Modification of the daily blood pressure profile in hypertensive patients with type 2 diabetes mellitus

Objective. To evaluate the effect of combinations azilsartan medoxomil / chlorthalidone (Az-M/Chl) vs. perindopril / indapamide (Pr / Yn) regarding the modification of the daily blood pressure profile (BP) and augmentation index level in hypertensive patients (hypertension 2^nd degree, HTN), the blood pressure profile “nondipper” or “night-peaker” and type 2 diabetes mellitus (DM).

Design and methods. The study included 51 HTN (mean age 73 ± 11,7 years) patients (25 patients in the group Az-M / Chl and 26 patients in the group Pr / Yn, the groups were comparable by the main clinical parameters) with blood pressure profile “non-dipper” or “night-peaker”, DM (compensation stage). All patients have been receiving stable but ineffective antihypertensive therapy for at least 3 months before inclusion. The level of salt consumption was defined by the questionnaire “Charlton: SaltScreener”. Ambulatory 24-hour blood pressure monitoring (ABPM) was performed using BPLab® device (software Vasotens, Russia) which enables analysis of central hemodynamics. Statistica 10.0 software and software R using readxl, psych, ggplot2, ggpubr, gridExtra packages were used for statistical data processing.

Results. Twenty-seven (53 %) patients reported consumption of more than 6 g of salt per day: 14 (56 %) patients in the Az-M / Chl group, and 13 (50 %) patients in the Pr / Yn group. Mean daily BP was 161,2 / 102 ± 8,77 / 9,31 mm Hg in the Az-M / Chl group, and 158,3 / 96,7 ± 10,4 / 7,21 mm Hg in the group Pr / In (p > 0,05); mean daily systolic BP (MAP) was 161,2/102,0 ± 8,8 / 9,3 mm Hg and 158,3 / 96,7 ± 10,4 / 7,2 mm Hg, respectively (p > 0,05); aortic augmentation index — 4,88 ± 15,9 % and 2,7 ± 10,9 %, respectively (p > 0,05). At randomization (baseline), the non-dipping BP profile was found in 86,3 % (n = 44) patients, and the night-peaker profile — in 13,7      % (n = 7) patients. At the final visit, all patients achieved target BP level; mean daily systolic BP was 130,2 ± 8,8 and 139,9 ± 8,2 mm Hg in the Az-M/Chl and Pr / In groups, respectively (W = 140, p-value = 0.000497). The Az-M / Chl group demonstrated a more significant reduction in arterial stiffness. In addition, in the AZ-M / Chl group, 18 (72 %) patients showed change to a dipping BP profile, while only 5 (19 %) patients demonstrated the change in the Pr / Yin group.

Conclusion. The combination of azilsartan medoxomil/chlorthalidone showed a more significant compared with the combination of perindopril/indapamide: (1) a decrease in mean blood pressure per day; (2) the effect on the modification of the daily profile of blood pressure; (3) alteration of GI in aorta.

1. Şen S, Demir M, Yiğit Z, Üresin AY Efficacy and safety of S-Amlodipine 2.5 and 5 mg/d in hypertensive patients who were treatment-naive or previously received antihypertensive monotherapy. J Cardiovasc Pharmacol Ther. 2018;23(4):318-328.

2. Boggia J, Li Y, Thijs L, Hansen TW, Kikuya M, Bjorklund-Bodegard K et al. Prognostic accuracy of day versus night ambulatory blood pressure: a cohort study. Lancet. 2007;370 (9594):1219-1229.

3. Nurnberger J, Keflioglu-Scheiber A, Opazo Saez AM, Wenzel RR, Philipp T, Schafers RF et al. Augmentation index is associated with cardiovascular risk. J Hypertens. 2002;20(12): 2407-2414.

4. FukudaM, Mizuno M, Yamanaka T, MotokawaM, ShirasawaY, Nishio T et al. Patients with renal dysfunction require a longer duration until blood pressure dips during the night. Hypertension. 2008;52(6):1155—1160.

5. Uzu T, Kazembe FS, Ishikawa K, Nakamura S, Inenaga T, Kimura G. High sodium sensitivity implicates nocturnal hypertension in essential hypertension. Hypertension. 1996;28(1): 139-142.

6. Uzu T, Kimura G. Diuretics shift circadian rhythm of blood pressure from nondipper to dipper in essential hypertension. Circulation. 1999;100(15):1635-1638.

7. Fukuda M, Yamanaka T, Mizuno M, Motokawa M, Shirasawa Y, Miyagi S et al. Angiotensin II type 1 receptor blocker, olmesartan, restores nocturnal blood pressure decline by enhancing daytime natriuresis. J Hypertens. 2008;26(3):583-588.

