Kowalik Maciej Michał, Lango Romuald, Siondalski Piotr, Chmara Magdalena, Brzeziński Maciej, Lewandowski Krzysztof, Jagielak Dariusz, Klapkowski Andrzej, Rogowski Jan
Department of Cardiac Anesthesiology, Medical University of Gdansk, Gdańsk, Poland.
Department of Cardiac and Vascular Surgery, Medical University of Gdansk, Gdańsk, Poland.
Acta Biochim Pol. 2018;65(2):241-250. doi: 10.18388/abp.2017_2361. Epub 2018 Apr 25.
There is increasing evidence that genetic variability influences patients' early morbidity after cardiac surgery performed using cardiopulmonary bypass (CPB). The use of mortality as an outcome measure in cardiac surgical genetic association studies is rare. We publish the 30-day and 5-year survival analyses with focus on pre-, intra-, postoperative variables, biochemical parameters, and genetic variants in the INFLACOR (INFLAmmation in Cardiac OpeRations) cohort. In a prospectively recruited cohort of 518 adult Polish Caucasians, who underwent cardiac surgery in which CPB was used, the clinical data, biochemical parameters, IL-6, soluble ICAM-1, TNFα, soluble E-selectin, and 10 single nucleotide polymorphisms were evaluated for their association with 30-day and 5-year mortality. The 30-day mortality was associated with: pre-operative prothrombin international normalized ratio, intra-operative blood lactate, postoperative serum creatine phosphokinase, and acute kidney injury requiring renal replacement therapy (AKI-RRT) in logistic regression. Factors that determined the 5-year survival included: pre-operative NYHA class, history of peripheral artery disease and severe chronic obstructive pulmonary disease, intra-operative blood transfusion; and postoperative peripheral hypothermia, myocardial infarction, infection, and AKI-RRT in Cox regression. Serum levels of IL-6 and ICAM-1 measured three hours after the operation were associated with 30-day and 5-year mortality, respectively. The ICAM1 rs5498 was associated with 30-day and 5-year survival with borderline significance. Different risk factors determined the early (30-day) and late (5-year) survival after adult cardiac surgery in which cardiopulmonary bypass was used. Future genetic association studies in cardiac surgical patients should account for the identified chronic and perioperative risk factors.
越来越多的证据表明，基因变异性会影响使用体外循环（CPB）进行心脏手术后患者的早期发病率。在心脏外科基因关联研究中，将死亡率作为结果指标的情况很少见。我们发表了关于INFLACOR（心脏手术中的炎症反应）队列的30天和5年生存分析，重点关注术前、术中和术后变量、生化参数以及基因变异。在一个前瞻性招募的518名成年波兰白种人队列中，他们接受了使用CPB的心脏手术，评估了临床数据、生化参数、白细胞介素-6（IL-6）、可溶性细胞间黏附分子-1（ICAM-1）、肿瘤坏死因子α（TNFα）、可溶性E-选择素以及10个单核苷酸多态性与30天和5年死亡率的关联。在逻辑回归中，30天死亡率与术前凝血酶原国际标准化比值、术中血乳酸、术后血清肌酸磷酸激酶以及需要肾脏替代治疗的急性肾损伤（AKI-RRT）相关。在Cox回归中，决定5年生存率的因素包括：术前纽约心脏协会（NYHA）分级、外周动脉疾病和严重慢性阻塞性肺疾病史、术中输血；以及术后外周体温过低、心肌梗死、感染和AKI-RRT。术后三小时测量的血清IL-6和ICAM-1水平分别与30天和5年死亡率相关。ICAM1基因的rs5498与30天和5年生存率相关，具有临界显著性。不同的风险因素决定了使用体外循环的成人心脏手术后的早期（30天）和晚期（5年）生存率。未来针对心脏手术患者的基因关联研究应考虑已确定的慢性和围手术期风险因素。
