高负荷剂量氯吡格雷对急性冠脉综合征患者介入治疗后血清sCD40L和hs-CRP浓度的影响

目的探讨高负荷剂量氯吡格雷对急性冠脉综合征(acute coronary syndrome,ACS)患者介入治疗后血清sCD40L和高敏C反应蛋白(high-sensitivity C-reactive protein,hs-CRP)水平的影响。方法选择ACS患者190例分为高负荷剂量组94例(首剂负荷剂量600 mg,以后每天氯吡格雷150 mg,共用7 d,而后以每天氯吡格雷75 mg维持治疗)和标准剂量组96例(首剂负荷剂量300 mg,以后每天氯吡格雷75 mg维持治疗)。于服氯吡格雷前,经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗前,术后第1天,术后第7天,术后第30天血清sCD40L和hs-CRP的浓度,并记录患者术后1、3、6个月发生主要心血管事件、出血事件的情况。结果高负荷剂量组PCI治疗后不同时间点血清可溶性CD40配体(sCD40L)、hs-CRP浓度均低于标准剂量组,差异有统计学意义(P<0.05)。sCD40L与hs-CRP的变化趋势的相关性检验结果显示两者呈正相关(皮尔森相关系数r=0.128,P<0.001)。结论高剂量氯吡格雷比标准剂量氯吡格雷对sCD40L、hs-CRP的抑制作用更强;当氯吡格雷抑制炎症反应产物hs-CRP产生的同时也会抑制炎症产物sCD40L的产生。     

氯吡格雷抵抗患者血妊娠相关蛋白A、肿瘤坏死因子-α的变化

目的:观察冠心病支架置入后发生氯吡格雷抵抗的患者术前、术后血清妊娠相关蛋白A(PAPP-A)和肿瘤坏死因子-α(TNF-α)水平的变化及意义。方法:选取因冠心病不稳定型心绞痛住院并成功接受冠状动脉支架置入术的患者102例,分别于术前、术后24h抽取外周血,根据比浊法检测ADP诱导的血小板聚集率结果,分为氯吡格雷抵抗组和正常反应组。酶联免疫法测定血清PAPP-A和TNF-α水平,分析氯吡格雷不同反应性的发生与PAPP-A和TNF-α水平的关系。结果:冠状动脉介入术后24h氯吡格雷抵抗的发生率为33.3%,氯吡格雷抵抗组患者术后24h血清PAPP-A水平(73·8±34mIU·L-1)与术前(47·6±37·3mIU·L-1)和正常反应组术后(22·5±6·3mIU·L-1)比较,差异均有统计学意义(P<0·05),TNF-α水平有升高趋势,但差异无统计学意义。其中血PAPP-A水平(r=1.216,P<0·05)与氯吡格雷抵抗的发生密切相关。结论:冠状动脉支架术后对氯吡格雷具有不同反应性的患者血PAPP-A、TNF-α水平存在差异,PAPP-A可能与氯吡格雷抵抗事件的发生有关。     

氯吡格雷抑制急性冠状动脉综合征患者血小板释放可溶性CD40配体

目的 探讨在非ST段抬高急性冠状动脉综合征(non-ST-segment elevation acute coronary syndromes,NSTEACS)患者短期应用氯吡格雷是否有抑制ADP诱导血小板释放可溶性CD40配体(sCD40L)的作用.方法 NSTEACS 42例,患者服用氯吡格雷6～8 d,治疗前后采静脉血,提取富含血小板血浆(platelet rich plasma,PRP)并用二磷腺苷诱导血小板聚集和释放sCD40L,在不同时间点终止反应,用酶联免疫法测量sCD40L浓度,进行自身前后对照.结果 治疗前后血浆sCD40L分别为(0.20±0.16)μg/L和(0.19±0.18)μg/L(P＞0.05);治疗前后PRP受ADP诱导后20 min释放的sCDdOL浓度分别为(4.3±2.5)μg/L和(2.8±1.9)μg/L(P＜0.001),诱导后40 min释放的sCD40L浓度分别为(5.3±3.1)μg/L和(2.9±1.6)μg/L(P＜0.001).结论 短期应用氯吡格雷可能对非ST段抬高急性冠状动脉综合征患者血小板炎症凶子sCD40L释放具有抑制作用,提示氯吡格雷很可能具有抗炎效应.     

