Carolina Soriano-Tárraga1, Marina Mola-Caminal1, Eva Giralt-Steinhauer1, Angel Ois1, Ana Rodríguez-Campello1, Elisa Cuadrado-Godia1, Alejandra Gómez-González1, Rosa M Vivanco-Hidalgo1, Israel Fernández-Cadenas1, Natalia Cullell1, Jaume Roquer2, Jordi Jiménez-Conde2. 1. From the Department of Neaurology (C.S.-T., M.M.-C., E.G.-S., A.O., A.R.-C., E.C.-G., A.G.-G., R.M.V.-H., J.R., J.J.-C.), Hospital del Mar, Barcelona; Neurovascular Research Group (C.S.-T., M.M.-C., E.G.-S., A.O., A.R.-C., E.C.-G., A.G.-G., R.M.V.-H., J.R., J.J.-C.), IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autònoma de Barcelona/DCEXS-Universitat Pompeu Fabra; Department of Genetics (M.M.-C.), Universitat de Barcelona; and Stroke Pharmacogenomics and Genetics (I.F.-C., N.C.), Fundació Docència i Recerca MutuaTerrassa, Hospital Mútua de Terrassa, Spain. 2. From the Department of Neaurology (C.S.-T., M.M.-C., E.G.-S., A.O., A.R.-C., E.C.-G., A.G.-G., R.M.V.-H., J.R., J.J.-C.), Hospital del Mar, Barcelona; Neurovascular Research Group (C.S.-T., M.M.-C., E.G.-S., A.O., A.R.-C., E.C.-G., A.G.-G., R.M.V.-H., J.R., J.J.-C.), IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autònoma de Barcelona/DCEXS-Universitat Pompeu Fabra; Department of Genetics (M.M.-C.), Universitat de Barcelona; and Stroke Pharmacogenomics and Genetics (I.F.-C., N.C.), Fundació Docència i Recerca MutuaTerrassa, Hospital Mútua de Terrassa, Spain. jjimenez@imim.es JRoquer@parcdesalutmar.cat.
Abstract
OBJECTIVE: To analyze the effect of age-related DNA methylation changes in multiple cytosine-phosphate-guanine (CpG) sites (biological age [b-age]) on patient outcomes at 3 months after an ischemic stroke. METHODS: We included 511 patients with first-ever acute ischemic stroke assessed at Hospital del Mar (Barcelona, Spain) as the discovery cohort. Demographic and clinical data, including chronological age (c-age), vascular risk factors, initial stroke severity, recanalization treatment, and previous and 3-month modified Rankin Scale (p-mRS and 3-mRS, respectively) were registered. B-age was estimated with an algorithm, based on DNA methylation in 71 CpGs. Bivariate analysis determined variables associated with 3-mRS for inclusion in ordinal multivariate analysis. RESULTS: After ordinal regressions for 3-month ischemic stroke outcome (3-mRS), b-age was associated with outcome (odds ratio 1.04 [95% confidence interval 1.01-1.07]), nullifying c-age. Stepwise regression kept b-age, basal NIH Stroke Scale, sex, p-mRS, and recanalization treatment as better explanatory variables, instead of c-age. These results were successfully replicated in an independent cohort. CONCLUSIONS: B-age, estimated by DNA methylation, is an independent predictor of ischemic stroke outcome regardless of chronological years.
OBJECTIVE: To analyze the effect of age-related DNA methylation changes in multiple cytosine-phosphate-guanine (CpG) sites (biological age [b-age]) on patient outcomes at 3 months after an ischemic stroke. METHODS: We included 511 patients with first-ever acute ischemic stroke assessed at Hospital del Mar (Barcelona, Spain) as the discovery cohort. Demographic and clinical data, including chronological age (c-age), vascular risk factors, initial stroke severity, recanalization treatment, and previous and 3-month modified Rankin Scale (p-mRS and 3-mRS, respectively) were registered. B-age was estimated with an algorithm, based on DNA methylation in 71 CpGs. Bivariate analysis determined variables associated with 3-mRS for inclusion in ordinal multivariate analysis. RESULTS: After ordinal regressions for 3-month ischemic stroke outcome (3-mRS), b-age was associated with outcome (odds ratio 1.04 [95% confidence interval 1.01-1.07]), nullifying c-age. Stepwise regression kept b-age, basal NIH Stroke Scale, sex, p-mRS, and recanalization treatment as better explanatory variables, instead of c-age. These results were successfully replicated in an independent cohort. CONCLUSIONS: B-age, estimated by DNA methylation, is an independent predictor of ischemic stroke outcome regardless of chronological years.