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Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis

BMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g4227 (Published 08 July 2014) Cite this as: BMJ 2014;349:g4227
  1. Philip C Haycock, postdoctoral research assistant12,
  2. Emma E Heydon, doctoral candidate1,
  3. Stephen Kaptoge, senior research associate1,
  4. Adam S Butterworth, university lecturer1,
  5. Alex Thompson, senior epidemiologist13,
  6. Peter Willeit, research associate14
  1. 1Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK
  2. 2Medical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK
  3. 3Roche, Welwyn Garden City, UK
  4. 4Department of Neurology, Innsbruck Medical University, Austria
  1. Correspondence to: P C Haycock philip.haycock{at}bristol.ac.uk
  • Accepted 12 June 2014

Abstract

Objective To assess the association between leucocyte telomere length and risk of cardiovascular disease.

Design Systematic review and meta-analysis.

Data sources Studies published up to March 2014 identified through searches of Medline, Web of Science, and Embase.

Eligibility criteria Prospective and retrospective studies that reported on associations between leucocyte telomere length and coronary heart disease (defined as non-fatal myocardial infarction, coronary heart disease death, or coronary revascularisation) or cerebrovascular disease (defined as non-fatal stroke or death from cerebrovascular disease) and were broadly representative of general populations—that is, they did not select cohort or control participants on the basis of pre-existing cardiovascular disease or diabetes.

Results Twenty four studies involving 43 725 participants and 8400 patients with cardiovascular disease (5566 with coronary heart disease and 2834 with cerebrovascular disease) were found to be eligible. In a comparison of the shortest versus longest third of leucocyte telomere length, the pooled relative risk for coronary heart disease was 1.54 (95% confidence interval 1.30 to 1.83) in all studies, 1.40 (1.15 to 1.70) in prospective studies, and 1.80 (1.32 to 2.44) in retrospective studies. Heterogeneity between studies was moderate (I2=64%, 41% to 77%, Phet<0.001) and was not significantly explained by mean age of participants (P=0.23), the proportion of male participants (P=0.45), or distinction between retrospective versus prospective studies (P=0.32). Findings for coronary heart disease were similar in meta-analyses restricted to studies that adjusted for conventional vascular risk factors (relative risk 1.42, 95% confidence interval 1.17 to 1.73); studies with ≥200 cases (1.44, 1.20 to 1.74); studies with a high quality score (1.53, 1.22 to 1.92); and in analyses that corrected for publication bias (1.34, 1.12 to 1.60). The pooled relative risk for cerebrovascular disease was 1.42 (1.11 to 1.81), with no significant heterogeneity between studies (I2=41%, 0% to 72%, Phet=0.08). Shorter telomeres were not significantly associated with cerebrovascular disease risk in prospective studies (1.14, 0.85 to 1.54) or in studies with a high quality score (1.21, 0.83 to 1.76).

Conclusion Available observational data show an inverse association between leucocyte telomere length and risk of coronary heart disease independent of conventional vascular risk factors. The association with cerebrovascular disease is less certain.

Footnotes

  • We gratefully acknowledge the assistance of Sharon Stein Merkin (David Geffen School of Medicine at UCLA), Ioakim Spyridopoulos (Newcastle University, Institute of Genetic Medicine), Andrie Panayiotou (Cyprus International Institute for Environmental and Public Health in association with the Harvard School of Public Health, Cyprus University of Technology), John M Starr (Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh), Cécilia Maubaret (Cardiovascular Genetics BHF Laboratories, University College London), Jackie A Cooper (Centre for Cardiovascular Genetics, University College London), Katarina Nordfjäll (department of medical biosciences, Pathology, Umeå University) and Göran Roos (department of medical biosciences, Pathology, Umeå University), Richard Cawthon (department of human genetics, University of Utah), Russell P Tracy (department of pathology, University of Vermont), and Anja Jochumsen (department of clinical biochemistry, Copenhagen University Hospital) who provided additional information about their studies for inclusion in this meta-analysis. Emanuele Di Angelantonio (department of public health and primary care, University of Cambridge) and Julia Gumy (school of social policy, sociology and social research, University of Kent) commented helpfully on the manuscript. No financial compensation was provided for any contributions or assistance.

  • Contributors: PCH, EEH, PW, and AT were involved in the design of the study; PCH, EEH, and PW acquired data from selected studies; all authors were involved in the analysis and interpretation of the data; PCH, EEH, and PW drafted the manuscript; all authors provided critical revision of the manuscript for important intellectual content; PCH carried out the statistical analyses; PCH is guarantor. AT and PW contributed equally.

  • Funding: The Cardiovascular Epidemiology Unit is supported by a core grant from the British Heart Foundation (RG/13/13/30194) and the UK Medical Research Council (MR/L003120/1).

  • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: PCH and EEH were supported by Medical Research Council studentships; SK has received research funding from the British Heart Foundation, Medical Research Council, UK National Institute of Health Research and Cambridge Biomedical Research Centre; AT has received research funding from the British Heart Foundation and Medical Research Council; PW was supported by a non-clinical PhD studentship from the British Heart Foundation; no support was received from any organisation for the submitted work; there were no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; there were no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required.

  • Transparency: PCH affirms that the manuscript is an honest, accurate, and transparent account of the study being reported and that no important aspects of the study have been omitted. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis.

  • Data sharing: No additional data available.

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