دورية أكاديمية
PCSK9 is associated with mortality in patients with septic shock: data from the ALBIOS study.
العنوان: | PCSK9 is associated with mortality in patients with septic shock: data from the ALBIOS study. |
---|---|
المؤلفون: | Vecchié A; From the, First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.; Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA., Bonaventura A; From the, First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.; Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA., Meessen J; Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy., Novelli D; Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy., Minetti S; From the, First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.; IRCCS Ospedale Policlinico San Martino Genova - Italian Cardiovascular Network, Genoa, Italy., Elia E; From the, First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy., Ferrara D; From the, First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy., Ansaldo AM; From the, First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy., Scaravilli V; Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milano, Italy., Villa S; Dipartimento di Anestesia e Rianimazione, Università degli Studi Milano Bicocca, ASST Monza, Monza, Italy., Ferla L; Dipartimento Emergenza Urgenza - Rianimazione, Azienda Socio Sanitaria Territoriale - Ovest Milanese, Ospedale di Legnano, Legnano, Italy., Caironi P; Department of Anesthesia and Critical Care, AOU San Luigi Gonzaga, Department of Oncology, University of Turin, Orbassano, Turin, Italy., Latini R; Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy., Carbone F; From the, First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.; IRCCS Ospedale Policlinico San Martino Genova - Italian Cardiovascular Network, Genoa, Italy., Montecucco F; IRCCS Ospedale Policlinico San Martino Genova - Italian Cardiovascular Network, Genoa, Italy.; First Clinic of Internal Medicine, Department of Internal Medicine and Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy. |
مؤلفون مشاركون: | ALBIOS Biomarkers Study Investigators |
المصدر: | Journal of internal medicine [J Intern Med] 2021 Feb; Vol. 289 (2), pp. 179-192. Date of Electronic Publication: 2020 Jul 30. |
نوع المنشور: | Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 8904841 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2796 (Electronic) Linking ISSN: 09546820 NLM ISO Abbreviation: J Intern Med Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Oxford : Blackwell Scientific Publications, c1989- |
مواضيع طبية MeSH: | Proprotein Convertase 9/*blood , Shock, Septic/*mortality, Aged ; Biomarkers/blood ; C-Reactive Protein/metabolism ; Female ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; Sepsis/mortality ; Sepsis/therapy ; Serum Amyloid P-Component/metabolism ; Shock, Septic/therapy |
مستخلص: | 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. (© 2020 The Association for the Publication of the Journal of Internal Medicine.) |
References: | Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315: 801-10. Conway SR, Wong HR. Biomarker panels in critical care. Crit Care Clin 2020; 36: 89-104. Caironi P, Masson S, Mauri T, et al. Pentraxin 3 in patients with severe sepsis or shock: the ALBIOS trial. Eur J Clin Invest 2017; 47: 73-83. Carbone F, Bonaventura A, Vecchiè A, et al. Early osteopontin levels predict mortality in patients with septic shock. Eur J Internal Med 2020. https://doi.org/10.1016/j.ejim.2020.04.035. Green P, Theilla M, Singer P. Lipid metabolism in critical illness. Curr Opin Clin Nutr Metab Care 2016; 19: 111-5. Shapiro MD, Tavori H, Fazio S. PCSK9: from basic science discoveries to clinical trials. Circ Res 2018; 122: 1420-38. Hailman E, Albers JJ, Wolfbauer G, Tu AY, Wright SD. Neutralization and transfer of lipopolysaccharide by phospholipid transfer protein. J Biol Chem 1996; 271: 12172-8. Levels JH, Marquart JA, Abraham PR, van den Ende AE, Molhuizen HO, van Deventer SJ, Meijers JC. Lipopolysaccharide is transferred from high-density to low-density lipoproteins by lipopolysaccharide-binding protein and phospholipid transfer protein. Infect Immun 2005; 73: 2321-6. Topchiy E, Cirstea M, Kong HJ, Boyd JH, Wang Y, Russell JA, Walley KR. Lipopolysaccharide is cleared from the circulation by hepatocytes via the low density lipoprotein receptor. PLoS One 2016; 11: e0155030. Walley KR, Francis GA, Opal SM, Stein EA, Russell JA, Boyd JH. The Central role of proprotein convertase subtilisin/kexin type 9 in septic pathogen lipid transport and clearance. Am J Respir Crit Care Med 2015; 192: 1275-86. Liberale L, Carbone F, Bertolotto M, et al. Serum PCSK9 levels predict the occurrence of acute coronary syndromes in patients with severe carotid artery stenosis. Int J Cardiol 2018; 263: 138-41. Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 2006; 354: 1264-72. Liberale L, Montecucco F, Camici GG, Dallegri F, Vecchie A, Carbone F, Bonaventura A. Treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to reduce cardiovascular inflammation and outcomes. Curr Med Chem 2017; 24: 1403-16. Dwivedi DJ, Grin PM, Khan M, et al. Differential expression of PCSK9 modulates infection, inflammation, and coagulation in a murine model of sepsis. Shock 2016; 46: 672-80. Azzam KM, Fessler MB. Crosstalk between reverse cholesterol transport and innate immunity. Trends Endocrinol Metab 2012; 23: 169-78. Boyd JH, Fjell CD, Russell JA, Sirounis D, Cirstea MS, Walley KR. Increased plasma PCSK9 levels are associated with reduced endotoxin clearance and the development of acute organ failures during sepsis. J Innate Immun 2016; 8: 211-20. Rannikko J, Jacome Sanz D, Ortutay Z, et al. Reduced plasma PCSK9 response in patients with bacteraemia is associated with mortality. J Intern Med 2019; 286: 553-61. Caironi P, Tognoni G, Masson S, et al. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med 2014; 370: 1412-21. Huttunen R, Syrjanen J, Aittoniemi J, et al. High activity of indoleamine 2,3 dioxygenase enzyme predicts disease severity and case fatality in bacteremic patients. Shock 2010; 33: 149-54. Kappelle PJ, Lambert G, Dullaart RP. Plasma proprotein convertase subtilisin-kexin type 9 does not change during 24h insulin infusion in healthy subjects and type 2 diabetic patients. Atherosclerosis 2011; 214: 432-5. Lambert G, Petrides F, Chatelais M, et al. Elevated plasma PCSK9 level is equally detrimental for patients with nonfamilial hypercholesterolemia and heterozygous familial hypercholesterolemia, irrespective of low-density lipoprotein receptor defects. J Am Coll Cardiol 2014; 63: 2365-73. Schoergenhofer C, Matzneller P, Muhlbacher J, Hell L, Zeitlinger M, Jilma B. PCSK9 decreases during experimental endotoxemia. J Intern Med 2020; 287: 333-5. Bone RC, Sibbald WJ, Sprung CL. The ACCP-SCCM consensus conference on sepsis and organ failure. Chest 1992; 101: 1481-3. Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150: 604-12. Walley KR, Thain KR, Russell JA, et al. PCSK9 is a critical regulator of the innate immune response and septic shock outcome. Sci Transl Med 2014; 6: 258ra143. Berger JM, Loza Valdes A, Gromada J, Anderson N, Horton JD. Inhibition of PCSK9 does not improve lipopolysaccharide-induced mortality in mice. J Lipid Res 2017; 58: 1661-9. Mitchell KA, Moore JX, Rosenson RS, et al. PCSK9 loss-of-function variants and risk of infection and sepsis in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. PLoS One 2019; 14: e0210808. Casula M, Montecucco F, Bonaventura A, Liberale L, Vecchie A, Dallegri F, Carbone F. Update on the role of Pentraxin 3 in atherosclerosis and cardiovascular diseases. Vascul Pharmacol 2017; 99: 1-12. Liu S, Qu X, Liu F, Wang C. Pentraxin 3 as a prognostic biomarker in patients with systemic inflammation or infection. Mediators Inflamm 2014; 2014: 421429. Muller B, Peri G, Doni A, Torri V, Landmann R, Bottazzi B, Mantovani A. Circulating levels of the long pentraxin PTX3 correlate with severity of infection in critically ill patients. Crit Care Med 2001; 29: 1404-7. Bastrup-Birk S, Munthe-Fog L, Skjoedt MO, et al. Pentraxin-3 level at admission is a strong predictor of short-term mortality in a community-based hospital setting. J Intern Med 2015; 277: 562-72. Mauri T, Bellani G, Patroniti N, et al. Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality. Intensive Care Med 2010; 36: 621-9. Bastrup-Birk S, Skjoedt MO, Munthe-Fog L, Strom JJ, Ma YJ, Garred P. Pentraxin-3 serum levels are associated with disease severity and mortality in patients with systemic inflammatory response syndrome. PLoS One 2013; 8: e73119. Uusitalo-Seppala R, Huttunen R, Aittoniemi J, Koskinen P, Leino A, Vahlberg T, Rintala EM. Pentraxin 3 (PTX3) is associated with severe sepsis and fatal disease in emergency room patients with suspected infection: a prospective cohort study. PLoS One 2013; 8: e53661. Ricci C, Ruscica M, Camera M, et al. PCSK9 induces a pro-inflammatory response in macrophages. Sci Rep 2018; 8: 2267. Yang CL, Zeng YD, Hu ZX, Liang H. PCSK9 promotes the secretion of pro-inflammatory cytokines by macrophages to aggravate H/R-induced cardiomyocyte injury via activating NF-kappaB signalling. Gen Physiol Biophys 2020; 39: 123-34. Ding Z, Liu S, Wang X, et al. Cross-talk between LOX-1 and PCSK9 in vascular tissues. Cardiovasc Res 2015; 107: 556-67. Feingold KR, Moser AH, Shigenaga JK, Patzek SM, Grunfeld C. Inflammation stimulates the expression of PCSK9. Biochem Biophys Res Commun 2008; 374: 341-4. |
فهرسة مساهمة: | Investigator: 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; GS Pasetti; MC Casadio; R Buontempo; S Carrer; F Piccoli; T Rizzi; A Caricato; M La Sala; A Antonaci; P Fassini; S Paganini; V Porta; G Moise; S Marell; M Furia; MC 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; FG 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; MD Morte; E Boselli; D Puscio; A Galzerano; M Carli; G Zagara Keywords: PCSK9; mortality; pentraxin 3; sepsis; septic shock |
المشرفين على المادة: | 0 (Biomarkers) 0 (Serum Amyloid P-Component) 148591-49-5 (PTX3 protein) 9007-41-4 (C-Reactive Protein) EC 3.4.21.- (PCSK9 protein, human) EC 3.4.21.- (Proprotein Convertase 9) |
تواريخ الأحداث: | Date Created: 20200721 Date Completed: 20210903 Latest Revision: 20210903 |
رمز التحديث: | 20240628 |
DOI: | 10.1111/joim.13150 |
PMID: | 32686253 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1365-2796 |
---|---|
DOI: | 10.1111/joim.13150 |