Vasoprotective effects hypotensive therapy in patients with coronary heart disease combined with chronic kidney disease stage 2-3 after coronary stenting

Aim      To study the condition of coronary vasculature by data of coronarography (CG) in patients with chronic ischemic heart disease (IHD) and arterial hypertension (AH) associated with stage 2-4 chronic kidney disease (CKD) and to evaluate the effect of a 12-week complex treatment with perindopril or with a combination of perindopril/amlodipine on changes in vascular wall stiffness, endothelial function, and structure and function parameters in this patient category after coronary stenting.

Material and methodsr This study included 87 patients with chronic IHD and AH associated with stage 2-3 CKD for whom CG was performed due to ineffectiveness of the antianginal therapy. The patients were divided into three subgroups: subgroup 1 included 28 patients who received a conservative treatment with perindopril 10 mg/day; subgroup 2 consisted of 25 patients who underwent coronary stenting and were prescribed perindopril; subgroup 3 consisted of 34 patients who underwent stenting and were prescribed the perindopril/amlodipine combination. The reference group included 47 patients with IHD and AH with preserved kidney function. Anatomic and functional parameters of the heart, arterial stiffness, pulse wave velocity, cardio-ankle vascular index, augmentation index, central aortic systolic and pulse pressure, endothelium-dependent vasodilation, plasma concentration of endothelin-1 (ET-1), and plasma concentration of nitric oxide metabolites were evaluated at baseline and after 12 weeks of treatment.

Results In patients with IHD, AH, and stage 2-3 CKD, arterial stiffness was more pronounced than in patients with preserved kidney function. Concentrations of ET-1 were significantly higher and levels of nitric oxide were lower in CKD. Supplementing the complex therapy with perindopril resulted in a considerable hypotensive effect in all subgroups, improvement of the kidney function, and positive dynamics of arterial stiffness and endothelial function. Changes in these parameters were more pronounced in patients after coronary stenting than in patients receiving only a conservative treatment. The use of perindopril/amlodipine following stenting exerted the most significant angioprotective and cardioprotective effect.

Conclusion      Patients with IHD and AH in combination with early CKD have pronounced impairment of the condition of arterial blood vessels and the heart. Addition of perindopril to the treatment not only exerted a hypotensive effect but also beneficially influenced mechanisms of progression of this combined pathology.

1. Boitsov S.A., Zairatiants O.V., Andreev E.M., Samorodskaya I.V. Comparison of mortality rate from ischemic heart disease among men and women over 50 years in Russia and USA. Russian Cardiology Journal. 2017; (7): 100-107. doi.org/10.15829/1560-4071-2017-6-100-107].

2. Henry RM, KostensePJ, Bos G, et all. Mild renal insuffi ciency is associated with increased cardiovascular mortality: The Hoorn Study. Kidney Int 2002;62:1402-1407. DOI: 10.1111 / j.1523-1755.2002.kid571.x

3. Briasoulis A., Bakris G.L. Chronic kidney disease as a coronary artery disease risk equivalent. Curr. Cardiol. Rep.2013; 15(3): 340. DOI: 10.1007/s11886-012-0340-4.

4. Scholz SS, Lauder L, Ewen S, Kulenthiran S, Marx N, Sakhov O, Kauer F, Witkowski A, Vaglimigli M, Wijns W, Scheller B, Böhm M, Mahfoud F. One-year clinical outcomes in patients with renal insufficiency after contemporary PCI: data from a multicenter registry. Clin Res Cardiol. 2020 Jul;109(7):845-856. doi: 10.1007/s00392-019-01575-y.

5. V.S. Moiseev, N.A. Muhin, A.V. Smirnov et al. Cardiovascular Risk and Chronic Kidney Disease: Strategies of Cardio-Nefroprotection. Russian Cardiology Journal. 2014; (8(11)): 7-37. doi.org/10.15829/1560-4071-2014-8-7-37].

6. Nagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T, Flachskampf FA, Gillebert TC, Klein AL, Lancellotti P, Marino P, Oh JK, Popescu BA, Waggoner AD. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echo-cardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016 Apr;29(4):277-314. doi: 10.1016/j.echo.2016.01.011.

7. Keane WF, Tomassini JE, Neff DR. Lipid abnormalities in patients with chronic kidney disease: implications for the pathophysiology of atherosclerosis. J Atheroscler Thromb. 2013;20(2):123-33. doi: 10.5551/jat.12849

8. Danilogorskaya Yu.A., Zheleznykh E.A., Privalova E.A., Belenkov Yu.N., Shchendrigina A.A., Kozhevnikova M.V. et all. Vasoprotective Effects of Prolonged Therapy With Perindopril A in Patients with Hypertension Including Concomitant Type 2 Diabetes Mellitus. Kardiologiia. 2020;60(1):4-9. doi.org/10.18087/cardio.2020.1.n888

9. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003; 362: 782-788. doi: 10.1016/s0140-6736(03)14286-9.

10. Bertrand ME, Fox KM, Remme WJ, Ferrari R, Simoons ML. Angiotensin-converting enzyme inhibition with perindopril in patients with prior myocardial infarction and/or revascularization: a subgroup analysis of the EUROPA trial. Arch Cardiovasc Dis. 2009 Feb;102(2):89-96. doi: 10.1016/j.acvd.2008.10.012.

11. Brugts JJ, Boersma E, Chonchol M, Deckers JW, Bertrand M, Remme WJ, Ferrari R, Fox K, Simoons ML; EUROPA Investigators. The cardioprotective effects of the angiotensin-converting enzyme inhibitor perindopril in patients with stable coronary artery disease are not modified by mild to moderate renal insufficiency: insights from the EUROPA trial. J Am Coll Cardiol. 2007 Nov 27;50(22):2148-55. doi: 10.1016/j.jacc.2007.08.029.

12. Svarovskaya A.V., Teplyakov A.T., Gusakova A.M., Garganeeva A.A. Role of markers of inflammation and endothelial dysfunction in the prognosis of the development of cardiovascular complications in patients with coronary artery disease and metabolic syndrome after coronary stenting. Kardiologiia. 2020;60(8):98-105. doi.org/10.18087/cardio.2020.8.n966

13. Cangiano E, Marchesini J, Campo G, Francolini G, Fortini C, Carrà G, Miccoli M, Ceconi C, Tavazzi L, Ferrari R. ACE inhibition modulates endothelial apoptosis and renewal via endothelial progenitor cells in patients with acute coronary syndromes. Am J Cardiovasc Drugs. 2011 Jun 1;11(3):189-98. doi: 10.2165/11589400-000000000-00000.

14. Baber U., Mehran R. Coronary Artery Revascularization in Chronic Kidney Disease Time for a Randomized Trial. Circ. Cardiovasc. Interv. 2015;8(1):e002140. DOI: 10.1161/CIRCINTERVENTIONS.114.002140.