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 ; 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).
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.
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