Abstract 18090: Telomere Shortening, Regenerative Capacity, and Cardiovascular Outcomes
Background: Leucocyte telomere length (LTL) is a biological marker of aging and reduced LTL is associated with adverse cardiovascular outcomes. Reduced regenerative capacity has been suggested as a plausible mechanism. Bone marrow-derived circulating progenitor cells (PCs) are involved in tissue repair and regeneration, and reduced PC counts are associated with adverse cardiovascular outcomes. We sought to test the relationship between LTL and PCs, and their impact on adverse cardiovascular outcomes.
Methods: 566 outpatients with CAD enrolled in the Mental Stress Ischemia Prognosis Study had LTL measured by quantitative PCR. Flow cytometry was used to identify CD45med circulating mononuclear cells enriched for hematopoietic PCs that expressed CD34. Patients were followed for adverse cardiovascular outcomes (death, myocardial infarction, coronary revascularization or cerebrovascular events) with a median (IQR) follow-up of 3.0 (2.0 - 3.6) years. Linear regression models were used to assess the association between PC counts and LTL after adjusting for age, gender, race, BMI, smoking and previous myocardial infarction. Cox regression analysis was used to test association between LTL and PCs and adverse cardiovascular outcomes.
Results: Mean age was 63 ± 9 years, 76% were male. After adjustment for the aforementioned factors, LTL shortening was associated with lower CD34+ cell count: for each 10% shortening in LTL, CD34+ levels were 5.2% (p<0.001) lower. After adjustment for the aforementioned factors, both short LTL (<Q1) and low CD34+ levels (<Q1) were independent of each other in predicting adverse cardiovascular outcomes [HR (95%CI) of 1.8 (1.1-2.0) and 2.1 (1.3-3.0), p=0.017 and p=0.003, respectively] for Q1 vs Q2-4. Furthermore, patients who had both short LTL (<Q1) and low CD34+ cell count (<Q1), had the greatest risk of adverse outcomes [HR(95%CI) of 3.6 (1.9-6.9), p<0.001].
Conclusion: Although shorter LTL is associated with decreased regenerative capacity, both LTL and circulating PC levels are independent and additive predictors of adverse cardiovascular outcomes. These results suggest that both biological aging and reduced regenerative capacity contribute to cardiovascular outcomes, independent of conventional risk factors.
Author Disclosures: M. Hammadah: None. I. Al Mheid: None. K. Wilmot: None. R. Ramadan: None. N. Abdelhadi: None. A. Alkhoder: None. M. Obideen: None. P. Pimple: None. O. Levantsevych: None. H. Mohamed Kelli: None. A.J. Shah: None. E. Garcia: None. Y.V. Sun: None. B. Pearce: None. M. Kutner: None. Q. Long: None. L. Ward: None. Y. Ko: None. K. Mohammed: None. E. Blackburn: None. J. Zhao: None. J. Lin: None. J. Bremner: None. J. Kim: None. E. Waller: None. P. Raggi: None. A.A. Quyyumi: None. V. Vaccarino: None.
- © 2016 by American Heart Association, Inc.