Plasma corin decreases after coronary artery bypass graft surgery and is associated with postoperative heart failure: a pilot study

Abstract

Objective: Corin is a natriuretic peptide-converting enzyme that cleaves precursor pro-B-type natriuretic peptide to active B-type natriuretic peptide (BNP) (diuretic, natriuretic, and vasodilatory properties). Increased plasma BNP is a known diagnostic and prognostic heart failure (HF) biomarker in ambulatory and surgical patients. Recent studies indicate that plasma corin is decreased significantly in chronic HF patients, yet perioperative plasma corin concentrations have not been assessed in cardiac surgical patients. The objectives of this study were to determine the effect of coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB) on plasma corin concentrations and to assess the association between change in perioperative plasma corin concentration and long-term postoperative HF hospitalization or death. It was hypothesized that plasma corin concentrations decrease significantly from preoperative baseline during postoperative days 1 to 4 and that hospitalization or death from HF during the 5 years after surgery is associated with higher relative difference (preoperative baseline to postoperative nadir) in plasma corin concentrations.

Design: Prospective observational pilot study.

Setting: Two institutions: Brigham and Women's Hospital, Boston, Massachusetts and the Texas Heart Institute, St. Luke's Hospital, Houston, Texas.

Participants: 99 patients of European ancestry who underwent isolated primary CABG surgery with CPB.

Interventions: Nonemergency isolated primary CABG surgery with CPB.

Measurements and main results: Plasma corin concentration was assessed preoperatively and at 4 postoperative time points (postoperative days 1-4). HF hospitalization or HF death events during the 5 years after surgery were identified by review of hospital and death records. Postoperative plasma corin concentrations were significantly lower than preoperative baseline concentrations (p<0.0001). Perioperative corin concentrations were significantly higher in males than in females (p<0.0001). Fifteen patients experienced long-term postoperative HF events. Patients who experienced HF hospitalization or HF death during study follow-up had significantly higher relative difference in plasma corin concentration (preoperative baseline to postoperative nadir) than patients who did not experience HF events during study follow-up (p=0.03).

Conclusions: Plasma corin concentrations decrease significantly from preoperative concentrations after CABG surgery. HF hospitalization or HF death during the 5 years after CABG surgery with CPB is associated with larger relative decrease in plasma corin concentration from preoperative baseline. Further investigation is warranted to determine the role of corin in postoperative HF biology.

Keywords: biologic markers; cardiac surgery; corin protein; coronary artery bypass grafting; heart failure; human corin; natriuretic peptide.

Copyright © 2015 Elsevier Inc. All rights reserved.

Figures

Figure 1

Illustration of precursor proBNP processing by corin to NT-proBNP (inactive fagment) and BNP (biologically active fragment).

Figure 2

Schematic illustrating the steps taken to select the study’s 99 subjects from the overall CABG Genomics study cohort. *One older subject in the minor allele homozygous group was matched 1:4 for age, gender, study site and left ventricular ejection fraction, with matching to 4 subjects in the heterozygote group and 4 subjects in the major allele homozygous group according to age >65 years instead of age by decile.

Figure 3. Plasma corin concentrations

The time effect on perioperative corin concentration was significant (P

Figure 4. Plasma corin concentrations stratified by gender

The time effect on perioperative corin concentration was significant for both males (P

Figure 5. Kaplan-Meier 5-year survival curves

Curves represent heart failure (HF) event free survival and are stratified according to top versus bottom half of relative decline in perioperative plasma corin concentration. There was a significant difference in HF event free survival between the two groups (log rank P=0.02). Relative decline in perioperative plasma corin concentration is the difference between preoperative baseline plasma corin concentration and nadir postoperative plasma corin concentration divided by preoperative baseline corin concentration.