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Background The involvement of traditional risk factors and combined genetic markers of recurrent arterial ischemic stroke (AIS) in adults remains unclear. Objective This study aims to determine significant clinical and genetic factors of AIS recurrence, and to investigate the combined effect of genotypes on the occurrence of a second cerebral ischemic attack. Methods We investigated a cohort study of AIS patients (18–50 years old) followed in the neurology department over 5 years. Traditional and genetic risk factors were carried through a multivariable logistic regression model. We used a Cox proportional hazard model for identifying predictors of recurrence. Results Two hundred and seventy patients were enrolled in our study. The risk of AIS recurrence was 36.2% within 5 years. The potential risk of recurrence of AIS increased with traditional and genetic risk factors such as hypertension, diabetes mellitus, heart failure, and family history of cerebrovascular diseases. This risk increased with increasing number of genetic factors. The hazard ratio (HR) was 0.66 (95% confidence interval [CI] 0.97–2.67) for the subject with one genetic factor, 1.61 (95% CI 0.97–2.25) for combined methylenetetrahydrofolate reductase (MTHFR) polymorphisms, and 2.57 (95% CI 1.32–4.99) for combined factor V Leiden (FVL) and MTHFR polymorphisms (677 or 1298). The HR for the three polymorphisms combined was 6.04 (95% CI 2.40–15.16). Conclusions Our findings suggest that cumulative effect of both traditional and common genetic risk factors was associated with recurrence of ischemic stroke. We demonstrated for the first time that a combined genotype FVL/MTHFR profile increase the risk of a second cerebral ischemic attack.

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