Perioperative urinary thromboxane metabolites and outcome of coronary artery bypass grafting: a nested case-control study

Abstract

Objective: As a marker of in vivo thromboxane generation, high-level urinary thromboxane metabolites (TXA-M) increase the occurrence of cardiovascular events in high-risk patients. To investigate whether perioperative urinary TXA-M level is associated with major adverse cardiac and cerebrovascular events (MACCE) after coronary artery bypass graft (CABG) surgery, we designed a nested case-control study.

Design: Observational, nested case-control study.

Setting: Single-centre outcomes research in Fuwai Hospital, Beijing, China.

Participants: One thousand six hundred and seventy Chinese patients undergoing CABG surgery from September 2011 to October 2013.

Methods: We obtained urinary samples from 1670 Chinese patients undergoing CABG 1 hour before surgery (pre-CABG), and 6 hours (post-CABG 6 hours) and 24 hours after surgery (post-CABG 24 hours). Patients were followed up for 1 year, and we observed 56 patients had MACCE. For each patient with MACCE, we matched three control subjects. Perioperative urinary TXA-M of the three time spots was detected in these 224 patients.

Results: Post-CABG 24 hours TXA-M is significantly higher than that of patients without MACCE (11 101vs8849 pg/mg creatine, P=0.007). In addition, patients in the intermediate tertile and upper tertile of post-CABG 24 hours urinary TXA-M have a 2.2 times higher (HR 2.22, 95% CI 1.04 to 4.71, P=0.038) and a 2.8 times higher (HR 2.81, 95% CI 1.35 to 5.85, P=0.006) risk of 1 year MACCE than those in the lower tertile, respectively.

Conclusions: In conclusion, post-CABG 24 hours urinary TXA-M elevation is associated with an increase of 1 year adverse events after CABG, indicating that the induction of cyclo-oxygenase-2 by surgery-related inflammatory stimuli or platelet turnover may be responsible for the high levels of post-CABG urinary TXA-M.

Trial registration number: NCT01573143.

Keywords: coronary artery bypass grafting; coronary heart disease; major adverse cardiac and cerebrovascular events; urine thromboxane metabolites.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Flow chart of study design. We recruited 1670 patients with CABG from the STICS trial. After 1 year follow-up, 56 patients had MACCE. With the use of a nested case-control analysis, we matched each patient with MACCE with three controls from the cohort; thus, a cohort of 224 patients was established for further study. CABG, coronary artery bypass graft; MACCE, major adverse cardiac and cerebrovascular events; STICS, Statin Therapy in Cardiac Surgery.

Figure 2

Kaplan-Meier curves of MACCE-free survival rate according to post-CABG 24 hours concentration of urinary thromboxane metabolite (TAX-M). Analysis of MACCE-free survival rate according to concentration tertiles of post-CABG 24 hours urinary TAX-M. (A) Unadjusted curve of MACCE-free survival rate; (B) Curve of MACCE-free survival rate adjusted by variables listed in online supplementary table S1. CABG, coronary artery bypass graft; MACCE, major adverse cardiac and cerebrovascular events.