STRUCTURAL AND FUNCTIONAL CONDITION OF THE HEART IN PATIENTS WITH ARTERIAL HYPERTENSION DEPENDING ON THE POLYMORPHISM OF GENES UNDER THE INFLUENCE OF FIXED COMBINATIONS OF ANTIHYPERTENSIVE DRUGS
DOI:
https://doi.org/10.11603/1811-2471.2024.v.i1.14527Keywords:
arterial hypertension, gene polymorphism, valsartan, olmesartan, amlodipineAbstract
SUMMARY. The influence of the interrelationship of genetic factors and external influences on the course of arterial hypertension remains an urgent problem today.
The aim – to find out the effect of fixed combinations of valsartan with amlodipine and olmesartan with amlodipine in patients with arterial hypertension with gene polymorphism on the structural and functional state of the heart.
Material and Methods. 86 patients with arterial hypertension took part in the study. The control group consisted of 30 practically healthy people. Structural and functional state of the heart was studied on the Acuson Sequoia 512 device according to the standard method according to the recommendations of the American Society of Echocardiography and the European Association of Echocardiography. The study of the allelic polymorphism A1166C of the angiotensin II receptor gene of the first type and T786C – the promoter of the eNOS gene was carried out by the method of polymerase chain reaction with electrophoretic detection of the results.
Results. After 6 months of treatment with the use of a fixed combination of valsartan and amlodipine in patients with arterial hypertension, the parameters of TPWLV, LVMMi, and the size of the LA significantly improved, and diastolic dysfunction decreased in patients with the AC genotype of the AGTR1 gene compared to the values before treatment. Also, the size of the LA and LVMMi in patients with the CC genotype of the same gene probably decreased. The use of a fixed combination of olmesartan and amlodipine contributed to a probable reduction of TPWLV, LVMMi and the size of the LA in carriers of the CC genotype of both studied genes. A significant decrease in IVS, LVMMi, and LA was observed in heterozygotes of the AGTR1 gene. In patients with the TT genotype of the eNOS gene, the IVS was probably reduced, and in carriers of the TC genotype of the same gene, the size of the LA was reliably reduced.
Conclusions. The use of a fixed combination of valsartan with amlodipine for 6 months in patients with arterial hypertension significantly improves the structural and functional state of the heart in carriers of the C allele (AC+CC genotype) of the AGTR1 gene, while in patients with the T786C polymorphism of the eNOS gene, the use of this combination does not leads to probable changes in ultrasound of the heart. The use of a fixed combination of olmesaratne with amlodipine contributes to a reliable improvement of the indicators of the structural and functional state of the heart in patients with the presence of the C allele of the AGTR1 gene and eNOS, as well as a decrease in the thickness of the posterior wall of the left ventricle in homozygotes for the T allele of the eNOS gene.
References
Williams, B., Mancia, G., Spiering, W., Agabiti Rosei, E., Azizi, M., Burnier, M., Clement, D.L., … Lip, G.Y.H. (2018). 2018 ESC/ESH Guidelines for the management of arterial hypertension. European heart journal, 39(33), 3021-3104. DOI: 10.1093/eurheartj/ehy339.
Camm, A.J., Luscher, T.F., Maurer, G., & Serruys, P.W. (Eds) (2018). The ESC Textbook of Cardiovascular Medicine. The European Society of Cardiology Series. Oxford University Press: DOI: 10.1093/med/9780198784906.001.0001.
Forouzanfar, M.H., Liu, P., Roth, G.A., Ng, M., Biryukov, S., Marczak, L., … Murray, C.J. (2017). Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015. JAMA, 317(2), 165-182. DOI: 10.1001/jama.2016.19043.
Mills, K.T., Bundy, J.D., Kelly, T.N., Reed, J.E., Kearney, P.M., Reynolds, K., Chen, J., & He, J. (2016). Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population-Based Studies From 90 Countries. Circulation, 134(6), 441-450. DOI: 10.1161/CIRCULATIONAHA.115.018912.
Aronow, W.S. (2017). Association of obesity with hypertension. Annals of translational medicine, 5(17), 350. DOI: 10.21037/atm.2017.06.69.
Holmes, L., Jr, Lim, A., Comeaux, C.R., Dabney, K.W., & Okundaye, O. (2019). DNA Methylation of Candidate Genes (ACE II, IFN-γ, AGTR 1, CKG, ADD1, SCNN1B and TLR2) in Essential Hypertension: A Systematic Review and Quantitative Evidence Synthesis. International journal of environmental research and public health, 16(23), 4829. DOI: 10.3390/ijerph16234829.
Muñoz-Durango, N., Fuentes, C.A., Castillo, A.E., González-Gómez, L.M., Vecchiola, A., Fardella, C.E., & Kalergis, A.M. (2016). Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension. International journal of molecular sciences, 17(7), 797. DOI: 10.3390/ijms17070797.
