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4 Association of Telomere Length and Telomerase Activity with Clinical Parameters in Older Patients Undergoing Invasive Management Of non-ST Elevation Acute Coronary Syndrome
  1. Vijay Kunadian1,
  2. Murugapathy Veerasamy2,
  3. Hannah Sinclair2,
  4. Jonathan Batty1,
  5. Meedya Sharifpour1,
  6. Jose Lima Junior1,
  7. Dermot Neely3,
  8. Carmen Martin-Ruiz4,
  9. Gabriele Saretzki5
  1. 1Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK
  2. 2Institute of Cellular Medicine, Newcastle University, United Kingdom and Cardiothoracic Centre, Freeman Hospital, Newcastle Upon Tyne, UK
  3. 3Department of Biochemistry, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
  4. 4Institute of Neurosciences, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK
  5. 5Institute for Cell and Molecular Biosciences, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK

Abstract

Background Telomerase acts to abrogate the deleterious attrition of telomeres (DNA-protein complexes, protecting chromosomes from degradation) in order to maintain genetic and cellular integrity. Although telomere length (TL) is an established determinant of cardiovascular ageing, it remains unclear whether elevated telomerase activity (TA) is cardioprotective, or associated with increased risk of coronary artery disease (CAD). In particular, few data exist regarding the significance of TL and TA in older patients. This study aimed to evaluate the correlation of these measures with clinical parameters, in an enriched, older population with CAD.

Methods Peripheral blood monocyte cell (PBMC) samples were obtained from 54 patients, aged >74 years-old, admitted for invasive management of non-ST-elevation acute coronary syndrome, and 98 healthy controls, aged <65 years-old. DNA was extracted from PBMCs: analysis of mean TL was performed using a quantitative polymerase chain reaction-based assay; TA was quantified using an ELISA based telomere repeat amplification protocol (TeloTAGGGTM; Roche, Switzerland). Cardiovascular risk factors were ascertained; angiographic CAD severity was evaluated using the SYNTAX Score. Data are presented: mean [standard deviation].

Results 54 patients (mean age 81 [4]; 56% male) had a median TL of 2.4 [1.0] kbp. TL was not significantly associated with conventional cardiovascular risk factors (age, p = 0.96; sex, p = 0.36; smoking status, p = 0.52; hypertension, p = 0.81 or diabetes, p = 0.34). In a subset of CAD patients with available data on telomerase activity (n = 35), TA was higher than in healthy controls aged 25–65 (1.6 [0.07] vs. 0.7 [0.05] units; Figure 1). In older participants with confirmed CAD, there was no association between TA and risk factors (age, p = 0.58; gender, p = 0.21; smoking status, p = 0.26; hypertension, p = 0.31; hyperlipidaemia, p = 0.53, or diabetes, p = 0.12). A strong, inverse correlation between TL and TA was observed in study patients (p < 0.001). Both were correlated with CAD severity (SYNTAX score; TL: r=–0.330, p = 0.03; TA: r = 0.406, p = 0.04) in unadjusted, and covariate-adjusted analyses (Figure 2).

Abstract 4 Figure 1

The relationship between age and telomerase activity (TA; n = 133)

Abstract 4 Figure 2

The correlation between telomere length (left) and telomerase activity (right) with CAD severity (n = 5)

Conclusion Despite a lack of association with established cardiovascular risk factors, TL and TA correlated significantly with angiographic severity of CAD. Further, longitudinal studies are required to evaluate long-term prognostic implications, and to elucidate key underlying biological interactions.

  • Elderly
  • Telomere
  • Telomerase

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