国产替格瑞洛与进口替格瑞洛对冠心病患者血小板抑制率影响

目的 比较同等剂量国产替格瑞洛（泰仪）与进口替格瑞洛（倍林达）对冠心病患者血小板抑制率的影响。方法 纳入2019年3月～2020年9月于西京医院心内科拟诊为冠心病的住院患者,近1月未服用过替格瑞洛或氯吡格雷。患者随机被分为泰仪组（试验）（泰仪180 mg负荷剂量,之后90 mg,2次/d）和倍林达组（对照）（倍林达180 mg负荷剂量,之后90 mg,2次/d）,共纳入患者200例,试验组和对照组各100例。两组无论入院前是否服用过阿司匹林,均给予阿司匹林100 mg,1次/d。均随访1个月。患者分别于服用替格瑞洛负荷剂量后2 h和服用第4次药物后8 h行血栓弹力图（TEG）检测,以评估国产和进口替格瑞洛对血小板的抑制效果。结果 根据TEG测定的血小板抑制效果,林达组和泰仪组不敏感（无效）的比例为3(3.0%)和4(4.0%);临床起效（药物起效和较好抑制）的比例为97(97.0%)和96(96.0%),两组间无统计学差异。第4次服药8 h后倍林达组和泰仪组不敏感（无效）的比例为5(5.0%)和3(3.0%),临床起效（药物起效和较好抑制）的比例为85(85.0%)和84(84.0%)...     

急性冠状动脉综合征合并糖尿病患者经皮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研究

目的应用血栓弹力图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(DM)患者经皮冠状动脉介入(PCI)术后抗血小板治疗的疗效和预后。方法入选2016年6月至2017年1月期间在陕西省第四人民医院心血管内科住院治疗的ACS合并DM患者100例。采用前瞻性、随机对照的研究方法,按随机数字表分为两组:氯吡格雷组和替格瑞洛组,每组50例。PCI术后24~48 h行血栓弹力图检测,比较两组花生四烯酸(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以及最大血凝块幅度(MAADP)。术后随访6个月,比较两组主要不良心血管事件(MACE)、出血事件和呼吸困难的发生率。采用SPSS 19.0软件进行数据处理。根据数据类型,分别采用t检验或x~2检验进行组间比较。结果与氯吡格雷组相比,替格瑞洛组AA抑制率[(72.3±26.6)%vs(54.0±31.4)%,P=0.041]和ADP抑制率[(76.5±22.1)%vs(43.4±28.7)%,P=0.016]均显著增高,MAADP幅度显著降低[(33.2±10.5)vs(48.2±13.6)mm,P=0.024]。替格瑞洛组AA抑制率50%(14.0%vs38.0%,P=0.006)和ADP抑制率30%(6.0%vs28.0%,P=0.003)的患者数量显著低于氯吡格雷组。术后6个月替格瑞洛组MACE发生率较氯吡格雷组显著降低(8.2%vs 22.9%,P=0.045);两组出血事件和呼吸困难发生率间差异无统计学意义。结论对于ACS合并DM患者,PCI术后服用替格瑞洛的抗血小板疗效明显优于氯吡格雷。     

氯吡格雷弱代谢患者改服替格瑞洛的安全性及临床疗效观察

目的　探讨氯吡格雷弱代谢患者改服替格瑞洛的临床疗效及安全性。方法　以本院心内科2014年2月至2014年12月期间住院行PCI术后存在氯吡格雷弱代谢的136例患者为研究对象,按照随机对照原则将其分为替格瑞洛组和氯吡格雷组,每组各68例。两组患者分别予以替格瑞洛（90　mg,2次/天）或氯吡格雷（150　mg,1次/天）治疗。治疗3天后予以复查血栓弹力图,并对血小板抑制率进行评价。随访半年,观察主要不良心血管事件（MACE）及出血事件发生情况。结果　治疗3天后替格瑞洛组ADP抑制率高于氯吡格雷组,ADP诱导的血小板-纤维蛋白凝块强度（MA_ADP）低于氯吡格雷组（P<0.05）。两组患者不良事件发生率比较差异无统计学意义（P>0.05）。两组患者随访期间均无严重出血事件、心血管死亡事件发生。氯吡格雷组出现1例支架内血栓形成,1例非致死性心肌梗死。结论　替格瑞洛应用于氯吡格雷弱代谢患者中起效迅速,抗血小板效果良好,严重并发症小,与氯吡格雷具有同样的安全性,值得在临床上推广。     

