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Lipoprotein(a) and stroke: a two-sample Mendelian randomization study.

Yi Huang1,2, Ruijie Zhang3,4, Liyuan Han3,4

  • 1Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo, China.

Frontiers in Aging Neuroscience
|May 30, 2023
PubMed
Summary

Elevated lipoprotein(a) (Lp(a)) levels are associated with an increased risk of total stroke, ischemic stroke, and large-artery atherosclerotic stroke. This genetic analysis confirms a potential causal link between Lp(a) and stroke incidence.

Keywords:
Mendelian randomizationischemic strokelarge-artery atherosclerotic strokelipoprotein(a)stroke

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Area of Science:

  • Cardiovascular Genetics
  • Epidemiology
  • Stroke Research

Background:

  • Lipoprotein(a) (Lp(a)) is a recognized risk factor for cardiovascular disease.
  • The causal relationship between Lp(a) and stroke risk requires further investigation.

Purpose of the Study:

  • To evaluate the potential causal relationship between lipoprotein(a) and stroke risk using genetic data.
  • To assess the association of Lp(a) with total, ischemic, and subtypes of stroke.

Main Methods:

  • Utilized two large-scale genome-wide association study (GWAS) databases for instrumental variable selection related to Lp(a).
  • Acquired summary-level data for stroke outcomes from the UK Biobank and MEGASTROKE consortium.
  • Performed two-sample Mendelian randomization (MR) analyses including inverse variance-weighted (IVW) meta-analysis, weighted median, and MR Egger regression.
  • Conducted multivariable-adjusted Cox regression models for observational analysis.

Main Results:

  • Genetically predicted Lp(a) showed a marginal association with increased odds of total stroke (OR: 1.003, p=0.010) and ischemic stroke (OR: 1.004, p=0.004) in the MEGASTROKE data.
  • A significant association was observed between genetically predicted Lp(a) and large-artery atherosclerotic stroke (OR: 1.012, p=0.002).
  • Consistent associations were found using UK Biobank data and in observational analyses, linking higher Lp(a) levels to increased stroke risk.

Conclusions:

  • Genetically predicted higher Lp(a) levels may increase the risk of total stroke, ischemic stroke, and large-artery atherosclerotic stroke.
  • These findings support a causal role for Lp(a) in stroke pathogenesis.