血小板膜糖蛋白I b的基因多态性与心肌梗塞发生关系的研究

目的　评价我国人群心肌梗塞的发生与血小板膜糖蛋白 (glycoprotein,GP)Ib基因多态性的关系。方法　采用病例对照研究 ,选择 10 0例确诊心肌梗塞的患者 (急性或陈旧性 )和 10 4例无心脏病史者作对照 ,用PCR SSP的方法进行血小板GPIbα链的基因多态性检测。结果　对照组无Met/Met纯合子 ,Thr/Met占 16.3 % ;心肌梗塞组Thr/Met Met/Met共占 3 0 % ,与对照组相比 ,P =0 .0 2 ,比数比 (oddsratio,OR)为 2 .2 (95 %可信区间 1.1～4 .3 )。在≤60岁发生心肌梗塞的患者Thr/Met Met/Met之和的频率(42 .2 % )更明显高于≤ 60岁的对照组 (14 .5 % ) (P =0 .0 0 2 ,OR =4 .3 ,95 %可信区间1.7～10 .8)。结论　血小板GPIb中Met等位基因与心肌梗塞之间呈显著的相关性 ,在≤60岁的人中 ,此种相关性更强。     

High on-treatment platelet reactivity by ADP and increased risk of MACE in good clopidogrel metabolizers

High on-treatment platelet reactivity (HPR) by ADP, which primarily reflects the effect of thienopyridines, has been found to be an independent predictor of ischemic events in patients with acute coronary syndrome (ACS) on dual antiplatelet therapy. CYP2C19*2 is associated with HPR by ADP. The aim of our study was to evaluate if high on-clopidogrel platelet reactivity (HPR) by ADP is associated with an increased risk of major adverse coronary events (MACE) after ACS independent of CYP2C19*2 allele, i.e. whether genotyping patients for CYP2C19*2 polymorphism is sufficient to identify those to be switched to novel antiplatelets. A total of 1187 patients were included (CYP2C19 *1/*1 n?=?892; *1/*2 n?=?264; *2/*2 n?=?31); 76 MACE (CV death and non-fatal MI) were recorded in non-carriers of CYP2C19*2 (8.5%) and 39 in carriers of CYP2C19*2 (13.2%). At the landmark analysis in the first 6 months, HPR by ADP and CYP2C19*2 allele were both significantly and independently associated with MACE [HPR by ADP: HR?=?2.0 (95% CI 1.2–3.4), p?=?0.01; CYP2C19*2 allele: HR?=?2.3 (95% CI 1.3–3.9), p?=?0.003]. At the land mark analysis from 7 to 12 months, only HPR by ADP remained significantly associated with the risk of MACE [HPR by ADP: HR?=?2.7 (95% CI 1.4–5.3), p?=?0.003; CYP2C19*2: HR?=?0.8 (95% CI 0.2–1.1), p?=?ns]. CYP2C19*2 allele and HPR by ADP are both independently associated with an increased risk of MACE in the first 6 months after ACS. HPR by ADP is associated with an increased risk until 12 months of follow-up. Therefore, both phenotype and genotype are clinically relevant for the evaluation of the antiplatelet effect of clopidogrel and for the prognostic stratification of ACS patients.     

ADP-induced Platelet Aggregation in Young Female Survivors of Acute Myocardial Infarction and Their Female Controls

ABSTRACT Adenosine diphosphate (ADP)-induced platelet aggregation was studied in 35 young female survivors of acute myocardial infarction (AMI) 14–46 (median 30) months after the infarction. The results were compared to those obtained for 35 control females of comparable age. Five different final ADP concentrations (0.2–1.0 μM) were employed, and the object was to assess the slope for the primary wave of aggregation as well as the threshold ADP concentration for secondary aggregation. The results showed that AMI patients and control subjects did not differ with respect to the primary wave of aggregation. However, secondary platelet aggregation was recorded to a significantly higher extent (p<0.02) in AMI patients than in their controls. The results therefore support the concept that enhanced platelet reactivity is present in patients with documented ischemic heart disease.     

Is TRAP-6 suitable as a positive control for platelet reactivity when assessing response to clopidogrel?