应用血栓弹力图评估ACS患者替格瑞洛与氯吡格雷抗血小板的疗效

目的通过血栓弹力图(TEG)检测血小板聚集率,观察接受双联抗血小板药物治疗的急性冠状动脉综合征(ACS)患者应用替格瑞洛或氯吡格雷的抗血小板疗效。方法选取清华大学第一附属医院心脏中心住院的84例急性冠状动脉综合征患者,随机分为两组,氯吡格雷组(n=42)与替格瑞洛组(n=42),通过TEG检测方法比较两组患者服用氯吡格雷和替格瑞洛后的血小板抑制率情况。结果氯吡格雷组中11例出现氯吡格雷抵抗,发生率为26.19%,替格瑞洛组中1例患者出现替格瑞洛抵抗,发生率为2.38%,两组发生率的比较差异有统计学意义(χ2=9.722,P=0.002);氯吡格雷组中有1例(2.38%)发生阿司匹林抵抗;替格瑞洛组中有2例(4.76%)发生阿司匹林抵抗,两者发生率比较差异无显著统计学意义(χ2=0.346,P=0.557)。结论接受标准抗血小板治疗的部分急性冠状动脉综合征患者存在抗血小板抵抗,TEG监测结果显示,替格瑞洛的抗血小板聚集效果明显优于氯吡格雷。     

老年冠心病患者服用替格瑞洛与氯吡格雷出血风险比较

目的比较≥70岁老年冠心病患者院外服用替格瑞洛与氯吡格雷时发生出血事件的风险。方法本研究连续入选2014年1月至2015年3月期间在解放军总医院心血管内科因急性冠脉综合征(ACS)住院并行冠状动脉支架植入术的患者597例。根据选择的双联抗血小板方案分为两组:替格瑞洛组(同时服用替格瑞洛和阿司匹林,n=99)和氯吡格雷组(同时服用氯吡格雷和阿司匹林,n=498)。随访1年,比较两组患者的出血风险,并分析影响出血事件的危险因素。结果替格瑞洛组患者出血事件的发生率显著高于氯吡格雷组(25.3%vs14.5%),差异具有统计学意义(P=0.008),且两组患者的Ⅰ型出血事件发生率间差异具有统计学意义(P=0.015),而Ⅱ型出血事件发生率间差异无统计学意义(P=0.261)。用药期间共有263例患者行血栓弹力图(TEG)检测,其中替格瑞洛组77例和氯吡格雷组186例。与氯吡格雷组相比,替格瑞洛组患者的二磷酸腺苷(ADP)抑制率显著增加[(80.29±20.67)%vs(61.65±26.81)%,P0.001]、ADP诱导的最大振幅(MA_(ADP))显著降低[(25.28±14.28)vs(36.41±16.20)mm,P0.001]。替格瑞洛组中MA_(ADP)31 mm的患者(68.8%vs40.3%,P0.001)以及此类患者中发生出血事件者(24.5%vs10.7%,P=0.037)均显著高于氯吡格雷组。多因素logistic回归分析表明,低体质量指数(BMI)(OR=0.910,95%CI:0.842~0.984,P=0.018)和高血压病(OR=1.301,95%CI:1.036~1.635,P=0.024)是≥70岁老年冠心病患者服用双联抗血小板药物期间发生出血事件的独立危险因素。结论老年冠心病患者口服替格瑞洛的出血风险比氯吡格雷高,且低BMI与高血压病患者更易发生出血事件,因此选用双联抗血小板治疗方案时应充分考虑危险因素并行TEG监测,以减少出血事件的发生。     

