Department of Anesthesiology, Michigan Medicine, Ann Arbor (N.J.D., A.L., C.M.B., S.K., M.E., M.R.M.).
Division of Cardiovascular Medicine, Department of Internal Medicine (I.S.), University of Michigan, Ann Arbor.
Circ Genom Precis Med. 2020 Aug;13(4):e002817. doi: 10.1161/CIRCGEN.119.002817. Epub 2020 Jun 9.
While postoperative myocardial injury remains a major driver of morbidity and mortality, the ability to accurately identify patients at risk remains limited despite decades of clinical research. The role of genetic information in predicting myocardial injury after noncardiac surgery (MINS) remains unknown and requires large scale electronic health record and genomic data sets.
In this retrospective observational study of adult patients undergoing noncardiac surgery, we defined MINS as new troponin elevation within 30 days following surgery. To determine the incremental value of polygenic risk score (PRS) for coronary artery disease, we added the score to 3 models of MINS risk: revised cardiac risk index, a model comprised entirely of preoperative variables, and a model with combined preoperative plus intraoperative variables. We assessed performance without and with PRSs via area under the receiver operating characteristic curve and net reclassification index.
Among 90 053 procedures across 40 498 genotyped individuals, we observed 429 cases with MINS (0.5%). PRS for coronary artery disease was independently associated with MINS for each multivariable model created (odds ratio=1.12 [95% CI, 1.02-1.24], =0.023 in the revised cardiac risk index-based model; odds ratio, 1.19 [95% CI, 1.07-1.31], =0.001 in the preoperative model; and odds ratio, 1.17 [95% CI, 1.06-1.30], =0.003 in the preoperative plus intraoperative model). The addition of clinical risk factors improved model discrimination. When PRS was included with preoperative and preoperative plus intraoperative models, up to 3.6% of procedures were shifted into a new outcome classification.
The addition of a PRS does not significantly improve discrimination but remains independently associated with MINS and improves goodness of fit. As genetic analysis becomes more common, clinicians will have an opportunity to use polygenic risk to predict perioperative complications. Further studies are necessary to determine if PRSs can inform MINS surveillance.
尽管经过几十年的临床研究，术后心肌损伤仍然是发病率和死亡率的主要驱动因素，但仍难以准确识别有风险的患者。遗传信息在预测非心脏手术后心肌损伤（MINS）中的作用尚不清楚，需要大规模的电子健康记录和基因组数据集。
在这项对接受非心脏手术的成年患者进行的回顾性观察性研究中，我们将 MINS 定义为手术后 30 天内新的肌钙蛋白升高。为了确定多基因风险评分（PRS）对冠状动脉疾病的增量价值，我们将该评分添加到 3 种 MINS 风险模型中：修订后的心脏风险指数、完全由术前变量组成的模型和包含术前加术中变量的模型。我们通过接受者操作特征曲线下面积和净重新分类指数评估有无 PRS 的表现。
在 40498 名接受基因分型的个体的 90053 例手术中，我们观察到 429 例 MINS（0.5%）病例。对于每个创建的多变量模型，冠状动脉疾病的 PRS 与 MINS 独立相关（比值比=1.12[95%CI，1.02-1.24]，=0.023 在基于修订后的心脏风险指数的模型中；比值比，1.19[95%CI，1.07-1.31]，=0.001 在术前模型中；比值比，1.17[95%CI，1.06-1.30]，=0.003 在术前加术中模型中）。添加临床危险因素可提高模型的区分度。当 PRS 与术前和术前加术中模型一起使用时，多达 3.6%的手术被转移到新的结局分类中。
PRS 的添加并未显著提高区分度，但仍与 MINS 独立相关，并可改善拟合优度。随着基因分析变得越来越普遍，临床医生将有机会利用多基因风险来预测围手术期并发症。还需要进一步的研究来确定 PRS 是否可以告知 MINS 的监测。