急性冠脉综合征患者氯吡格雷抵抗的影响因素

目的评价急性冠状动脉综合征(ACS)患者氯吡格雷抵抗的发生情况及其可能的影响因素。方法所有入选患者均给予阿司匹林100mg/d,氯吡格雷负荷剂量300mg及维持量75mg/d,于服氯吡格雷前、服药后24h分别测定二磷酸腺苷(ADP,浓度25#mol/L)诱导的血小板聚集率,计算血小板聚集抑制率〔△A〕。△A≤10%(包括负值)时考虑存在氯吡格雷抵抗。结果102例ACS患者,其中△A≤10%(包括负值)者43例(42.2%),急性非ST段抬高心肌梗死及置入支架患者氯吡格雷抵抗的发生率高。结论ACS和冠状动脉介入治疗后的抗血栓治疗中,部分患者存在氯吡格雷抵抗。其发生与患者的疾病状态及是否置入支架明显相关。     

冠心病患者PCI术后氯吡格雷抵抗的发生率及其影响因素

目的：探讨冠心病患者冠状动脉介入治疗术（PCI）后氯吡格雷抵抗的影响因素。方法：159例行PCI术治疗的冠心病患者,术前予氯吡格雷300 mg负荷剂量治疗,术后予75 mg/d持续治疗。测其服药前、术后24 h和术后5 d以5 μmol/L的二磷酸腺苷诱导的血小板最大聚集率。以血小板聚集抑制率≤10%定义为氯吡格雷抵抗,分为氯吡格雷抵抗组（抵抗组,n=48）和对氯吡格雷反应正常组（正常组,n=111）,比较两组临床基本资料、相关常规检查、手术资料,Logistic回归分析氯吡格雷抵抗的独立危险因素。结果：159例患者中发生氯吡格雷抵抗48例,氯吡格雷抵抗发生率为30.2%。两组患者吸烟比例、并发糖尿病、三酰甘油水平的差异均有统计学意义（均P〈0.05）,两组患者手术资料各项参数比较差异无统计学意义。Logistic回归分析结果显示氯吡格雷抵抗的独立危险因素有糖尿病、长期吸烟。三酰甘油水平无统计学意义。结论：糖尿病、长期吸烟是冠心病患者PCI术后发生氯吡格雷抵抗的独立危险因素。     

氯吡格雷对冠心病患者PCI前后CD40配体的影响

目的：探讨冠心病患者血小板膜CD40配体（CD40L）和血清可溶性CD40配体（sCD40L）在冠脉内介入治疗（PCI）前后的变化及其临床意义。方法：选择30例经冠状动脉造影确诊为冠心病的患者,接受规范的抗心绞痛治疗,术前给予氯吡格雷75mg／d,行PCI术前及术后6h,采用流式细胞仪测定患者活化血小板CD40L的表达率,采用酶联免疫吸附法测定血清sCD40L的含量。结果：30例冠心病患者PCI术前血小板CD40L的表达率水平为（3．73±2．15）％,术后6h为（2．46±0．90）％,较术前显著降低（P〈0.01）。PCI术前血清sCD40L的含量为（11．72±4．25）ng／ml,术后6h为（9．98±3．32）ng／ml,较术前显著降低（P〈0.01）。结论：氯吡格雷降可低冠心病患者PCI术后早期血清和血小板膜CD40L的含量和表达,预防血栓栓塞事件发生。     