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。     

血栓弹力图评价替格瑞洛和氯吡格雷在急性ST段抬高型心肌梗死中抗血小板的疗效

目的:通过血栓弹力图评价替格瑞洛和氯吡格雷在急性ST段抬高型心肌梗死(STEMI)中抗血小板的疗效。方法:60例STEMI患者分为两组,阿司匹林+氯吡格雷组(Ⅰ组,n=30)和阿司匹林+替格瑞洛组(Ⅱ组,n=30),于抗血小板药物负荷剂量给药2 h后和维持治疗3个月后,使用血栓弹力图检测花生四烯酸(AA)途径和二磷酸腺苷(ADP)受体途径诱导的血小板抑制率。结果:抗血小板药物负荷剂量给药2 h后和维持治疗3个月后,Ⅱ组ADP受体途径诱导的血小板抑制率均明显高于Ⅰ组[(54.67±5.83)%对(45.75±16.72)%,P0.05;(59.53±12.18)%对(45.10±16.26)%,P0.05],AA途径诱导的血小板抑制率两组间无明显差异,患者的出血和缺血事件发生率两组间无明显差异。结论:替格瑞洛较氯吡格雷在STEMI治疗中能更快速充分地抑制血小板,血栓弹力图可用于指导STEMI患者抗血小板治疗。     

冠心病患者外周血单核细胞表面晚期糖基化终末产物受体水平的表达

目的探讨外周血单核细胞表面晚期糖基化终末产物受体(RAGE)的表达水平与冠心病患者临床表现及冠状动脉病变严重程度的关系,并评估其对冠心病患者风险的预测价值.方法 选择因胸痛住院并行冠状动脉造影的患者80例,据其不同临床表现、冠状动脉病变的Gensini积分、病变血管支数进行相应分组,采用流式细胞学方法测定外周血单核细胞表面RAGE水平.结果 急性心肌梗死组、不稳定型心绞痛组外周血单核细胞表面RAGE表达水平均高于稳定型心绞痛组和对照组(P＜0.01).RAGE水平与高敏C反应蛋白水平呈正相关(r=0.476,P=0.01);多支病变组和两支病变组外周血单核细胞表面RAGE表达水平高于单支病变组(P＜0.05);多支病变组RAGE水平高于两支病变组(P＜0.05);根据冠状动脉造影Gensini评分分为三组,三组间外周血单核细胞表面RAGE水平逐渐升高,且各组间差异均具有统计学差异.外周血单核细胞表面RAGE水平与冠状动脉造影评分之间呈正相关(r＝0.376,P=0.007);采用Logistic回归法分析高水平的外周血单核细胞表面RAGE水平是冠心痛患者发生急性冠状动脉综合征的独立危险因素(OR=1.180,P=0.02).结论 冠心病患者外周血单核细胞表面RAGE表达水平明显增加,且随着临床表现严重程度的增加呈逐渐升高趋势,对冠心病患者的临床表现有预测价值.外周血单核细胞RAGE水平与冠状动脉病变狭窄程度相关,对冠状动脉病变严重程度有一定的预测价值.高水平外周血单核细胞RAGE的表达是冠心痛患者临床表现严重程度的独立危险因素.     

糖基化终末产物对冠心病患者支架术后再狭窄的影响

目的探讨糖基化终末产物(AGEs)对经皮冠状动脉介入(PCI)术后1年再狭窄率的影响。方法择期PCI治疗的患者依据AGEs水平的平均值分成低AGEs和高AGEs组,记录介入血管支数,支架数目、再狭窄发生率。结果两组基础状态包括性别、年龄、高血压病史等均无统计学差异(P0.05),两组间介入血管支数,支架数目无统计学差异(P0.05)。两组间PCI术后再狭窄发生率存在明显差异。结论 AGEs增加冠心病患者PCI术后1年再狭窄发生率。     

糖基化终末产物与冠心病相关性的临床观察

目的探讨糖基化终末产物与冠心病的相关性。方法分别检测正常对照组、冠心病组、糖尿病组及冠心病合并糖尿病组的血清糖基化终末产物、糖化血红蛋白,并进行相关分析。结果各观察组血清糖基化终末产物均较正常对照组升高,且各组间的差异有显著性(P<0.05),糖基化终末产物与糖化血红蛋白呈正相关(r=0.738,P=0.000)。结论血清糖基化终末产物与冠心病具有相关性,并且是糖尿病心血管合并症的相关危险因素。     

