Telomere shortening and telomerase activity in ischaemic cardiomyopathy patients: Potential markers of ventricular arrhythmia

V Sawhney, N G Campbell, S W Brouilette, S R Coppen, Maria Harbo, V Baker, C Ikebe, Y Shintani, R J Hunter, M Dhinoja, A Johnston, M J Earley, S Sporton, Laila Bendix, K Suzuki, R J Schilling

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

BACKGROUND: Implantable cardioverter defibrillators (ICDs) reduce mortality in patients with ischaemic cardiomyopathy at high risk of ventricular arrhythmias (VA). However, the current indication for ICD prescription needs improvement. Telomere and telomerase in leucocytes have been shown to associate with biological ageing and pathogenesis of cardiovascular diseases. We hypothesised that leucocyte telomere length, load-of-short telomeres and/or telomerase activity are associated with VA occurrence in ischaemic cardiomyopathy patients.

METHODS AND RESULTS: 90 ischaemic cardiomyopathy patients with primary prevention ICDs were recruited. 35 had received appropriate therapy from the ICD for potentially-fatal VA while the remaining 55 patients had not. No significant differences in baseline demographic data relevant to telomere biology were seen between the two groups. There was no significant difference in the age and sex adjusted mean telomere length analysed by qPCR between the groups (p=0.88). In contrast, the load-of-short telomeres assessed by Universal-STELA method and telomerase activity by TRAP assay were both higher in patients who had appropriate ICD therapy and were significantly associated with incidence of ICD therapy (p=0.02, p=0.02). ROC analyses demonstrated that the sensitivity and specificity of these telomere dynamics in predicting potentially-fatal VA was higher than the current gold-standard - left ventricular ejection fraction (AUC 0.82 versus 0.47).

CONCLUSION: The load-of-short telomeres and telomerase activity had a significant association with ICD therapy (for VA) in ischaemic cardiomyopathy patients. These biomarkers should be tested in prospective studies to assess their clinical utility in predicting VA after myocardial infarction and guiding primary prevention ICD prescription.

OriginalsprogEngelsk
TidsskriftInternational Journal of Cardiology
Vol/bind207
Sider (fra-til)157-163
ISSN0167-5273
DOI
StatusUdgivet - 2016

Fingeraftryk

Telomere Shortening
Implantable Defibrillators
Telomerase
Telomere
Primary Prevention
Prescriptions
ROC Curve
Gold
Area Under Curve
Prospective Studies
Incidence

Citer dette

Sawhney, V ; Campbell, N G ; Brouilette, S W ; Coppen, S R ; Harbo, Maria ; Baker, V ; Ikebe, C ; Shintani, Y ; Hunter, R J ; Dhinoja, M ; Johnston, A ; Earley, M J ; Sporton, S ; Bendix, Laila ; Suzuki, K ; Schilling, R J. / Telomere shortening and telomerase activity in ischaemic cardiomyopathy patients : Potential markers of ventricular arrhythmia. I: International Journal of Cardiology. 2016 ; Bind 207. s. 157-163.
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title = "Telomere shortening and telomerase activity in ischaemic cardiomyopathy patients: Potential markers of ventricular arrhythmia",
abstract = "BACKGROUND: Implantable cardioverter defibrillators (ICDs) reduce mortality in patients with ischaemic cardiomyopathy at high risk of ventricular arrhythmias (VA). However, the current indication for ICD prescription needs improvement. Telomere and telomerase in leucocytes have been shown to associate with biological ageing and pathogenesis of cardiovascular diseases. We hypothesised that leucocyte telomere length, load-of-short telomeres and/or telomerase activity are associated with VA occurrence in ischaemic cardiomyopathy patients.METHODS AND RESULTS: 90 ischaemic cardiomyopathy patients with primary prevention ICDs were recruited. 35 had received appropriate therapy from the ICD for potentially-fatal VA while the remaining 55 patients had not. No significant differences in baseline demographic data relevant to telomere biology were seen between the two groups. There was no significant difference in the age and sex adjusted mean telomere length analysed by qPCR between the groups (p=0.88). In contrast, the load-of-short telomeres assessed by Universal-STELA method and telomerase activity by TRAP assay were both higher in patients who had appropriate ICD therapy and were significantly associated with incidence of ICD therapy (p=0.02, p=0.02). ROC analyses demonstrated that the sensitivity and specificity of these telomere dynamics in predicting potentially-fatal VA was higher than the current gold-standard - left ventricular ejection fraction (AUC 0.82 versus 0.47).CONCLUSION: The load-of-short telomeres and telomerase activity had a significant association with ICD therapy (for VA) in ischaemic cardiomyopathy patients. These biomarkers should be tested in prospective studies to assess their clinical utility in predicting VA after myocardial infarction and guiding primary prevention ICD prescription.",
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author = "V Sawhney and Campbell, {N G} and Brouilette, {S W} and Coppen, {S R} and Maria Harbo and V Baker and C Ikebe and Y Shintani and Hunter, {R J} and M Dhinoja and A Johnston and Earley, {M J} and S Sporton and Laila Bendix and K Suzuki and Schilling, {R J}",
note = "Copyright {\circledC} 2016 Elsevier Ireland Ltd. All rights reserved.",
year = "2016",
doi = "10.1016/j.ijcard.2016.01.066",
language = "English",
volume = "207",
pages = "157--163",
journal = "International Journal of Cardiology",
issn = "0167-5273",
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Sawhney, V, Campbell, NG, Brouilette, SW, Coppen, SR, Harbo, M, Baker, V, Ikebe, C, Shintani, Y, Hunter, RJ, Dhinoja, M, Johnston, A, Earley, MJ, Sporton, S, Bendix, L, Suzuki, K & Schilling, RJ 2016, 'Telomere shortening and telomerase activity in ischaemic cardiomyopathy patients: Potential markers of ventricular arrhythmia', International Journal of Cardiology, bind 207, s. 157-163. https://doi.org/10.1016/j.ijcard.2016.01.066

