ArticleEBioMedicine2018
Impact of PCSK9 loss-of-function genotype on 1-year mortality and recurrent infection in sepsis survivors.
Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 44 citations in OpenAlex.
- PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection.Journal of the American College of Cardiology · 2023Trial
- Genetic associations in sepsis and ARDS.Frontiers in pharmacology · 2026Review
- A narrative review of PCSK9 inhibitors: from evolocumab to novel discoveries.Frontiers in pharmacology · 2026Review
- PCSK9 Promotes Platelet Activation and NET Formation, Aggravating Pulmonary Microthrombosis in Sepsis-Induced Lung Injury.Biomedicines · 2025Article
- Protective impact of circulating ω-3 PUFAs on sepsis susceptibility throughFrontiers in medicine · 2025Article
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside.Signal transduction and targeted therapy · 2024Review
- Pharmacologic and Genetic Downregulation of Proprotein Convertase Subtilisin/Kexin Type 9 and Survival From Sepsis.Critical care explorations · 2023Article
- Elevated circulating PCSK9 level is associated with 28-day mortality in patients with sepsis: a prospective cohort study.BMC emergency medicine · 2023Article
- The evolving landscape of PCSK9 inhibition in cancer.European journal of pharmacology · 2023Review
- Anti-Inflammatory Effects of Lipid-Lowering Drugs and Supplements-A Narrative Review.Nutrients · 2023Review
- A bibliometric analysis of PCSK9 inhibitors from 2007 to 2022.Frontiers in endocrinology · 2023Article
- Impact of High-Density Lipoproteins on Sepsis.International journal of molecular sciences · 2022Review
- The Multifaceted Biology of PCSK9.Endocrine reviews · 2022Review
- Construction of point mutation rabbits using CRISPR/Cas9.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2021Article
- Plasma PCSK9 levels and sepsis severity: an early assessment in the emergency department.Clinical and experimental medicine · 2021Article
- LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients.Journal of lipid research · 2020Article
- Low PCSK-9 levels Are Associated with Favorable Neurologic Function after Resuscitation from out of Hospital Cardiac Arrest.Journal of clinical medicine · 2020Article
- Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Is Not Induced in Artificial Human Inflammation and Is Not Correlated with Inflammatory Response.Infection and immunity · 2020Article
- Inhibition of Proprotein Convertase Subtilisin/Kexin Type 9 Ameliorates Liver Fibrosis via Mitigation of Intestinal Endotoxemia.Inflammation · 2020Article
- Coming Back to Physiology: Extra Hepatic Functions of Proprotein Convertase Subtilisin/Kexin Type 9.Frontiers in physiology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundReduced activity of proprotein convertase subtilisin/kexin type 9 (PCSK9) has been associated with decreased short-term death in patients with septic shock. Whether PCSK9 genotype influences long-term outcomes in sepsis survivors is unknown.
methodsWe evaluated the impact of PCSK9 loss-of-function (LOF) genotype on both 1-year mortality and infection-related readmission (IRR) after an index sepsis admission. The Derivation cohort included 342 patients who survived 28 days after a sepsis admission in a tertiary hospital (Vancouver/Canada, 2004-2014), while an independent Validation cohort included 1079 septic shock patients admitted at the same hospital (2000-2006). All patients were genotyped for three common missense PCSK9 LOF variants rs11591147, rs11583680, rs562556 and were classified in 3 groups: Wildtype, single PCSK9 LOF, and multiple PCSK9 LOF, according to the number of LOF alleles per patient. We also performed a meta-analysis using both cohorts to investigate the effects of PCSK9 genotype on 90-day survival.
findingsIn the Derivation cohort, patients carrying multiple PCSK9 LOF alleles showed lower risk for the composite outcome 1-year death or IRR (HR: 0.40, P = 0.006), accelerated reduction on neutrophil counts (P = 0.010), and decreased levels of PCSK9 (P = 0.037) compared with WT/single LOF groups. Our meta-analysis revealed that the presence of multiple LOF alleles was associated with lower 90-day mortality risk (OR = 0.69, P = 0.020).
interpretationThe presence of multiple PCSK9 LOF alleles decreased the risk of 1-year death or IRR in sepsis survivors. Biological measures suggest this may be related to an enhanced resolution of the initial infection.
fundingCanadian Institutes of Health Research (PJT-156056).
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.