Decreased Clearance of Low-Density Lipoprotein Cholesterol is Causally Associated With Increased Mortality of Septic Shock
Authors' conclusion
Low LDL-C clearance explains the causal association between high genetically predicted pre-infection LDL-C levels and increased septic shock mortality.
Study context
- Population
- Genotyped septic shock patients in multicentre ICUs in Japan
- Participants
- 614 patients
- Comparison
- Genetically predicted pre-infection low-density lipoprotein cholesterol (LDL-C) levels and 28-day mortality
- Outcome
- Septic shock mortality
- Follow-up
- 28 days
Methodological detailstwo-sample Mendelian randomization, multicentre
- Two-sample Mendelian randomization
- Multicentre
Main finding
As reported in the abstract
28-day mortality per high predicted pre-infection LDL-C
- High predicted pre-infection LDL-C causally associated with increased 28-day mortality, HR
- 2.78
- P
- p = 0.039
Further findings
Predicted pre-infection vs measured LDL-C at septic shock onset
- Predicted pre-infection LDL-C
- 141 mg/dL
- Measured LDL-C at onset
- 40 mg/dL
- P
- P < 0.001
PCSK9 variants increasing LDL-C clearance (genetically proxied PCSK9 inhibitor)
- Associated with decreased mortality
- P = 0.003
HMGCR variants decreasing LDL-C production (genetically proxied statin)
- Not associated with decreased mortality; opposite effect observed
- P = 0.039
Main genetic variants driving the association
- Apolipoprotein genes ApoB100-rs13306206 and ApoE-rs7412, involved in LDL-C binding to LDL receptor
Original publication
Decreased Clearance of Low-Density Lipoprotein Cholesterol is Causally Associated With Increased Mortality of Septic Shock. Crit Care Med. Published 5 August 2025. doi:10.
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