Circulating secretoneurin concentrations predict mortality in middle-aged subjects from the general population

Background Circulating secretoneurin (SN) concentrations have been found to predict mortality in patients with established cardiovascular disease. Whether circulating SN concentrations can predict mortality also in subjects from the general population is not clear. Purpose To examine variables associated with higher SN concentrations and whether SN concentrations can predict mortality in subjects from the general population. Methods We performed SN measurements in 1889 men and 1803 women born 1950 from the general population. The participants were examined during 2012-15 and we collected self-reported medical history and performed clinical examination and echocardiography in all participants. We collected blood samples at the baseline visit and we used an automated SN CLIA assay to measure serum SN concentrations in 2024. We identified variables associated with higher (log)SN concentrations using multivariable linear regression analysis. We assessed the association between (log)SN concentrations and mortality up to December 31, 2023 by Cox proportional hazard regression analysis. We adjusted for age, sex, body mass index (BMI), current smoking, history of cardiovascular disease, diabetes mellitus, hypertension, total cholesterol, estimated glomerular filtration rate (eGFR), and cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations in the multivariable Cox model. The association between SN and mortality was visualized by Kaplan-Meier plot divided according to sex-specific Youden index. Results Median (quartile 1-3) SN concentration in this cohort was 36 (30-41) ng/L for women and 32 (27-37) ng/L for men. Higher age, female sex, lower BMI, current smoking, diabetes mellitus, hypertension, lower eGFR, and higher C-reactive peptide and NT-proBNP concentrations were all associated with increasing SN concentrations. In contrast, no significant associations were found between SN concentrations and left ventricular mass or left ventricular ejection fraction. During follow-up, 236 participants (6%) died. SN concentrations separated participants with a poor and favorable outcome (Figure 1). SN concentrations were also associated with all-cause mortality in the multivariable model: hazard ratio per doubling of SN 1.42 (95% CI 1.03-1.96) (Figure 2). Conclusion Circulating SN concentrations integrate information from different pathophysiological axes and provide independent prognostic information in middle-aged subjects recruited from the general population.