Influence of dapagliflozin on cardiovascular remodeling in hypertensive patients with accompanying type 2 diabetes

Authors

DOI:

https://doi.org/10.14739/2310-1237.2024.1.299196

Keywords:

dapagliflozin, SGLT2 inhibitors, vascular stiffness, hypertension, type 2 diabetes

Abstract

Aim. To compare the results of 12-week treatment of patients with stage II hypertension (HTN) with accompanying diabetes mellitus (DM) type 2 between the combination of metformin + dapagliflozin and metformin monotherapy by studying changes in the elastic properties of the common carotid arteries (CCA), echocardiographic indicators, 24-hour ambulatory blood pressure monitoring (ABPM) and laboratory parameters of lipid and carbohydrate metabolism.

Materials and methods. 24 patients with stage II HTN with type 2 DM were involved in the study, the average age was 60.4 years, 50 % – men. Patients in the first group were randomized to receive metformin, and the second group – to receive a combination of metformin and dapagliflozin. At inclusion and after 3 months of treatment, basic anthropometric data, laboratory indicators of lipid and carbohydrate metabolism, ABPM, echocardiography, and indicators of CCA local stiffness were studied. Statistical analysis was performed, the probability of differences is at the level of p < 0.05.

Results. In both observation groups, there was a comparable decrease in SCORE 2-Diabetes range, glucose and glycated hemoglobin, total cholesterol, LDL cholesterol, average daily systolic blood pressure (SBP), daily SBP load, day and night pulse BP, as well as an increase in speed systolic movement of the lateral fibrous ring of the mitral valve (S lat).

Only in the metformin + dapagliflozin group a decrease in the adipose tissue level, the average daily diastolic blood pressure (DBP), the burden of DBP, the size of the left atrium and right ventricle, an increase in the movement speeds of the medial (e’med), lateral (e’lat) ring of the mitral and of the tricuspid (e’tk) valve in the period of early diastolic filling of the ventricles, velocities of systolic movement of the medial fibrous ring of the mitral (S med) and tricuspid (S tk) valves, a decrease in the ratio E/e’, and an improvement in the elastic properties of general carotid arteries were observed.

Conclusions. In persons with HTN stage II with DM type 2 the addition of dapagliflozin to the treatment regimen was associated with better control of blood pressure, improvement of diastolic function and longitudinal contractility of the left ventricle, elastic properties of CCA.

Author Biography

A. O. Bohun, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

MD, Postgraduate student of the Department of Propaedeutics of Internal Medicine, Radiation Diagnostics and Radiation Therapy

References

Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022;183:109119. doi: https://doi.org/10.1016/j.diabres.2021.109119

Kaze AD, Santhanam P, Musani SK, Ahima R, Echouffo-Tcheugui JB. Metabolic Dyslipidemia and Cardiovascular Outcomes in Type 2 Diabetes Mellitus: Findings From the Look AHEAD Study. J Am Heart Assoc. 2021;10(7):e016947. doi: https://doi.org/10.1161/JAHA.120.016947

Wang Q, Gan Z, Gao Q, Wang M, Zhan B. The associations of risk of cardiovascular disease with development stages of diabetes in Chinese population: findings from a retrospective cohort study in QuZhou city. BMC Endocr Disord. 2024;24(1):18. doi: https://doi.org/10.1186/s12902-024-01544-1

Kelsey MD, Nelson AJ, Green JB, Granger CB, Peterson ED, McGuire DK, et al. Guidelines for Cardiovascular Risk Reduction in Patients With Type 2 Diabetes: JACC Guideline Comparison. J Am Coll Cardiol. 2022;79(18):1849-57. doi: https://doi.org/10.1016/j.jacc.2022.02.046

McMurray JJ, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008. doi: https://doi.org/10.1056/NEJMoa1911303

Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020;383(15):1413-24. doi: https://doi.org/10.1056/NEJMoa2022190

Patoulias D, Papadopoulos C, Stavropoulos K, Zografou I, Doumas M, Karagiannis A. Prognostic value of arterial stiffness measurements in cardiovascular disease, diabetes, and its complications: The potential role of sodium-glucose co-transporter-2 inhibitors. J Clin Hypertens (Greenwich). 2020;22(4):562-71. doi: https://doi.org/10.1111/jch.13831

González-Clemente JM, García-Castillo M, Gorgojo-Martínez JJ, Jiménez A, Llorente I, Matute E, et al. Beyond the Glycaemic Control of Dapagliflozin: Impact on Arterial Stiffness and Macroangiopathy. Diabetes Ther. 2022;13(7):1281-98. doi: https://doi.org/10.1007/s13300-022-01280-6

