Prognosis after cerebral ischaemia of arterial origin: clinical characteristics and genetic information

Abstract

Background. Patients who have suffered from cerebral ischemia have a high risk of recurrent vascular events. Predictive models based on classical risk factors typically have limited prognostic value. Given that cerebral ischemia has a heritable component, addition of genetic information might improve performance of these risk models. Our aim was to develop and compare two models: one containing traditional vascular risk factors, the other also including genetic information. Methods and Results. We studied 1020 patients with cerebral ischemia and genotyped them with the Illumina Immunochip. Median follow-up time was 6.5 years; the annual incidence of new ischemic events (primary outcome, n=198) was 3.0% and of major bleedings (n=55) 0.8%. The prognostic model based on classical vascular risk factors had an area under the receiver operating characteristics curve (AUC-ROC) of 0.65 (95% confidence interval 0.62-0.69). When we added a genetic risk score based on a genome-wide association study of ischemic stroke, the AUC-ROC remained the same. Similar results were found for the secondary outcomes ischemic stroke and major bleeding. Conclusions. We found no additional value of genetic information in a prognostic model for the risk of ischemic or hemorrhagic events in patients with cerebral ischemia of arterial origin. This is consistent with a complex, polygenic architecture, where many genes of weak effect likely act in concert to influence the heritable risk of an individual to develop (recurrent) cerebrovascular accidents.