Telomere length and the risk of atrial fibrillation: insights into the role of biological versus chronological aging.
BACKGROUND
Advanced age is the most important risk factor for atrial fibrillation (AF); however, the mechanism remains unknown. Telomeres, regions of DNA that shorten with cell division, are considered reliable markers of biological aging. We sought to examine the association between leukocyte telomere length (LTL) and incident AF in a large population-based cohort using direct LTL measurements and genetic data. To further explore our findings, we compared atrial cell telomere length and LTL in cardiac surgery patients.


RESULTS
Mean LTL and the TERT rs2736100 single nucleotide polymorphism were assessed as predictors of incident AF in the Cardiovascular Health Study (CHS). Among the surgical patients, within subject comparison of atrial cell telomere length versus LTL was assessed. Among 1639 CHS participants, we observed no relationship between mean LTL and incident AF before and after adjustment for potential confounders (adjusted hazard ratio, 1.09; 95% confidence interval: 0.92-1.29; P=0.299); chronologic age remained strongly associated with AF in the same model. No association was observed between the TERT rs2736100 single nucleotide polymorphism and incident AF (adjusted hazard ratio: 0.95; 95% confidence interval: 0.88-1.04; P=0.265). In 35 cardiac surgery patients (26 with AF), atrial cell telomere length was longer than LTL (1.19 ± 0.20 versus 1.02 ± 0.25 [T/S ratio], P<0.001), a finding that remained consistent within the AF subgroup.


CONCLUSIONS
Our study revealed no evidence of an association between LTL and incident AF and no evidence of relative atrial cell telomere shortening in AF. Chronological aging independent of biological markers of aging is the primary risk factor for AF.
From the Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine (J.D.R., T.A.D., J.E.O., G.M.M.), Institute of Human Genetics and Department of Medicine (E.Z., D.H.), Department of Biochemistry and Biophysics (J.L., E.H.B.), Department of Epidemiology and Biostatistics (D.V.G.), Department of Medicine (E.G.B.), and Department of Bioengineering and Therapeutic Sciences (E.G.B.), University of California, San Francisco; Division of Cardiovascular Surgery, Sutter Health, Sacramento, CA (J.L.); Department of Epidemiology (A.L.F., S.R.H.) and Cardiovascular Health Research Unit (B.M.P., S.R.H.), University of Washington, Seattle; and Departments of Medicine and Health Services, University of Washington and Group Health Research Institute, Group Health, Seattle (B.M.P., S.R.H.).
Jason D
JD
Roberts
From the Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine (J.D.R., T.A.D., J.E.O., G.M.M.), Institute of Human Genetics and Department of Medicine (E.Z., D.H.), Department of Biochemistry and Biophysics (J.L., E.H.B.), Department of Epidemiology and Biostatistics (D.V.G.), Department of Medicine (E.G.B.), and Department of Bioengineering and Therapeutic Sciences (E.G.B.), University of California, San Francisco; Division of Cardiovascular Surgery, Sutter Health, Sacramento, CA (J.L.); Department of Epidemiology (A.L.F., S.R.H.) and Cardiovascular Health Research Unit (B.M.P., S.R.H.), University of Washington, Seattle; and Departments of Medicine and Health Services, University of Washington and Group Health Research Institute, Group Health, Seattle (B.M.P., S.R.H.).
Thomas A
TA
Dewland
From the Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine (J.D.R., T.A.D., J.E.O., G.M.M.), Institute of Human Genetics and Department of Medicine (E.Z., D.H.), Department of Biochemistry and Biophysics (J.L., E.H.B.), Department of Epidemiology and Biostatistics (D.V.G.), Department of Medicine (E.G.B.), and Department of Bioengineering and Therapeutic Sciences (E.G.B.), University of California, San Francisco; Division of Cardiovascular Surgery, Sutter Health, Sacramento, CA (J.L.); Department of Epidemiology (A.L.F., S.R.H.) and Cardiovascular Health Research Unit (B.M.P., S.R.H.), University of Washington, Seattle; and Departments of Medicine and Health Services, University of Washington and Group Health Research Institute, Group Health, Seattle (B.M.P., S.R.H.).
James
J
Longoria
From the Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine (J.D.R., T.A.D., J.E.O., G.M.M.), Institute of Human Genetics and Department of Medicine (E.Z., D.H.), Department of Biochemistry and Biophysics (J.L., E.H.B.), Department of Epidemiology and Biostatistics (D.V.G.), Department of Medicine (E.G.B.), and Department of Bioengineering and Therapeutic Sciences (E.G.B.), University of California, San Francisco; Division of Cardiovascular Surgery, Sutter Health, Sacramento, CA (J.L.); Department of Epidemiology (A.L.F., S.R.H.) and Cardiovascular Health Research Unit (B.M.P., S.R.H.), University of Washington, Seattle; and Departments of Medicine and Health Services, University of Washington and Group Health Research Institute, Group Health, Seattle (B.M.P., S.R.H.).