Li, H., Horke, S., & Förstermann, U. (2014). Vascular oxidative stress, nitric oxide and atherosclerosis. Atherosclerosis, 237(1), 208-219. DOI: 10.1016/j.atherosclerosis. 2014.09.001.
Chen, J.Y., Ye, Z.X., Wang, X.F., Chang, J., Yang, M.W., Zhong, H.H., Hong, F.F., & Yang, S.L. (2018). Nitric oxide bioavailability dysfunction involves in atherosclerosis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 97, 423-428. DOI: 10.1016/j.biopha.2017.10.122.
Kong, X.Z., Zhang, Z.Y., Wei, L.H., Li,R., & Yu, J. (2017). The Endothelial Nitric Oxide Synthase Gene T-786C Polymorphism Increases Myocardial Infarction Risk: A Meta-Analysis. Medical science monitor : international medical journal of experimental and clinical research, 23, 759-766. DOI: 10.12659/msm.899905.
Liu, D., Jiang, Z., Dai, L., Zhang, X., Yan, C., & Han, Y. (2014). Association between the - 786T>C 1polymorphism in the promoter region of endothelial nitric oxide synthase (eNOS) and risk of coronary artery disease: a systematic review and meta-analysis. Gene, 545(1), 175-183. DOI: 10. 1016/j.gene.2013.09.099.
Mach, F., Baigent, C., Catapano, A.L., Koskinas, K.C., Casula, M., Badimon, L., Chapman, M.J., … ESC Scientific Document Group (2020). 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. European heart journal, 41(1), 111-188. DOI: 10.1093/eurheartj/ehz455.
Liu, Y., Kong, X., Jiang, Y., Zhao, M., Gao, P., Cong, X., Cao, Y., & Ma, L. (2022). Association of AGTR1 A1166C and CYP2C9*3 Gene Polymorphisms with the Antihypertensive Effect of Valsartan. International journal of hypertension, 2022, 7677252. DOI: 10.1155/2022/7677252.
Jin, Y., Kuznetsova, T., Thijs, L., Schmitz, B., Liu, Y., Asayama, K., Brand, S.M., … Staessen, J.A. (2012). Association of left ventricular mass with the AGTR1 A1166C polymorphism. American journal of hypertension, 25(4), 472-478. DOI: 10.1038/ajh.2011.244.
Wang, X., Zhu, H., Dong, Y., Treiber, F.A., & Snieder, H. (2006). Effects of angiotensinogen and angiotensin II type I receptor genes on blood pressure and left ventricular mass trajectories in multiethnic youth. Twin research and human genetics : the official journal of the International Society for Twin Studies, 9(3), 393-402. DOI: 10.1375/183242706777591335.
Sun, Y., Liao, Y., Yuan, Y., Feng, L., Ma, S., Wei, F., Wang, M., & Zhu, F. (2014). Influence of autoantibodies against AT1 receptor and AGTR1 polymorphisms on candesartan-based antihypertensive regimen: results from the study of optimal treatment in hypertensive patients with anti-AT1-receptor autoantibodies trial. Journal of the American Society of Hypertension : JASH, 8(1), 21-27. DOI: 10.1016/j.jash.2013.08.002.
Wang, Q., You, L., Li, Z., Zhang, L., Li, X., & Yang, X. (2022). Influence of AGTR1 and ABCB1 Gene Polymorphism on the Curative Effect of Irbesartan. International journal of hypertension, 2022, 4278675. DOI: 10.1155/2022/4278675.
Rossi, G.P., Taddei, S., Virdis, A., Cavallin, M., Ghiadoni, L., Favilla, S., Versari, D., Sudano, I., Pessina, A. C., & Salvetti, A. (2003). The T-786C and Glu298Asp polymorphisms of the endothelial nitric oxide gene affect the forearm blood flow responses of Caucasian hypertensive patients. Journal of the American College of Cardiology, 41(6), 938-945. DOI: 10.1016/s0735-1097(02)03011-5.
Zhu, H., Wang, X., Dong, Y., Treiber, F. A., & Snieder, H. (2005). Influence of the eNOS gene on development of blood pressure and left ventricular mass: longitudinal findings in multiethnic youth. Pharmacogenetics and genomics, 15(9), 669-675. DOI: 10.1097/01.fpc. 0000172244.65417.7a.
Nunes, R.A.B., Lima, L.B., Tanaka, N.I., da Costa Pereira, A., Krieger, J.E., & Mansur, A.J. (2018). Genetic associations of bradykinin type 2 receptor, alpha-adrenoceptors and endothelial nitric oxide synthase with blood pressure and left ventricular mass in outpatients without overt heart disease. International journal of cardiology. Heart & vasculature, 21, 45-49. DOI: 10.1016/j.ijcha.2018.09.002.