Adenosine 5′-diphosphate (ADP) inducible aggregation is used to assess platelet response to thienopyridines. Thrombin receptor-activating peptide-6 (TRAP-6) inducible aggregation may serve as a positive control because it acts via the thrombin receptor protease-activating receptor-1, which is not blocked by thienopyridines. We therefore investigated if TRAP-6 is suitable as a positive control when assessing residual platelet reactivity to ADP. Platelet response to clopidogrel was assessed in 200 patients on dual antiplatelet therapy using ADP inducible platelet aggregation by light transmission aggregometry (LTA), multiple electrode aggregometry (MEA), and the shear-dependent Impact-R. Test specificities were monitored by TRAP-6 inducible platelet aggregation. The aggregation-independent vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay served for comparisons. ADP inducible aggregation was correlated to that by TRAP-6 (r = 0.33 to 0.72; p < 0.001 for all assays). A linear correlation was seen within MEA (r = 0.72). LTA TRAP-6 correlated weakly with the VASP assay (r = 0.19; p = 0.01), while there were no correlations of TRAP-6 responses by MEA or the Impact-R with the VASP assay (r = 0.03 and ?0.09; p > 0.05). In all three assays, differences between ADP and TRAP-6 inducible aggregation varied considerably. Within MEA, TRAP-6 inducible aggregation was almost always stronger than ADP inducible aggregation, while within LTA and the Impact-R, weak responses to ADP were associated with both, weak and strong responses to TRAP-6. In conclusion, the application of TRAP-6 as a positive control for platelet reactivity has major limitations and results need to be cautiously interpreted on an individual basis.     

血小板受体糖蛋白Ⅲa基因与心肌梗塞关系的研究

目的探讨血小板受体糖蛋白（ＧＰＩＩａ）基因变异与心肌梗塞（ＭＩ）发病的关系。方法运用变性梯度凝胶电泳（ＤＧＧＥ）技术对４０例ＭＩ患者和相应数量健康人作对照行ＧＰＩＩａ基因全部外显子筛查。同时,以ＲＦＬＰ和ＡＳＯ技术检测８２例ＭＩ和６８例健康人对照的ＧＰＩＩａ基因ＰｌＡ多态性,并与５０例美国健康白种人比较。结果发现ＧＰＩＩａ基因外显子５中存在核苷酸静止突变;１５０例中国人的ＧＰＩＩａＰＩＡ多态基因型均为ＰｌＡ１／ＰｌＡ１,与美国白种人比较,差异有显著性。结论表明中国人群的血小板受体ＧＰＩＩａ基因与ＭＩ发病无相关性。     

急性下壁心肌梗死的高危合并症

目的 评价急性下壁心肌梗死及其高危合并症的临床意义。方法 总结214例住院急性心肌梗死患者,其中下壁心肌梗死104例,全部病例在病史,心电图改变及心肌酶谱均符合急性心肌梗死的诊断标准,单纯下壁梗死64例,下壁及正后壁梗死21例,下壁及右心室梗死6例,下壁右心室及正后壁梗死4例,前壁加下壁梗死4例,下壁及高侧壁梗死5例。结果 主要合并症有高度房室传导阻滞18例,前壁缺血23例,右心室梗死出现低血压状态5例,下壁心肌梗死出现高危合并症者住院病死率为17%,而无合并症的住院病死率是8.6%。结论 下壁心肌梗死出现上述三大并发症提示梗死面积较大,病死率高,预后差。     

P物质前体与血小板活化及血小板参数的相关性

目的探讨P物质前体(Pro-SP)与血小板活化及血小板参数的相关性。方法总共纳入心内科患者76例,根据急性心肌梗死诊断标准将患者分为非急性心肌梗死组(39例)和急性心肌梗死组(38例)。采用流式细胞仪测定血小板-单核细胞聚集体(PMA)形成率评估血小板活化程度,酶联免疫吸附实验测定Pro-SP浓度。比较Pro-SP与PMA形成率及血小板参数相关性,以及两组间Pro-SP差异。结果 Pro-SP与PMA形成率(Pearson相关系数为0. 407,P0. 001)、血小板分布宽度(Pearson相关系数为0. 269,P=0. 018)呈正相关,与血小板总数、血小板平均容积、血小板比积、大血小板比例不相关(P0. 05)。多元线性回归分析显示Pro-SP是PMA形成率的独立影响因素,急性心肌梗死组Pro-SP较非急性心肌梗死组显著升高(P0. 05)。结论 Pro-SP与血小板活化正相关,且与血小板分布宽度呈正相关,与血小板总数、血小板平均容积、血小板比积、大血小板比例不相关(P0. 05)。     

