Associations of serially measured PCSK9, LDLR and MPO with clinical outcomes in heart failure
- 1 March 2021
- journal article
- research article
- Published by Future Medicine Ltd in Biomarkers in Medicine
- Vol. 15 (4), 247-255
- https://doi.org/10.2217/bmm-2020-0585
Abstract
Aim: To investigate the temporal evolution of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9), low-density lipoprotein receptor (LDLR) and myeloperoxidase (MPO) in relation to clinical outcome in chronic heart failure (CHF). Methodology & results: Trimonthly blood sampling was performed during a median follow-up of 2.2 (IQR 1.4–2.5) years in 263 CHF patients. Seventy patients reached the primary end point (PE) (cardiovascular death, heart transplantation, left ventricular assist device implantation or HF-hospitalization). MPO level was independently associated with the PE; the adjusted (for clinical factors) hazard ratio (aHR) per standard deviation difference in MPO was 1.71 (95% CI: 1.23–2.43) at any time during follow-up. PCSK9 level (HR: 1.45 [1.04–2.06]) and LDLR (HR: 0.66 [0.49–0.87]) were statistical significantly associated with the PE but only in unadjusted analyses. Slope of temporal MPO evolution (aHR: 1.34 [1.12–1.76] per 0.1 standard deviation/year difference in slope) and LDLR (aHR: 0.78 [0.61–0.90]) however, were associated with PE. Conclusion: Temporal patterns of MPO and LDLR are independently associated with clinical outcome in CHF, which illustrates the importance of assessing temporal evolutions. Clinical trial registration information: registered in ClinicalTrials.gov, number NCT01851538. https://clinicaltrials.gov/ct2/show/NCT01851538.Keywords
Funding Information
- Noordwest Academie
- Jaap Schouten Foundation
This publication has 28 references indexed in Scilit:
- PCSK9 inhibitors – past, present and futureExpert Opinion on Drug Metabolism & Toxicology, 2015
- PCSK9 and LDLR degradationCurrent Opinion in Lipidology, 2014
- Antibody‐based proteomics and biomarker research—Current status and limitationsProteomics, 2014
- Oxidative stress and heart failureAmerican Journal of Physiology-Heart and Circulatory Physiology, 2011
- Dynamic Predictions and Prospective Accuracy in Joint Models for Longitudinal and Time-to-Event DataBiometrics, 2011
- PCSK9: a convertase that coordinates LDL catabolismJournal of Lipid Research, 2009
- Prognostic Value and Echocardiographic Determinants of Plasma Myeloperoxidase Levels in Chronic Heart FailureJournal of the American College of Cardiology, 2007
- Plasma Myeloperoxidase Levels in Patients With Chronic Heart FailureThe American Journal of Cardiology, 2006
- Myeloperoxidase and Cardiovascular DiseaseArteriosclerosis, Thrombosis, and Vascular Biology, 2005
- Myeloperoxidase Functions as a Major Enzymatic Catalyst for Initiation of Lipid Peroxidation at Sites of InflammationOnline Journal of Public Health Informatics, 2002