Dipal M Patel1, Heather Thiessen-Philbrook2, Jeremiah R Brown3, Eric McArthur4, Dennis G Moledina5, Sherry G Mansour5, Michael G Shlipak6, Jay L Koyner7, Peter Kavsak8, Richard P Whitlock9, Allen D Everett10, David J Malenka3, Amit X Garg11, Steven G Coca12, Chirag R Parikh13. 1. Program of Applied Translational Research, Department of Medicine, Yale University School of Medicine, New Haven, CT. 2. Division of Nephrology, School of Medicine, Johns Hopkins University, Baltimore, MD. 3. Dartmouth Institute for Health Policy and Clinical Practice, and the Departments of Biomedical Data Science and Epidemiology, Geisel School of Medicine, Lebanon, NH. 4. ICES, Toronto, ON, Canada. 5. Program of Applied Translational Research, Department of Medicine, Yale University School of Medicine, New Haven, CT; Section of Nephrology, Yale University School of Medicine, New Haven, CT. 6. Kidney Health Research Collaborative, University of California San Francisco, San Francisco, CA; Department of Medicine, San Francisco VA Medical Center and University of California, San Francisco, CA. 7. Section of Nephrology, Department of Medicine, University of Chicago, Pritzker School of Medicine, Chicago, IL. 8. Departments of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. 9. Population Health Research Institute and Department of Surgery, McMaster University, Hamilton, ON, Canada. 10. Division of Cardiology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD. 11. ICES, Toronto, ON, Canada; Division of Nephrology, Department of Medicine, Western University, London, ON, Canada. 12. Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY. 13. Division of Nephrology, School of Medicine, Johns Hopkins University, Baltimore, MD. Electronic address: chirag.parikh@jhmi.edu.
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. Crown
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. Crown
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