Proprotein convertase subtilisin/kexin type 9 (PCSK9) levels in primary antiphospholipid syndrome. The multicenter ATHERO-APS study

J Autoimmun. 2022 May:129:102832. doi: 10.1016/j.jaut.2022.102832. Epub 2022 May 2.

Abstract

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) is emerging as a novel cardiovascular risk factor. Levels of PCSK9 in thrombotic primary antiphospholipid syndrome (PAPS) have never been investigated.

Methods: Cross sectional comparison of baseline characteristics of 91 PAPS patients enrolled in the multicenter prospective ATHERO-APS cohort study. PCSK9 levels were categorized into tertiles and the association with arterial and recurrent thrombosis were assessed by univariable and multivariable logistic regression analysis.

Results: Median age was 51 years and 71.4% (n = 65) were women. Overall, 33% (n = 30) experienced an arterial event while 31% (n = 28) had recurrent thrombotic events. Median PCSK9 levels were 1243 (1100-1650) pg/ml. Patients in the third PCSK9 tertile (>1458 pg/ml) showed a higher prevalence of dyslipidemia, lupus anticoagulant positivity and a history of previous arterial and recurrent thrombosis than patients in the first and second tertile. PCSK9 levels were higher in arterial than venous thrombosis (1502 vs. 1180 pg/ml, p = 0.002), and in patients with recurrent vs isolated thrombosis (1680 vs. 1150 pg/m, p < 0.001). High plasma PCSK9 levels were associated with a 4-fold increase risk for arterial events and with a 10-fold increase risk for recurrent thrombosis after adjustment for confounding factors.

Conclusion: These preliminary data suggest that PCSK9 levels are increased in PAPS patients with arterial and recurrent thrombosis. Its role as a possible therapeutic target in PAPS needs further studies.

Keywords: Antiphospholipid syndrome; PCSK9; Thrombosis.

Publication types

  • Multicenter Study

MeSH terms

  • Antiphospholipid Syndrome* / epidemiology
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Proprotein Convertase 9
  • Prospective Studies
  • Thrombosis* / epidemiology

Substances

  • PCSK9 protein, human
  • Proprotein Convertase 9