Original Articles

The Association between Cytokines and 365-Day Readmission or Mortality in Adult Cardiac Surgery

^* Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland
^† The Dartmouth Institute for Health Policy & Clinical Practice, Geisel School of Medicine, Lebanon, New Hampshire
^‡ Department of Cardiac Surgery, University of Michigan, Ann Arbor, Michigan
^§ Department of Internal Medicine and Program of Applied Translational Research Yale University School of Medicine, New Haven, Connecticut
^¶ Department of Thoracic and Cardiovascular Surgery, Duke University School of Medicine, Durham, North Carolina
^‖ Carolinas Healthcare System, Charlotte, North Carolina
^** Department of Biomedical Data Science, Geisel School of Medicine, Lebanon, New Hampshire
^†† Division of Cardiac Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
^‡‡ Division of Cardiovascular Surgery, Department of Surgery, Johns Hopkins All Children’s Hospital, Saint Petersburg, Florida
^§§ Department of Surgery and Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
^¶¶ Section of Cardiac Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; and
^‖‖ Department of Epidemiology, Geisel School of Medicine, Lebanon, New Hampshire

Address correspondence to: Jeremiah R. Brown, PhD, MS, Clinical Research Section Rubin 505, The Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth-Hitchcock Medical Center, HB 7251, 1 Medical Center Drive, Lebanon, NH 03756. E-mail: jeremiah.r.brown@dartmouth.edu

Received: 4 April 2019
Accepted: 26 August 2019

Abstract

Cardiac surgery results in a multifactorial systemic inflammatory response with inflammatory cytokines, such as interleukin-10 and 6 (IL-10 and IL-6), shown to have potential in the prediction of adverse outcomes including readmission or mortality. This study sought to measure the association between IL-6 and IL-10 levels and 1-year hospital readmission or mortality following cardiac surgery. Plasma biomarkers IL-6 and IL-10 were measured in 1,047 patients discharged alive after isolated coronary artery bypass graft surgery from eight medical centers participating in the Northern New England Cardiovascular Disease Study Group between 2004 and 2007. Readmission status and mortality were ascertained using Medicare, state all-payer claims, and the National Death Index. We evaluated the association between preoperative and postoperative cytokines and 1-year readmission or mortality using Kaplan–Meier estimates and Cox’s proportional hazards modeling, adjusting for covariates used in the Society of Thoracic Surgeons 30-day readmission model. The median follow-up time was 1 year. After adjustment, patients in the highest tertile of postoperative IL-6 values had a significantly increased risk of readmission or death within 1 year (HR: 1.38; 95% CI: 1.03–1.85), and an increased risk of death within 1 year of discharge (HR: 4.88; 95% CI: 1.26–18.85) compared with patients in the lowest tertile. However, postoperative IL-10 levels, although increasing through tertiles, were not found to be significantly associated independently with 1-year readmission or mortality (HR: 1.25; 95% CI: .93–1.69). Pro-inflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10 may be postoperative markers of cardiac injury, and IL-6, specifically, shows promise in predicting readmission and mortality following cardiac surgery.