8. Rakugi H, Enya K, Sugiura K, Ikeda Y. Comparison of the efficacy and safety of azilsartan with that of candesartan cilexetil in Japanese patients with grade I-II essential hypertension: a randomized, double-blind clinical study. Hypertens Res. 2012;35(5): 552-558.

9. Cushman WC, Bakris GL, White WB, Weber MA, Sica D, Roberts A et al. Azilsartan medoxomil plus chlorthalidone reduces blood pressure more effectively than olmesartan plus hydrochlorothiazide in stage 2 systolic hypertension. Hypertension. 2012;60(2):310-318.

10. Anderson VR, Perry CM, Robinson DM. Ramipril: A Review of its Use in Preventing Cardiovascular Outcomes in High-Risk Patients. Am J Cardiovasc Drugs. 2006;6(6):417-432.

11. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342(3):145-153.

12. Azilsartan compared to ACE inhibitors in anti-hypertensive therapy: one-year outcomes of the observational EARLY registry for the EARLY Registry Group et al. BMC Cardiovasc Disord. 2016;16(1):56. doi:10.1186/s12872-016-0222-6

13. Sowers JR, Zemel MB. Clinical implications of hypertension in the diabetic patient. Am J Hypertens. 1990;3(5 Pt 1): 415-424.

14. White WB, Cuadra RH, Lloyd E, Bakris GL, Kupfer S. Effects of azilsartan medoxomil compared with olmesartan and valsartan on ambulatory and clinic blood pressure in patients with type 2 diabetes and prediabetes. J Hypertens. 2016;34 (4):788-797.

15. Bakris GL, Sica D, White WB, Cushman WC, Weber MA, Handley A et al. Antihypertensive efficacy of hydrochlorothiazide vs chlorthalidone combined with azilsartan medoxomil. Am J Med. 2012;125(12):1229.e1-1229.e10.

16. Charlton KE, Steyn K, Levitt NS, Jonathan D, Zulu JV, Nel JH. Development and validation of a short questionnaire to assess sodium intake. Public Health Nutr. 2008;11(1):83—94.

17. Kidney International Supplements | KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease | ScienceDirect. com [Electronic resource]. URL: https://www.sciencedirect.com/journal/kidney-international-supplements/vol/3/issue/1 (accessed: 26.01.2018).

18. Preobrazhenskiy DV, Sidorenko BA, Marenich AV Diuretics in treatment of hypertension. Consilium-medicum. Consilium Provisorum. 2002;2 (1):22-24. In Russian.

19. Paul M, Poyan Mehr A, Kreutz R. Physiology of local renin-angiotensin systems. Physiol Rev. 2006;86(3):747-803.

20. Kobori H, Nangaku M, Navar LG, Nishiyama A. The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev. 2007;59(3):251-287.

21. Roson MI, Cavallero S, Della Penna S, Cao G, Gorzalczany S, Pandolfo M et al. Acute sodium overload produces renal tubulo interstitial inflammation in normal rats. Kidney Int. 2006;70(8): 1439-1446.

22. Chirinos JA, Townsend R. Sodium, potassium, and target organ damage: a case for central hemodynamics. Hypertension. 2010;56(4):578-580.

23. Oberleithner H. Two barriers for sodium in vascular endothelium? Ann Med. 2012;44(Suppl 1): S143-S148.

24. Fukuda M, Munemura M, Usami T, Nakao N, Takeuchi O, Kamiya Y et al. Nocturnal blood pressure is elevated with natriuresis and proteinuria as renal function deteriorates in nephropathy. Kidney Int. 2004;65(2):621-625.

25. Jacobsen PK, Rossing P, Parving HH. Impact of renin angiotensin system blockade on night to day blood pressure ratio in diabetic nephropathy. Nephrol Dial. Transplant. 2006;21(7): 2030-2031.

26. Sokolova AV, Dragunov DO, Arutyunov GP. Urine conductivity as a screening test to detect an adverse circadian blood pressure profile. Clinical Nephrology. 2017;1:36-41. In Russian.

27. Isobe-Sasaki Y, Fukuda M, Ogiyama Y, Sato R, Miura T, Fuwa D et al. Sodium balance, circadian BP rhythm, heart rate variability, and intrarenal renin-angiotensin-aldosterone and dopaminergic systems in acute phase of ARB therapy. Physiol Rep. 2017;5(11): e13309.

28. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365(9455):217-223.