Common genetic markers and prediction of recurrent events after ischemic stroke in young adults

Neurology. 2009 Sep 1;73(9):717-23. doi: 10.1212/WNL.0b013e3181b59aaf.

Abstract

Background: Scarce information is available on the usefulness of new prediction markers for identifying young ischemic stroke patients at highest risk of recurrence.

Methods: The predictive effect of traditional risk factors as well as of the 20210A variant of prothrombin gene, the 1691A variant of factor V gene, and the TT677 genotype of the methylenetetrahydrofolate reductase (MTHFR) gene on the risk of recurrence was investigated in a hospital-based cohort study of 511 ischemic stroke patients younger than 45 years followed up for a mean of 43.4 months. Outcome measures were fatal/nonfatal myocardial infarction, ischemic stroke, or TIA. Risk prediction was assessed with the use of the concordance c (c index), and the Net Reclassification Improvement (NRI).

Results: The risk of recurrence increased with increasing number of traditional factors (hazard ratio [HR] 2.29, 95% confidence interval [CI] 1.57-3.35 for subjects with 1 factor: HR 5.25, 95% CI 2.45-11.2 for subjects with 2), as well as with that of predisposing genotypes (HR 1.96, 95% CI 1.33-2.89 for subjects carrying 1 at-risk genotype; HR 3.83, 95% CI 1.76-8.34 for those carrying 2). The c statistics increased significantly when the genotypes were included into a model with traditional risk factors (0.696 vs 0.635, test z = 2.41). The NRI was also significant (NRI = 0.172, test z = 2.17).

Conclusions: Addition of common genetic variants to traditional risk factors may be an effective method for discriminating young stroke patients at different risk of future ischemic events.

MeSH terms

  • Adolescent
  • Adult
  • Age Distribution
  • Age Factors
  • Brain Ischemia / diagnosis
  • Brain Ischemia / epidemiology*
  • Brain Ischemia / genetics*
  • DNA Mutational Analysis
  • Factor V / genetics
  • Female
  • Genetic Markers / genetics*
  • Genetic Predisposition to Disease / epidemiology*
  • Genetic Testing
  • Genetic Variation
  • Genotype
  • Humans
  • Male
  • Mass Screening
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Middle Aged
  • Proportional Hazards Models
  • Prothrombin / genetics
  • Recurrence
  • Risk Factors
  • Stroke / diagnosis
  • Stroke / epidemiology*
  • Stroke / genetics*
  • Young Adult

Substances

  • Genetic Markers
  • Factor V
  • Prothrombin
  • Methylenetetrahydrofolate Reductase (NADPH2)