Reduced Plasma PCSK9 Response in Patients With Bacteraemia Is Associated With Mortality

J Intern Med. 2019 Nov;286(5):553-561. doi: 10.1111/joim.12946. Epub 2019 Jun 19.

Abstract

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme controls blood cholesterol levels by downregulating the expression of the low-density lipoprotein receptor (LDLR). Pathogenic lipids (e.g. lipopolysaccharide) are removed from the circulation by an LDLR/PCSK9-dependent mechanism; thus, it has been suggested that PCSK9 inhibitors may be beneficial in the treatment of infections. We measured plasma PCSK9 levels in patients with culture-positive bacteraemia and explored pathogen-dependent and infection site-dependent effects as well as correlations between patient characteristics and outcome.

Methods: Proprotein convertase subtilisin/kexin type 9 in the plasma was measured with an enzyme-linked immunosorbent assay from 481 patients with blood culture-positive infection on days 0 to 4 after admission to the emergency department. Patient outcome and clinical and laboratory data were gathered retrospectively from patient records.

Results: The plasma PCSK9 level was elevated equally in patients with Gram-positive or Gram-negative bacterial infections; particularly high levels were seen in patients with a lower respiratory tract infection and Streptococcus pneumoniae bacteraemia. PCSK9 levels showed a significant positive correlation with C-reactive protein (CRP) level. Bacteraemia patients with liver disease or a history of alcohol abuse had significantly lower levels of plasma PCSK9. Reduced PCSK9 plasma responses in patients were significantly associated with mortality at days 7, 28 and 90.

Conclusion: Proprotein convertase subtilisin/kexin type 9 is upregulated in blood culture-positive infections. Plasma PCSK9 resembles acute-phase proteins; its expression is induced during an infection, reduced in liver disease and correlates positively with CRP level. We have shown that PCSK9 levels are lower in patients with a fatal prognosis.

Keywords: CRP; PCSK9; bacteraemia; sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bacteremia / blood*
  • Bacteremia / microbiology
  • Bacteremia / mortality*
  • Female
  • Gram-Negative Bacterial Infections / blood*
  • Gram-Negative Bacterial Infections / mortality
  • Gram-Positive Bacterial Infections / blood*
  • Gram-Positive Bacterial Infections / mortality
  • Humans
  • Male
  • Middle Aged
  • Proprotein Convertase 9 / blood*
  • Retrospective Studies
  • Survival Rate

Substances

  • PCSK9 protein, human
  • Proprotein Convertase 9