Predictors of Long-Term Recurrent Vascular Events After Ischemic Stroke at Young Age: The Italian Project on Stroke in Young Adults

Study Questions:

What are the long-term risks and predictors of recurrent thrombotic events after ischemic stroke at a young age?


The investigators followed 1,867 patients with first-ever ischemic stroke who were 18-45 years of age (mean age, 36.8 ± 7.1 years; women, 49.0%), as part of the Italian Project on Stroke in Young Adults (IPSYS). Median follow-up was 40 months (25th-75th percentile, 53). The primary endpoint was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. The authors computed a cumulative index (from 0-4) based on the number of traditional risk factors (hypertension, diabetes mellitus, smoking, and hypercholesterolemia). To evaluate the cumulative influence of these markers, they were included in the risk predictor set, regardless of their independent effect on the risk of recurrence. Kaplan-Meier survival analysis was used to estimate the cumulative incidence of recurrent events by follow-up time.


One hundred sixty-three patients had recurrent thrombotic events (average rate, 2.26 per 100 person-years at risk). At 10 years, cumulative risk was 14.7% (95% confidence interval [CI], 12.2%-17.9%) for the primary endpoint, 14.0% (95% CI, 11.4%-17.1%) for brain ischemia, and 0.7% (95% CI, 0.4%-1.3%) for myocardial infarction or other arterial events. Familial history of stroke, migraine with aura, circulating antiphospholipid antibodies, discontinuation of antiplatelet and antihypertensive medications, and any increase of one traditional vascular risk factor were independent predictors of the composite endpoint in multivariable Cox proportional hazards analysis. A point-scoring system for each variable was generated by their β-coefficients, and a predictive score (IPSYS score) was calculated as the sum of the weighted scores. The area under the receiver operating characteristic curve of the 0- to 5-year score was 0.66 (95% CI, 0.61-0.71; mean, 10-fold internally cross-validated area under the receiver operating characteristic curve, 0.65).


The authors concluded that among patients with ischemic stroke, ages 18-45 years, the long-term risk of recurrent thrombotic events is associated with modifiable, age-specific risk factors.


This study indicates that subjects ages 18-45 years, who survive the first 30 days after an ischemic stroke, are at substantial risk of recurrent arterial thrombosis over time, and that such a risk is partly attributable to modifiable factors including discontinuation of antiplatelet and antihypertensive medications. The study findings emphasize the importance of extending the use of secondary prevention treatments beyond the acute and early post-acute phase of brain ischemia into the long-term. Implementation of appropriate therapeutic and lifestyle treatment strategies in this age category of young patients is likely to impact the individual susceptibility to recurrence and improve outcomes.

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