替格瑞洛对急性冠状动脉综合征患者经皮冠状动脉介入治疗后QT离散度及高敏C反应蛋白与可溶性CD40配体的影响

目的 探讨替格瑞洛对急性冠状动脉综合征(ACS)患者在经皮冠状动脉介入治疗(PCI)后QT离散度(QTd)以及对炎性因子高敏C反应蛋白(hs-CRP)、可溶性CD40配体(sCD40L)的影响.方法 抽取本院2017年1~12月接受PCI的ACS患者69例,随机分为对照组34例(口服氯吡格雷)、试验组35例(口服替格瑞洛),两组均使用阿司匹林行双联抗血小板聚集(DAPT)治疗1年.测量两组治疗前及术后24 h、1个月、1年QTd值以及静脉血hs-CRP、sCD40L值.术后6个月随访恶性心律失常的发生情况.结果 术后24 h,试验组QTd值及hs-CRP、sCD40L水平均低于对照组[(42.66±4.32)比(46.61±4.86),(3.73±0.39)mg/L比(4.06±0.42)mg/L,(593.94±61.69)ng/ml比(640.35±66.21)ng/ml](P<0.05);术后1个月,试验组QTd值及hs-CRP、sCD40L水平均低于对照组[(37.86±3.89)比(41.00±4.32),(1.87±0.21)mg/L比(2.03±0.22)mg/L,(417.20±43.21)ng/ml比(457.15±48.25)ng/ml](P<0.05);术后1年,试验组QTd值及hs-CRP、sCD40L水平均低于对照组[(32.19±3.35)比(37.36±3.81),(1.41±0.16)mg/L比(1.69±0.18)mg/L,(336.28±3.56)ng/ml比(387.96±3.91)ng/ml](P<0.05).术后6个月内,试验组恶性心律失常发生率(22.9%)小于对照组(47.1%)(P<0.05).结论 ACS患者PCI围术期应用替格瑞洛能显著缩短QTd,降低炎性因子hs-CRP、sCD40L水平,降低恶性心律失常发生率,显著改善预后.     

氯吡格雷不同给药方案预防支架内血栓形成疗效观察

目的比较冠心病介入治疗中氯吡格雷两种给药方案预防支架内血栓形成的有效性和安全性。方法对63例择期行冠状动脉介入治疗的患者进行回顾性分析。按照不同的氯吡格雷给药方案分为两组,观察组(29例)于术前48h及24h分别给予氯吡格雷300mg、225mg双重负荷量,以后按常规口服75mg/d;对照组(34例)于术前6h给予氯吡格雷300mg单负荷量,以后口服75mg/d。随访2~40个月,统计两组出现支架内急性、亚急性、晚期血栓形成以及出血并发症的情况。结果观察组比对照组支架内血栓形成比例明显减少,差异有统计学意义(0/29比3/34,P<0·05)。两组均未发生明显出血并发症。结论冠心病患者行择期冠状动脉介入治疗时,术前给予双重负荷量氯吡格雷安全、有效,能显著降低支架内血栓形成的风险,是值得进一步研究的给药方案。     

急性冠状动脉综合征合并2型糖尿病患者冠状动脉介入术后替格瑞洛与氯吡格雷抗血小板疗效及预后

目的应用血栓弹力图(TEG)评价替格瑞洛与氯吡格雷在急性冠状动脉综合征(ACS)合并糖尿病患者经皮冠状动脉介入治疗(PCI)后抗血小板的疗效及预后。方法纳入ACS合并糖尿病行PCI术的患者180例。随机分为两组,氯吡格雷组(n=92)术前接受负荷量阿司匹林300 mg+氯吡格雷300 mg,术后给予阿司匹林100mg/d,氯吡格雷75 mg/d;替格瑞洛组(n=88)术前接受负荷量阿司匹林300 mg+替格瑞洛180 mg,术后给予阿司匹林100 mg/d,替格瑞洛90 mg,每天两次。血栓弹力图检测两组患者PCI术后24 h花生四烯酸(AA)诱导的血小板抑制率和二磷酸腺苷(ADP)诱导的血小板抑制率,观察并比较两组3个月内不良心血管事件及出血等安全性事件。结果替格瑞洛组ADP激活血小板形成最大血凝块强度(MA-ADP),低于氯吡格雷组(34.94%±11.91%比47.16%±14.90%,P0.001)。血小板AA抑制率、ADP抑制率替格瑞洛组明显高于氯吡格雷组(68.24%±22.96%比48.21%±32.91%,58.16%±23.52%比33.34%±26.67%,P0.001)。结论 ACS合并2型糖尿病患者中,替格瑞洛抗血小板聚集的效果明显优于氯吡格雷,可显著降低3个月内心血管终点事件的发生率,不增加出血风险。     

