Plasma PCSK9 levels and sepsis severity: an early assessment in the emergency department
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ORIGINAL ARTICLE
Plasma PCSK9 levels and sepsis severity: an early assessment in the emergency department Francesca Innocenti1 · Anna Maria Gori2 · Betti Giusti2 · Camilla Tozzi1 · Chiara Donnini1 · Federico Meo1 · Irene Giacomelli1 · Maria Luisa Ralli1 · Alice Sereni2 · Elena Sticchi2 · Irene Tassinari1 · Rossella Marcucci2 · Riccardo Pini1 Received: 23 June 2020 / Accepted: 25 August 2020 © Springer Nature Switzerland AG 2020
Abstract The aim of the study is to evaluate the prognostic value of early PCSK9 levels in non-intubated septic patients admitted to the emergency department. This report utilized a portion of the data collected in a prospective study, with the aim of identifying reliable biomarkers for an early sepsis diagnosis. In the period November 2011–December 2016, we enrolled 268 patients, admitted to our High-Dependency Unit from the emergency department with a diagnosis of sepsis. Study-related blood samplings were performed at ED-HDU admission (T0), after 6 h (T6) and 24 h (T24). The primary endpoint was inhospital mortality rate. PCSK9 circulating levels were higher than the normal value (≤ 313 ng/mL): at T0 661 ± 405 ng/mL, at T6 687 ± 417 ng/mL, at T24 718 ± 430 ng/mL. We divided the study population based on T0 quartiles distribution (≤ 370, 370–600, 600–900 and > 900 ng/ml). At T0, patients with normal PCSK9 showed the highest mortality compared to those in higher quartiles (T0: 39%, 20%, 23% and 18%, p = 0.036). By T6, the mortality curve tended to become U-shaped, with the lowest mortality among patients in the intermediate subgroups and an adverse prognosis in the presence of normal or very high levels of PCSK9 (35%, 26%, 18% and 23%, p = 0.235). A Kaplan–Meier analysis showed an increased mortality in patients with T0 and T6 PCSK9 ≤ 313 ng/ml (T0: 55 vs. 80%, p = 0.001; T6: 62 vs. 78%, p = 0.034). In subgroups with increasing levels of PCSK9, we found the best prognosis in the intermediate subgroups and an increased mortality among patients with normal and high values. Keywords Sepsis · Lipid metabolism · Prognosis
Introduction During sepsis organ dysfunction is caused by the activation of several pathways, within a global dysregulation of the host response to infection [1]. Among them, pathogen’s cholesterol and lipids play an essential role in generating intracellular signals and consequently in the regulation of the host response to different pathogens. Lipopolysaccharide (LPS) in Gram-negative bacteria and lipoteichoic acid (LTA) * Francesca Innocenti [email protected] 1
High‑Dependency Unit, Department of Clinical and Experimental Medicine, Azienda OspedalieroUniversitaria Careggi, Lg. Brambilla 3, 50134 Florence, Italy
Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy
2
in Gram-positive bacteria are key lipid moieties of bacterial cell walls, which stimulate the immune system. Low-density lipoproteins (LDL) have turned out to be involved in hepatic clearance of these pathogenic lipids from the bloodstream during sepsis:
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