Low levels of small high-density lipoprotein (HDL) particles predict but do not influence risk of sepsis
Main finding · Sepsis (small HDL particle count)Result — go to the resultHazard ratio 0.80 95% CI 0.74–0.86Authors' conclusion
Low number of small HDL particles are associated with increased hazard of sepsis, sepsis-related death, and sepsis-related critical care admission. However, genetic analyses did not strongly support this as causal.
Study context
- Population
- UK Biobank participants with NMR-derived HDL subclass dataUK Biobank
- Participants
- ≈270,000 participants
- Exposure
- Small HDL particle count, highest vs lowest quartile
- Outcome
- Sepsis
Methodological detailsCox regression, bidirectional Mendelian randomisation, UK Biobank and FinnGen genetic data
- Cox regression
- Bidirectional Mendelian randomisation
- UK Biobank and FinnGen genetic data
Main finding
Sepsis (small HDL particle count)
Hazard ratio
0.80
95% CI 0.74–0.86
P = 4 × 10-9
Quartile 4 vs Quartile 1
HR 0.80 (95% CI 0.74–0.86); P = 4 × 10-9
As reported in the abstract
Observational data: associations, not effects.
Further findings
| Outcome | HR (95% CI) | P value | |
|---|---|---|---|
| Critical care admission with sepsis (small HDL) | 0.72 (0.60–0.85) | P = 2 × 10-4 | |
| 0.512Hazard ratio (log scale) |
Mendelian randomisation (MR): small HDL particle count on sepsis incidence
| OR (95% CI) | P value | ||
|---|---|---|---|
| Small HDL particle countDid not strongly support causality | 0.98 (0.89–1.07) | P = 0.6 | |
| 0.512Odds ratio (log scale) |
MR: small HDL particle count on sepsis death
| OR (95% CI) | P value | ||
|---|---|---|---|
| Small HDL particle count | 0.94 (0.75–1.17) | P = 0.56 | |
| 0.512Odds ratio (log scale) |
MR: small HDL particle count on critical care admission with sepsis
| OR (95% CI) | P value | ||
|---|---|---|---|
| Small HDL particle count | 0.73 (0.57–0.95) | P = 0.02 | |
| 0.512Odds ratio (log scale) |
| Outcome | Estimate | P value |
|---|---|---|
| MR: IL-6 signalling on small HDL particle countBidirectional MR | beta - 0.16 per natural log change in SD-scaled CRP (95% CI - 0.10 to - 0.21) | P = 9 × 10-8 |
| MR: IL-6 signalling on total HDL particle count | beta - 0.13 (95% CI - 0.09 to - 0.17) | P = 7 × 10-10 |
Other HDL subclasses
- Parallel associations likely driven by changes in the small HDL compartment
MR: IL-6 signalling on total HDL particle count
- Reverse effect of HDL on IL-6 signalling largely null
Original publication
Low levels of small HDL particles predict but do not influence risk of sepsis. Crit Care. Published 9 October 2023. doi:10.
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