经皮冠状动脉腔内介入围术期应用高维持剂量氯吡格雷对炎症因子的影响

目的:探讨高维持剂量(150 mg/d)氯吡格雷是否能抑制动脉粥样硬化炎症反应。方法:经Grace评分分级的高危急性冠状动脉综合征(ACS)患者80例,经皮冠状动脉腔内介入术(PCI)后随机分为氯吡格雷75 mg/d组(n=40)与氯吡格雷150 mg/d组(n=40),30 d后均以75 mg/d维持治疗。分别检测PCI术前、30 d的高敏C反应蛋白(hs-CRP)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平。随访术后6个月的主要不良心脏事件(MACE)及出血事件的发生情况。结果:1.氯吡格雷150 mg/d组和75 mg/d组,术前hs-CRP、IL-6、TNF-α水平比较差异无统计学意义(P>0.05);2.2组PCI术后30 d血清hs-CRP、IL-6、TNF-α水平均较术前显著降低(P<0.01),且氯吡格雷150 mg/d组较75 mg/d组对上述炎症因子的抑制程度更明显(P<0.05);3.2组MACE发生情况差异有统计学意义(P<0.05),而出血事件发生率差异无统计学意义(P>0.05)。结论:PCI围术期应用高维持剂量氯吡格雷,可以进一步抑制高危ACS患者动脉炎症反应而不增加出血风险,有助于降低短期MACE发生率。     

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.     

椎动脉支架置入术后sICAM-1、hs-CRP和TNF-α血清浓度的变化及其临床意义

目的 观察椎动脉支架置入术后血清炎性细胞因子的动态变化并探讨其临床意义.方法 纳入48例椎动脉支架置入术患者,以48例单纯接受脑血管造影的患者作为对照组,在支架置入(血管造影)前以及支架置入后24 h、48 h、3 d、1周和3周时检测血清可溶性细胞间黏附分子-1(soluble intercellular adhension molecule-1,sICAM-1)、高敏C-反应蛋白(high-sensitivity C-reactive protein,hs-CRP)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平.结果 与支架置入前相比,支架置入组支架置入后24 h时血清ks-CRP[(4.85 4±0.53)mg/L对(2.57±0.36)mg/L,P＜0.05]、TNF-α[(2.42±0.34)μg/L对(1.08±0.37)μg/L,P＜0.05]和sICAM-1[(449.43±47.16)μg/L对(269.15±37.46)μg/L,P＜0.05]水平均显著增高.hs-CRP水平在支架置入后48 h时达高峰[(6.24±0.59)mg/L],3周时[(2.51±0.29)mg/L]恢复至支架置入前水平[(2.57±0.36)mg/L];TNF-α水平支架置入后3 d时[(2.30±0.25)μg/L]达高峰,3周时[(1.89±0.13)μg/L]仍维持在较高水平;sICAM-1水平则持续升高至3周时[(296.95±59.72)μg/L].支架置入组支架置入后24 h血清hs-CRP、TNF-α和sICAM-1水平分别显著高于对照组造影后24 h时的(3.25±0.40)mg/L、(1.184±0.19)μg/L和(336.57±50.18)μg/L(P均＜0.05).结论 椎动脉支架置入术后血清hs-CRP、TNF-α和sICAM-1水平显著增高,提示支架置入引起了持续时间较长的炎症反应.

