Proprotein convertase subtilisin/kexin type 9 in rheumatoid arthritis

Clin Exp Rheumatol. 2016 Nov-Dec;34(6):1013-1019. Epub 2016 Aug 31.

Abstract

Objectives: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism through low-density lipoprotein receptor degradation and that has been linked with cardiovascular risk. The purpose of the present study was to examine whether PCSK9 levels are related to both abnormalities in the lipid profile and the severe atherosclerosis that occur in rheumatoid arthritis (RA) patients.

Methods: Cross-sectional study that encompassed 520 individuals; 326 patients with RA and 194 age- and sex-matched controls. PCSK9 and lipoproteins serum concentrations, standard lipid profile and carotid intima-media thickness (cIMT) and carotid plaques were assessed in patients and controls. A multivariable analysis, adjusted for standard cardiovascular risk factors, was performed to evaluate the influence of PCSK9 on RA related dyslipidaemia and subclinical carotid atherosclerosis.

Results: After adjusting for classical cardiovascular risk factors, lipid profile and statins, RA patients showed lower PCSK9 serum concentrations than controls (beta coefficient -45 95%CI [-53, -38] ng/ml, p=0.00). PCSK9 was associated with both cIMT and the presence of carotid plaques in RA patients. However, this association was lost after adjusting for classical cardiovascular risk factors.

Conclusions: PCSK9 is down-regulated in patients with RA.

MeSH terms

  • Aged
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / diagnostic imaging
  • Carotid Artery Diseases / blood*
  • Carotid Artery Diseases / complications
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Intima-Media Thickness
  • Cross-Sectional Studies
  • Female
  • Humans
  • Lipids / blood
  • Lipoproteins / blood
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic / blood*
  • Plaque, Atherosclerotic / complications
  • Plaque, Atherosclerotic / diagnostic imaging
  • Proprotein Convertase 9 / blood*
  • Up-Regulation*

Substances

  • Lipids
  • Lipoproteins
  • PCSK9 protein, human
  • Proprotein Convertase 9