A Vecchié1,2, A Bonaventura1,2, J Meessen3, D Novelli3, S Minetti1,4, E Elia1, D Ferrara1, A M Ansaldo1, V Scaravilli5, S Villa6, L Ferla7, P Caironi8, R Latini3, F Carbone1,4, F Montecucco4,9. 1. From the, First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy. 2. Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA. 3. Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy. 4. IRCCS Ospedale Policlinico San Martino Genova - Italian Cardiovascular Network, Genoa, Italy. 5. Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milano, Italy. 6. Dipartimento di Anestesia e Rianimazione, Università degli Studi Milano Bicocca, ASST Monza, Monza, Italy. 7. Dipartimento Emergenza Urgenza - Rianimazione, Azienda Socio Sanitaria Territoriale - Ovest Milanese, Ospedale di Legnano, Legnano, Italy. 8. Department of Anesthesia and Critical Care, AOU San Luigi Gonzaga, Department of Oncology, University of Turin, Orbassano, Turin, Italy. 9. First Clinic of Internal Medicine, Department of Internal Medicine and Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy.
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.
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.
Authors: Daniel A Hofmaenner; Anna Kleyman; Adrian Press; Michael Bauer; Mervyn Singer Journal: Am J Respir Crit Care Med Date: 2022-02-15 Impact factor: 30.528