Common genetic markers and prediction of recurrent events after ischemic stroke in young adults.
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.
Pezzini
A
A
Clinica Neurologica, Università degli Studi di Brescia, P.le Spedali Civili, 1, 25100 Brescia, Italia. ale_pezzini@hotmail.com
Grassi
M
M
Del Zotto
E
E
Lodigiani
C
C
Ferrazzi
P
P
Spalloni
A
A
Patella
R
R
Giossi
A
A
Volonghi
I
I
Iacoviello
L
L
Magoni
M
M
Rota
L L
LL
Rasura
M
M
Padovani
A
A
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000367:Age Factors; D002545:Brain Ischemia / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005165:Factor V / Q000235:genetics; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005820:Genetic Testing; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008403:Mass Screening; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D016016:Proportional Hazards Models; D011516:Prothrombin / Q000235:genetics; D012008:Recurrence; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D055815:Young Adult
D005819:Genetic Markers; D005165:Factor V; D011516:Prothrombin; D042965:Methylenetetrahydrofolate Reductase (NADPH2)