Abstract：

Objective To observe the dynamic changes of serum inflammatory factors after vertebral artery stenting and to investigate its clinical significance. Methods A total of 48 patients treated with vertebral artery stenting were included, and 48 patients only received cerebral angiography were used as a control group. The levels of soluble intercellular adhesion molecule-1 (sICAM-1), high-sensitivity C-reactive protein (hs-CRP) and tumor-necrosis factor-α (TNF-α) were detected before procedure (angiography), at 24 h, 48 h, 3 d, and 1 and 3 weeks after procedure (angiography). Results The serum levels of hs-CRP (4. 85 ± 0. 53 mg/L vs. 2. 57 ±0. 36 mg/L,P＜0. 05), TNF-α (2.42 ±0. 34 μg/L vs. 1. 08 ±0. 37 μg/L,P ＜0. 05) and sICAM-1 (449.43 ± 47. 16 μg/L vs. 269. 15 ± 37. 46 μg/L, P ＜ 0. 05) at 24 hours after procedure in the stenting group were significantly elevated compared with those before procedure. The Hs-CRP level (6.24 ± 0.59 mg/L) reached the peak at 48 hours after procedure. At week 3 (2. 51 ±0.29 mg/L), it returned to the level before procedure (2. 57 ±0. 36 mg/L); TNF-α level reached the peak at day 3 (2.30 ± 0.25 μg/L), and it remained higher level at week 3 (1. 89 ±0. 13 μg/L); the sICAM-1 level continued to rise at week 3 (296. 95 ± 59. 72 μg/L). The serum hs-CRP, TNF-α and sICAM-1 levels at 24 hours after procedure in the stenting group were significantly higher than those (3. 25 ±0.40 mg/L、J. 18 ±0. 19 μg/L and 336. 57 ± 50. 18μg/L) in the control group (all P＜0.05). Conclusions The serum hs-CRP, TNF-α, sICAM-1 levels were significantly elevated after vertebral artery stenting. It was suggested that the stenting caused a longer duration of inflammatory response.     

Increase in Interleukin-6 in the First Hour after Coronary Stenting: An Early Marker of the Inflammatory Response

Background: Inflammation after coronary stenting presages adverse outcomes after percutaneous coronary intervention (PCI). While changes in inflammatory markers have been defined 24–72 hours after PCI, potential changes during the first few hours have not. This study was designed to determine if a systemic inflammatory response could be measured within the first hour after stenting. Methods: Patients (n = 25) undergoing coronary stenting, with predominantly (n = 23) acute coronary syndromes were enrolled prospectively in this registry. Blood samples were collected before PCI, and 10 minutes, 1 hour and 18–24 hours later. No patient received a glycoprotein IIb-IIIa inhibitor. Concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), and interleukin-1 receptor antagonist (IL-1Ra) and soluble CD40 ligand (sCD40L) were measured using ELISA. Results: CRP and sCD40L did not change in the first hour after stenting. By contrast, IL-6 increased in the first hour (before = 7.6 ± 7.7 pg/ml, 1 hour = 12 ± 12 pg/ml; p < 0.001). The concentration of IL-1Ra tended to be greater after 1 hour (before = 426 ± 261 pg/ml, 1 hour = 511 ± 406 pg/ml; p = 0.11). Increase in IL-1Ra was apparent only in female subjects (p = 0.004 for the difference in trend between the two genders). A correlation was not observed between the increase in IL-6 at 1 hour and the increase in CRP at 24 hours (r = –0.21). Conclusions: In patients undergoing coronary stenting, increase in IL-6 can be detected 1 hour after PCI, and thus IL-6 may be an early initiator of the systemic inflammatory response to stenting.     

冠状动脉支架置入术后血浆P-选择素水平的动态变化

目的观察经皮冠状动脉支架置入术(CS)后血浆P-选择素水平的动态变化,并分析其机制和意义。方法选择2003年9月至2004年9月我院行CS的患者为研究对象(n=30),同时选择一组同期进行冠状动脉造影(CAG)的患者作为对照(n=26),CS组于术前1h及术后1h,4h,24h,48,1周采静脉血;CAG组于术前1h及术后1h,4h,24h采静脉血。采用流式细胞术测定血小板表面-选择素的表达。结果CS组患者术后血浆P-选择素水平显著高于术前(P<0·05)。造影前后血浆-选择素水平差异无统计学意义。结论冠状动脉支架置入术后血浆P-选择素水平升高可能是局部急性炎症反应增强的表现。     

Soluble CD40 ligand is an early initiator of inflammation after coronary intervention

