Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt, Germany.
Department of Anaesthesiology, Medical Faculty, RWTH Aachen, University Aachen, Aachen, Germany.
BMC Cardiovasc Disord. 2019 Jan 24;19(1):26. doi: 10.1186/s12872-019-1002-x.
The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery.
We conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery.
A total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance (PHLPP2, rs78064607, p = 3.77 × 10) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10 from the GWAS.
We identified several potential loci, in particular PHLPP2, BBS9, RyR2, DUSP4 and HSPA8, associated with new-onset of atrial fibrillation, delirium, myocardial infarction, acute kidney injury and stroke after cardiac surgery.
The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.
本研究旨在确定与心脏手术后并发症相关的遗传变异。
我们进行了一项前瞻性、双盲、多中心、随机试验（RIPHeart）。我们对 RIPHeart 研究队列中的 1170 名男女患者（871 名男性，299 名女性）进行了全基因组关联研究（GWAS）。纳入非紧急心脏手术的患者。主要终点包括直到出院时的心房颤动、谵妄、非致命性心肌梗死、急性肾衰竭和/或任何新中风的二元复合并发症发生率，术后最多 14 天。
共有 547,644 个经基因分型的标记物可用于分析。经过质量控制和临床协变量调整后，一个 SNP 达到全基因组显著水平（PHLPP2，rs78064607，p=3.77×10），GWAS 中还有 139 个（调整了所有其他结局）SNP 显示出与 p<1×10 有希望的关联。
我们确定了几个潜在的位点，特别是 PHLPP2、BBS9、RyR2、DUSP4 和 HSPA8，与心脏手术后新发心房颤动、谵妄、心肌梗死、急性肾损伤和中风有关。
该研究在 ClinicalTrials.gov 上注册为 NCT01067703，于 2010 年 2 月 11 日前瞻性注册。
