured in two studies. In study 1, a modified Boyden chamber assay was used to assess spontaneous cellular migration rates. In study 2, optical analysis of MC membrane fluidity was correlated with soluble CD14 (sCD14), a cellular activation marker. RESULTS: Increased rates of spontaneous monocyte migration (p < 0.01) were detected in patients with unstable angina (UA) (Canadian Cardiovascular Society [CCS] angina class IV) on comparison to patients with acute myocardial infarction (MI), stable angina (CCS angina classes I to III) or normal donors. No significant increase in lymphocyte migration was detected in any patient category. Baseline MC membrane fluidity measurements and sCD14 levels in patients with CCS class IV angina were significantly increased on comparison with MCs from normal volunteers (p < 0.001). A concomitant reduction in the MC response to activation was detected (p < 0.05). CONCLUSIONS: Using two complementary assays, activated monocytes with increased invasive capacity were detected in the circulation of patients with unstable angina. This is the first demonstration of increased monocyte invasive potential in unstable patients, raising the issue that systemic inflammation may both reflect and potentially drive plaque instability.     

急性冠状动脉综合征患者血清sCD40L升高的临床价值

目的观察冠心病不同类型患者中可溶性CD40L(sCD40L)水平的变化及其与白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β)之间的关系,进一步探讨急性冠状动脉综合征(ACS)临床识别和预测的炎症指标。方法采用酶联免疫吸附法测定血清可溶性CD40L浓度,采用放免方法测定IL-6和IL-1β浓度。结果急性心肌梗死(AMI)患者sCD40L水平[(4.923±3.41)ng/ml]和不稳定型心绞痛(UAP)患者sCD40L水平[(5.387±3.04)ng/ml]显著高于稳定型心绞痛(SAP)[(2.856±2.34)ng/ml,P<0.05]和对照组患者[(2.221±2.42)ng/ml,P<0.01]。ACS患者sCD40水平与IL-6呈正相关(r=0.49,P=0.008),与IL-1β无相关性(r=0.258,P=0.183),而SAP和对照组患者sCD40L与IL-6、IL-1β无相关性。同时ACS患者sCD40L水平与低密度脂蛋白有显著相关性(r=0.471,P=0.011)。结论ACS患者血清sCD40L与IL-6、IL-1β水平升高,提示其可能与ACS发生有关,是动脉粥样硬化和斑块不稳定的标志。     

64层CTA结合血清MMP-9、sCD40L评价冠脉临界病变斑块成分及稳定性

目的:通过64层计算机体层摄影冠状动脉血管造影识别冠状动脉临界病变患者的冠脉斑块成分,并检测血清基质金属蛋白酶-9（MMP-9）、可溶性CD40配体（sCD40L）水平,探讨其斑块稳定性及临床意义。方法: 选择经64层计算机体层摄影冠状动脉血管造影证实至少有1支冠脉某一阶段狭窄30%～70%的患者65例,其中稳定型心绞痛36例,不稳定型心绞痛29例,通过斑块CT值及冠脉管腔碘造影剂CT值确定其斑块类型:非钙化斑块,钙化斑块和混合斑块;并用ELISA方法测定患者及37例无心血管疾病对照组血清MMP-9、sCD40L水平,比较其差异性并探讨其相互关系。结果: 冠脉临界病变患者混合斑块最多,其次为非钙化斑块,钙化斑块最少,“混合斑块+非钙化斑块”显著多于钙化斑块数目;患者血清MMP-9、sCD40L水平显著高于无心血管疾病对照组。结论: 冠心病冠脉临界病变斑块多为易损斑块。     

Association between circulating level of CD40 ligand and angiographic morphologic features indicating high-burden thrombus formation in patients with acute myocardial infarction undergoing primary coronary intervention.

BACKGROUND: This study tested the hypothesis that in the acute phase of myocardial infarction (MI), the circulating level of soluble CD40 ligand (sCD40L), an index of platelet activation, is predictive of angiographic morphologic features that indicate high-burden thrombus formation (HBTF) in the infarct-related artery (IRA). METHODS AND RESULTS: This prospective study included 162 consecutive patients: 64 with HBTF and 98 with low-burden thrombus formation (LBTF). All patients had a Killip's classification相似文献   

Plasma matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-2, and CD40 ligand levels in patients with stable coronary artery disease

