Reduced plasma PCSK 9 response in patients with bacteraemia is associated with mortality

Background The proprotein convertase subtilisin/kexin type 9 ( PCSK 9) 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 / PCSK 9‐dependent mechanism; thus, it has been suggested that PCSK 9 inhibitors may be beneficial in the treatment of infections. We measured plasma PCSK 9 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 PCSK 9 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. PCSK 9 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 PCSK 9. Reduced PCSK 9 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 PCSK 9 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 PCSK 9 levels are lower in patients with a fatal prognosis.