Feng M, Lv H, Xu X, Wang J, Lyu W, Fu S. Efficacy and safety of dapagliflozin as monotherapy in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials. Medicine (Baltimore). 2019;98(30):e16575. doi: https://doi.org/10.1097/MD.0000000000016575

Calapkulu M, Cander S, Gul OO, Ersoy C. Lipid profile in type 2 diabetic patients with new dapagliflozin treatment; actual clinical experience data of six months retrospective lipid profile from single center. Diabetes Metab Syndr. 2019;13(2):1031-4. doi: https://doi.org/10.1016/j.dsx.2019.01.016

Sjöström CD, Johansson P, Ptaszynska A, List J, Johnsson E. Dapagliflozin lowers blood pressure in hypertensive and non-hypertensive patients with type 2 diabetes. Diab Vasc Dis Res. 2015;12(5):352-8. doi: https://doi.org/10.1177/1479164115585298

Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020;41(2):255-323. doi: https://doi.org/10.1093/eurheartj/ehz486

Nikolajević Starčević J, Janić M, Šabovič M. Molecular Mechanisms Responsible for Diastolic Dysfunction in Diabetes Mellitus Patients. Int J Mol Sci. 2019;20(5):1197. doi: https://doi.org/10.3390/ijms20051197

Nair N. Epidemiology and pathogenesis of heart failure with preserved ejection fraction. Rev Cardiovasc Med. 2020;21(4):531-540. doi: https://doi.org/10.31083/j.rcm.2020.04.154

Mochizuki Y, Tanaka H, Matsumoto K, Sano H, Shimoura H, Ooka J, et al. Impact of left ventricular longitudinal functional mechanics on the progression of diastolic function in diabetes mellitus. Int J Cardiovasc Imaging. 2017;33(12):1905-14. doi: https://doi.org/10.1007/s10554-017-1198-8

Machino-Ohtsuka T, Seo Y, Ishizu T, Hamada-Harimura Y, Yamamoto M, Sato K, et al. Clinical utility of the 2016 ASE/EACVI recommendations for the evaluation of left ventricular diastolic function in the stratification of post-discharge prognosis in patients with acute heart failure. Eur Heart J Cardiovasc Imaging. 2019;20(10):1129-37. doi: https://doi.org/10.1093/ehjci/jez082

Solomon SD, McMurray JJ, Claggett B, de Boer RA, DeMets D, Hernandez AF, et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. 2022;387(12):1089-98. doi: https://doi.org/10.1056/NEJMoa2206286

Santos-Gallego CG, Requena-Ibanez JA, San Antonio R, Garcia-Ropero A, Ishikawa K, Watanabe S, et al. Empagliflozin Ameliorates Diastolic Dysfunction and Left Ventricular Fibrosis/Stiffness in Nondiabetic Heart Failure: A Multimodality Study. JACC Cardiovasc Imaging. 2021;14(2):393-407. doi: https://doi.org/10.1016/j.jcmg.2020.07.042

Kang S, Verma S, Hassanabad AF, Teng G, Belke DD, Dundas JA, et al. Direct Effects of Empagliflozin on Extracellular Matrix Remodelling in Human Cardiac Myofibroblasts: Novel Translational Clues to Explain EMPA-REG OUTCOME Results. Can J Cardiol. 2020;36(4):543-53. doi: https://doi.org/10.1016/j.cjca.2019.08.033

Lee SG, Kim D, Lee JJ, Lee HJ, Moon RK, Lee YJ, et al. Dapagliflozin attenuates diabetes-induced diastolic dysfunction and cardiac fibrosis by regulating SGK1 signaling. BMC Med. 2022;20(1):309. doi: https://doi.org/10.1186/s12916-022-02485-z

Tanaka H, Soga F, Tatsumi K, Mochizuki Y, Sano H, Toki H, et al. Positive effect of dapagliflozin on left ventricular longitudinal function for type 2 diabetic mellitus patients with chronic heart failure. Cardiovasc Diabetol. 2020;19(1):6. doi: https://doi.org/10.1186/s12933-019-0985-z

Cinti F, Leccisotti L, Sorice GP, Capece U, D'Amario D, Lorusso M, et al. Dapagliflozin treatment is associated with a reduction of epicardial adipose tissue thickness and epicardial glucose uptake in human type 2 diabetes. Cardiovasc Diabetol. 2023;22(1):349. doi: https://doi.org/10.1186/s12933-023-02091-0

Soga F, Tanaka H, Tatsumi K, Mochizuki Y, Sano H, Toki H, et al. Impact of Dapagliflozin on the Left Ventricular Diastolic Function in Diabetic Patients with Heart Failure Complicating Cardiovascular Risk Factors. Intern Med. 2021;60(15):2367-74. doi: https://doi.org/10.2169/internalmedicine.6127-20

