Association of plasma-soluble ST2 and galectin-3 with cardiovascular events and mortality following cardiac surgery - 05/02/20

Doi : 10.1016/j.ahj.2019.11.014

Dipal M. Patel, MD, PhD ^a, Heather Thiessen-Philbrook, BMath, MMath ^b, Jeremiah R. Brown, PhD ^c, Eric McArthur, MSc ^d, Dennis G. Moledina, MBBS, PhD ^a,^e, Sherry G. Mansour, DO ^a,^e, Michael G. Shlipak, MD ^f,^g, Jay L. Koyner, MD ^h, Peter Kavsak, PhD, FCACB, FACB, FCCS ⁱ, Richard P. Whitlock, MD, PhD, FRCSC ^j, Allen D. Everett, MD ^k, David J. Malenka, MD ^c, Amit X. Garg, MD PhD ^d,^l, Steven G. Coca, DO, MS ^m, Chirag R. Parikh, MD, PhD, FACP ^b,^{^⁎}
^a Program of Applied Translational Research, Department of Medicine, Yale University School of Medicine, New Haven, CT
^b Division of Nephrology, School of Medicine, Johns Hopkins University, Baltimore, MD
^c Dartmouth Institute for Health Policy and Clinical Practice, and the Departments of Biomedical Data Science and Epidemiology, Geisel School of Medicine, Lebanon, NH
^d ICES, Toronto, ON, Canada
^e Section of Nephrology, Yale University School of Medicine, New Haven, CT
^f Kidney Health Research Collaborative, University of California San Francisco, San Francisco, CA
^g Department of Medicine, San Francisco VA Medical Center and University of California, San Francisco, CA
^h Section of Nephrology, Department of Medicine, University of Chicago, Pritzker School of Medicine, Chicago, IL
ⁱ Departments of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
^j Population Health Research Institute and Department of Surgery, McMaster University, Hamilton, ON, Canada
^k Division of Cardiology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD
^l Division of Nephrology, Department of Medicine, Western University, London, ON, Canada
^m Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY

^⁎Reprint requests: Chirag Parikh, MD PhD, Director, Division of Nephrology, Ronald Peterson Professor of Medicine, 1830 E. Monument St. 4th Floor, Suite 416, Baltimore, MD 21287.1830 E. Monument St. 4th Floor, Suite 416BaltimoreMD21287

Abstract

Background

Cardiac surgery induces hemodynamic stress on the myocardium, and this process can be associated with significant post-operative morbidity and mortality. Soluble suppression of tumorigenicity 2 (sST2) and galectin-3 (gal-3) are biomarkers of myocardial remodeling and fibrosis; however, their potential association with post-operative changes is unknown.

Methods

We measured peri-operative plasma sST2 and gal-3 levels in two prospective cohorts (TRIBE-AKI and NNE) of over 1800 patients who underwent cardiac surgery. sST2 and gal-3 levels were evaluated for association with a composite primary outcome of cardiovascular event or mortality over median follow-up periods of 3.4 and 6.0 years, respectively, for the two cohorts. Meta-analysis of hazard ratio estimates from the cohorts was performed using random effects models.

Results

Cohorts demonstrated event rates of 70.2 and 66.8 per 1000 person-years for the primary composite outcome. After adjustment for clinical covariates, higher post-operative sST2 and gal-3 levels were significantly associated with cardiovascular event or mortality [pooled estimate HRs: sST2 1.29 (95% CI 1.16, 1.44); gal-3 1.26 (95% CI 1.09, 1.46)]. These associations were not significantly modified by pre-operative congestive heart failure or AKI.

Conclusions

Higher post-operative sST2 and gal-3 values were associated with increased incidence of cardiovascular event or mortality. These two biomarkers should be further studied for potential clinical utility for patients undergoing cardiac surgery.

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Baseline characteristics

Association of biomarkers with the primary composite outcome

Association of biomarkers stratified by clinically important subgroups

Discussion

Declarations of interest: SGC and CRP are on the Advisory Board of RenalytixAI, and both own equity in the same. SGC has served as a consultant for AKI therapeutics for Quark Biopharma and CHF Solutions. Dr. Parikh also serves as a consultant for Genfit and TriCida. The remaining authors have no disclosures.

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Vol 220

P. 253-263 - Febbraio 2020 Ritorno al numero

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Association of plasma-soluble ST2 and galectin-3 with cardiovascular events and mortality following cardiac surgery - 05/02/20

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