The association of telomere length and telomerase activity with adverse outcomes in older patients with non-ST-elevation acute coronary syndrome


Autoři: Danny Chan aff001;  Carmen Martin-Ruiz aff003;  Gabriele Saretzki aff004;  Dermot Neely aff005;  Weiliang Qiu aff006;  Vijay Kunadian aff001
Působiště autorů: Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom aff001;  Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom aff002;  BioScreening Facility, Newcastle University, Newcastle upon Tyne, United Kingdom aff003;  Ageing Biology Centre and Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom aff004;  Department of Biochemistry, Newcastle upon Tyne Hospitals NHS Foundations Trust, United Kingdom aff005;  Sanofi Genzyme, Framingham, MA, United States of America aff006
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pone.0227616

Souhrn

Background

Non-ST elevation acute coronary syndrome (NSTEACS) occurs more frequently in older patients with an increased occurrence of recurrent cardiac events following the index presentation. Telomeres are structures consisting of repeated DNA sequences as associated shelterin proteins at the ends of chromosomes. We aim to determine whether telomere length (TL) and telomerase activity (TA) predicted poor outcomes in older patients presenting with NSTEACS undergoing invasive care.

Method

Older patients undergoing invasive management for NSTEACS were recruited to the ICON-1 biomarker study (NCT01933581). Peripheral blood mononuclear cells (PBMC) were recovered on 153 patients. DNA was isolated and mean TL was measured by quantitative PCR expressed as relative T (telomere repeat copy number) to S (single copy gene number) ratio (T/S ratio), and a telomere repeat amplification assay was used to assess TA during index presentation with NSTEACS. Primary clinical outcomes consisted of death, myocardial infarction (MI), unplanned revascularisation, stroke and significant bleeding recorded at 1 year. TL and TA were divided into tertile groups for analysis. Cox proportional hazards regression was performed. Ordinal regression was performed to evaluate the relationship between TL and TA and traditional cardiovascular risk factors at baseline.

Results

298 patients were recruited in the ICON-1 study of which 153 had PBMC recovered. The mean age was 81.0 ± 4.0 years (64% male). Mean telomere length T/S ratio was 0.47 ± 0.25 and mean TA was 1.52 ± 0.61 units. The primary composite outcome occurred in 44 (28.8%) patients. There was no association between short TL or low TA and incidence of the primary composite outcome (Hazard Ratio [HR] 1.50, 95% Confidence Interval [CI] 0.68–3.34, p = 0.32 and HR 1.33, 95% CI 0.52–3.36, p = 0.51 respectively).

Conclusion

TL and TA are not found to be associated with the incidence of adverse outcomes in older patients presenting with NSTEACS undergoing invasive care.

Clinical trial registration

URL: https://www.clinicaltrials.gov Unique identifier: NCT01933581

Klíčová slova:

Cardiovascular diseases – Coronary heart disease – Elderly – Hemorrhage – Chromosome structure and function – Myocardial infarction – Telomere length – Telomeres


Zdroje

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