Prognostic Value of Secretoneurin in Critically Ill Patients With Infections

Abstract

1Objectives : Secretoneurin is produced in neuroendocrine cells, and the myocardium and circulating secretoneurin levels provide incremental prognostic information to established risk indices in cardiovascular disease. As myocardial dysfunction contributes to poor outcome in critically ill patients, we wanted to assess the prognostic value of secretoneurin in two cohorts of critically ill patients with infections. Design: Two prospective, observational studies. Setting: Twenty-four and twenty-five ICUs in Finland. Patients: A total of 232 patients with severe sepsis (cohort #1) and 94 patients with infections and respiratory failure (cohort #2). Interventions: None. Measurements and Main Results: We measured secretoneurin levels by radioimmunoassay in samples obtained early after ICU admission and compared secretoneurin with other risk indices. In patients with severe sepsis, admission secretoneurin levels (logarithmically transformed) were associated with hospital mortality (odds ratio, 3.17 [95% CI, 1.12-9.00]; p = 0.030) and shock during the hospitalization (odds ratio, 2.17 [1.06-4.46]; p = 0.034) in analyses that adjusted for other risk factors available on ICU admission. Adding secretoneurin levels to age, which was also associated with hospital mortality in the multivariate model, improved the risk prediction as assessed by the category-free net reclassification index: 0.35 (95% CI, 0.06-0.64) (p = 0.02). In contrast, N-terminal pro-B-type natriuretic peptide levels were not associated with mortality in the multivariate model that included secretoneurin measurements, and N-terminal pro-B-type natriuretic peptide did not improve patient classification on top of age. Secretoneurin levels were also associated with hospital mortality after adjusting for other risk factors and improved patient classification in cohort #2. In both cohorts, the optimal cutoff for secretoneurin levels at ICU admission to predict hospital mortality was ≈ 175 pmol/L, and higher levels were associated with mortality also when adjusting for Simplified Acute Physiology Score II and Sequential Organ Failure Assessment scores. Conclusions: Secretoneurin levels provide incremental information to established risk indices for the prediction of mortality and shock in critically ill patients with severe infections. (Crit Care Med 2016; XX:00-00)

Glycosylated Chromogranin A: Potential Role in the Pathogenesis of Heart Failure

“…This is also in line with data so far where CgB provided prognostic information regardless of etiology for acute respiratory failure [62], while SN concentrations only predicted outcome in the patients with cardiovascular relatedacute respiratory failure in the same study [65]. Of note, we found circulating SN concentrations to provide stronger prognostic information than CgA concentrations in patients with acute HF [48] and in patients with severe sepsis and septic shock [64], which supports the potential of SN as a novel prognostic biomarker in subjects with myocardial dysfunction. Circulating concentrations of the granin proteins are also influenced by renal dysfunction and, although we have adjusted for indices of renal function in multivariate analyses in the different cohorts, this could also explain some of the prognostic value of these proteins in patients with cardiovascular disease.…”

“…Several studies have also failed to demonstrate significant correlations between circulating granin concentrations and catecholamine concentrations [48,54,55,67], but this could at least partly relate to analytical issues as catecholamine measurements require stringent pre-analytical handling of blood samples and the half-lives of epinephrine and norepinephrine are very short. We have demonstrated a positive correlation between circulating SN concentrations and free cortisol concentrations in patients with severe sepsis and septic shock[64], thus measurements of granin protein concentration should be considered reflective of important endocrine stress pathways. Accordingly; circulating granin protein concentrations could integrate information on endocrine stress pathways and specific myocardial pathophysiology in patients with myocardial dysfunction, which could explain the strong and additional prognostic information by these biomarkers to established biomarkers and risk indices in patients with myocardial dysfunction[48, 51, 53-58, 62, 64-66].…”

“…We have also validated the presence of free SN in the circulation of patients with HF by liquid chromatography mass spectrometry [48]. Moreover, using an in-house radioimmunoassay, we and collaborators have found circulating SN concentrations to add to established risk indices in patients with acute HF [48], patients with ventricular arrhythmiainduced cardiac arrest [48], patients with severe sepsis and septic shock [64], and in patients with cardiovascular related-acute respiratory failure [65]. Other groups have also demonstrated prognostic value of circulating SN concentrations after cardiac arrest [66].…”

“…Circulating concentrations of CgA, CgB, and SN are only moderately correlated (rho≈0.5), and these peptides are also weakly to moderately correlated with established biomarkers like BNP/NT-proBNP and high-sensitivity troponin concentrations (rho≈0.3-0.4)[21, 51,57,64,67]. Several studies have also failed to demonstrate significant correlations between circulating granin concentrations and catecholamine concentrations [48,54,55,67], but this could at least partly relate to analytical issues as catecholamine measurements require stringent pre-analytical handling of blood samples and the half-lives of epinephrine and norepinephrine are very short.…”

Circulating secretoneurin concentrations in patients with moderate to severe aortic stenosis

“…230 SN is, as most other peptides, eliminated from the body through the kidneys. 233 There have been a number of recent reports on a possible role for SN as a prognostic biomarker across different cohorts, including patients with acute HF, 31 after cardiac arrest, 31, 234 severe infections 235 and sepsis, 236 and in patients with acute respiratory failure. 237 SN also seems to influence cardiovascular pathophysiology, and the putative role of SN as a biomarker and functional peptide in cardiovascular disease will be discussed later.…”