No additional prognostic value of genetic information in the prediction of vascular events after cerebral ischemia of arterial origin: The PROMISe study
Achterberg S. Kappelle L.J. De Bakker P.I.W. Traylor M. Algra A. Van Der Graaf Y. Grobbee D.E. Rutten G.E.H.M. Visseren F.L.J. Moll F.L.
Achterberg S.
Kappelle L.J.
De Bakker P.I.W.
Traylor M.
Algra A.
Van Der Graaf Y.
Grobbee D.E.
Rutten G.E.H.M.
Visseren F.L.J.
Moll F.L.
Citations
Altmetric:
Alternative Title
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, 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%. 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. Conclusions: We 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. © 2015 Achterberg et al.
Keywords
adult, aged, area under the curve, Article, brain ischemia, cardiovascular disease, cardiovascular risk, cohort analysis, controlled study, female, follow up, genetic association, genetic risk, genotyping technique, heart infarction, heredity, human, incidence, major clinical study, male, prediction, prognosis, receiver operating characteristic, risk factor, single nucleotide polymorphism, vascular disease, artery, brain infarction, brain ischemia, cerebrovascular accident, genetics, genome-wide association study, genotype, middle aged, pathology, procedures, risk factor, Aged, Area Under Curve, Arteries, Brain Ischemia, Cerebral Infarction, Female, Genome-Wide Association Study, Genotype, Humans, Incidence, Male, Middle Aged, Polymorphism, Single Nucleotide, Prognosis, Risk Factors, ROC Curve, Stroke, Vascular Diseases
Source Title
PLoS ONE
Publisher
Public Library of Science
Series/Report No.
Collections
Rights
Date
2015
DOI
10.1371/journal.pone.0119203
Type
Article