Apolipoprotein B-containing lipoproteins: distinct roles in atherosclerosis revealed by plasma proteomic profiling
Authors' conclusion
Beyond arterial lipid deposition, TRL and Lp(a) converge on inflammatory and vascular remodeling pathways that, under the assumptions of observational mediation analysis, may explain their excess per-particle atherogenicity compared with LDL.
Study context
- Population
- Primary prevention cohort, UK Biobank; replication in the Multi-Ethnic Study of Atherosclerosis1,599 coronary artery disease (CAD) events
- Participants
- 35,269 participants
- Outcome
- Association of lipoprotein-specific multi-protein scores (LDL, TRL, Lp(a)) with incident CAD
Methodological detailsone-sample Mendelian randomization, high-dimensional mediation analysis, external replication (MESA)
- One-sample Mendelian randomization
- High-dimensional mediation analysis
- External replication (MESA)
Main finding
As reported in the abstract
Incident CAD per 1-SD of lipoprotein-specific multi-protein score
Hazard ratio per 1-SD (95% CI)
TRLadjusted for confounders and measured lipoprotein concentrations
1.16(1.08–1.24)
Lp(a)adjusted for confounders and measured lipoprotein concentrations
1.09(1.03–1.15)
LDLnot associated
0.95(0.89–1.02)
Per 1-SD of lipoprotein-specific multi-protein score, as printed
Observational data: associations, not effects.
Further findings
Proteins associated with each lipoprotein (concordant observational and MR, Bonferroni-adjusted P<0.05)
- Low-density lipoprotein (LDL)-associated proteins
- 30
- Triglyceride-rich lipoproteins (TRL)-associated proteins
- 471
- Lp(a)-associated proteins
- 53
- Proteins shared by TRL and Lp(a) signatures (distinct from LDL; common enrichment in inflammatory pathways)
- 36
Proportion of CAD risk mediated by immune activation and vascular remodeling markers
- TRL-associated CAD risk
- 62%
- Lp(a)-associated CAD risk
- 14%
Original publication
Apolipoprotein B-containing lipoproteins: distinct roles in atherosclerosis revealed by plasma proteomic profiling. Eur Heart J. Published 31 August 2026. doi:10.
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