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

A. Vecchie; 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; P. Bruzzone; F. Pagan; R. Russo; A. Confalonieri; C. Abbruzzese; B. Vergnano; S. Faenza; A. Siniscalchi; E. Pierucci; A. Noto; A. Pezzi; P. Spanu; V. Parrini; R. Oggioni; G. S. Pasetti; M. C. Casadio; R. Buontempo; S. Carrer; F. Piccoli; T. Rizzi; Anselmo Caricato; Sala M. La; A. Antonaci; P. Fassini; S. Paganini; V. Porta; G. Moise; S. Marell; M. Furia; M. C. Urbano; R. Carobbi; S. Poleni; H. Kandil; A. Ballotta; F. Bettini; M. Sanseverino; A. Gatta; F. Cecchini; L. Guatteri; G. Ciceri; F. Raimondi; R. Colombo; S. Ferraris; M. Borelli; V. Bellato; F. Cancellieri; S. Senni; N. Sacchi; P. Ferri; G. Moioli; A. Fedele; A. Molin; G. Salati; P. Salsi; E. Brunori; D. Elisei; G. Maggio; F. G. Nicola; M. Cavana; G. Morelli; A. Guarino; M. Isetta; G. Tulli; V. Mangani; N. Rossi; M. Ferrari; F. Bona; M. Vay; T. Bartoli; M. Gallo; M. D. Morte; E. Boselli; D. Puscio; A. Galzerano; M. Carli; G. Zagara

doi:10.1111/joim.13150

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

A. Vecchie^*, 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, P. Bruzzone, F. Pagan, R. Russo, A. Confalonieri, C. AbbruzzeseB. Vergnano, S. Faenza, A. Siniscalchi, E. Pierucci, A. Noto, A. Pezzi, P. Spanu, V. Parrini, R. Oggioni, G. S. Pasetti, M. C. Casadio, R. Buontempo, S. Carrer, F. Piccoli, T. Rizzi, Anselmo Caricato, Sala M. La, A. Antonaci, P. Fassini, S. Paganini, V. Porta, G. Moise, S. Marell, M. Furia, M. C. Urbano, R. Carobbi, S. Poleni, H. Kandil, A. Ballotta, F. Bettini, M. Sanseverino, A. Gatta, F. Cecchini, L. Guatteri, G. Ciceri, F. Raimondi, R. Colombo, S. Ferraris, M. Borelli, V. Bellato, F. Cancellieri, S. Senni, N. Sacchi, P. Ferri, G. Moioli, A. Fedele, A. Molin, G. Salati, P. Salsi, E. Brunori, D. Elisei, G. Maggio, F. G. Nicola, M. Cavana, G. Morelli, A. Guarino, M. Isetta, G. Tulli, V. Mangani, N. Rossi, M. Ferrari, F. Bona, M. Vay, T. Bartoli, M. Gallo, M. D. Morte, E. Boselli, D. Puscio, A. Galzerano, M. Carli, G. Zagara

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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 language	English
Pages (from-to)	N/A-N/A
Journal	Journal of Internal Medicine
Volume	2020
Issue number	N/A
DOIs	https://doi.org/10.1111/joim.13150
Publication status	Published - 2020

All Science Journal Classification (ASJC) codes

Internal Medicine

Keywords

PCSK9
mortality
pentraxin 3
sepsis
septic shock

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10.1111/joim.13150

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Vecchie, 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-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. Vecchie 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 P. Bruzzone and F. Pagan and R. Russo and A. Confalonieri and C. Abbruzzese and B. Vergnano and S. Faenza and A. Siniscalchi and E. Pierucci and A. Noto and A. Pezzi and P. Spanu and V. Parrini and R. Oggioni and Pasetti, \{G. S.\} and Casadio, \{M. C.\} and R. Buontempo and S. Carrer and F. Piccoli and T. Rizzi and Anselmo Caricato and La, \{Sala M.\} and A. Antonaci and P. Fassini and S. Paganini and V. Porta and G. Moise and S. Marell and M. Furia and Urbano, \{M. C.\} and R. Carobbi and S. Poleni and H. Kandil and A. Ballotta and F. Bettini and M. Sanseverino and A. Gatta and F. Cecchini and L. Guatteri and G. Ciceri and F. Raimondi and R. Colombo and S. Ferraris and M. Borelli and V. Bellato and F. Cancellieri and S. Senni and N. Sacchi and P. Ferri and G. Moioli and A. Fedele and A. Molin and G. Salati and P. Salsi and E. Brunori and D. Elisei and G. Maggio and Nicola, \{F. G.\} and M. Cavana and G. Morelli and A. Guarino and M. Isetta and G. Tulli and V. Mangani and N. Rossi and M. Ferrari and F. Bona and M. Vay and T. Bartoli and M. Gallo and Morte, \{M. D.\} and E. Boselli and D. Puscio and A. Galzerano and M. Carli and G. 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",

number = "N/A",

}

Vecchie, 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, SM, 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, no. N/A, pp. 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 - Vecchie, 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, P.

AU - Pagan, F.

AU - Russo, R.

AU - Confalonieri, A.

AU - Abbruzzese, C.

AU - Vergnano, B.

AU - Faenza, S.

AU - Siniscalchi, A.

AU - Pierucci, E.

AU - Noto, A.

AU - Pezzi, A.

AU - Spanu, P.

AU - Parrini, V.

AU - Oggioni, R.

AU - Pasetti, G. S.

AU - Casadio, M. C.

AU - Buontempo, R.

AU - Carrer, S.

AU - Piccoli, F.

AU - Rizzi, T.

AU - Caricato, Anselmo

AU - La, Sala M.

AU - Antonaci, A.

AU - Fassini, P.

AU - Paganini, S.

AU - Porta, V.

AU - Moise, G.

AU - Marell, S.

AU - Furia, M.

AU - Urbano, M. C.

AU - Carobbi, R.

AU - Poleni, S.

AU - Kandil, H.

AU - Ballotta, A.

AU - Bettini, F.

AU - Sanseverino, M.

AU - Gatta, A.

AU - Cecchini, F.

AU - Guatteri, L.

AU - Ciceri, G.

AU - Raimondi, F.

AU - Colombo, R.

AU - Ferraris, S.

AU - Borelli, M.

AU - Bellato, V.

AU - Cancellieri, F.

AU - Senni, S.

AU - Sacchi, N.

AU - Ferri, P.

AU - Moioli, G.

AU - Fedele, A.

AU - Molin, A.

AU - Salati, G.

AU - Salsi, P.

AU - Brunori, E.

AU - Elisei, D.

AU - Maggio, G.

AU - Nicola, F. G.

AU - Cavana, M.

AU - Morelli, G.

AU - Guarino, A.

AU - Isetta, M.

AU - Tulli, G.

AU - Mangani, V.

AU - Rossi, N.

AU - Ferrari, M.

AU - Bona, F.

AU - Vay, M.

AU - Bartoli, T.

AU - Gallo, M.

AU - Morte, M. D.

AU - Boselli, E.

AU - Puscio, D.

AU - Galzerano, A.

AU - Carli, M.

AU - Zagara, G.

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 - https://publicatt.unicatt.it/handle/10807/164706

UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85087758673&origin=inward

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85087758673&origin=inward

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

IS - N/A

ER -

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

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