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

Abstract

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.

Conflict of interest statement

The authors have declared that no competing interests exist. VK has received research funding from NIHR BRC Newcastle, AstraZeneca, and British Heart Foundation. WQ is salaried by Sanofi Genzyme. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Telomere length and cumulative event rates.

Cumulative event-free survival from the composite primary end-point by tertile of telomere length. LTL ≥ 0.5 T/S ratio, MTL 0.3468 to 0.5 T/S ratio and STL ≤ 0.3467 T/S ratio. P value from the Log-rank test. LTL, long telomere length; MTL; medium telomere length and STL; short telomere length.

Fig 2. Telomerase activity and cumulative event rates.

Cumulative event-free survival from the composite primary end-point by tertile of telomerase activity. High telomerase activity denotes ≥1.86 units, mid telomerase activity 1.32 to 1.86 units, and low telomerase activity ≤1.31 units. P value from the Log-rank test.