Causal Relevance of Lp(a) for Coronary Heart Disease and Stroke Types in East Asian and European Ancestry Populations: A Mendelian Randomization Study
Authors' conclusion
The effects of Lp(a) on risk of myocardial infarction and large-artery IS were comparable in East Asian and European individuals, suggesting that people with either ancestry could expect comparable proportional benefits for equivalent reductions in Lp(a), but there was little effect on other stroke types.
Study context
- Population
- East Asian (China Kadoorie Biobank) and European ancestry individualsChina Kadoorie Biobank (CKB) nested case-control
- Participants
- 18,174 participants
- Comparison
- Genetically predicted lower Lp(a) (per 100 nmol/L) and risk of MI, ischemic stroke subtypes and intracerebral hemorrhage
- Outcome
- Rate ratio per 100 nmol/L lower genetically predicted Lp(a), both ancestries combined
Methodological detailsnested case-control, genome-wide association analysis, 2-sample Mendelian randomization
- Nested case-control
- Genome-wide association analysis
- 2-sample Mendelian randomization
Main finding
As reported in the abstract
Rate ratio (95% CI)
MI3-fold greater proportional reduction than for total IS
0.78(0.76–0.81)
Total IS
0.94(0.92–0.96)
Large-artery ISn=8134
0.80(0.73–0.87)
Cardioembolic ISn=11 730
0.92(0.86–0.98)
Small-vessel ISn=12 343; no association
0.99(0.91–1.07)
Intracerebral hemorrhagen=5845; no association
1.08(0.96–1.21)
Per 100 nmol/L lower genetically predicted Lp, as printed
Observational data: associations, not effects.
Further findings
Observational association of plasma Lp(a) (CKB)
- Log-linear positive association with MI and IS, not with intracerebral hemorrhage
GWAS of Lp(a)
- SNPs independently associated with Lp(a)
- 29
- Variance in Lp(a) explained in Chinese individuals
- 33%
- Lead Chinese variants replicated in UK Biobank Chinese individuals (n)
- 1260
- Variance in Lp(a) explained in European individuals
- 10%
Original publication
Causal Relevance of Lp(a) for Coronary Heart Disease and Stroke Types in East Asian and European Ancestry Populations: A Mendelian Randomization Study. Circulation. Published 29 April 2025. doi:10.
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