BACKGROUND: This prospective study evaluated the early increase in markers of inflammation after coronary stenting, and the predictors of early rise. Elevation of markers of inflammation after percutaneous coronary intervention correlates with an increased risk of adverse events. The role of soluble CD40 ligand (sCD40L) as a potential initiator of inflammation after stenting has not been described. METHODS: Seventy-five patients were treated with heparin alone (n=25), or randomized to adjuvant treatment with eptifibatide (n=26) or abciximab (n=24) during stenting. Systemic blood was obtained before coronary stenting and at 10 min after stenting. C-reactive protein (CRP), interleukin (IL)-6, IL-1 receptor antagonist and sCD40L were determined by enzyme liberated immunosorbent assay. RESULTS: sCD40L exhibited the greatest relative rise (35%, P=0.01 compared to concentrations before intervention) in the first 10 min after stenting. In a logistic regression model, an early increase in the concentration of sCD40L was predicted by baseline laboratory values (white blood count and sCD40L level before stenting) and procedural characteristics (number of stents and glycoprotein IIb-IIIa inhibitor assignment). CONCLUSIONS: In conclusion, a systemic inflammatory response is detectable 10 min after coronary stent placement. The early increase in sCD40L suggests a possible role for this marker in the initiation of inflammation after coronary stenting.     

Pre-procedural plasma levels of C-reactive protein and interleukin-6 do not predict late coronary angiographic restenosis after elective stenting.

AIMS: Inflammatory markers may serve as an important prognostic predictor in patients with coronary heart diseases. In patients undergoing coronary interventions, it has been shown that baseline C-reactive protein (CRP) could predict late clinical restenosis. Only a few small studies have examined the possible relationship with angiographic restenosis. In patients with stable angina pectoris,we examined whether baseline CRP and IL-6 predict late coronary angiographic restenosis after stenting. METHODS AND RESULTS: Pre-procedural plasma levels of CRP and IL-6 were measured in 216 patients with stable angina pectoris undergoing elective coronary stenting. Angiographic follow-up was performed in all patients at 6 months. Baseline CRP levels were 6.15 +/- 0.78 mg/L versus 5.24 +/- 1.17 mg/L in the patent and restenosis groups, respectively (P=0.64). IL-6 levels were 0.46 +/- 0.03 ng/L versus 0.40 +/- 0.07 ng/L in the patent and restenosis groups, respectively (P=0.50). CRP levels were obtained again at the time of angiographic follow-up and were found to be similar in both groups (2.89 +/- 0.29 mg/L versus 2.61 +/- 0.63 mg/L, P=0.72). Moreover, in a sub-group of 43 patients, serial blood samples were obtained at several time points after the procedure up to 6 months. Both CRP and IL-6 plasma levels increased significantly in response to the procedure. CRP levels peaked at 3 days (11.27 +/- 1.53 mg/L versus 4.26 +/- 0.72 mg/L at baseline, P<0.0001). IL-6 levels reached maximum values after 24 h (1.08 +/- 0.14 ng/L versus 0.53 +/- 0.08 ng/L at baseline, P<0.0001). However, in this sub-group of patients, neither peak CRP nor IL-6 levels were found to predict late angiographic restenosis. CONCLUSIONS: Coronary stenting is associated with transient increases in both CRP and IL-6 levels. However, pre-procedural CRP and IL-6 levels do not predict late coronary angiographic restenosis.     

冠心病患者介入治疗后血CRP、MMP-9水平与预后的关系

目的：探讨冠心病（CHD）患者介入治疗前后外周血 C 反应蛋白（CRP）、基质金属蛋白酶-9（MMP-9s）水平变化,并分析其与患者预后之间的关系。方法：入选2009年7月～2011年4月在我院行冠脉支架植入术的CHD 患者278例为介入组,未行支架植入的 CHD 患者234例为 CHD 对照组。根据冠脉造影结果,介入组进一步分为单支（143例）、双支（92例）和三支病变组（43例）。比较两组患者不同时间 CRP、MMP-9水平变化,并分析其与冠脉病变及患者预后之间的关系。结果：与入院时比较,支架植入术后24h,48h,介入组患者 CRP [（2.43±0.62）mg/L 比（2.87±0.73）mg/L,（2.98±0.87）mg/L]、MMP-9水平[（12.63±2.68）ng/ml 比（14.62±3.49）ng/ml,（19.62±4.63）ng/ml]显著上升（P ＜0.05～＜0.01）;而术后第14d 与患者入院时差异无统计学意义,P ＞0.05;CHD 对照组患者在治疗过程中 CRP 和 MMP-9水平差异均无统计学意义,P ＞0.05;冠脉病变越严重,CRP、MMP-9水平越高,三支病变组的 CRP、MMP-9水平[（2.51±0.64）mg/L,（14.67±2.97）ng/ml]显著高于单支病变[（1.83±0.51）mg/L,（9.68±1.42）ng/ml]、双支病变组[（2.17±0.59）mg/L,（11.62±2.19） ng/ml],P ＜0.05～＜0.01;CRP≥3 mg/L、MMP-9≥15 ng/ml 者心血管事件发生率（33.3％、29.1％）分别显著高于 CRP ＜3 mg/L、MMP-9＜15 ng/ml 者（16.1％、18.2％）,差异均有统计学意义,P 均＜0.05。结论：冠心病患者行支架植入术后48h 内其血清 C 反应蛋白、基质金属蛋白酶-9水平显著升高,并且升高水平与冠脉病变程度及预后有关。     

