Prevention & lipidsCase-control study

Causal Relevance of Lp(a) for Coronary Heart Disease and Stroke Types in East Asian and European Ancestry Populations: A Mendelian Randomization Study

CirculationPublished

  • Mendelian randomisation study
  • nested case-control
  • genome-wide association analysis
  • 2-sample Mendelian randomization

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

Main finding

As reported in the abstract

Rate ratio per 100 nmol/L lower genetically predicted Lp(a), both ancestries combined
Rate ratio
MI3-fold greater proportional reduction than for total IS
0.78(95% CI 0.76–0.81)
Total IS
0.94(CI 0.92–0.96)
Large-artery ISn=8134
0.80(CI 0.73–0.87)
Cardioembolic ISn=11 730
0.92(95% CI 0.86–0.98)
Small-vessel ISn=12 343; no association
0.99(CI 0.91–1.07)
Intracerebral hemorrhagen=5845; no association
1.08(CI 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:10.1161/circulationaha.124.072086

Summarised from the published abstract; every number is checked against it