CLINICAL RESEARCH: HEART FAILURE
Telomere Length of Circulating Leukocytes Is Decreased in Patients With Chronic Heart Failure
Pim van der Harst, MD, PhD*, ,1,*,
Gerrit van der Steege, PhD ,
Rudolf A. de Boer, MD, PhD*,2,
Adriaan A. Voors, MD, PhD*,
Alistair S. Hall, MD, PhD ,
Marcel J. Mulder ,
Wiek H. van Gilst, PhD ,
Dirk J. van Veldhuisen, MD, PhD, FACC*,3 on behalf of the MERIT-HF Study Group
* Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Department of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Department of Medical Biomics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
British Heart Foundation Research Center, University of Leeds, Leeds, United Kingdom.
Manuscript received April 4, 2006;
revised manuscript received October 16, 2006,
accepted November 27, 2006.
* Reprint requests and correspondence: Dr. Pim van der Harst, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700RB Groningen, the Netherlands. (Email: p.van.der.harst{at}thorax.umcg.nl).
Objectives: This study sought to test the hypothesis that patients with chronic heart failure (CHF) have shorter telomeres compared with age-balanced and gender-balanced healthy individuals.
Background: Telomere length is considered to be a marker of biological aging. Chronic heart failure might be viewed as a condition associated with accelerated biological aging.
Methods: The telomere length ratio of leukocytes was determined prospectively by a quantitative polymerase chain reactionbased method in a case-control setting involving 803 participants: 183 healthy individuals and 620 CHF patients, ages 40 to 80 years, New York Heart Association functional class II to IV, and left ventricular ejection fraction of 0.40 or less.
Results: The median telomere length ratio was 0.64 (interquartile range [IQR] 0.47 to 0.88) in CHF patients compared with 1.05 (IQR 0.86 to 1.29) in control patients (p < 0.001). The telomere length ratio in CHF patients related to severity of disease (median value [IQR] of patients with New York Heart Association class II, III, or IV function was 0.67 [0.48 to 0.92], 0.63 [0.46 to 0.86], and 0.55 [0.46 to 0.75], respectively; p for trend <0.05). In addition, telomeres were shorter in patients with an ischemic compared with a nonischemic etiology of CHF. Patients with none, 1 (coronary, cerebral, or peripheral vascular disease), 2 (any combination of the previous), or 3 atherosclerotic manifestations had a median (IQR) telomere length of 0.72 (0.51 to 1.01), 0.65 (0.48 to 0.87), 0.48 (0.39 to 0.72), and 0.43 (0.27 to 0.67), respectively (p for trend <0.001).
Conclusions: Telomere length is shorter in patients with CHF compared with age-balanced and gender-balanced control patients, and related to the severity of disease. In addition, telomere length was incrementally shorter according to the presence and extent of atherosclerotic disease manifestations.
|
Abbreviations and Acronyms
| | CHF = chronic heart failure | | DNA = deoxyribonucleic acid | | IQR = interquartile range | | PCR = polymerase chain reaction |
|
This article has been cited by other articles:

