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 Abbruzzese; Beatrice 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

doi:10.1111/joim.13150

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

Risultato della ricerca: Contributo in rivista › Articolo in rivista

1 Citazioni (Scopus)

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.

Lingua originale	English
pagine (da-a)	N/A-N/A
Rivista	Journal of Internal Medicine
Volume	2020
DOI	https://doi.org/10.1111/joim.13150
Stato di pubblicazione	Pubblicato - 2020

Keywords

PCSK9
mortality
pentraxin 3
sepsis
septic shock

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10.1111/joim.13150

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Vecchié, A., Bonaventura, A., Meessen, J., Novelli, D., Minetti, S., Elia, E., Ferrara, D., Ansaldo, A. M., Scaravilli, V., Villa, S., Ferla, L., Caironi, P., Latini, R., Carbone, F., Montecucco, F., Bruzzone, P., Pagan, F., Russo, R., Confalonieri, A., ... Zagara, G. (2020). PCSK9 is associated with mortality in patients with septic shock: data from the ALBIOS study. Journal of Internal Medicine, 2020, N/A-N/A. https://doi.org/10.1111/joim.13150

@article{c095a0205bcc4963a2f3ca4ce016650f,

title = "PCSK9 is associated with mortality in patients with septic shock: data from the ALBIOS study",

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{\textquoteright}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.",

keywords = "PCSK9, mortality, pentraxin 3, sepsis, septic shock, PCSK9, mortality, pentraxin 3, sepsis, septic shock",

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

year = "2020",

doi = "10.1111/joim.13150",

language = "English",

volume = "2020",

pages = "N/A--N/A",

journal = "Journal of Internal Medicine",

issn = "0954-6820",

publisher = "Wiley-Blackwell Publishing Ltd",

}

Vecchié, A, Bonaventura, A, Meessen, J, Novelli, D, Minetti, S, Elia, E, Ferrara, D, Ansaldo, AM, Scaravilli, V, Villa, S, Ferla, L, Caironi, P, Latini, R, Carbone, F, Montecucco, F, Bruzzone, P, Pagan, F, Russo, R, Confalonieri, A, Abbruzzese, C, Vergnano, B, Faenza, S, Siniscalchi, A, Pierucci, E, Noto, A, Pezzi, A, Spanu, P, Parrini, V, Oggioni, R, Pasetti, GS, Casadio, MC, Buontempo, R, Carrer, S, Piccoli, F, Rizzi, T, Caricato, A, La Sala, M, Antonaci, A, Fassini, P, Paganini, S, Porta, V, Moise, G, Marell, S, Furia, M, Urbano, MC, Carobbi, R, Poleni, S, Kandil, H, Ballotta, A, Bettini, F, Sanseverino, M, Gatta, A, Cecchini, F, Guatteri, L, Ciceri, G, Raimondi, F, Colombo, R, Ferraris, S, Borelli, M, Bellato, V, Cancellieri, F, Senni, S, Sacchi, N, Ferri, P, Moioli, G, Fedele, A, Molin, A, Salati, G, Salsi, P, Brunori, E, Elisei, D, Maggio, G, Nicola, FG, Cavana, M, Morelli, G, Guarino, A, Isetta, M, Tulli, G, Mangani, V, Rossi, N, Ferrari, M, Bona, F, Vay, M, Bartoli, T, Gallo, M, Morte, MD, Boselli, E, Puscio, D, Galzerano, A, Carli, M & Zagara, G 2020, 'PCSK9 is associated with mortality in patients with septic shock: data from the ALBIOS study', Journal of Internal Medicine, vol. 2020, pagg. N/A-N/A. https://doi.org/10.1111/joim.13150

TY - JOUR

T1 - PCSK9 is associated with mortality in patients with septic shock: data from the ALBIOS study

AU - Vecchié, A.

AU - Bonaventura, A.

AU - Meessen, J.

AU - Novelli, D.

AU - Minetti, S.

AU - Elia, E.

AU - Ferrara, D.

AU - Ansaldo, A. M.

AU - Scaravilli, V.

AU - Villa, S.

AU - Ferla, L.

AU - Caironi, P.

AU - Latini, R.

AU - Carbone, F.

AU - Montecucco, F.

AU - Bruzzone, Paola

AU - Pagan, Francesca

AU - Russo, Riccarda

AU - Confalonieri, Andrea

AU - Abbruzzese, Chiara

AU - Vergnano, Beatrice

AU - Faenza, Stefano

AU - Siniscalchi, Antonio

AU - Pierucci, Elisabetta

AU - Noto, Andrea

AU - Pezzi, Angelo

AU - Spanu, Paolo

AU - Parrini, Vieri

AU - Oggioni, Roberto

AU - Pasetti, Giovanni Stefano

AU - Casadio, Maria Cinzia

AU - Buontempo, Rosa

AU - Carrer, Sara

AU - Piccoli, Francesca

AU - Rizzi, Tatiana

AU - Caricato, Anselmo

AU - La Sala, Monica

AU - Antonaci, Alessandra

AU - Fassini, Paola

AU - Paganini, Silvia

AU - Porta, Virginia

AU - Moise, Gabriella

AU - Marell, Silvia

AU - Furia, Mirella

AU - Urbano, Maria Cristina

AU - Carobbi, Roberta

AU - Poleni, Simona

AU - Kandil, Hassan

AU - Ballotta, Andrea

AU - Bettini, Fabrizio

AU - Sanseverino, Manlio

AU - Gatta, Alessandro

AU - Cecchini, Francesca

AU - Guatteri, Luca

AU - Ciceri, Gabriella

AU - Raimondi, Ferdinando

AU - Colombo, Roberto

AU - Ferraris, Sandra

AU - Borelli, Massimo

AU - Bellato, Valentina

AU - Cancellieri, Franco

AU - Senni, Silvia

AU - Sacchi, Noemi

AU - Ferri, Paola

AU - Moioli, Gianpietro

AU - Fedele, Andrea

AU - Molin, Alexandra

AU - Salati, Giovanni

AU - Salsi, Pierpaolo

AU - Brunori, Emanuela

AU - Elisei, Daniele

AU - Maggio, Giuseppe

AU - Nicola, Federico Guardia

AU - Cavana, Marco

AU - Morelli, Giacomo

AU - Guarino, Arturo

AU - Isetta, Michele

AU - Tulli, Giorgio

AU - Mangani, Valerio

AU - Rossi, Nicola

AU - Ferrari, Marta

AU - Bona, Francesco

AU - Vay, Monica

AU - Bartoli, Teresa

AU - Gallo, Mauro

AU - Morte, Mauro Della

AU - Boselli, Enrico

AU - Puscio, Daniela

AU - Galzerano, Antonio

AU - Carli, Manuela

AU - Zagara, Giovanni

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - PCSK9

KW - mortality

KW - pentraxin 3

KW - sepsis

KW - septic shock

KW - PCSK9

KW - mortality

KW - pentraxin 3

KW - sepsis

KW - septic shock

UR - http://hdl.handle.net/10807/164706

U2 - 10.1111/joim.13150

DO - 10.1111/joim.13150

M3 - Article

SN - 0954-6820

VL - 2020

SP - N/A-N/A

JO - Journal of Internal Medicine

JF - Journal of Internal Medicine

ER -

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

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Keywords

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