Faraday Nauder, Martinez Elizabeth A, Scharpf Robert B, Kasch-Semenza Laura, Dorman Todd, Pronovost Peter J, Perler Bruce, Gerstenblith Gary, Bray Paul F, Fleisher Lee A
Critical Care Medicine and Department of Surgery (Vascular), Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Anesthesiology. 2004 Dec;101(6):1291-7. doi: 10.1097/00000542-200412000-00008.
Current perioperative cardiac risk assessment tools use historic and surgical factors to stratify patient risk. Polymorphisms in platelet glycoprotein (GP) IIIa and GPIbalpha are associated with myocardial ischemic risk in nonsurgical settings, but their relation to perioperative ischemia is unclear. The authors hypothesized that platelet genotype would be an independent predictor of postoperative myocardial ischemia and would improve risk assessment when added to clinical factors.
One hundred ninety-six patients who underwent infrainguinal, abdominal aortic, or thoracoabdominal vascular surgery were evaluated for clinical and genetic factors that might predict the development of postoperative myocardial ischemia. Genomic DNA was genotyped for the Leu33Pro polymorphism of GPIIIa and the Thr145Met polymorphism of GPIbalpha. Myocardial ischemic outcome was determined by review of the medical record for cardiac death or myocardial infarction and by surveillance troponin I and automated continuous 12-lead electrocardiographic analysis.
Sixty-five patients (33%) experienced one or more ischemic endpoints (2% death, 5% myocardial infarction, 20% troponin+, 22% electrocardiogram+). The Pro33 (adjusted odds ratio [OR], 2.4 [95% confidence interval, 1.2-6.2]) and Met145 (OR 3.4 [1.4-9.3]) genotypes were independent predictors of composite ischemic outcome by multivariate regression, as were diabetes mellitus (OR 4.0 [1.7-12.5]), abdominal aortic surgery (OR 4.1 [1.7-14.4]), and thoracoabdominal aortic surgery (OR 6.4 [2.7-23.8]). The addition of platelet gene polymorphisms to clinical factors improved fit (likelihood ratio testing chi-square = 13.5, P < 0.001) of an ischemia prediction model. The derived risk assessment tool had a receiver operator characteristic curve of 0.73 (0.65-0.81) compared with 0.64 (0.57-0.74) for a model excluding genetic factors (P = 0.04). A significant relation between the GPIbalpha polymorphism and ischemic outcome remained after excluding electrocardiographic ischemia from the composite endpoint.
Platelet polymorphisms are independent risk factors for postoperative myocardial ischemia and improve a risk prediction model when added to historic and surgical risk factors.
目前的围手术期心脏风险评估工具利用既往病史和手术因素对患者风险进行分层。血小板糖蛋白（GP）IIIa和GPIbalpha的多态性在非手术情况下与心肌缺血风险相关，但其与围手术期缺血的关系尚不清楚。作者推测血小板基因型将是术后心肌缺血的独立预测因素，并且在加入临床因素后可改善风险评估。
对196例行腹股沟下、腹主动脉或胸腹主动脉血管手术的患者评估可能预测术后心肌缺血发生的临床和遗传因素。对基因组DNA进行GPIIIa的Leu33Pro多态性和GPIbalpha的Thr145Met多态性基因分型。通过查阅心脏死亡或心肌梗死的病历记录以及监测肌钙蛋白I和自动连续12导联心电图分析来确定心肌缺血结局。
65例患者（33%）经历了一个或多个缺血终点（2%死亡，5%心肌梗死，20%肌钙蛋白阳性，22%心电图阳性）。通过多因素回归分析，Pro33（校正比值比[OR]，2.4[95%置信区间，1.2 - 6.2]）和Met145（OR 3.4[1.4 - 9.3]）基因型是复合缺血结局的独立预测因素，糖尿病（OR 4.0[1.7 - 12.5]）、腹主动脉手术（OR 4.1[1.7 - 14.4]）和胸腹主动脉手术（OR 6.4[2.7 - 23.8]）也是如此。将血小板基因多态性加入临床因素后改善了缺血预测模型的拟合度（似然比检验卡方 = 13.5，P < 0.001）。与排除遗传因素的模型（0.64[0.57 - 0.74]）相比，推导的风险评估工具的受试者工作特征曲线为0.73（0.65 - 0.81）（P = 0.04）。从复合终点中排除心电图缺血后，GPIbalpha多态性与缺血结局之间仍存在显著关系。
血小板多态性是术后心肌缺血的独立危险因素，在加入既往病史和手术危险因素后可改善风险预测模型。