|
 |

|
 |
 
P. van der Harst, R. A. de Boer, and D. J. van Veldhuisen
The Nobel Prize for medicine for telomere biology and relevance to heart failure research
Eur J Heart Fail,
December 1, 2009;
11(12):
1113 - 1115.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. Spyridopoulos, J. Hoffmann, A. Aicher, T. H. Brummendorf, H. W. Doerr, A. M. Zeiher, and S. Dimmeler
Accelerated Telomere Shortening in Leukocyte Subpopulations of Patients With Coronary Heart Disease: Role of Cytomegalovirus Seropositivity
Circulation,
October 6, 2009;
120(14):
1364 - 1372.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. S. Vasan, S. Demissie, M. Kimura, L. A. Cupples, C. White, J. P. Gardner, X. Cao, D. Levy, E. J. Benjamin, and A. Aviv
Association of Leukocyte Telomere Length With Echocardiographic Left Ventricular Mass: The Framingham Heart Study
Circulation,
September 29, 2009;
120(13):
1195 - 1202.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. De Meyer, E. R. Rietzschel, M. L. De Buyzere, M. R. Langlois, D. De Bacquer, P. Segers, P. Van Damme, G. G. De Backer, P. Van Oostveldt, W. Van Criekinge, et al.
Systemic telomere length and preclinical atherosclerosis: the Asklepios Study
Eur. Heart J.,
August 17, 2009;
(2009)
ehp324v1.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M Mukherjee, S Brouilette, S Stevens, K R Shetty, and N J Samani
Association of shorter telomeres with coronary artery disease in Indian subjects
Heart,
April 1, 2009;
95(8):
669 - 673.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Z. Yang, X. Huang, H. Jiang, Y. Zhang, H. Liu, C. Qin, G. M. Eisner, P. Jose, L. Rudolph, and Z. Ju
Short Telomeres and Prognosis of Hypertension in a Chinese Population
Hypertension,
April 1, 2009;
53(4):
639 - 645.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Aviv, W. Chen, J. P. Gardner, M. Kimura, M. Brimacombe, X. Cao, S. R. Srinivasan, and G. S. Berenson
Leukocyte Telomere Dynamics: Longitudinal Findings Among Young Adults in the Bogalusa Heart Study
Am. J. Epidemiol.,
February 1, 2009;
169(3):
323 - 329.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. S.M. Wong, H. Oeseburg, R. A. de Boer, W. H. van Gilst, D. J. van Veldhuisen, and P. van der Harst
Telomere biology in cardiovascular disease: the TERC-/- mouse as a model for heart failure and ageing
Cardiovasc Res,
February 1, 2009;
81(2):
244 - 252.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Huzen, D. J. van Veldhuisen, and P. van der Harst
Letter by Huzen et al Regarding Article, "Association of Leukocyte Telomere Length With Circulating Biomarkers of the Renin-Angiotensin-Aldosterone System: The Framingham Heart Study"
Circulation,
November 4, 2008;
118(19):
e688 - e688.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. A Nettleton, A. Diez-Roux, N. S Jenny, A. L Fitzpatrick, and D. R Jacobs Jr
Dietary patterns, food groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA)
Am. J. Clinical Nutrition,
November 1, 2008;
88(5):
1405 - 1412.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. S.M. Wong, R. A. de Boer, N. J. Samani, D. J. van Veldhuisen, and P. van der Harst
Telomere biology in heart failure
Eur J Heart Fail,
November 1, 2008;
10(11):
1049 - 1056.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. T. Cronkhite, C. Xing, G. Raghu, K. M. Chin, F. Torres, R. L. Rosenblatt, and C. K. Garcia
Telomere Shortening in Familial and Sporadic Pulmonary Fibrosis
Am. J. Respir. Crit. Care Med.,
October 1, 2008;
178(7):
729 - 737.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Aviv
The Epidemiology of Human Telomeres: Faults and Promises
J. Gerontol. A Biol. Sci. Med. Sci.,
September 1, 2008;
63(9):
979 - 983.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Werner, M. Hanhoun, T. Widmann, A. Kazakov, A. Semenov, J. Poss, J. Bauersachs, T. Thum, M. Pfreundschuh, P. Muller, et al.
Effects of Physical Exercise on Myocardial Telomere-Regulating Proteins, Survival Pathways, and Apoptosis
J. Am. Coll. Cardiol.,
August 5, 2008;
52(6):
470 - 482.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Farzaneh-Far, R. M. Cawthon, B. Na, W. S. Browner, N. B. Schiller, and M. A. Whooley
Prognostic Value of Leukocyte Telomere Length in Patients With Stable Coronary Artery Disease: Data From the Heart and Soul Study
Arterioscler Thromb Vasc Biol,
July 1, 2008;
28(7):
1379 - 1384.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Dimmeler and A. Leri
Aging and Disease as Modifiers of Efficacy of Cell Therapy
Circ. Res.,
June 6, 2008;
102(11):
1319 - 1330.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. J. O'Donnell, S. Demissie, M. Kimura, D. Levy, J. P. Gardner, C. White, R. B. D'Agostino, P. A. Wolf, J. Polak, L. A. Cupples, et al.
Leukocyte Telomere Length and Carotid Artery Intimal Medial Thickness: The Framingham Heart Study
Arterioscler Thromb Vasc Biol,
June 1, 2008;
28(6):
1165 - 1171.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. van der Harst, D. J. van Veldhuisen, and N. J. Samani
Expanding the Concept of Telomere Dysfunction in Cardiovascular Disease
Arterioscler Thromb Vasc Biol,
May 1, 2008;
28(5):
807 - 808.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. J Samani and P. van der Harst
Biological ageing and cardiovascular disease
Heart,
May 1, 2008;
94(5):
537 - 539.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. Spyridopoulos, Y. Erben, T. H. Brummendorf, J. Haendeler, K. Dietz, F. Seeger, C. K. Kissel, H. Martin, J. Hoffmann, B. Assmus, et al.
Telomere Gap Between Granulocytes and Lymphocytes Is a Determinant for Hematopoetic Progenitor Cell Impairment in Patients With Previous Myocardial Infarction
Arterioscler Thromb Vasc Biol,
May 1, 2008;
28(5):
968 - 974.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. F. Cherkas, J. L. Hunkin, B. S. Kato, J. B. Richards, J. P. Gardner, G. L. Surdulescu, M. Kimura, X. Lu, T. D. Spector, and A. Aviv
The Association Between Physical Activity in Leisure Time and Leukocyte Telomere Length
Arch Intern Med,
January 28, 2008;
168(2):
154 - 158.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. De Meyer, E. R. Rietzschel, M. L. De Buyzere, D. De Bacquer, W. Van Criekinge, G. G. De Backer, T. C. Gillebert, P. Van Oostveldt, S. Bekaert, and on behalf of the Asklepios investigators
Paternal age at birth is an important determinant of offspring telomere length
Hum. Mol. Genet.,
December 15, 2007;
16(24):
3097 - 3102.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Oeseburg, B. D. Westenbrink, R. A. de Boer, W. H. van Gilst, D. J. van Veldhuisen, and P. van der Harst
Can Critically Short Telomeres Cause Functional Exhaustion of Progenitor Cells in Postinfarction Heart Failure?
J. Am. Coll. Cardiol.,
November 6, 2007;
50(19):
1911 - 1912.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J B. Richards, A. M Valdes, J. P Gardner, D. Paximadas, M. Kimura, A. Nessa, X. Lu, G. L Surdulescu, R. Swaminathan, T. D Spector, et al.
Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women
Am. J. Clinical Nutrition,
November 1, 2007;
86(5):
1420 - 1425.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|