Annette L
AL
Fitzpatrick
From the Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine (J.D.R., T.A.D., J.E.O., G.M.M.), Institute of Human Genetics and Department of Medicine (E.Z., D.H.), Department of Biochemistry and Biophysics (J.L., E.H.B.), Department of Epidemiology and Biostatistics (D.V.G.), Department of Medicine (E.G.B.), and Department of Bioengineering and Therapeutic Sciences (E.G.B.), University of California, San Francisco; Division of Cardiovascular Surgery, Sutter Health, Sacramento, CA (J.L.); Department of Epidemiology (A.L.F., S.R.H.) and Cardiovascular Health Research Unit (B.M.P., S.R.H.), University of Washington, Seattle; and Departments of Medicine and Health Services, University of Washington and Group Health Research Institute, Group Health, Seattle (B.M.P., S.R.H.).
Elad
E
Ziv
From the Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine (J.D.R., T.A.D., J.E.O., G.M.M.), Institute of Human Genetics and Department of Medicine (E.Z., D.H.), Department of Biochemistry and Biophysics (J.L., E.H.B.), Department of Epidemiology and Biostatistics (D.V.G.), Department of Medicine (E.G.B.), and Department of Bioengineering and Therapeutic Sciences (E.G.B.), University of California, San Francisco; Division of Cardiovascular Surgery, Sutter Health, Sacramento, CA (J.L.); Department of Epidemiology (A.L.F., S.R.H.) and Cardiovascular Health Research Unit (B.M.P., S.R.H.), University of Washington, Seattle; and Departments of Medicine and Health Services, University of Washington and Group Health Research Institute, Group Health, Seattle (B.M.P., S.R.H.).
Donglei
D
Hu
From the Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine (J.D.R., T.A.D., J.E.O., G.M.M.), Institute of Human Genetics and Department of Medicine (E.Z., D.H.), Department of Biochemistry and Biophysics (J.L., E.H.B.), Department of Epidemiology and Biostatistics (D.V.G.), Department of Medicine (E.G.B.), and Department of Bioengineering and Therapeutic Sciences (E.G.B.), University of California, San Francisco; Division of Cardiovascular Surgery, Sutter Health, Sacramento, CA (J.L.); Department of Epidemiology (A.L.F., S.R.H.) and Cardiovascular Health Research Unit (B.M.P., S.R.H.), University of Washington, Seattle; and Departments of Medicine and Health Services, University of Washington and Group Health Research Institute, Group Health, Seattle (B.M.P., S.R.H.).
Jue
J
Lin
From the Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine (J.D.R., T.A.D., J.E.O., G.M.M.), Institute of Human Genetics and Department of Medicine (E.Z., D.H.), Department of Biochemistry and Biophysics (J.L., E.H.B.), Department of Epidemiology and Biostatistics (D.V.G.), Department of Medicine (E.G.B.), and Department of Bioengineering and Therapeutic Sciences (E.G.B.), University of California, San Francisco; Division of Cardiovascular Surgery, Sutter Health, Sacramento, CA (J.L.); Department of Epidemiology (A.L.F., S.R.H.) and Cardiovascular Health Research Unit (B.M.P., S.R.H.), University of Washington, Seattle; and Departments of Medicine and Health Services, University of Washington and Group Health Research Institute, Group Health, Seattle (B.M.P., S.R.H.).
David V
DV
Glidden
From the Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine (J.D.R., T.A.D., J.E.O., G.M.M.), Institute of Human Genetics and Department of Medicine (E.Z., D.H.), Department of Biochemistry and Biophysics (J.L., E.H.B.), Department of Epidemiology and Biostatistics (D.V.G.), Department of Medicine (E.G.B.), and Department of Bioengineering and Therapeutic Sciences (E.G.B.), University of California, San Francisco; Division of Cardiovascular Surgery, Sutter Health, Sacramento, CA (J.L.); Department of Epidemiology (A.L.F., S.R.H.) and Cardiovascular Health Research Unit (B.M.P., S.R.H.), University of Washington, Seattle; and Departments of Medicine and Health Services, University of Washington and Group Health Research Institute, Group Health, Seattle (B.M.P., S.R.H.).
