Biological Age is a predictor of mortality in Ischemic Stroke

Abstract

Age and stroke severity are the main mortality predictors after ischemic stroke. However, chronological age and biological age are not exactly concordant. Age-related changes in DNA methylation in multiple CpG sites across the genome can be used to estimate biological age, which is influenced by lifestyle, environmental factors, and genetic variation. We analyzed the impact of biological age on 3-month mortality in ischemic stroke. We assessed 594 patients with acute ischemic stroke in a cohort from Hospital del Mar (Barcelona) and validated the results in an independent cohort. Demographic and clinical data, including chronological age, vascular risk factors, initial stroke severity (NIHSS score), recanalization treatment, and previous modified Rankin scale were registered. Biological age was estimated with an algorithm based on DNA methylation in 71 CpGs. Biological age was predictive of 3-month mortality (p = 0.041; OR = 1.05, 95% CI 1.00-1.10), independently of NIHSS score, chronological age, TOAST, vascular risk factors, and blood cell composition. Stratified by TOAST classification, biological age was associated with mortality only in large-artery atherosclerosis etiology (p = 0.004; OR = 1.14, 95% CI 1.04-1.25). As estimated by DNA methylation, biological age is an independent predictor of 3-month mortality in ischemic stroke regardless of chronological age, NIHSS, previous modified Rankin scale, and vascular risk factors.

Figure 1

Mean age acceleration relates to mortality, p‐value of Student T-test. Age acceleration is the linear regression of biological age adjusted by chronological age, sex, stroke severity, TOAST and p-mRs. By definition, the mean age of participants alive at 3 months is zero. Each bar plot reports 1 standard error. TOAST, trial of ORG 10172 in acute stroke treatment; p-mRs, previous modified Rankin scale.

Figure 2

Mean age acceleration associated to mortality, stratified by stroke etiology: alive (white bars); deceased (grey bars); and p‐value of Student T-test. Age acceleration was adjusted by chronological age, sex, stroke severity, TOAST and p-mRs values. Each bar plot reports 1 standard error. LAA, large-artery atherosclerosis; CE, cardioembolic; TOAST, trial of ORG 10172 in acute stroke treatment; p-mRs, previous modified Rankin scale.