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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 reaction–based 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

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