Bruce M
BM
Psaty
From the Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine (J.D.R., T.A.D., J.E.O., G.M.M.), Institute of Human Genetics and Department of Medicine (E.Z., D.H.), Department of Biochemistry and Biophysics (J.L., E.H.B.), Department of Epidemiology and Biostatistics (D.V.G.), Department of Medicine (E.G.B.), and Department of Bioengineering and Therapeutic Sciences (E.G.B.), University of California, San Francisco; Division of Cardiovascular Surgery, Sutter Health, Sacramento, CA (J.L.); Department of Epidemiology (A.L.F., S.R.H.) and Cardiovascular Health Research Unit (B.M.P., S.R.H.), University of Washington, Seattle; and Departments of Medicine and Health Services, University of Washington and Group Health Research Institute, Group Health, Seattle (B.M.P., S.R.H.).
Esteban G
EG
Burchard
From the Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine (J.D.R., T.A.D., J.E.O., G.M.M.), Institute of Human Genetics and Department of Medicine (E.Z., D.H.), Department of Biochemistry and Biophysics (J.L., E.H.B.), Department of Epidemiology and Biostatistics (D.V.G.), Department of Medicine (E.G.B.), and Department of Bioengineering and Therapeutic Sciences (E.G.B.), University of California, San Francisco; Division of Cardiovascular Surgery, Sutter Health, Sacramento, CA (J.L.); Department of Epidemiology (A.L.F., S.R.H.) and Cardiovascular Health Research Unit (B.M.P., S.R.H.), University of Washington, Seattle; and Departments of Medicine and Health Services, University of Washington and Group Health Research Institute, Group Health, Seattle (B.M.P., S.R.H.).
Elizabeth H
EH
Blackburn
From the Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine (J.D.R., T.A.D., J.E.O., G.M.M.), Institute of Human Genetics and Department of Medicine (E.Z., D.H.), Department of Biochemistry and Biophysics (J.L., E.H.B.), Department of Epidemiology and Biostatistics (D.V.G.), Department of Medicine (E.G.B.), and Department of Bioengineering and Therapeutic Sciences (E.G.B.), University of California, San Francisco; Division of Cardiovascular Surgery, Sutter Health, Sacramento, CA (J.L.); Department of Epidemiology (A.L.F., S.R.H.) and Cardiovascular Health Research Unit (B.M.P., S.R.H.), University of Washington, Seattle; and Departments of Medicine and Health Services, University of Washington and Group Health Research Institute, Group Health, Seattle (B.M.P., S.R.H.).
Jeffrey E
JE
Olgin
From the Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine (J.D.R., T.A.D., J.E.O., G.M.M.), Institute of Human Genetics and Department of Medicine (E.Z., D.H.), Department of Biochemistry and Biophysics (J.L., E.H.B.), Department of Epidemiology and Biostatistics (D.V.G.), Department of Medicine (E.G.B.), and Department of Bioengineering and Therapeutic Sciences (E.G.B.), University of California, San Francisco; Division of Cardiovascular Surgery, Sutter Health, Sacramento, CA (J.L.); Department of Epidemiology (A.L.F., S.R.H.) and Cardiovascular Health Research Unit (B.M.P., S.R.H.), University of Washington, Seattle; and Departments of Medicine and Health Services, University of Washington and Group Health Research Institute, Group Health, Seattle (B.M.P., S.R.H.).
Susan R
SR
Heckbert
From the Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine (J.D.R., T.A.D., J.E.O., G.M.M.), Institute of Human Genetics and Department of Medicine (E.Z., D.H.), Department of Biochemistry and Biophysics (J.L., E.H.B.), Department of Epidemiology and Biostatistics (D.V.G.), Department of Medicine (E.G.B.), and Department of Bioengineering and Therapeutic Sciences (E.G.B.), University of California, San Francisco; Division of Cardiovascular Surgery, Sutter Health, Sacramento, CA (J.L.); Department of Epidemiology (A.L.F., S.R.H.) and Cardiovascular Health Research Unit (B.M.P., S.R.H.), University of Washington, Seattle; and Departments of Medicine and Health Services, University of Washington and Group Health Research Institute, Group Health, Seattle (B.M.P., S.R.H.). marcusg@medicine.ucsf.edu.
Gregory M
GM
Marcus
D000367:Age Factors; D000368:Aged; D000375:Aging / Q000235:genetics*; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000601:surgery; D002140:California / Q000453:epidemiology; D006348:Cardiac Surgical Procedures; D016922:Cellular Senescence; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D007962:Leukocytes / Q000737:chemistry*; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000235:genetics*; D013997:Time Factors
C509186:TERT protein, human; D019098:Telomerase
aging; atrial fibrillation; genetics