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BMC Cardiovasc Disord. 2019 Jan 24;19(1):26. doi: 10.1186/s12872-019-1002-x.

Genome-wide association study of myocardial infarction, atrial fibrillation, acute stroke, acute kidney injury and delirium after cardiac surgery - a sub-analysis of the RIPHeart-Study.

Author information

1
Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt, Germany.
2
Department of Anaesthesiology, Medical Faculty, RWTH Aachen, University Aachen, Aachen, Germany.
3
Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
4
Department of Anaesthesiology, Intensive Care Medicine, Emergency Medicine and Pain Therapy, Asklepios Klinik St. Georg, Hamburg, Germany.
5
Department of Cardiovascular Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
6
Department of Cardiovascular Surgery, University of Giessen, Giessen, Germany.
7
Clinic of Anaesthesiology and Intensive Care Medicine, University Hospital Rostock, Rostock, Germany.
8
Department of Anaesthesiology and Intensive Care, Suedstadt Hospital Rostock, Rostock, Germany.
9
Department of Anesthesiology, Medical Center of Johannes Gutenberg-University, Mainz, Germany.
10
Department of Anaesthesiology and Intensive Care Medicine, University Hospital Goettingen, Goettingen, Germany.
11
Department of Anaesthesiology and Intensive Care, Klinikum Region Hannover, Hannover, Germany.
12
Department of Anaesthesiology and Intensive Care Medicine and Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
13
Department of Anesthesiology and Intensive Care Medicine, University Hospital Leipzig, Leipzig, Germany.
14
Department of Anaesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.
15
Department of Anaesthesiology and Intensive Care Medicine, Johanniter Hospital Bonn, Bonn, Germany.
16
Department of Anaesthesiology and Intensive Care Medicine, University Hospital Duesseldorf, Duesseldorf, Germany.
17
Department of Anaesthesiology and Intensive Care Medicine, University Luebeck, Luebeck, Germany.
18
Department of Anaesthesiology and Intensive Care Medicine, Hospital Neuruppin, Neuruppin, Germany.
19
Department of Anaesthesiology and Intensive Care, University of Giessen, Giessen, Germany.
20
Department of Anaesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
21
Department of Anaesthesiology, University Hospital Wuerzburg, Wuerzburg, Germany.
22
Institute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
23
University Heart Center Luebeck, Medical Clinic II (Cardiology/Angiology/Intensive Care Medicine), University Hospital Schleswig-Holstein, Luebeck, Luebeck, Germany.
24
Clinical Trial Centre, University Leipzig, Leipzig, Germany.
25
Institute for Medical Informatics, Statistics and Epidemiology, University Leipzig, Leipzig, Germany.
26
Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt, Germany. patrick.meybohm@kgu.de.

Abstract

BACKGROUND:

The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery.

METHODS:

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.

RESULTS:

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- 8) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10- 5 from the GWAS.

CONCLUSIONS:

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.

TRIAL REGISTRATION:

The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.

KEYWORDS:

Acute kidney injury; Atrial fibrillation; Cardiac surgery; Delirium; Genome-wide association study; Myocardial infarction; Stroke

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