冠心病并代谢综合征患者血清糖基化终末产物的水平及其临床意义

目的:研究冠心病并代谢综合征(MS)患者血清糖基化终末产物(AGE)含量的变化及其临床意义。方法:选择单纯MS患者(A组)32例,单纯冠心病患者(B组)36例,冠心病并MS患者(C组)39例和正常对照(D组)28例。对所有受试者测量其身高、体重、腰围(WC)、臀围(HC);测血脂、空腹血糖(FBG)、胰岛素(FIN)、AGE;计算体质指数(BMI)、腰臀比(WHR)、胰岛素抵抗指数(HOMA-IR)并进行比较。结果:A、B、C组患者的FIN、HOMA-IR、AGE均高于D组,C组的HOMA-IR、AGE分别高于A、B组。直线相关分析显示,HOMA-IR与BMI、WC、TG、FBG、FIN和AGE呈正相关,与HDL呈负相关。结论:冠心病并MS患者AGE的表达异常升高。     

Association between serum levels of soluble receptor for advanced glycation end products and circulating advanced glycation end products in type 2 diabetes

Aims/hypothesis Activation of the receptor for advanced glycation end products (RAGE, also known as AGE-specific receptor [AGER]) has been implicated in the development of diabetic vascular complications. Blockade of RAGE using a soluble form of the receptor (sRAGE) suppressed vascular hyperpermeability and atherosclerosis in animal models. Since little is known about the regulation of endogenous sRAGE levels, we determined whether serum sRAGE is influenced by circulating AGEs and the severity of nephropathy in type 2 diabetic patients.Materials and methods We recruited 150 healthy control and 318 diabetic subjects. Diabetic subjects were subdivided into those with proteinuria, microalbuminuria or normoalbuminuria. Serum sRAGE was assayed by ELISA and serum AGEs by competitive ELISA using a polyclonal rabbit antiserum raised against AGE-RNase.Results Diabetic subjects had higher sRAGE (1,029.5 pg/ml [766.1–1,423.0] interquartile range vs 1,002.6 [726.5–1,345.3], p<0.05) and AGEs (4.07±1.13, SD, unit/ml vs 3.39±1.05, p<0.01) than controls. Proteinuric subjects had the highest sRAGE levels and there was a significant trend between the severity of nephropathy and sRAGE (p=0.01). In diabetic subjects, serum log(sRAGE) correlated with AGEs (r=0.27, p<0.001), log(plasma creatinine) (r=0.31, p<0.001), log(urine AER) (r=0.24, p<0.01) and log(triglycerides) (r=0.15, p<0.01). On stepwise linear regression analysis, AGEs and creatinine levels were the main independent determinants of sRAGE concentration.Conclusions/interpretation Serum sRAGE levels and circulating AGEs are associated with the severity of nephropathy in type 2 diabetic patients. Prospective studies are required to determine whether endogenous sRAGE potentially influences the development of diabetic vascular complications.     

冠心病患者血清糖基化终产物水平升高的意义

目的探讨糖基化终产物(AGEs)与冠心病的关系。方法分别运用荧光法和ELISA法测定冠心病患者血清F-AGE和E-AGE水平,并与健康人、糖尿病患者比较。结果35例冠心病患者血清F-AGE和E-AGE水平分别为(10.4±0.6)U/ml和(14.7±1.8)U/ml,明显高于健康人［分别为(7.5±0.2)U/ml,P<0.01和（8.6±1.5)U/ml,P<0.0001］;但与糖尿病患者差异无显著性［分别为(11.0±0.3)U/ml,P>0.05和(18.1±1.3)U/ml,P>0.05)］。结论增高的AGEs水平可能与冠心病发病有密切关系。     

Role of advanced glycation end products in cardiovascular disease

Advanced glycation end products(AGEs) are produced through the non enzymatic glycation and oxidation of proteins,lipids and nucleic acids.Enhanced formation of AGEs occurs particularly in conditions associated with hyperglycaemia such as diabetes mellitus(DM).AGEs are believed to have a key role in the development and progression of cardiovascular disease in patients with DM through the modif ication of the structure,function and mechanical properties of tissues through crosslinking intracellular as well as extracellular matrix proteins and through modulating cellular processes through binding to cell surface receptors [receptor for AGEs(RAGE)].A number of studies have shown a correlation between serum AGE levels and the development and severity of heart failure(HF).Moreover,some studies have suggested that therapies targeted against AGEs may have therapeutic potential in patients with HF.The purpose of this review is to discuss the role of AGEs in cardiovascular disease and in particular in heart failure,focussing on both cellular mechanisms of action as well as highlighting how targeting AGEs may represent a novel therapeutic strategy in the treatment of HF.     