Telomere shortening and telomerase activity in ischaemic cardiomyopathy patients : Potential markers of ventricular arrhythmia. / Sawhney, V; Campbell, N G; Brouilette, S W; Coppen, S R; Harbo, Maria; Baker, V; Ikebe, C; Shintani, Y; Hunter, R J; Dhinoja, M; Johnston, A; Earley, M J; Sporton, S; Bendix, Laila; Suzuki, K; Schilling, R J.

I: International Journal of Cardiology, Bind 207, 2016, s. 157-163.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Telomere shortening and telomerase activity in ischaemic cardiomyopathy patients

T2 - Potential markers of ventricular arrhythmia

AU - Sawhney, V

AU - Campbell, N G

AU - Brouilette, S W

AU - Coppen, S R

AU - Harbo, Maria

AU - Baker, V

AU - Ikebe, C

AU - Shintani, Y

AU - Hunter, R J

AU - Dhinoja, M

AU - Johnston, A

AU - Earley, M J

AU - Sporton, S

AU - Bendix, Laila

AU - Suzuki, K

AU - Schilling, R J

N1 - Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

PY - 2016

Y1 - 2016

N2 - BACKGROUND: Implantable cardioverter defibrillators (ICDs) reduce mortality in patients with ischaemic cardiomyopathy at high risk of ventricular arrhythmias (VA). However, the current indication for ICD prescription needs improvement. Telomere and telomerase in leucocytes have been shown to associate with biological ageing and pathogenesis of cardiovascular diseases. We hypothesised that leucocyte telomere length, load-of-short telomeres and/or telomerase activity are associated with VA occurrence in ischaemic cardiomyopathy patients.METHODS AND RESULTS: 90 ischaemic cardiomyopathy patients with primary prevention ICDs were recruited. 35 had received appropriate therapy from the ICD for potentially-fatal VA while the remaining 55 patients had not. No significant differences in baseline demographic data relevant to telomere biology were seen between the two groups. There was no significant difference in the age and sex adjusted mean telomere length analysed by qPCR between the groups (p=0.88). In contrast, the load-of-short telomeres assessed by Universal-STELA method and telomerase activity by TRAP assay were both higher in patients who had appropriate ICD therapy and were significantly associated with incidence of ICD therapy (p=0.02, p=0.02). ROC analyses demonstrated that the sensitivity and specificity of these telomere dynamics in predicting potentially-fatal VA was higher than the current gold-standard - left ventricular ejection fraction (AUC 0.82 versus 0.47).CONCLUSION: The load-of-short telomeres and telomerase activity had a significant association with ICD therapy (for VA) in ischaemic cardiomyopathy patients. These biomarkers should be tested in prospective studies to assess their clinical utility in predicting VA after myocardial infarction and guiding primary prevention ICD prescription.

AB - BACKGROUND: Implantable cardioverter defibrillators (ICDs) reduce mortality in patients with ischaemic cardiomyopathy at high risk of ventricular arrhythmias (VA). However, the current indication for ICD prescription needs improvement. Telomere and telomerase in leucocytes have been shown to associate with biological ageing and pathogenesis of cardiovascular diseases. We hypothesised that leucocyte telomere length, load-of-short telomeres and/or telomerase activity are associated with VA occurrence in ischaemic cardiomyopathy patients.METHODS AND RESULTS: 90 ischaemic cardiomyopathy patients with primary prevention ICDs were recruited. 35 had received appropriate therapy from the ICD for potentially-fatal VA while the remaining 55 patients had not. No significant differences in baseline demographic data relevant to telomere biology were seen between the two groups. There was no significant difference in the age and sex adjusted mean telomere length analysed by qPCR between the groups (p=0.88). In contrast, the load-of-short telomeres assessed by Universal-STELA method and telomerase activity by TRAP assay were both higher in patients who had appropriate ICD therapy and were significantly associated with incidence of ICD therapy (p=0.02, p=0.02). ROC analyses demonstrated that the sensitivity and specificity of these telomere dynamics in predicting potentially-fatal VA was higher than the current gold-standard - left ventricular ejection fraction (AUC 0.82 versus 0.47).CONCLUSION: The load-of-short telomeres and telomerase activity had a significant association with ICD therapy (for VA) in ischaemic cardiomyopathy patients. These biomarkers should be tested in prospective studies to assess their clinical utility in predicting VA after myocardial infarction and guiding primary prevention ICD prescription.

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.ijcard.2016.01.066

DO - 10.1016/j.ijcard.2016.01.066

M3 - Journal article

C2 - 26803233

VL - 207

SP - 157

EP - 163

JO - International Journal of Cardiology

JF - International Journal of Cardiology

SN - 0167-5273

ER -