Endogenous matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs), are important mediators of extracellular matrix remodeling, which is integral to plaque progression in coronary artery disease. In addition, high levels of the soluble fragment of CD40 ligand (sCD40L) have previously been associated with adverse cardiovascular outcomes. We hypothesized that circulating levels of MMP-9, TIMP-1, TIMP-2, and sCD40L were abnormal in patients who had stable coronary artery disease, and these levels were compared with those in matched controls. We also hypothesized correlations of MMPs, TIMPs, and sCD40L to each other and to high-sensitivity C-reactive protein (a proinflammatory marker), white blood cell count, severity of coronary artery disease (based on angiographic measurements of atherosclerotic burden), and coronary collateralization. We studied 204 adult patients who attended our unit for outpatient diagnostic cardiac catheterization for the investigation of suspected coronary artery disease. Coronary angiograms were scored for atheroma burden and stenosis by 2 independent observers. Circulating levels of MMP-9, TIMP-1, TIMP-2, and sCD40L were measured by enzyme-linked immunosorbent assay. Plasma levels of MMP-9 (p = 0.0099), TIMP-2 (p = 0.0019), and sCD40L (p <0.001), but not TIMP-1 (p = 0.463) were high in patients compared with healthy controls. In patients who had coronary artery disease, MMP-9 and high-sensitivity C-reactive protein levels were significantly higher in women than in men. Only MMP-9 correlated modestly with total white blood cell count (Spearman's correlation, r = 0.274, p = 0.002). Logistic regression of cardiovascular risk factors showed that only white blood cell count was independently associated with MMP-9 (p = 0.02). After standardizing for atheroma and stenosis scores, there were no statistically significant differences in our research indexes in patients who had angiographic collaterals compared with those who did not. In conclusion, stable coronary artery disease is associated with abnormal circulating levels of MMP-9, TIMP-2, and sCD40L, which do not appear to related to each other or to severity of coronary artery disease or collateralization. The gender difference in high-sensitivity C-reactive protein and MMP-9 levels may provide insight into the pathophysiology of coronary artery disease in men and women, and further studies are warranted to explore this potential link.     

阿托伐他汀钙片对心绞痛患者血清可溶性CD40配体与C反应蛋白的干预研究

目的 探讨阿托伐他汀钙片对心绞痛患者血清可溶性CD40配体(CD40L)与高敏C反应蛋白(hs-CRP)的干预作用.方法 65例冠心病患者,其中稳定型心绞痛患者30例(SA组),不稳定型心绞痛患者35例(UA组),所有患者于入院当天清晨、治疗后2、4、6周静脉血,测定血清hsCRP、血清可溶性CD40L水平,并对两组结果进行比较.结果 治疗前UA组血清可溶性CD40L、hs-CRP浓度分别为(20.52±2.91)μg/L、(7.96±1.69) mg/L,明显高于SA组(7.96±1.35)μg/L、(1.58±0.91) mg/L(t=21.705、18.493,均P＜0.05),而两组治疗后血清可溶性CD40L、hs-CRP浓度均较治疗前明显降低(均P＜0.01).结论 血清可溶性CD40L、hs-CRP参与了不稳定型心绞痛的病理生理过程,可以作为反映易损斑块的指标,阿托伐他汀钙片可通过降低血清可溶性CD40L、hs-CRP而加强粥样硬化斑块的稳定性.     

Increased circulating platelet-derived microparticles are associated with stent-induced vascular inflammation

Inflammation as well as platelet activation at the site of local vessel-wall injury plays an essential role in the mechanism of restenosis after Percutaneous coronary intervention (PCI). Platelet-derived microparticles (PDMPs) released from activated platelets are thought to play a role in the inflammatory process, possibly interacting with leukocyte integrin Mac-1. We serially measured circulating PDMPs, high-sensitive C-reactive protein (hs-CRP) and activated Mac-1 on the surface of neutrophils in 61 patients undergoing coronary stenting. PDMPs, hs-CRP and Mac-1 increased after coronary stenting in a time-dependent manner with the maximum response at 48 h in coronary sinus blood (PDMPs: 10.3+/-8.9-32.8+/-13.8 U/ml; P<0.001, hs-CRP: 0.27+/-0.23-1.46+/-0.99 mg/dl; P<0.001, activated Mac-1, 134+/-19% relative increase, P<0.001). PDMPs were correlated with hs-CRP (R=0.58, P<0.001) and the relative increase in Mac-1 (R=0.69, P<0.001) 48 h after coronary stenting. Multiple regression analysis showed that each of PDMPs (R=0.40, P<0.05), hs-CRP (R=0.33, P<0.05) and Mac-1 (R=0.48, P<0.01) was an independent predictor of the late lumen loss. Coronary stenting enhanced circulating PDMPs in association with an inflammatory response in the injured vessel wall. PDMPs may be a useful marker for evaluation of stent-induced inflammatory status and a powerful predictor of restenosis equivalent to activated Mac-1.