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

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.

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.

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.

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.