Short telomere length in blood leucocytes contributes to the presence of atherothrombotic stroke and haemorrhagic stroke and risk of post-stroke death

Abstract

Inter-individual differences in biological aging could affect susceptibility to stroke. To date, the relationship between stroke and telomere shortening remain inconclusive; and sparse data are available for haemorrhagic stroke. A Chinese case-control study was conducted, comprising 1756 cases (767 atherothrombosis, 503 lacunar infarction and 486 haemorrhagic strokes) and 1801 controls. Stroke patients were prospectively followed up for a median of 4.5 (range, 0.1-6.0) years. Individuals with shorter telomere length had a higher presence of atherothrombotic stroke {multivariate OR (odds ratio) 1.37 [95% CI (confidence interval), 1.06-1.77]; P=0.015} or haemorrhagic stroke [multivariate OR 1.48 (95% CI, 1.08-2.02); P=0.016] in comparison of the lowest to highest tertile of telomere length. Particularly, in subjects with a family history of stroke, there was a significant 2.55-fold increased presence of atherothrombotic stroke (95% CI, 1.87-3.48; Ptrend<0.0001) and a 2.33-fold increased presence of haemorrhagic stroke (95% CI, 1.62-3.36; Ptrend<0.0001). During the follow-up, 338 recurrent strokes and 312 deaths (181 from stroke or coronary heart disease and 131 from other causes) were documented. Associations with stroke recurrence were not observed in the follow-up patients, whereas atherothrombotic stroke cases with shorter telomeres had 69% increased risk of post-stroke death [relative risk, 1.69 (95% CI, 1.07-2.67); P=0.02]. Finally, we compared telomere lengths in 12 paired samples of circulating leucocytes and carotid atherosclerotic plaques from patients undergoing carotid endarterectomy; there was a positive correlation between vessel wall tissue and leucocyte telomere length. In conclusion, shorter telomere length may serve as a potential marker for the presence of atherothrombotic and haemorrhagic stroke and for the risk of post-stroke death.