血小板糖蛋白受体ⅠaC807T基因多态性与心肌梗死关系的研究

目的 :检测中国人群血小板糖蛋白 （GP）受体 a C80 7T基因多态性 ,以明确中国人群血小板 GP a C80 7T的基因型 ,并探讨其多态性与心肌梗死 （MI）之间的关系。方法 :提取人基因组 DNA,应用引物序列特异性多聚酶链反应 （SSP- PCR）技术对小于 6 0岁的 MI患者 72例和对照者 70例分别进行血小板 GP受体 a C80 7T基因多态性检测。结果 :中国人群血小板 GP a C80 7T具 3种基因型 （TC,CC,TT） ,MI患者 T等位基因携带频率明显高于对照组 （6 4 % vs4 7% ,P<0 .0 5 ）。结论 :年龄小于 6 0岁的 MI患者 T等位基因携带频率高 ,血小板膜 GP a受体的遗传性差异在 MI发病中可能具有重要作用     

Plasma Levels of Platelet Factor 4 in Patients Admitted to a Coronary Care Unit

Blood was obtained from 63 consecutive patients within a 24 h period after the admission to a coronary care unit for the determination of plasma platelet factor 4 (PF-4) concentration. 28 of the subjects proved to have an acute myocardial infarction (MI), 24 had evidence of ischaemic heart disease (IHD) but no MI, and the remaining 11 patients had no signs of IHD. 40 healthy subjects served as controls. The mean PF-4 value in the MI group was 10.5 ±0.8 ng/ml. The corresponding values for patients with and without IHD were 8.7 ±0.6 and 8.3 ±0.6 ng/ml, respectively. The control mean (5.4 ±0.3 ng/ml) was significantly lower (P < 0.001) than the means for all 3 groups of patients studied. The difference between the group of MI patients and patients with IHD as well as patients without IHD was only of borderline significance (0.10 > P > 0.05).     

Platelet Number and Volume during Myocardial Infarction in Relation to Infarct Size

ABSTRACT Platelet number and mean platelet volume (MPV) were measured in 100 patients with acute chest pain, 41 with acute myocardial infarction (AMI), 33 with angina pectoris (AP) and 26 with non-coronary event (NCE), and compared with 21 controls. We found no significant difference in platelet count on admission in the patient groups, but it was lower compared with controls. There were no significant differences in MPV between the patient groups nor between patients and controls. Thirty patients with AMI were followed for 10 days and showed an initial 12% fall in platelet count followed by a 36% increase. Initially there was an increase in MPV (2%) followed by a fall (8%). The fall in platelet count and increase in MPV correlated with infarct size (maximum activity of lactate dehydrogenase (LDH)) and might reflect consumption of platelets. The precise role of platelets in the process of infarction is still unknown.     

ADP-induced Platelet Aggregation and Metoprolol Treatment of Myocardial Infarction Patients

ABSTRACT The effect of metoprolol on platelet aggregation was investigated in a group of postmyocardial infarction (MI) patients. The study was double-blind and included 63 subjects; 30 patients were maintained on metoprolol and 33 received placebo treatment. Adenosine diphosphate (ADP)-induced platelet aggregation was carried out in each subject close to 4 weeks after the acute MI. It was demonstrated that metoprolol as compared to placebo did not influence ADP-induced platelet aggregation in the present clinical setting.     

Prediction of degree of residual stenosis in coronary thrombolysis

In order to predict the residual stenosis in coronary thrombolysis, the factors easily obtained from clinical history--age, gender, history of angina before acute myocardial infarction (AMI), family history, hypertension, diabetes, hypercholesterolemia, smoking, and interval between onset of AMI and recanalization--were observed in 114 patients with successful coronary thrombolysis. In 55 patients with angina before AMI, 29 patients had residual stenosis greater than or equal to 75% and 26 patients had residual stenosis less than 75%. In 59 patients without angina before AMI, 15 patients had residual stenosis greater than or equal to 75%, and 44 patients had residual stenosis less than 75%. The presence or absence of angina before AMI was the main variable that discriminated the groups of residual stenosis of more or less than 75%, which was the only significant independent variable to predict the residual stenosis. These data suggest that the presence of angina pectoris before AMI is likely to be associated with a significant degree of residual stenosis after thrombolysis.