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.

Frauke Degenhardt, Rafael Struck, Tanja Meyer-Treschan, Peter Kienbaum, Matthias Heringlake, Julika Schoen, Michael Sander, Sascha Treskatsch, Thorsten Smul, Ewa Wolwender, Thomas Schilling, Georg Baumgarten, Andre Franke, Soeren Mucha, Lukas Tittmann, Madeline Kohlhaas, Georg Fuernau, Oana Brosteanu, Dirk Hasenclever, Kai Zacharowski, Patrick Meybohm, Jan Roesner, Christian Stoppe, Matthias Gruenewald, Berthold Bein, Jochen Renner, Jochen Cremer, Mark Coburn, Gereon Schaelte, Andreas Boening, Bernd Niemann, Frank Kletzin, Sabine Westphal, Ulrich Strouhal, Christian Reyher, Rita Laufenberg-Feldmann, Marion Ferner, Ivo F Brandes, Martin Bauer, Andreas Kortgen, Sebastian N Stehr, Maria Wittmann

Journal: BMC cardiovascular disorders 2019;19(1):26

PMID: 30678657

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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) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10 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.

Address: 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.; Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.; Department of Anaesthesiology, Intensive Care Medicine, Emergency Medicine and Pain Therapy, Asklepios Klinik St. Georg, Hamburg, Germany.; Department of Cardiovascular Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.; Department of Cardiovascular Surgery, University of Giessen, Giessen, Germany.; Clinic of Anaesthesiology and Intensive Care Medicine, University Hospital Rostock, Rostock, Germany.; Department of Anaesthesiology and Intensive Care, Suedstadt Hospital Rostock, Rostock, Germany.; Department of Anesthesiology, Medical Center of Johannes Gutenberg-University, Mainz, Germany.; Department of Anaesthesiology and Intensive Care Medicine, University Hospital Goettingen, Goettingen, Germany.; Department of Anaesthesiology and Intensive Care, Klinikum Region Hannover, Hannover, Germany.; Department of Anaesthesiology and Intensive Care Medicine and Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.; Department of Anesthesiology and Intensive Care Medicine, University Hospital Leipzig, Leipzig, Germany.; Department of Anaesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.; Department of Anaesthesiology and Intensive Care Medicine, Johanniter Hospital Bonn, Bonn, Germany.; Department of Anaesthesiology and Intensive Care Medicine, University Hospital Duesseldorf, Duesseldorf, Germany.; Department of Anaesthesiology and Intensive Care Medicine, University Luebeck, Luebeck, Germany.; Department of Anaesthesiology and Intensive Care Medicine, Hospital Neuruppin, Neuruppin, Germany.; Department of Anaesthesiology and Intensive Care, University of Giessen, Giessen, Germany.; Department of Anaesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.; Department of Anaesthesiology, University Hospital Wuerzburg, Wuerzburg, Germany.; Institute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.; University Heart Center Luebeck, Medical Clinic II (Cardiology/Angiology/Intensive Care Medicine), University Hospital Schleswig-Holstein, Luebeck, Luebeck, Germany.; Clinical Trial Centre, University Leipzig, Leipzig, Germany.; Institute for Medical Informatics, Statistics and Epidemiology, University Leipzig, Leipzig, Germany.; Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt, Germany. [email protected].

DOI: 10.1186/s12872-019-1002-x

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MeSH Terms: Acute Kidney Injury, Aged, Atrial Fibrillation, Cardiac Surgical Procedures, Cytoskeletal Proteins, Delirium, Dual-Specificity Phosphatases, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, HSC70 Heat-Shock Proteins, Humans, Male, Middle Aged, Mitogen-Activated Protein Kinase Phosphatases, Multicenter Studies as Topic, Myocardial Infarction, Phosphoprotein Phosphatases, Polymorphism, Single Nucleotide, Randomized Controlled Trials as Topic, Risk Factors, Ryanodine Receptor Calcium Release Channel, Stroke, Treatment Outcome