Telomere length is independently associated with all-cause mortality in chronic heart failure

Simon P. R. Romaine; Matthew Denniff; Veryan Codd; Mintu Nath; Andrea Koekemoer; Stefan D. Anker; John G. Cleland; Gerasimos Filippatos; Daniel Levin; Marco Metra; Ify R. Mordi; Wouter Ouwerkerk; Jozine M. Ter Maaten; Dirk J. van Veldhuisen; Faiez Zannad; Leong L. Ng; Pim van der Harst; Chim C. Lang; Adriaan A. Voors; Christopher P. Nelson; Nilesh J. Samani

doi:10.1136/heartjnl-2020-318654

Telomere length is independently associated with all-cause mortality in chronic heart failure

Simon P. R. Romaine (Lead / Corresponding author), Matthew Denniff, Veryan Codd, Mintu Nath, Andrea Koekemoer, Stefan D. Anker, John G. Cleland, Gerasimos Filippatos, Daniel Levin, Marco Metra, Ify R. Mordi, Wouter Ouwerkerk, Jozine M. Ter Maaten, Dirk J. van Veldhuisen, Faiez Zannad, Leong L. Ng, Pim van der Harst, Chim C. Lang, Adriaan A. Voors, Christopher P. NelsonNilesh J. Samani

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	318654
Number of pages	6
Journal	Heart
Volume	108
Early online date	31 Mar 2021
DOIs	https://doi.org/10.1136/heartjnl-2020-318654
Publication status	Published - 22 Dec 2021

Keywords

biomarkers
genetics
heart failure

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

Access to Document

10.1136/heartjnl-2020-318654

Author Accepted ManuscriptAccepted author manuscript, 508 KBLicence: CC BY-NC

Cite this

Romaine, S. P. R., Denniff, M., Codd, V., Nath, M., Koekemoer, A., Anker, S. D., Cleland, J. G., Filippatos, G., Levin, D., Metra, M., Mordi, I. R., Ouwerkerk, W., Ter Maaten, J. M., van Veldhuisen, D. J., Zannad, F., Ng, L. L., van der Harst, P., Lang, C. C., Voors, A. A., ... Samani, N. J. (2021). Telomere length is independently associated with all-cause mortality in chronic heart failure. Heart, 108, Article 318654. https://doi.org/10.1136/heartjnl-2020-318654

@article{b3000388a56b457e8bb5d2c69af600c7,

title = "Telomere length is independently associated with all-cause mortality in chronic heart failure",

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.",

keywords = "biomarkers, genetics, heart failure",

author = "Romaine, {Simon P. R.} and Matthew Denniff and Veryan Codd and Mintu Nath and Andrea Koekemoer and Anker, {Stefan D.} and Cleland, {John G.} and Gerasimos Filippatos and Daniel Levin and Marco Metra and Mordi, {Ify R.} and Wouter Ouwerkerk and {Ter Maaten}, {Jozine M.} and {van Veldhuisen}, {Dirk J.} and Faiez Zannad and Ng, {Leong L.} and {van der Harst}, Pim and Lang, {Chim C.} and Voors, {Adriaan A.} and Nelson, {Christopher P.} and Samani, {Nilesh J.}",

note = "Funding for this research was provided by: Seventh Framework Programme (FP7-242209-BIOSTAT-CHF)",

year = "2021",

month = dec,

day = "22",

doi = "10.1136/heartjnl-2020-318654",

language = "English",

volume = "108",

journal = "Heart",

issn = "1355-6037",

publisher = "BMJ Publishing Group",

}

Romaine, SPR, Denniff, M, Codd, V, Nath, M, Koekemoer, A, Anker, SD, Cleland, JG, Filippatos, G, Levin, D, Metra, M, Mordi, IR, Ouwerkerk, W, Ter Maaten, JM, van Veldhuisen, DJ, Zannad, F, Ng, LL, van der Harst, P, Lang, CC, Voors, AA, Nelson, CP & Samani, NJ 2021, 'Telomere length is independently associated with all-cause mortality in chronic heart failure', Heart, vol. 108, 318654. https://doi.org/10.1136/heartjnl-2020-318654

TY - JOUR

T1 - Telomere length is independently associated with all-cause mortality in chronic heart failure

AU - Romaine, Simon P. R.

AU - Denniff, Matthew

AU - Codd, Veryan

AU - Nath, Mintu

AU - Koekemoer, Andrea

AU - Anker, Stefan D.

AU - Cleland, John G.

AU - Filippatos, Gerasimos

AU - Levin, Daniel

AU - Metra, Marco

AU - Mordi, Ify R.

AU - Ouwerkerk, Wouter

AU - Ter Maaten, Jozine M.

AU - van Veldhuisen, Dirk J.

AU - Zannad, Faiez

AU - Ng, Leong L.

AU - van der Harst, Pim

AU - Lang, Chim C.

AU - Voors, Adriaan A.

AU - Nelson, Christopher P.

AU - Samani, Nilesh J.

N1 - Funding for this research was provided by: Seventh Framework Programme (FP7-242209-BIOSTAT-CHF)

PY - 2021/12/22

Y1 - 2021/12/22

N2 - 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.

AB - 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.

KW - biomarkers

KW - genetics

KW - heart failure

UR - http://www.scopus.com/inward/record.url?scp=85103634048&partnerID=8YFLogxK

U2 - 10.1136/heartjnl-2020-318654

DO - 10.1136/heartjnl-2020-318654

M3 - Article

C2 - 33789973

SN - 1355-6037

VL - 108

JO - Heart

JF - Heart

M1 - 318654

ER -

Telomere length is independently associated with all-cause mortality in chronic heart failure

Abstract

Keywords

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Aref#d: 21596. BIOSTAT-CHF: A Systems Biology Study to Tailored Treatment in Chronic Heart Failure

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Telomere length is independently associated with all-cause mortality in chronic heart failure

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

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Aref#d: 21596. BIOSTAT-CHF: A Systems Biology Study to Tailored Treatment in Chronic Heart Failure

Cite this