Circulating secretoneurin concentrations provide independent prognostic information to established risk indices in patients with chronic heart failure
Authors: Rosjo H , Meessen J , Ottesen A H , Latini R , Omland T 
Published: October 2022

Abstract

Background
Secretoneurin (SN) is a 33-amino acid peptide that directly influences cardiomyocyte Ca2+ handling. Circulating SN concentrations increase in situations of systemic stress, myocardial dysfunction, and renal failure, and SN concentrations provide independent prognostic information in patients with acute myocardial dysfunction. Whether SN concentrations provide prognostic information in patients with chronic heart failure (HF) is not known.

Purpose
To examine whether SN concentrations provide incremental prognostic information to established risk indices and biomarkers in patients with chronic HF from a large, randomized controlled trial.

Methods
We measured SN concentrations at randomization (n=1224) and after 3 months (n=1103) in the GISSI-HF trial that used a 2x2 factorial design to test the addition of rosuvastatin and n-3 PUFA to established HF therapy. The co-primary outcome measures of GISSI-HF were (1) all-cause mortality, and (2) mortality or hospitalization for cardiovascular disease during follow-up. Rosuvastatin did not improve outcomes, while the addition of n-3 PUFA provided a small beneficial effect on both primary outcome measures. SN measurements were performed with a new CE-marked SN assay (ELISA).

Results
Mean age was 67 years and 80% were male. Median (quartile 1–3) SN concentrations were 42.6 (35.0–62.8) pmol/L on randomization and 42.0 (34.5–53.1) pmol/L after 3 months, which are higher than SN concentrations in healthy subjects. SN concentrations at randomization were associated with lower body-mass index (BMI), lower systolic blood pressure, lower estimated glomerular filtration rate (eGFR), higher B-type natriuretic peptide (BNP) concentrations, and diagnosis of chronic obstructive pulmonary disease. SN concentrations did not correlate with left ventricular ejection fraction. During median follow-up of 3.9 years, 344 patients (27.0%) died. SN concentrations on randomization stratified patients with a poor and favourable prognosis (Figure 1). SN concentrations were associated with mortality in multivariable analysis that adjusted for age, sex, left ventricular ejection fraction, BMI, functional class, ischemic etiology, heart rate, blood pressure, eGFR, bilirubin, comorbidities, and BNP concentrations: HR (logarithmical transformed SN) 2.60 (95% CI 1.01–6.70), p=0.047. SN concentrations were also associated with risk of mortality or hospitalization for cardiovascular disease, but the association was attenuated and no longer significant in multivariable analysis. SN concentrations were mainly stable from randomization to 3 months (rho=0.66, p&lt;0.001) and the addition of rosuvastatin and n-3 PUFA did not influence SN concentrations.

Conclusion
We found SN concentrations to provide incremental prognostic information to established risk indices and biomarkers in patients with chronic HF from a large multicenter, randomized controlled trial.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Council of Norway