A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk
An erratum to this article was published (Nat Med, Jun 2024 ↗)
Authors' conclusion
Collectively, these results indicate that the terminal breakdown products of excess niacin, 2PY and 4PY, are both associated with residual CVD risk.
Study context
- Population
- Stable cardiac patients (discovery and validation cohorts, US and European)discovery cohort
- Participants
- 1,162 patients
- Outcome
- Incident major adverse cardiovascular events (MACE) by serum 2PY and 4PY (terminal niacin metabolites)
- Follow-up
- 3 years
Methodological detailsuntargeted metabolomics, prospective discovery cohort, validation cohorts, phenome-wide association analysis, meta-analysis, mouse experiments
- Untargeted metabolomics
- Prospective discovery cohort
- Validation cohorts
- Phenome-wide association analysis
- Meta-analysis
- Mouse experiments
Main finding
As reported in the abstract
Adjusted hazard ratio (95% CI)
2PYUS validation cohort (n = 2,331)
1.64(1.10–2.42)
2PYEuropean validation cohort (n = 832)
2.02(1.29–3.18)
4PYUS validation cohort (n = 2,331)
1.89(1.26–2.84)
4PYEuropean validation cohort (n = 832)
1.99(1.26–3.14)
Further findings
rs10496731 and sVCAM-1 (meta-analysis)
- rs10496731 associated with sVCAM-1 (n = 106,000)
- P = 3.6 × 10-18
Correlation of sVCAM-1 with 2PY and 4PY (validation cohort n = 974)
- 2PY: rho = 0.13
- P = 7.7 × 10-5
- 4PY: rho = 0.18
- P = 1.1 × 10-8
VCAM-1 expression and leukocyte adherence in mice
- Physiological 4PY, but not 2PY, induced VCAM-1 expression and leukocyte adherence to vascular endothelium
Original publication
A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. Nat Med. Published 19 February 2024. doi:10.
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