剑三玩家npc故事:JAMA：特殊因子提高冠状动脉支架内血块形成风险

据10月26日刊《美国医学会杂志》（JAMA）上的一则研究披露，带有某些基因或与使用抗凝血药物氯吡格雷有关的特别因子的患者，更可能在支架放置后不久在其冠状动脉支架内出现凝血块。

根据文章的背景资料：“安放支架的经皮冠状动脉介入治疗（PCI；人们用诸如球囊血管成形术或支架放置等术疗来打开狭窄的冠状动脉）已经成为心肌血管重建术的治疗标准，特别是在病人存在不稳定性冠心病的情况下。尽管使用双重抗血小板治疗（DAPT；阿司匹林和氯吡格雷）可减少80%以上的PCI后的心血管事件，但确定性的支架血栓形成（血块）仍然令人担忧。”支架血栓形成可以是一种致命的（死亡率可高达40%）且不可预知的PCI的并发症。大多数的支架血栓形成发生在支架放置后的第一个月，它们被定义为早期支架血栓形成。

巴黎Pitie-Salpetriere 医院的Guillaume Cayla, M.D., Ph.D.及其同事开展了一项对与确定性早期支架血栓形成有关的临床和遗传因素的分析。这项于2007年1月至2010年5月间在法国的10个中心内开展的研究包括了123名接受了PCI并有确定性早期支架血栓形成（发生在支架放置后30天内）的患者和他们的DNA样本，这些患者及DNA样本与246名没有发生支架血栓症的对照者进行了年龄和性别的匹配。检测的主要结果是对带有23种遗传变异者发生早期支架血栓的预测准确性。

研究人员进行了多变量分析以确定哪些临床、血管造影和遗传变量独立地与早期支架血栓形成的发生有关系。在对15个不同基因内的23个遗传变异的调查中，研究人员发现，3个与氯吡格雷代谢和血小板功能有关的基因型（CYP2C19、 ABCB1和 ITGB3）是早期支架血栓形成的独立风险因子。文章的作者还发现了早期支架血栓形成的2个可能被更改的因子：氯吡格雷的负荷剂量及氯吡格雷与质子泵抑制剂的相互作用。与处于最低三分位数中的患者相比，那些在应用某种临床与遗传学组合模型中的处于最高三分位数（3组中的1组）中的患者发生早期支架血栓的风险会增加7倍。

研究人员写道：“我们的研究增加了对接受氯吡格雷治疗并有发生早期支架血栓形成风险患者的遗传特征的理解。”

“将遗传因子与临床因子相结合可改善支架血栓形成的风险度分层。但基于这种综合性风险度分层而对治疗进行调整，是否能改善接受了PCI的病人的预后还需要在将来在独立群组研究中得到确认。”（生物谷 Bioon.com）

doi:10.1001/jama.2011.1529
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Clinical, Angiographic, and Genetic Factors Associated With Early Coronary Stent Thrombosis

Cayla, Guillaume; Hulot, Jean-Sébastien; O’Connor, Stephen A.; Pathak, Atul; Scott, Stuart A.; Gruel, Yves; Silvain, Johanne; Vignalou, Jean-Baptiste; Huerre, Yves; de la Briolle, Axel; Allanic, Frédérick; Beygui, Farzin; Barthélémy, Olivier; Montalescot, Gilles; Collet, Jean-Philippe

Context Despite dual antiplatelet therapy, stent thrombosis remains a devastating and unpredictable complication of percutaneouscoronary intervention (PCI).Objective To perform a sequential analysis of clinical and genetic factors associated with definite early stent thrombosis.Design, Setting, and Participants Case-control study conducted in 10 centers in France between January 2007 and May 2010 among 123 patients undergoing PCIwho had definite early stent thrombosis and DNA samples available, matched on age and sex with 246 stent thrombosis–free controls.Main Outcome Measure Accuracy of early stent thrombosis prediction by 23 genetic variants.Results Among the 23 genetic variants investigated in 15 different genes, the significant determinants of early stent thrombosiswere CYP2C19 metabolic status (adjusted odds ratio [OR], 1.99; 95% CI, 1.47-2.69), ABCB1 3435 TT genotype (adjusted OR, 2.16; 95% CI, 1.21-3.88), and ITGB3 PLA2 carriage (adjusted OR, 0.52; 95% CI, 0.28-0.95). Nongenetic independent correlates were acuteness of PCI (adjusted OR, 3.05;95% CI, 1.54-6.07), complex lesions (American College of Cardiology/American Heart Association type C) (adjusted OR, 2.33;95% CI, 1.40-3.89), left ventricular function less than 40% (adjusted OR, 2.25; 95% CI, 1.09-4.70), diabetes mellitus (adjustedOR, 1.82; 95% CI, 1.02-3.24), use of proton pump inhibitors (adjusted OR, 2.19; 95% CI, 1.29-3.75), and higher clopidogrelloading doses (adjusted OR, 0.73; 95% CI, 0.57-0.93). The discriminative accuracy of the clinical-only model was similar tothat of a genetic-only model (area under the curve, 0.73 [95% CI, 0.67-0.78] vs 0.68 [95% CI, 0.62-0.74], respectively; P = .34). A combined clinical and genetic model led to a statistically significant increase in the discriminatory power ofthe model compared with the clinical-only model (area under the curve, 0.78 [95% CI, 0.73-0.83] vs 0.73 [95% CI, 0.67-0.78];P = .004).Conclusions This case-control study identified 3 genes (CYP2C19, ABCB1, and ITGB3) and 2 clopidogrel-related factors (loading dose and proton pump inhibitors) that were independently associated with earlystent thrombosis. Future studies are needed to validate the prognostic accuracy of these risk factors in prospective cohorts.