The different roles for the advanced glycation end products axis in heart failure and acute coronary syndrome settings

AimsThis work aimed to compare the behavior of the advanced glycation end products (AGEs) and their soluble receptor (sRAGE) in two cohorts of patients: those with heart failure (HF) and acute coronary syndrome (ACS).Methods and resultsA unicentric observational clinical study was performed in 102 patients with ACS and 102 patients with chronic HF matched by age and gender. At inclusion, fluorescent AGEs were measured by quantitative fluorescence spectroscopy of plasma, and total sRAGE and endogenous secretory RAGE (esRAGE) levels were determined by enzyme-linked immunosorbent assay kits. A 5-year follow-up period was established for recording cardiac death (primary endpoint) and the incidence of non-fatal myocardial infarction or HF readmission (secondary endpoints). Higher glycation parameters were observed in HF patients, whereas no differences in sRAGE forms were found between HF and ACS cohorts, except for cRAGE, which was higher in HF. Associations between glycation parameters and sRAGE forms were observed in HF, but not in ACS. Differences were also evidenced in the long-term prognosis of each cohort: esRAGE showed an independent prognostic value for cardiac death or non-fatal cardiovascular events in HF, but none of the AGE–RAGE variables were predictors in ACS.ConclusionsA different role for the AGE–RAGE axis was observed in HF and ACS. All the sRAGE forms were directly related with glycation parameters in HF, but not in ACS. The independent value of the sRAGE forms on each cardiovascular disease was supported by esRAGE being an independent predictor of bad long-term prognosis only for HF.     

糖基化终末产物与肝病

肝脏是糖基化终末产物的主要代谢部位,肝病时伴随的氧化应激、糖耐量损害以及肝肾功能降低导致糖基化终末产物增加,而糖基化终末产物可通过促进氧应激/脂质过氧化、炎症反应以及纤维化等途径,加重肝脏损伤。     

高级糖基化终末产物的合成及其与疾病的关系

高级糖基化终末产物(advanced glycation end products,AGEs)是由蛋白或者脂质暴露于还原糖中而形成的一组复杂且具有异质性的物质.该物质可通过内源性或外源性途径形成,大体可分为6种.AGEs可在不同种类的细胞内累积,影响细胞内及细胞外的结构和功能,同时它还可以通过和细胞表面的受体作用,通过信号传导,引发一系列的病理生理过程.AGEs沉积在细胞内,影响细胞功能,导致糖尿病血管并发症的发生.AGEs还与各种肿瘤的生物学特性相关,它可以修饰热休克蛋白27或者与AGEs受体相结合来影响肿瘤细胞的生长和浸润.AGEs的抑制物,如OPB-9195,可抑制这一系列病理生理过程.     

Elevated levels of serum advanced glycation end products in patients with non-alcoholic steatohepatitis

BACKGROUND AND AIM: Advanced glycation end products (AGE), senescent macroprotein derivatives formed at an accelerated rate in diabetes, play important roles in the pathogenesis of diabetic vascular complications. Recently, AGE have also been found to be involved in insulin resistance. Although non-alcoholic steatohepatitis (NASH) is generally considered a hepatic manifestation of insulin resistance, there are no reports showing the link of AGE to NASH. The aim of this study was to evaluate the clinical significance of AGE in patients with NASH. METHODS: Glyceraldehyde-derived AGE levels were assayed from serum obtained from 106 patients: 66 with NASH, 10 with simple steatosis, and 30 controls. RESULTS: Serum glyceraldehyde-derived AGE levels (U/mL) were significantly elevated in NASH patients (9.78 +/- 3.73) compared with simple steatosis (7.17 +/- 2.28, P = 0.018) or healthy controls (6.96 +/- 2.36, P = 0.003). Moreover, these were inversely correlated with adiponectin, an adipocytokine with insulin-sensitizing and anti-inflammatory properties. In addition, immunohistochemistry of glyceraldehyde-derived AGE showed intense staining in the livers of NASH patients. CONCLUSION: The present data suggest that the sustained increase of glyceraldehyde-derived AGE could at least in part contribute to the pathogenesis of NASH. The serum glyceraldehyde-derived AGE level may be a useful biomarker for discriminating NASH from simple steatosis.