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NEUROLOGY 2009;73:717-723
© 2009 American Academy of Neurology

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

A. Pezzini, MD, M. Grassi, PhD, E. Del Zotto, MD, C. Lodigiani, MD, P. Ferrazzi, MD, A. Spalloni, MD, R. Patella, MD, A. Giossi, MD, I. Volonghi, MD, L. Iacoviello, MD, PhD, M. Magoni, MD, L. L. Rota, MD, M. Rasura, MD and A. Padovani, MD, PhD

From the Dipartimento di Scienze Mediche e Chirurgiche (A. Pezzini, E.D.Z., A.G., I.V., A. Padovani), Clinica Neurologica, Dipartimento di Scienze Biomediche e Biotecnologie (E.D.Z.), Università degli Studi di Brescia; Dipartimento di Scienze Sanitarie Applicate (M.G.), Sezione di Statistica Medica e Epidemiologia, Università di Pavia; Centro Trombosi (C.L., P.F., L.L.R.), IRCCS Istituto Clinico Humanitas, Rozzano-Milano; Stroke Unit (A.S., R.P., M.R.), Azienda Ospedaliera Sant'Andrea, Roma; Research Laboratories (L.I.), Centro di Ricerca e Formazione ad Alta Tecnologia nelle Scienze Biomediche, Università Cattolica del Sacro Cuore, Campobasso; and Stroke Unit (M.M.), Neurologia Vascolare, Spedali Civili di Brescia, Italia.

Address correspondence and reprint requests to Dr. Alessandro Pezzini, Clinica Neurologica, Università degli Studi di Brescia, P.le Spedali Civili, 1, 25100 Brescia, Italia ale_pezzini{at}hotmail.com.

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.

Abbreviations: AIC = Akaike information criterion; BIC = Bayes information criterion; CI = confidence interval; HR = hazard ratio; IS = ischemic stroke; MA = migraine with aura; MI = myocardial infarction; MO = migraine without aura; MTHFR = methylenetetrahydrofolate reductase; NRI = Net Reclassification Improvement.

Disclosure: The authors report no disclosures.

Received January 2, 2009. Accepted in final form June 9, 2009.






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