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Heart failure and cardiomyopathies
Original research
Telomere length is independently associated with all-cause mortality in chronic heart failure
  1. Simon P R Romaine1,2,
  2. Matthew Denniff1,
  3. Veryan Codd1,2,
  4. Mintu Nath1,3,
  5. Andrea Koekemoer1,2,
  6. Stefan D Anker4,
  7. John G Cleland5,6,
  8. Gerasimos Filippatos7,8,
  9. Daniel Levin9,
  10. Marco Metra10,
  11. Ify R Mordi11,
  12. Wouter Ouwerkerk12,13,
  13. Jozine M ter Maaten14,
  14. Dirk J van Veldhuisen14,
  15. Faiez Zannad15,16,17,
  16. Leong L Ng1,
  17. Pim van der Harst14,
  18. Chim C Lang18,
  19. Adriaan A Voors14,
  20. Christopher P Nelson1,2,
  21. Nilesh J Samani1,2
  1. 1 Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
  2. 2 NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK
  3. 3 Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK
  4. 4 Department of Cardiology (CVK) and Berlin Institute of Health Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin Berlin, Berlin, Germany
  5. 5 Robertson Centre for Biostatistics and Clinical Trials Unit, University of Glasgow, Glasgow, UK
  6. 6 National Heart and Lung Institute, Royal Brompton and Harefield Hospitals, Imperial College London, London, UK
  7. 7 School of Medicine, National and Kapodistian University of Athens, Athens, Greece
  8. 8 School of Medicine, University of Cyprus, Nicosia, Cyprus
  9. 9 Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK
  10. 10 Cardiology, University of Brescia, Brescia, Italy
  11. 11 Division of Molecular & Clinical Medicine, Ninewells Hospital, University of Dundee, Dundee, Angus, UK
  12. 12 Department of Dermatology, Infection and Immunity, Amsterdam UMC, location Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
  13. 13 National Heart Centre Singapore, Singapore
  14. 14 Department of Cardiology, University of Groningen, University Medical Center of Groningen, Groningen, The Netherlands
  15. 15 Clinical investigation Center CIC1433, Université de Lorraine, Nancy, France
  16. 16 Clinical investigation Center CIC1433, CHRU Nancy, Vandoeuvre les Nancy, France
  17. 17 FCRIN INI-CRCT, Inserm, Vandoeuvre les Nancy, France
  18. 18 Cardiology, Ninewells Hospital and Medical School, Dundee, UK
  1. Correspondence to Dr Simon P R Romaine, Department of Cardiovascular Sciences, University of Leicester, Leicester, LE3 9QP, UK; simon.romaine{at}leicester.ac.uk

Abstract

Objective Patients with heart failure have shorter mean leucocyte telomere length (LTL), a marker of biological age, compared with healthy subjects, but it is unclear whether this is of prognostic significance. We therefore sought to determine whether LTL is associated with outcomes in patients with heart failure.

Methods We measured LTL in patients with heart failure from the BIOSTAT-CHF Index (n=2260) and BIOSTAT-CHF Tayside (n=1413) cohorts. Cox proportional hazards analyses were performed individually in each cohort and the estimates combined using meta-analysis. Our co-primary endpoints were all-cause mortality and heart failure hospitalisation.

Results In age-adjusted and sex-adjusted analyses, shorter LTL was associated with higher all-cause mortality in both cohorts individually and when combined (meta-analysis HR (per SD decrease in LTL)=1.16 (95% CI 1.08 to 1.24); p=2.66×10−5), an effect equivalent to that of being four years older. The association remained significant after adjustment for the BIOSTAT-CHF clinical risk score to account for known prognostic factors (HR=1.12 (95% CI 1.05 to 1.20); p=1.04×10−3). Shorter LTL was associated with both cardiovascular (HR=1.09 (95% CI 1.00 to 1.19); p=0.047) and non-cardiovascular deaths (HR=1.18 (95% CI 1.05 to 1.32); p=4.80×10−3). There was no association between LTL and heart failure hospitalisation (HR=0.99 (95% CI 0.92 to 1.07); p=0.855).

Conclusion In patients with heart failure, shorter mean LTL is independently associated with all-cause mortality.

  • heart failure
  • genetics
  • biomarkers

Data availability statement

Data are available on reasonable request.

https://doi.org/10.1136/heartjnl-2020-318654

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    Data availability statement

    Data are available on reasonable request.

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    Footnotes

    • Contributors SPRR, VC, MN, CPN and NJS were responsible for project conceptualisation, methodology, formal data analyses and drafting the manuscript. MD, VC, AK, SDA, JGC, GF, DL, MM, MRI, WO, JtM, DJvV, FZ, LLN, PvdH, CCL, AV and NJS were responsible for data acquisition. All authors contributed to critical revision of the manuscript, approved the final version for publication and are accountable for all aspects of the work. SPRR and NJS are responsible for the overall content as guarantors.

    • Funding BIOSTAT-CHF was funded by a grant from the European Commission (FP7-242209-BIOSTAT-CHF).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Author note Additional references w1-9 can be found in online supplemental file 1.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.