Abstract TMP57: The Influence of Telomere Length on Ischemic Stroke Risk and Phenotype

Abstract

Background: Telomeres are specific nucleotide repeats that play a central role in control of DNA damage related to cell division and aging. The degree of telomere shortening that occurs as part of aging is associated with age-related non-cancer diseases like hypertension, diabetes mellitus and coronary artery disease. Although a number of studies have highlighted that a similar relationship might exist with ischemic stroke, contradictory reports are also present in the literature. In this study we investigated the association between telomere length and ischemic stroke, not only in terms of stroke risk in general, but also from the perspective of stroke etiology and severity. Methods: In a Caucasian cohort, telomere length was determined by Southern blot from peripheral blood leukocytes in 163 consecutive ischemic stroke patients, and 210 controls without any prior history of ischemic stroke. Univariate and multivariate analyses were performed to determine the contribution of telomere length to stroke risk, stroke etiology, admission NIHSS score and DWI lesion volume. Results: The median (interquartile range) telomere length was 7.0 (5.5-9.0) kb in the overall population. Expectedly, telomere length was negatively correlated with aging (r=-0.23; p<0.001). A short telomere length (i.e. lowest quartile; ≤5.5 kb) was significantly associated with ischemic stroke (OR 3.0, 95%CI 1.8-5.1) when adjusted for age, gender and cardiovascular risk factors. This significant relationship persisted for all stroke etiologies, except for other rare causes of stroke. There was no significant relationship between admission lesion volume and telomere length; however, patients with short telomeres presented with more severe strokes (NIHSS score ≥16) when adjusted for age, risk factors, stroke etiology and infarct volume (OR 7.0; 95%CI 1.7-28.7). Conclusion: Almost all etiologic subtypes of ischemic stroke are related to shortened telomere length, irrespective of the age of the subject. Furthermore, presence of short telomeres negatively influences the tolerance of brain to ischemia, thereby causing more severe clinical phenotypes in these patients in the setting of ischemic stroke.