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Association between renin-angiotensin system gene polymorphism and cardio-ankle vascular index in patients with COVID-19

https://doi.org/10.20996/1819-6446-2024-3114

EDN: MKVZDY

Abstract

Aim. To assess the relationship between arterial stiffness and renin-angiotensin system (RAS) gene polymorphism in patients with COronaVIrus Disease 2019 (COVID-19).
Material and methods: 100 patients (mean age of 58.1±11.98 years; 51% women, 49% men) were included in the cross-ectional study. This study included adult patients with laboratory-confirmed diagnosis of COVID-19 admitted to the University Hospital. All patients were evaluated for arterial stiffness using cardio-ankle vascular index (CAVI) by sphygmomanometry. Also alleles and genotypes of several polymorphic markers were identified by real-time polymerase chain reaction in human DNA preparations: rs4762 of angiotensinogen (AGT) gene, rs1799752 of angiotensin-converting enzyme type 1 gene (ACE1), rs5186 of angiotensin II type 1 receptor gene (ATP1), and rs1403543 of angiotensin II type 2 receptor gene (ATP2). The distributions of alleles and genotypes in groups with normal and elevated arterial stiffness (CAVI ≥9.5) were compared.
Results. Elevated arterial stiffness (CAVI ≥9.5) was found in 29%. A significantly higher frequency of ATP1 rs5186 genotypes including the A allele, i.e., A/A+A/C versus C/C, was found in subjects with normal CAVI: 95.0% and 5.0% compared with 87.5% and 12.5% in those with CAVI ≥9.5 (χ2=3.907, p=0.049). A significantly higher frequency of genotypes involving the D allele (DD and ID) was detected in patients with increased stiffness: 95.0% compared to 81.3% in the group with normal stiffness (χ2=9.280, p<0.003), and a significantly higher frequency of genotypes including the A-allele: 68.7% and 31.3% compared to 55.0% and 45.0% in individuals with normal arterial stiffness (χ2=4.160, p=0.042). As a result, in patients hospitalized with COVID-19, the presence of increased arterial stiffness with a CAVI level ≥9.5 was associated with a higher frequency of adverse D/D genotype of ACE1 rs1799752, C/C genotype of ATP1 rs5186, A/A genotype and A allele of ATP2 rs1403543.
Conclusion. Thus, the presence of certain unfavorable genotypes of ACE1, ATP1 and ATP2 may contribute to the formation of higher arterial stiffness in COVID-19 and be considered as a non-modifiable risk factor for increased vascular wall stiffness along with such a significant factor as age.

About the Authors

V. I. Podzolkov
I. M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Valery I. Podzolkov 

Moscow



A. E. Bragina
I. M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Anna E. Bragina 

Moscow



E. S. Ogibenina
I. M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Ekaterina S. Ogibenina 

Moscow



I. I. Shvedov
I. M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Ilya I. Shvedov 

Moscow



A. R. Komelkova
I. M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Anastasiia R. Komelkova 

Moscow



References

1. Mizurini DM, Hottz ED, Bozza PT, Monteiro RQ. Fundamentals in Covid-19-Associated Thrombosis: Molecular and Cellular Aspects. Front Cardiovasc Med. 2021;8:785738. DOI: 10.3389/fcvm.2021.785738.

2. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 2020;383(2):120-8. DOI: 10.1056/nejmoa2015432.

3. Podzolkov VI, Tarzimanova AI, Bragina AE, et al. Damage to the Cardiovascular System in Patients with SARS- CoV-2 Coronavirus Infection. Part 1: Predictors of the Development of an Unfavorable Prognosis. Rational Pharmacotherapy in Cardiology. 2021;17(6):825-30 (In Russ.) DOI: 10.20996/1819-6446-2021-11-03.

4. Podzolkov VI, Bragina AE, Tarzimanova AI, et al. Arterial Hypertension and Severe COVID-19 in Hospitalized Patients: Data from a Cohort Study. Rational Pharmacotherapy in Cardiology. 2023;19(1):4-10 (In Russ.) DOI: 10.20996/1819-6446-2023-01-10.

5. Xiong TY, Redwood S, Prendergast B, Chen M. Coronaviruses and the cardiovascular system: acute and long-term implications. Eur Heart J. 2020;41(19):1798-800. DOI: 10.1093/eurheartj/ehaa231.

6. Liu PP, Blet A, Smyth D, Li H. The Science Underlying COVID-19: Implications for the Cardiovascular System. Circulation. 2020;142(1):68-78. DOI: 10.1161/ CIRCULATIONAHA.120.047549.

7. Markel АL. Essential systemic hypertension: genetics, clinics, experiment. Russian Journal of Cardiology. 2017;(10):133-9 (In Russ.) DOI: 10.15829/1560-4071-2017-10-133-139.

