Associations of serially measured PCSK9, LDLR and MPO with clinical outcomes in heart failure

Biomark Med. 2021 Mar;15(4):247-255. doi: 10.2217/bmm-2020-0585. Epub 2021 Feb 16.

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: biomarkers; epidemiology; heart failure; low-density lipoprotein receptor (LDLR); myeloperoxidase (MPO); proprotein convertase subtilisin/kexin type 9 (PCSK9); repeated measurements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood*
  • Female
  • Heart Failure / blood
  • Heart Failure / pathology*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Peroxidase / blood*
  • Prognosis
  • Proprotein Convertase 9 / blood*
  • Prospective Studies
  • Receptors, LDL / blood*

Substances

  • Biomarkers
  • LDLR protein, human
  • Receptors, LDL
  • MPO protein, human
  • Peroxidase
  • PCSK9 protein, human
  • Proprotein Convertase 9

Associated data

  • ClinicalTrials.gov/NCT01851538