. 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

Sabine Westphal¹, Christian Stoppe², Matthias Gruenewald³, Berthold Bein^{4

3}, Jochen Renner³, Jochen Cremer⁵, Mark Coburn², Gereon Schaelte², Andreas Boening⁶, Bernd Niemann⁶, Frank Kletzin⁷, Jan Roesner⁸, Ulrich Strouhal¹, Christian Reyher¹, Rita Laufenberg-Feldmann⁹, Marion Ferner⁹, Ivo F Brandes¹⁰, Martin Bauer¹¹, Andreas Kortgen¹², Sebastian N Stehr¹³, Maria Wittmann¹⁴, Georg Baumgarten¹⁵, Rafael Struck¹⁴, Tanja Meyer-Treschan¹⁶, Peter Kienbaum¹⁶, Matthias Heringlake¹⁷, Julika Schoen¹⁸, Michael Sander¹⁹, Sascha Treskatsch²⁰, Thorsten Smul²¹, Ewa Wolwender²¹, Thomas Schilling²¹, Frauke Degenhardt²², Andre Franke²², Soeren Mucha²², Lukas Tittmann²², Madeline Kohlhaas¹, Georg Fuernau²³, Oana Brosteanu²⁴, Dirk Hasenclever²⁵, Kai Zacharowski¹, Patrick Meybohm²⁶; RIPHeart-Study Collaborators

Collaborators, Affiliations

Collaborators

RIPHeart-Study Collaborators:
Ana Stevanovic, Rolf Rossaint, Marc Felzen, Andreas Goetzenich, Tobias Moormann, Katharina Chalk, Pascal Knuefermann, Olaf Boehm, Andreas Hoeft, Michael Winterhalter, Sonja Iken, Christian Weber, Carolin Wiedenbeck, Gerhard Schwarzmann, Karin Pense, Andreas Zierer Stephan Fichtlscherer, Gerold Goerlach, Matthias Wollbrueck, Ursula Boening, Markus Weigand, Julia Strauchmann, Konrad August, Kai U Morsbach, Markus Paxian, Konrad Reinhard, Matthias Gruenewald, Jens Scholz, Ole Broch, Helga Francksen, Martin Albrecht, Bernd Kuhr, Hermann Heinze, Hauke Paarmann, Hans-Hinrich Sievers, Stefan Klotz, Thomas Hachenberg, Christian Werner, Susanne Mauff, Angela Alms, Stefan Bergt, Norbert Roewer

Affiliations

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.

PMID: 30678657
PMCID: PMC6345037
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

Sabine Westphal et al. BMC Cardiovasc Disord. 2019.

. 2019 Jan 24;19(1):26.

doi: 10.1186/s12872-019-1002-x.

Authors

Collaborators

RIPHeart-Study Collaborators:
Ana Stevanovic, Rolf Rossaint, Marc Felzen, Andreas Goetzenich, Tobias Moormann, Katharina Chalk, Pascal Knuefermann, Olaf Boehm, Andreas Hoeft, Michael Winterhalter, Sonja Iken, Christian Weber, Carolin Wiedenbeck, Gerhard Schwarzmann, Karin Pense, Andreas Zierer Stephan Fichtlscherer, Gerold Goerlach, Matthias Wollbrueck, Ursula Boening, Markus Weigand, Julia Strauchmann, Konrad August, Kai U Morsbach, Markus Paxian, Konrad Reinhard, Matthias Gruenewald, Jens Scholz, Ole Broch, Helga Francksen, Martin Albrecht, Bernd Kuhr, Hermann Heinze, Hauke Paarmann, Hans-Hinrich Sievers, Stefan Klotz, Thomas Hachenberg, Christian Werner, Susanne Mauff, Angela Alms, Stefan Bergt, Norbert Roewer

Affiliations

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.

PMID: 30678657
PMCID: PMC6345037
DOI: 10.1186/s12872-019-1002-x

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.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

The ethics committees of the Medical Faculty of Christian-Albrechts-University of Kiel, Germany, and of all participating centers approved the study protocol, patient information and informed consent. Each patient gave written informed consent for DNA analysis. The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.

Consent for publication

Not applicable.

Competing interests

No competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

**Fig. 1**
Randomization and Follow-up. Of the 1403 randomized patients, 1170 were included in the GWAS annotation analysis

**Fig. 2**
**a-f** SNP loci with lowest p-values associated with a) AF, b) delirium, c) MI, d) renal failure and e) stroke

See this image and copyright information in PMC

References

1. Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol. 2000;190(3):255–266. - PubMed
1. Kraft F, Schmidt C, van Aken H, Zarbock A. Inflammatory response and extracorporeal circulation. Best Pract Res Clin Anaesthesiol. 2015;29(2):113–123. - PubMed
1. Kertai MD, Li Y-J, Li Y-W, Ji Y, Alexander J, Newman MF, et al. Genome-wide association study of perioperative myocardial infarction after coronary artery bypass surgery. BMJ Open. 2015;5(5):e006920. - PMC - PubMed
1. Kertai MD, Li Y-J, Ji Y, Qi W, Lombard FW, Shah SH, et al. Genome-wide association study of new-onset atrial fibrillation after coronary artery bypass grafting surgery. Am Heart J. 2015;170(3):580–90.e28. - PMC - PubMed
1. Stafford-Smith M, Li Y-J, Mathew JP, Li Y-W, Ji Y, Phillips-Bute BG, et al. Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci. Kidney Int. 2015;88(4):823–832. - PMC - PubMed

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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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Ethics approval and consent to participate

Consent for publication

Competing interests

Publisher’s Note

Figures

References

Publication types

MeSH terms

Substances

Associated data

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous