TELOMERE LENGTH AND CARDIOVASCULAR RISK FACTORS RELATIONSHIP IN CORONARY ARTERY DISEASE WITH BORDERLINE CORONARY ARTERY STENOSIS PATIENTS
https://doi.org/10.17802/2306-1278-2025-14-2-21-31
Abstract
Highlights
Telomere length and cardiovascular risk factors relationship in stable coronary artery disease patients with borderline coronary arteries stenosis with and without metabolic risk factors (diabetes mellitus and obesity) indicate complex and various mechanisms of coronary artery disease development in this category patients.
Abstract
Aim. To identify the relationship between telomere length and cardiovascular risk factors in patients with different clinical phenotypes of coronary artery disease (CAD) with borderline stenosis of the coronary arteries (CA).
Methods. The study included 201 patients with stable angina 1–3 class and borderline (50–70%) CA stenosis. Patients underwent physical examination, clinical and biochemical blood tests, assessment of systemic inflammation markers and atherosclerotic plaque stability, genetic markers (relative telomere length (RTL) was determined by real-time PCR), instrumental studies (ECG, ultrasound of the heart, neck vessels, coronary angiography, determination of stiffness markers, moreover, cognitive functions and the presence of early vascular aging (EVA) were assessed. Statistical calculations were performed using the RStudio program. Pairwise associations between two continuous variables were investigated by calculating Spearman`s correlation coefficients, between other types of variables it was investigated by using biserial correlation coefficients. Testing of statistical hypotheses was performed at a critical significance level of p = 0.05, i.e. the difference was considered statistically significant if p < 0.05.
Results. The 1st group consisted of patients with stable CAD phenotype without diabetes mellitus (DM) and obesity (71 (35.3%) patients), the 2nd group consisted of patients with stable CAD phenotype and type 2 DM (51 (25.4%) patients), the 3rd group consisted of patients with stable CAD phenotype and metabolically unhealthy obesity phenotype (MUO) (79 (39.3%) patients). When assessing the correlation relationships in the group of patients with the stable CAD phenotype without DM and MUO, the telomere length (TL) indicator correlated positively with the augmentation index (p = 0.036) and negatively with the number of points on the MMSE scale (p = 0.045), with the level of IL-1 (p = 0.022), with the level of MMP-9 (p = 0.040). In the group of patients with the stable CAD phenotype and diabetes mellitus, negative correlations were found between the TL and the levels of TC (p < 0.001), LDL (p = 0.001), the presence of right coronary artery (RCA) lesion (p = 0.025), the level of MMP-9 (p = 0.035), tEAT (p = 0.044) and the level of micro-RNA-208a (p < 0.001) and positive correlations with the age of myocardial infarction (p = 0.023), the level of blood urea (p = 0.005) and the level of micro-RNA-21 (p = 0.019). In the group of patients with the stable CAD phenotype and MNF, the TL indicators positively correlated with the presence of lesion of the anterior descending artery (p = 0.018) and RCA (p = 0.018).
Conclusion. The revealed correlation relationships of TL with various cardiovascular risk factors indicate complex mechanisms of development of coronary artery disease with borderline stenosis of the coronary arteries.
About the Authors
Yuliya O. OstaninaRussian Federation
PhD, Associate Professor at the Federal State Budgetary Educational Institution of Higher Education “Novosibirsk State Medical University” Novosibirsk State Medical University, Novosibirsk, Russian Federation
Davyd A. Yakhontov
Russian Federation
PhD, Professor at the Federal State Budgetary Educational Institution of Higher Education “Novosibirsk State Medical University” Novosibirsk State Medical University, Novosibirsk, Russian Federation
Dmitry S. Shilo
Russian Federation
6th-year Student, Faculty of Medicine, Federal State Budgetary Educational Institution of Higher Education “Novosibirsk State Medical University” Novosibirsk State Medical University, Novosibirsk, Russian Federation
References
1. Hoang T.H., Lazarev P.V., Maiskov V.V., Meray I.A., Kobalava Z.D. Myocardial Infarction with Non-Obstructive Coronary Arteries: Contemporary Diagnostic and Management Approaches. Rational Pharmacotherapy in Cardiology 2019;15(6):881-891. doi: 10.20996/1819- 6446-2019-15-6-881-891 (In Russian)
2. Poznyak A., Grechko A.V., Poggio P., Myasoedova V.A., Alfieri V., Orekhov A.N. The Diabetes Mellitus-Atherosclerosis Connection: The Role of Lipid and Glucose Metabolism and Chronic Inflammation. Int J Mol Sci. 2020; 21 (5): 1835. doi: 10.3390/ijms21051835
3. Opstad T. B., Kalstad A. A., Holte K. B., Berg T.J., Solheim S., Arnesen H., Seljeflot I. Shorter Leukocyte Telomere Lengths in Healthy Relatives of Patients with Coronary Heart Disease. Rejuvenation Res. 2020; 23 (4): 324–332. doi: 10.1089/rej.2019.2258
4. Yin H., Akawi O., Fox S. A., Li F., O'Neil C., Balint B., Arpino J.M., Watson A., Wong J., Guo L., Quantz M.A., Nagpal A.D., Kiaii B., Chu M.W.A., Pickering J.G. Cardiac-referenced leukocyte telomere length and outcomes after cardiovascular surgery. JACC Basic Transl Sci. 2018; 3 (5): 591–600. doi: 10.1016/j.jacbts.2018.07.004.
5. Nassour J., Przetocka S., Karlseder J. Telomeres as hotspots for innate immunity and inflammation. DNA Repair (Amst). 2024; 133:103591. doi: 10.1016/j.dnarep.2023.103591.
6. Doroshсhuk N.A., Lankin V.Z., Tikhaze A.K., Kheimets G.I, Doroshсhuk A.D., Smirnova M.D., Chazova I.E. Telomere length as a biomarker of the risk of cardiovascular complications in patients with coronary heart disease. Terapevticheskii Arkhiv (Ter. Arkh.). 2021; 93 (1): 20–24. doi: 10.26442/00403660.2021.01.200588 (In Russian)
7. Cheng F., Carroll L., Joglekar M.V., Januszewski A.S., Wong K.K., Hardikar A.A., Jenkins A.J., Ma R.C.W. Diabetes, metabolic disease, and telomere length. Lancet Diabetes Endocrinol. 2021;9(2):117-126. doi: 10.1016/S2213-8587(20)30365-X.
8. 2018 ESC/EACTS guidelines on myocardial revascularization. Russian Journal of Cardiology. 2019;(8):151-226. doi:10.15829/1560-4071-2019-8-151-226 (In Russian)
9. Yakhontov D.A., Ostanina J.O. Early vascular aging syndrome in young and middle age patients with hypertension and coronary artery disease. Medical alphabet. 2018;1(3):33-36. (In Russian)
10. Boccardi M., Boccardi V. Psychological wellbeing and healthy aging: focus on telomeres. Geriatrics (Basel). 2019; 4: 25. doi: 10.3390/geriatrics4010025.
11. Arsenis N.C., You T., Ogawa E.F., Tinsley G.M., Zuo L. Physical activity and telomere length: Impact of aging and potential mechanisms of action. Oncotarget. 2017; 8: 45008–45019. doi: 10.18632/oncotarget.16726
12. Lin J,, Epel E. Stress and telomere shortening: Insights from cellular mechanisms. Ageing Res Rev. 2022 Jan; 73:101507. doi: 10.1016/j.arr.2021.101507.
13. Honkonen M., Vääräniemi K., Saijonmaa O., Nyman A., Tikkakoski A.J., Koskela J., Lehtimäki T., Kähönen M., Mustonen J., Fyhrquist F., Pörsti I. Leukocyte telomere length is inversely associated with arterial wave reflection in 566 normotensive and never-treated hypertensive subjects. Aging (Albany NY). 2020;12(12):12376-12392. doi: 10.18632/aging.103459.
14. Vasan R.S., Pan S., Xanthakis V., Beiser A., Larson M.G., Seshadri S., Mitchell G.F. Arterial Stiffness and Long-Term Risk of Health Outcomes: The Framingham Heart Study. Hypertension. 2022;79(5):1045-1056. doi: 10.1161/HYPERTENSIONAHA.121.18776.
15. Kim J.M., Kim S.S., Kim I.J., Kim J.H., Kim B.H., Kim M.K., Lee S.H., Lee C.W., Kim M.C., Ahn J.H., Kim J; Relationship between Cardiovascular disease and Brachial-ankle Pulse Wave Velocity (baPWV) in Patients with Type 2 Diabetes (REBOUND) Study Group. Arterial stiffness is an independent predictor for risk of mortality in patients with type 2 diabetes mellitus: the REBOUND study. Cardiovasc Diabetol. 2020;19(1):143. doi: 10.1186/s12933-020-01120-6.
16. Wei D., Melgarejo J.D., Thijs L., Temmerman X., Vanassche T., Van Aelst L., Janssens S., Staessen J.A., Verhamme P., Zhang Z.Y. Urinary Proteomic Profile of Arterial Stiffness Is Associated with Mortality and Cardiovascular Outcomes. J Am Heart Assoc. 2022;11(8): e024769. doi: 10.1161/JAHA.121.024769.
17. Van der Spek A., Karamujić-Čomić H., Pool R., Bot M., Beekman M., Garmaeva S., Arp P.P., Henkelman S., et al. Fat metabolism is associated with telomere length in six population-based studies. Hum Mol Genet. 2022;31(7):1159-1170. doi: 10.1093/hmg/ddab281. PMID: 34875050.
18. Schunk S. J., Triem S., Schmit D., Zewinger S., Sarakpi T., Becker E., Hütter G., Wrublewsky S. et al. Interleukin-1α Is a Central Regulator of Leukocyte-Endothelial Adhesion in Myocardial Infarction and in Chronic Kidney Disease. Circulation. 2021;144 (11): 893–908. doi: 10.1161/circulationaha.121.053547
19. Zhang J., Rane G., Dai X., Shanmugam M.K., Arfuso F., Samy R.P., Lai M.K., Kappei D., Kumar A.P., Sethi G. Ageing and the telomere connection: An intimate relationship with inflammation. Ageing Res Rev. 2016; 25:55-69 doi: 10.1016/j.arr.2015.11.006.
20. Armanios M. The Role of Telomeres in Human Disease. Annu Rev Genomics Hum Genet. 2022; 23:363-381. doi: 10.1146/annurev-genom-010422-091101
21. Chen S., Hong X., Wu Y., Chen Z. Diagnostic and Prognostic Significance of microRNA-208a in Acute Myocardial Infarction. Dis Markers. 2022; 2022:7030722. doi: 10.1155/2022/7030722
22. Fernandes T., Barretti D.L., Phillips M.I., Menezes Oliveira E. Exercise training prevents obesity-associated disorders: Role of miRNA-208a and MED13. Mol Cell Endocrinol. 2018; 476:148-154. doi: 10.1016/j.mce.2018.05.004.
23. Hortmann M., Walter J.E., Benning L., Follo M., Mayr R.M., Honegger U., Robinson S., Stallmann D., Duerschmied D., Twerenbold R., Badertscher P., du Fay de Lavallaz J., Puelacher C., Bode C., Ahrens I., Mueller C. Droplet digital PCR of serum miR-499, miR-21 and miR-208a for the detection of functionally relevant coronary artery disease. Int J Cardiol. 2019; 275:129-135. doi: 10.1016/j.ijcard.2018.08.031.
Supplementary files
Review
For citations:
Ostanina Yu.O., Yakhontov D.A., Shilo D.S. TELOMERE LENGTH AND CARDIOVASCULAR RISK FACTORS RELATIONSHIP IN CORONARY ARTERY DISEASE WITH BORDERLINE CORONARY ARTERY STENOSIS PATIENTS. Complex Issues of Cardiovascular Diseases. 2025;14(2):21-31. (In Russ.) https://doi.org/10.17802/2306-1278-2025-14-2-21-31