Reduced plasma PCSK9 response in patients with bacteraemia is associated with mortality.

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.