The signal peptide of CNP is a novel predictor of MI, MACE and bleeding risk in chest pain patients

Abstract Aim CNP is an important vascular and cardiac derived member of the natriuretic peptide family. We have previously provided the first reports that the signal peptide of CNP (CNPsp) is present in the human circulation and is elevated in those with chest pain suspicious of ACS. Here, show that CNPsp levels are highly predictive of new MI, MACE and post-index bleeding in patients presenting with potential ACS. Methods We prospectively recruited 493 patients presenting with the primary complaint of acute chest pain to our hospital ED. Patients were adjudicated as ACS by 2 independent cardiologists in accordance with ESC guidelines with hsTnI as biomarker. Plasma EDTA samples taken at presentation and 2 hours after were interrogated for CNPsp measurements using our validated, specific assay. Clinical data/variables, standard biochemistry analytes, hsTnT and NT-proBNP (both Roche Cobas e411) were also measured. Statistical assessments were made using SPSS v23. Data for all biomarkers were treated as continuous variables and are presented as median (interquartile range, (IQR)). Statistical assessment of the comparative abilities of CNPsp, hsTnT, NT-proBNP and hsTnI (log values) to predict new MACE, MI, bleeding and mortality within 2 yrs of index presentation was undertaken using a logistic regression base model (95% CI) that included all clinical variables and hsTnI and hsTnT and NT-proBNP, with CNPsp added to into the multivariate analyses. Results Of the 493 recruited patients (median age 63 (IQR: 54–73, 35% female), 148 were adjudicated to have ACS (30%, 109 MI, 39 UAP). Presentation CNPsp levels were not higher in those with adjudicated ACS versus non-ACS (51, (45–65) vs. 50, (42–63) pmol/L, P=0.412), did not correlate with hsTnI, hsTnT or NT-proBNP, but were significantly lower in those with a history of MI (49, (42–59) vs. 51, (43–64) pmol/L, P=0.044). In contrast, they were significantly higher in those with ECG ST-depression (56, (47–85) vs. 50 (42–62) pmol/L, P=0.038). In the multivariate regression model of all 493 patients, lower values of CNPsp were a significant multivariate predictor of new MI (n=37, 95% CI: 0.06–0.89, P=0.038), MACE (n=64, 95% CI: 0.08–0.81, P=0.020) and new bleeding (n=40, 95% CI: 0.05–0.63, P=0.005) within 2 years of presentation. This predictive ability was additive and independent from NT-proBNP and troponin. Conclusion This is the first report that CNPsp measurement provides meaningful and independent risk assessment of important outcomes in ACS patients. In particular, the fact that lower levels of CNPsp are predictive of negative MI, MACE and bleeding outcomes suggests that CNPsp may have an unappreciated protective role in the cardiovascular system. Acknowledgement/Funding Health Research Council of New Zealand; Heart Foundation of New Zealand