Abstract 19292: Blood Telomere Length Predicts Clinical Outcome After Acute Myocardial Infarction: The Role of Oxidative Stress
Background: Experimental evidence suggests that telomere length (TL) is shortened by oxidative DNA damage, reflecting biological aging. We explore the value of blood TL (BTL) as a biomarker of oxidative stress in humans and test the clinical predictive value of BTL in acute myocardial infarction (AMI).
Methods: Cohort 1 consists of 290 patients with AMI (prospective 1-year follow-up). Cohort 2 comprises 727 patients undergoing coronary artery bypass grafting (CABG). In both cohorts, blood samples on admission were used to measure BTL. In cohort 2, superoxide (O2.-) was measured in peripheral blood mononuclear cells (PBMNCs) and genotyping for genetic polymorphisms in the CYBA locus encoding for p22phox NADPH-oxidase subunit was performed.
Results: In Cohort 1, BTL on admission was a strong predictor of cardiovascular mortality (4.121[1.39-12.22], P=0.011) during the 1st year post-AMI (Figure A, highest vs lowest tertile, P adjusted for age and other predictors: Age (per decade) 2.195[1.39-3.46], P=0.001, Peak troponin 1.004[1.001-1.007], P=0.01, BNP on admission (per 100 pg/ml) 1.06[1.03-1.09], P=0.0001, Change in creatinine (admission to peak value) 1.52[1.15-1.99], P=0.003). BTL was not related with new non-fatal acute coronary events (HR[95%CI]: 1.561[0.897-2.717], P=0.115). In cohort 2, short BTL was linked to high NADPH-stimulated O2.- in PBMNCs (B). The effect of rs4673C+rs1049255G alleles was linked to high NADPH-stimulated O2.- generation in PBMNCs (C) and short BTL (D), suggesting causal association.
Conclusion: We show for the first time in humans that BTL predicts cardiovascular outcomes post-AMI, independently of age. Importantly, high oxidative stress in PBMNCs in causally linked to shorter BTL. These novel findings reveal the importance of oxidative stress in mediating the pathophysiological changes associated with cardiovascular disease and highlight a potential role for TL measurement in cardiovascular risk stratification.
Author Disclosures: M. Margaritis: None. F. Sanna: None. G. Lazaros: None. I. Akoumianakis: None. A.A. Antonopoulos: None. L. Herdman: None. R. Sayeed: None. D. Tousoulis: None. K.M. Channon: None. C. Antoniades: None.
- © 2016 by American Heart Association, Inc.