Relationship between plasma inflammatory markers and platelet aggregation in patients with clopidogrel resistance after angioplasty

We evaluated the relationship between plasma inflammation markers and clopidogrel resistance in patients after stent implantation. The plasma levels of C-reactive protein (CRP), P-selectin, platelet soluble CD40 ligand (sCD40L), interleukin 6 (IL-6) and platelet aggregation were measured in 352 patients undergoing percutaneous coronary intervention (PCI) at baseline and after 6 months. The plasma levels of CRP, P-selectin, sCD40L, IL-6 was higher in 65 (18.5%) patients with clopidogrel resistance than in those with normal responsiveness at 6 months after PCI. There was a significant positive correlation between soluble CD40L levels and platelet aggregation (r = .28, P < .05). Diabetes (DM) and sCD40L level were independent predictors for unresponsiveness after stent implantation according to stepwise multivariate analyses. The hazard ratio (HR) for sCD40L level was 3.02 (95% CI = 1.28 to 3.25; P = .036) and for DM 2.53 (95% CI = 1.28 to 6.55, P = .03). We conclude that sCD40L and DM may influence clopidogrel resistance.     

急性冠状动脉综合征患者支架植入术后再狭窄与基质金属蛋白酶相关性的研究

目的 测定急性冠状动脉综合征(ACS)支架植入术后再狭窄患者动脉血基质金属蛋白酶(MMP)-3、-9及其组织抑制剂TIMI-1水平变化,初步分析支架内再狭窄与基质金属蛋白酶水平之间可能存在的相关性. 方法 132例ACS患者,分别收集其冠状动脉内支架植入术前和术后即刻、8、48 h和1周的股动脉血标本,采用酶联免疫吸附试验(ELISA)法检测MMP-3、MMP-9和TIMI-1水平;随访5～10个月后行冠状动脉造影,根据造影结果分为再狭窄组21例,非再狭窄组111例,均于造影术前股动脉采集动脉血标本重复指标测定.50例冠状动脉造影正常者为对照组. 结果 与对照组比较,ACS组动脉血MMP-3和MMP-9浓度明显升高[MMP-3:(15.99±4.30)ng/L与(4.86±2.98)ng/L,t=2.290,P=0.022;MMP-9:(1.41±3.06)ng/L与(3.79±1.46)ng/L,t=2.011,P=0.041],TIMP-1浓度有升高趋势.支架植入术后MMP-3和MMP-9水平均较术前明显升高,48 h达到高峰,1周时仍明显升高,TIMP-1水平也具有类似的变化,但高峰时间延迟.再狭窄组术前MMP-9水平较非再狭窄组升高[(17.94±6.44)ng/L与(9.93±2.19)ng/L,t=3.180,P=0.003],而两组间术前MMP-3和TIMP-1水平差异无统计学意义;随访时再狭窄组MMP-3和MMP-9水平均较非再狭窄组明显升高[MMP-3:(21.66±2.72)ng/L与(14.27±1.28)ng/L,t=2.181,P=0.033;MMP-9:(22.81±5.31)ng/L与(12.10±2.76)ng/L,t=2.108,P=0.039],而TIMP-1水平差异无统计学意义. 结论 动脉血MMP-3和MMP-9水平升高可能参与了ACS患者支架置入术后的病理、生理过程,并可能与术后再狭窄的发生有一定相关性.