Fu Q, Zhou L, Fan Y, Liu F, Fan Y, Zhang X, et al. Effect of SGLT-2 inhibitor, dapagliflozin, on left ventricular remodeling in patients with type 2 diabetes and HFrEF. BMC Cardiovasc Disord. 2023;23(1):544. doi: https://doi.org/10.1186/s12872-023-03591-3

Verma S, Mazer CD, Yan AT, Mason T, Garg V, Teoh H, et al. Effect of Empagliflozin on Left Ventricular Mass in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease: The EMPA-HEART CardioLink-6 Randomized Clinical Trial. Circulation. 2019;140(21):1693-702. doi: https://doi.org/10.1161/CIRCULATIONAHA.119.042375

Baradaran H, Gupta A. Carotid Artery Stiffness: Imaging Techniques and Impact on Cerebrovascular Disease. Front Cardiovasc Med. 2022;9:852173. doi: https://doi.org/10.3389/fcvm.2022.852173

Chow B, Rabkin SW. The relationship between arterial stiffness and heart failure with preserved ejection fraction: a systemic meta-analysis. Heart Fail Rev. 2015;20(3):291-303. doi: https://doi.org/10.1007/s10741-015-9471-1

Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens. 2018;36(10):1953-2041. doi: https://doi.org/10.1097/HJH.0000000000001940

Patoulias D, Papadopoulos C, Stavropoulos K, Zografou I, Doumas M, Karagiannis A. Prognostic value of arterial stiffness measurements in cardiovascular disease, diabetes, and its complications: The potential role of sodium-glucose co-transporter-2 inhibitors. J Clin Hypertens (Greenwich). 2020;22(4):562-71. doi: https://doi.org/10.1111/jch.13831

Kimoto E, Shoji T, Shinohara K, Inaba M, Okuno Y, Miki T, et al. Preferential stiffening of central over peripheral arteries in type 2 diabetes. Diabetes. 2003;52(2):448-52. doi: https://doi.org/10.2337/diabetes.52.2.448

Chang S, Kim J, Sohn T, Son H, Lee J. Effects of glucose control on arterial stiffness in patients with type 2 diabetes mellitus and hypertension: An observational study. J Int Med Res. 2018;46(1):284-92. doi: https://doi.org/10.1177/0300060517722697

Oelze M, Kröller-Schön S, Welschof P, Jansen T, Hausding M, Mikhed Y, et al. The sodium-glucose co-transporter 2 inhibitor empagliflozin improves diabetes-induced vascular dysfunction in the streptozotocin diabetes rat model by interfering with oxidative stress and glucotoxicity. PLoS One. 2014;9(11):e112394. doi: https://doi.org/10.1371/journal.pone.0112394

Shin SJ, Chung S, Kim SJ, Lee EM, Yoo YH, Kim JW, et al. Effect of Sodium-Glucose Co-Transporter 2 Inhibitor, Dapagliflozin, on Renal Renin-Angiotensin System in an Animal Model of Type 2 Diabetes. PLoS One. 2016;11(11):e0165703. doi: https://doi.org/10.1371/journal.pone.0165703

Lunder M, Janić M, Japelj M, Juretič A, Janež A, Šabovič M. Empagliflozin on top of metformin treatment improves arterial function in patients with type 1 diabetes mellitus. Cardiovasc Diabetol. 2018;17(1):153. doi: https://doi.org/10.1186/s12933-018-0797-6

Hidalgo Santiago JC, Maraver Delgado J, Cayón Blanco M, López Saez JB, Gómez-Fernández P. Effect of dapagliflozin on arterial stiffness in patients with type 2 diabetes mellitus. Med Clin (Barc). 2020;154(5):171-4. English, Spanish. doi: https://doi.org/10.1016/j.medcli.2019.05.028

Hong JY, Park KY, Kim JD, Hwang WM, Lim DM. Effects of 6 Months of Dapagliflozin Treatment on Metabolic Profile and Endothelial Cell Dysfunction for Obese Type 2 Diabetes Mellitus Patients without Atherosclerotic Cardiovascular Disease. J Obes Metab Syndr. 2020;29(3):215-21. doi: https://doi.org/10.7570/jomes20040

Published

2024-04-22

How to Cite

1.
Bohun AO. Influence of dapagliflozin on cardiovascular remodeling in hypertensive patients with accompanying type 2 diabetes. Pathologia [Internet]. 2024Apr.22 [cited 2024Jul.18];21(1):41-50. Available from: http://pat.zsmu.edu.ua/article/view/299196

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Original research