Abstract
BackgroundPatients 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, 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 ResultsWe 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%. 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 0.61-0.69). When we added a genetic risk score based on prioritized SNPs from a genome-wide association study of ischemic stroke (using summary statistics from the METASTROKE study which included 12389 cases and 62004 controls), the AUC-ROC remained the same. Similar results were found for the secondary outcome ischemic stroke.ConclusionsWe found no additional value of genetic information in a prognostic model for the risk of ischemic 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) vascular events. At present, genetic information cannot help clinicians to distinguish patients at high risk for recurrent vascular events.
Highlights
Patients who suffered from cerebral ischemia have an increased risk of new cerebrovascular and cardiovascular events
The prognostic model based on classical vascular risk factors had an area under the receiver operating characteristics curve (AUC-receiver-operator characteristics (ROC)) of 0.65 (95% confidence interval 0.61-0.69)
When we added a genetic risk score based on prioritized single nucleotide polymorphisms (SNPs) from a genome-wide association study of ischemic stroke, the area under the curve (AUC)-ROC remained the same
Summary
Patients who suffered from cerebral ischemia have an increased (long-term) risk of new cerebrovascular and cardiovascular events. Two loci (PITX2 and ZFHX3) were found to be associated with atrial fibrillation and cardioembolic stroke risk.[4, 5] Subsequently, two loci (9p21 and HDAC9) were identified as robust associations with large vessel stroke.[6, 7] These findings were recently confirmed in a metaanalysis of genome-wide association studies (GWAS) carried out by the METASTROKE consortium.[8] These common genetic polymorphisms account only for a small increase in disease risk, suggesting that large sample sizes will be needed to find additional susceptibility alleles.[9]. Patients who have suffered from cerebral ischemia have a high risk of recurrent vascular events. Given that cerebral ischemia has a heritable component, 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 including genetic information.
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