8. Palombo C, Kozakova M. Arterial stiffness, atherosclerosis and cardiovascular risk: Pathophysiologic mechanisms and emerging clinical indications. Vascul Pharmacol. 2016;77:1-7. DOI: 10.1016/j.vph.2015.11.083.

9. Sakuma K, Shimoda A, Shiratori H, et al. Angiotensin II acutely increases arterial stiffness as monitored by cardio-ankle vascular index (CAVI) in anesthetized rabbits. J Pharmacol Sci. 2019;140(2):205-9. DOI: 10.1016/j.jphs.2019.06.004.

10. Szeghy RE, Province VM, Stute NL, et al. Carotid stiffness, intima-media thickness and aortic augmentation index among adults with SARS-CoV-2. Exp Physiol. 2022;107(7):694-707. DOI: 10.1113/EP089481.

11. Ratchford SM, Stickford JL, Province VM, et al. Vascular alterations among young adults with SARS-CoV-2. Am J Physiol Heart Circ Physiol. 2021;320(1):H404-H410. DOI: 10.1152/ajpheart.00897.2020.

12. Schnaubelt S, Oppenauer J, Tihanyi D, et al. Arterial stiffness in acute COVID-19 and potential associations with clinical outcome. J Intern Med. 2021;290(2):437-43. DOI: 10.1111/joim.13275.

13. Faria D, Moll-Bernardes RJ, Testa L, et al. Sympathetic Neural Overdrive, Aortic Stiffening, Endothelial Dysfunction, and Impaired Exercise Capacity in Severe COVID-19 Survivors: A Mid-Term Study of Cardiovascular Sequelae. Hypertension. 2023;80(2):470-81. DOI: 10.1161/HYPERTENSIONAHA.122.19958.

14. Stamatelopoulos K, Georgiopoulos G, Baker KF, et al; Pisa COVID-19 Research Group; Newcastle COVID-19 Research Group. Estimated pulse wave velocity improves risk stratification for all-cause mortality in patients with COVID-19. Sci Rep. 2021;11(1):20239. DOI: 10.1038/s41598-021-99050-0.

15. Aydın E, Kant A, Yilmaz G. Evaluation of the cardio-ankle vascular index in COVID-19 patients. Rev Assoc Med Bras (1992). 2022;68(1):73-6. DOI: 10.1590/1806-9282.20210781.

16. Podzolkov V, Bragina A, Tarzimanova A, et al. Association of COVID-19 and Arterial Stiffness Assessed using Cardiovascular Index (CAVI). Curr Hypertens Rev. 2024;20(1):44-51. DOI: 10.2174/0115734021279173240110095037.

17. Podzolkov VI, Pokrovskaya AE, Vanina DD, Safronova TA. The Relationship Between Resistin with Vascular Stiffness and Severity of Novel Coronavirus Infection COVID-19 in Patients with Different Body Mass Index. Lechebnoe delo. 2023;(1): 72-80 (In Russ.) DOI: 10.24412/2071-5315-2023-12953.

18. Podzolkov VI, Bragina AE, Tarzimanova AI, et al. Association between cardioankle vascular index and markers of thrombosis in hospitalized patients COVID-19. Terapevticheskii arkhiv. 2023;95(7):548-53 (In Russ.) DOI: 10.26442/00403660.2023.07.202292.

19. Kobalava ZhD, Konradi AO, Nedogoda SV, et al. Arterial hypertension in adults. Clinical guidelines 2020. Russian Journal of Cardiology. 2020;25(3):3786 (In Russ.) DOI: 10.15829/1560-4071-2020-3-3786.

20. Miyoshi T, Ito H, Shirai K, et al; CAVI‐J (Prospective Multicenter Study to Evaluate Usefulness of Cardio‐Ankle Vascular Index in Japan) investigators. Predictive Value of the Cardio-Ankle Vascular Index for Cardiovascular Events in Patients at Cardiovascular Risk. J Am Heart Assoc. 2021;10(16):e020103. DOI: 10.1161/JAHA.120.020103.

21. Saz-Lara A, Bruno RM, Cavero-Redondo I, et al. Association Between Arterial Stiffness and Blood Pressure Progression With Incident Hypertension: A Systematic Review and Meta-Analysis. Front Cardiovasc Med. 2022;9:798934. DOI: 10.3389/fcvm.2022.798934.

22. Wu CH, Mohammadmoradi S, Chen JZ, et al. Renin-Angiotensin System and Cardiovascular Functions. Arterioscler Thromb Vasc Biol. 2018;38(7):e108-e116. DOI: 10.1161/ATVBAHA.118.311282.

23. Santos RAS, Oudit GY, Verano-Braga T, et al. The renin-angiotensin system: going beyond the classical paradigms. Am J Physiol Heart Circ Physiol. 2019;316(5):H958-H970. DOI: 10.1152/ajpheart.00723.2018.

24. Palmirotta R, Barbanti P, Ludovici G, et al. Association between migraine and ace gene (insertion/deletion) polymorphism: The BIOBIM study. Pharmacogenomics. 2014;15(2):147-55. DOI: 10.2217/pgs.13.186.

