Study of the diagnostic significance of telomere length and telomerase activity in patients with cerebral atherosclerosis and type 2 diabetes mellitus

Abstract

Cerebrovascular diseases areamongst the most important causes of morbidity and mortality in adult population. Objective — to determine the relationship between telomere length and telomerase activity with lipid spectrum, structural and functional status of the heart and cerebral vessels and heart rate variability in patients with cerebral atherosclerosis (CA) of stages 1—3and type 2 diabetes mellitus. Materials and methods. In a comprehensive clinical and instrumental study, 161 patients with CA 1—3stages were included. Telomerase activity was determined using a real-time tandem repeat amp­lification protocol. The relative lengths of telomeres were measured using multiplex quantitative poly­merase chain reaction in real time. Results and discussion. Patients were divided into 2 groups: 1 — with CA ofstage 1-2, 2 — with CA of stage 3 (with history of ischemic atherothrombotic stroke — AS). Mean age = 65.1 ± 10.5 and 65.4 ± 9.1 years, respectively. The percentage of men was 21.2 % in group1 and 52 % in the group 2. To identify factors that influence telomere size as a marker of early aging, the method of constructing logistic regression models was used. In building the models, the following categories were used: shorter telomere length — T/S < 2.61 (lowest and middle tercile); longer telomere length — T/S over 2.61. For selection of a set of significant risk factors, the method of step-by-step inclusion/exclusion of signs was used withexclusion threshold p > 0.15 and inclusion threshold p < 0.03. A multivariate logistic regression model was built on the identified significant risk factors. A statistically significant positive relationship was established between the telomere length and the E/A (diastolic function of the heart) and LPVLD, as well as negative relationships with the EF and the intima-media complex (IMC) on the right. To identify factors affecting telomerase activity, the method of constructing logistic regression models was used. In building the models, the following categories were used: lower telomerase activity — T/S < 3.16 (lowest and middle terciles); higher telomerase activity — T/S above 3.16. A sta­­tistically significant positive correlation of telomerase activity with the total stress index of the vegetative regulation HRV was also established, as well as a negative correlation with the atherogenic index. Conclusions. Telomere length and telomerase activity are comparable in elderly patients with CA of stage 1—2 and history of ischemic atherothrombotic stroke, including type 2 diabetes mellitus. Based on a multifactor regression analysis, the relationship between telomeres length and LPVLD, IMC, EF and LV diastolic function was detected in patients at different stages of CA, includingtype 2 diabetes (AUC 0.79; CI 0.69—0.87). Based on multivariate regression analysis the association of telomerase activity with atherogenic index and total stress index of vegetative regulation of heart rhythm was revealed in patients at different stages of CA, including type 2 diabetes (AUC 0.73; 95 % CI 0.63—0.83).