Telomere Shortening, Regenerative Capacity, and Cardiovascular Outcomes.
Author: Hammadah M1, Al Mheid I1, Wilmot K2, Ramadan R2, Abdulhadi N2, Alkhoder A2, Obideen M2, Pimple P3, Levantsevych O3, Kelli H2, Shah A3, Sun Y3, Pearce B3, Kutner M4, Long Q5, Ward L4, Ko YA4, Hosny Mohammed K2, Lin J6, Zhao J7, Bremner J8, Kim J9, Waller E9, Raggi P10, Sheps D11, Quyyumi A1, Vaccarino V12
Affiliation:
1Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine.
2Cardiology, Emory University School of Medicine.
3Epidemiology, Rollins School of Public health, Emory University.
4Biostatistics and Bioinformatics, Emory University.
5Biostatistics and Epidemiology, The University of Pennsylvania.
6Biochemistry and Biophysics, University of California, San Francisco.
7Epidemiology, Tulane University.
8Psychiatry and Behavioral Sciences, Emory University School of Medicine.
9Hematology and Oncology, Emory University School of Medicine.
10Mazankowski Alberta Heart Institute, University of Alberta.
11Epidemiology, University of Florida.
12Cardiology, Emory University School of Medicine lvaccar@emory.edu.
Conference/Journal: Circ Res.
Date published: 2016 Dec 12
Other:
Pages: CIRCRESAHA , Word Count: 264
RATIONALE: Leucocyte telomere length (LTL) is a biological marker of aging, and shorter LTL is associated with adverse cardiovascular outcomes. Reduced regenerative capacity has been proposed as a mechanism. Bone marrow-derived circulating progenitor cells (PCs) are involved in tissue repair and regeneration.
OBJECTIVE: To examine the relationship between LTL and PCs, and their impact on adverse cardiovascular outcomes.
METHODS AND RESULTS: We measured LTL by quantitative PCR in 566 outpatients (age 63±9 years, 76% male) with coronary artery disease (CAD). Circulating PCs were enumerated by flow cytometry. After adjustment for age, gender, race, BMI, smoking and previous myocardial infarction, a shorter LTL was associated with a lower CD34+ cell count: for each 10% shorter LTL, CD34+ levels were 5.2% lower (p<0.001). After adjustment for the aforementioned factors, both short LTL (<Q1) and low CD34+ levels (<Q1) predicted adverse cardiovascular outcomes (death, myocardial infarction, coronary revascularization or cerebrovascular events) independently of each other, with a hazards ratio (HR) of 1.8, 95% confidence interval (CI), 1.1-2.0, and a HR of 2.1, 95% CI, 1.3-3.0, respectively, comparing Q1 to Q2-4. Patients who had both short LTL (<Q1) and low CD34+ cell count (<Q1), had the greatest risk of adverse outcomes (HR=3.5, 95% CI, 1.7-7.1).
CONCLUSIONS: Although shorter LTL is associated with decreased regenerative capacity, both LTL and circulating PC levels are independent and additive predictors of adverse cardiovascular outcomes in CAD patients. Our results suggest that both biological aging and reduced regenerative capacity contribute to cardiovascular events, independent of conventional risk factors.
KEYWORDS: CD133; CD34; CXCR4; Telomere length; aging; cardiac outcomes; coronary artery disease; progenitor cell; regenerative capacity
PMID: 27956416 DOI: 10.1161/CIRCRESAHA.116.309421
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