Journal Article

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

Neely, Dermot, Qiu, Weiliang, Saretzki, Gabriele, Kunadian, Vijay, Martin-Ruiz, Carmen, Chan, Danny

2020

Overview

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. 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. 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). TL and TA are not found to be associated with the incidence of adverse outcomes in older patients presenting with NSTEACS undergoing invasive care. URL: https://www.clinicaltrials.gov Unique identifier: NCT01933581.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acute Coronary Syndrome - blood / Acute Coronary Syndrome - genetics / Acute Coronary Syndrome - metabolism / Acute coronary syndromes / Age / Aged / Aged, 80 and over / Biology and Life Sciences / Biomarkers / Bleeding / Cardiovascular disease / Cardiovascular diseases / Cell division / Cerebral infarction / Chromosomes / Confidence intervals / Copy number / Coronary Angiography / Deoxyribonucleic acid / DNA / Female / Frailty / Gene sequencing / Health hazards / Health risks / Heart attacks / Hemorrhage - complications / Hospitals / Humans / Incidence / Leukocytes (mononuclear) / Leukocytes, Mononuclear - metabolism / Male / Medicine and Health Sciences / Middle Aged / Myocardial infarction / Myocardial Infarction - complications / Non-ST Elevated Myocardial Infarction - blood / Non-ST Elevated Myocardial Infarction - genetics / Non-ST Elevated Myocardial Infarction - metabolism / Nucleotide sequence / Older people / People and Places / Peripheral blood mononuclear cells / Prognosis / Proportional Hazards Models / Regression analysis / Risk analysis / Risk Factors / Statistical analysis / Stroke - complications / Studies / Survival analysis / Telomerase / Telomerase - genetics / Telomere - genetics / Telomere - metabolism / Telomere Homeostasis - genetics / Telomere Homeostasis - physiology / Telomeres / Treatment Outcome