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

BMJ 2014; 349 doi: http://dx.doi.org/10.1136/bmj.g4227 (Published 08 July 2014)Cite this as: BMJ 2014;349:g4227

Philip C Haycock, postdoctoral research assistant1 2,
Emma E Heydon, doctoral candidate1,
Stephen Kaptoge, senior research associate1,
Adam S Butterworth, university lecturer1,
Alex Thompson, senior epidemiologist1 3,
Peter Willeit, research associate1 4

Author affiliations

Correspondence to: P C Haycock philip.haycock@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.