PCSK9 is associated with mortality in patients with septic shock: data from the ALBIOS study

A. Vecchié, A. Bonaventura, J. Meessen, D. Novelli, S. Minetti, E. Elia, D. Ferrara, A. M. Ansaldo, V. Scaravilli, S. Villa, L. Ferla, P. Caironi, R. Latini, F. Carbone, F. Montecucco, Paola Bruzzone, Francesca Pagan, Riccarda Russo, Andrea Confalonieri, Chiara AbbruzzeseBeatrice Vergnano, Stefano Faenza, Antonio Siniscalchi, Elisabetta Pierucci, Andrea Noto, Angelo Pezzi, Paolo Spanu, Vieri Parrini, Roberto Oggioni, Giovanni Stefano Pasetti, Maria Cinzia Casadio, Rosa Buontempo, Sara Carrer, Francesca Piccoli, Tatiana Rizzi, Anselmo Caricato, Monica La Sala, Alessandra Antonaci, Paola Fassini, Silvia Paganini, Virginia Porta, Gabriella Moise, Silvia Marell, Mirella Furia, Maria Cristina Urbano, Roberta Carobbi, Simona Poleni, Hassan Kandil, Andrea Ballotta, Fabrizio Bettini, Manlio Sanseverino, Alessandro Gatta, Francesca Cecchini, Luca Guatteri, Gabriella Ciceri, Ferdinando Raimondi, Roberto Colombo, Sandra Ferraris, Massimo Borelli, Valentina Bellato, Franco Cancellieri, Silvia Senni, Noemi Sacchi, Paola Ferri, Gianpietro Moioli, Andrea Fedele, Alexandra Molin, Giovanni Salati, Pierpaolo Salsi, Emanuela Brunori, Daniele Elisei, Giuseppe Maggio, Federico Guardia Nicola, Marco Cavana, Giacomo Morelli, Arturo Guarino, Michele Isetta, Giorgio Tulli, Valerio Mangani, Nicola Rossi, Marta Ferrari, Francesco Bona, Monica Vay, Teresa Bartoli, Mauro Gallo, Mauro Della Morte, Enrico Boselli, Daniela Puscio, Antonio Galzerano, Manuela Carli, Giovanni Zagara

Research output: Contribution to journalArticle

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Abstract

Background: Pro-protein convertase subtilisin/kexin 9 (PCSK9) is a proenzyme primarily known to regulate low-density lipoprotein receptor re-uptake on hepatocytes. Whether PCSK9 can concurrently trigger inflammation or not remains unclear. Here, we investigated the potential association between circulating levels of PCSK9 and mortality in patients with severe sepsis or septic shock. Methods: Plasma PCSK9 levels at days 1, 2 and 7 were measured in 958 patients with severe sepsis or septic shock previously enrolled in the Albumin Italian Outcome Sepsis (ALBIOS) trial. Correlations between levels of PCSK9 and pentraxin 3 (PTX3), a biomarker of disease severity, were evaluated with ranked Spearman’s coefficients. Cox proportional hazards models were used to assess the association of PCSK9 levels at day 1 with 28- and 90-day mortality. Results: Median plasma PCSK9 levels were 278 [182–452] ng mL−1 on day 1. PCSK9 correlated positively with PTX3 at the three time-points, and patients with septic shock within the first quartile of PCSK9 showed higher levels of PTX3. Similar mortality rates were observed in patients with severe sepsis across PCSK9 quartiles. Patients with septic shock with lower PCSK9 levels on day 1 (within the first quartile) showed the highest 28- and 90-day mortality rate as compared to other quartiles. Conclusion: In our sub-analysis of the ALBIOS trial, we found that patients with septic shock presenting with lower plasma PCSK9 levels experienced higher mortality rate. Further studies are warranted to better evaluate the pathophysiological role of PCSK9 in sepsis.
Original languageEnglish
Pages (from-to)N/A-N/A
JournalJournal of Internal Medicine
Volume2020
DOIs
Publication statusPublished - 2020

Keywords

  • PCSK9
  • mortality
  • pentraxin 3
  • sepsis
  • septic shock

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