25. Rebrova TYu, Muslimova EF, Panova NV, et al. I/D polymorphism of angiotensine converting enzyme in CHD patients of different age and gender. Russian Journal of Cardiology. 2014;(10):77-81 (In Russ.) DOI: 10.15829/1560-4071-2014-10-77-81.

26. Saygitov RT, Glezer MG, Sementsov DP, Malygina NA. ACE gene ID polymorphism in acute coronary syndrome patients. Cardiovascular Therapy and Prevention. 2006;5(8):34-41 (In Russ.)

27. Atamantchuk AA, Kuzmina LP, Khotuleva AG, Kolyaskina MM. Polymorphism of genes of renin-angiotensin-aldosterone system in the development of hypertension in workers exposed to physical factors. Russian Journal of Occupational Health and Industrial Ecology. 2019;(12):972-7 (In Russ.) DOI: 10.31089/1026-9428-2019-59-12-972-977.

28. Larsson SC, Mason AM, Bäck M, et al; Million Veteran Program; Michaëlsson K, Burgess S. Genetic predisposition to smoking in relation to 14 cardiovascular diseases. Eur Heart J. 2020;41(35):3304-10. DOI:10.1093/eurheartj/ehaa193.

29. Kim HK, Lee H, Kwon JT, Kim HJ. A polymorphism in AGT and AGTR1 gene is associated with lead-related high blood pressure. J Renin Angiotensin Aldosterone Syst. 2015;16(4):712-9. DOI: 10.1177/1470320313516174.

30. Zhu M, Yang M, Lin J, et al. Association of seven renin angiotensin system gene polymorphisms with restenosis in patients following coronary stenting. J Renin Angiotensin Aldosterone Syst. 2017;18(1):147032031668877. DOI: 10.1177/1470320316688774.

31. Akopyan AA, Kirillova KI, Strazhesko ID, et al. Association of AGT, ACE, NOS3, TNF, MMP9, CYBA polymorphism with subclinical arterial wall changes. Kardiologiia. 2021;61(3):57-65 (In Russ.) DOI: 10.18087/cardio.2021.3.n1212.

32. Balkestein EJ, Wang JG, Struijker-Boudier HA, et al. Carotid and femoral intimamedia thickness in relation to three candidate genes in a Caucasian population. J Hypertens. 2002;20(8):1551-61. DOI: 10.1097/00004872-200208000-00018.

33. Benetos A, Gautier S, Ricard S, et al. Influence of angiotensin-converting enzyme and angiotensin II type 1 receptor gene polymorphisms on aortic stiffness in normotensive and hypertensive patients. Circulation. 1996;94(4):698-703. DOI: 10.1161/01.cir.94.4.698.

34. Mayer O Jr, Filipovský J, Pesta M, et al. Synergistic effect of angiotensin II type 1 receptor and endothelial nitric oxide synthase gene polymorphisms on arterial stiffness. J Hum Hypertens. 2008;22(2):111-8. DOI: 10.1038/sj.jhh.1002279.

35. Benetos A, Giron A, Joly L, et al. Influence of the AGTR1 A1166C genotype on the progression of arterial stiffness: A 16-year longitudinal study. Am J Hypertens. 2013;26(12):1421-7. DOI: 10.1093/ajh/hpt141.

36. Bragina AE, Rodionova YuN, Ogibenina ES, et al. Polymorphism of RAAS genes in patients with COVID-19: comparison with frequency in population and relationship with severity of course. Terapevticheskii Arkhiv. 2024;96(9):872-8. (In Russ.) DOI: 10.26442/00403660.2024.09.202849.

37. Gemmati D, Tisato V. Genetic hypothesis and pharmacogenetics side of reninangiotensin-system in COVID-19. Genes (Basel). 2020;11(9):1044. DOI: 10.3390/genes11091044.

38. Szeghy RE, Stute NL, Province VM, et al. Six-month longitudinal tracking of arterial stiffness and blood pressure in young adults following SARSCoV-2 infection. J Appl Physiol (1985). 2022;132(5):1297-1309. DOI: 10.1152/japplphysiol.00793.2021.

39. Zanoli L, Gaudio A, Mikhailidis DP, et al.; Methuselah Study Group. Vascular Dysfunction of COVID-19 Is Partially Reverted in the Long-Term. Circ Res. 2022;130(9):1276-85. DOI: 10.1161/CIRCRESAHA.121.320460.


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Podzolkov V.I., Bragina A.E., Ogibenina E.S., Shvedov I.I., Komelkova A.R. Association between renin-angiotensin system gene polymorphism and cardio-ankle vascular index in patients with COVID-19. Rational Pharmacotherapy in Cardiology. 2024;20(5):525-531. (In Russ.) https://doi.org/10.20996/1819-6446-2024-3114. EDN: MKVZDY

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ISSN 1819-6446 (Print)
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