Predictors of cardiovascular and renal complications in patients with resistant arterial hypertension during long-term follow-up

Main Article Content

O. O. Matova
L. А. Mishchenko
T. V. Talayeva
O. B. Kuchmenko

Abstract

The aim – to evaluate the incidence of cardiovascular and renal complications and its predictors in resistant hypertensive (RH) patients during the long-term follow-up.
Materials and methods. The frequency of cardiovascular and renal events was studied in 240 true resistant hypertensive patients. The duration of observation was 5.1±0.1 years. The comparison group consisted of 228 patients with controlled arterial hypertension (CAH) on a triple combination antihypertensive therapy. Cardiovascular endpoints included stroke/transient ischemic attack, myocardial infarction, cardiovascular death, myocardial revascularization, development of atrial fibrillation, hospitalization due to heart failure, and lower limb arterial disease. Kidney outcomes included dialysis or GFR decline by 40 % or greater. All the endpoints formed a composite primary endpoint. New cases of type 2 diabetes mellitus were also estimated.
Results and discussion. The patients with resistant hypertension on multi-component antihypertensive therapy and significant reduction in arterial blood pressure (BP) levels (achievement of controlled office BP in 49.6 % of patients, office and ambulatory BP in 34.2 % of patients), maintained a higher risk of cardiovascular and renal events compared to patients with controlled arterial hypertension. It was found that the frequency of occurrence of the composite primary endpoint in resistant hypertensive patients was four times higher than in the group of patients with controlled hypertension – 30.0 % (72/240) versus 7.0 % (16/228) (p=0.001). The frequency of new cases of type 2 diabetes mellitus in patients with RH exceeded compared to CAH patients by 3.7 times (p=0.03).
Conclusions. Independent predictors of the risk of cardiovascular and renal complications in patients with RH were the initial indicators of circulating endothelial progenitor cells if their concentration in the blood was ≤ 1818 cells/ml (HR 0.41; 95 % CI (0.21–0.79); p=0.007), the content of citrulline in the blood is more than 68 μmol/l (HR 1.13; 95 % CI (1.07–1.20); p<0.001); value of initial average daily systolic BP > 163 mm Hg (HR 1.10; 95 % CI (1.03–1.18); p=0.008).

Article Details

Keywords:

resistant arterial hypertension, predictors of cardiovascular and renal complications, circulating endothelial progenitor cells, citrulline

References

NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants (2022) [published correction appears in Lancet. 2022 Feb 5;399(10324):520]. Lancet, 398(10304), 957-80. https://doi.org/10.1016/S0140-6736(21)01330-1.

Fuchs FD, Whelton PK. High Blood Pressure and Cardiovascular Disease. Hypertension. 2020 Feb;75(2):285-92. https://doi.org/10.1161/HYPERTENSIONAHA.119.14240.

Shalaeva EV, Messerli FH. What is resistant arterial hypertension? Blood Press. 2023 Dec;32(1):2185457. https://doi.org/ 10.1080/08037051.2023.2185457.

Thomas G, Xie D, Chen HY, Anderson AH, Appel LJ, Bodana S, Brecklin CS, Drawz P, Flack JM, Miller ER 3rd, Steigerwalt SP, Townsend RR, Weir MR, Wright JT Jr, Rahman M; CRIC Study Investigators. Prevalence and Prognostic Significance of Apparent Treatment Resistant Hypertension in Chronic Kidney Disease: Report From the Chronic Renal Insufficiency Cohort Study. Hypertension. 2016 Feb;67(2):387-96. https://doi.org/10.1161/HYPERTENSIONAHA.115.06487.

Achelrod D, Wenzel U, Frey S. Systematic review and meta-analysis of the prevalence of resistant hypertension in treated hypertensive populations. Am J Am J Hypertens. 2015 Mar;28(3):355-61. https://doi.org/10.1093/ajh/hpu151.

Mancia G, Kreutz R, Brunström M, Burnier M, Grassi G, Januszewicz A, Muiesan ML, Tsioufis K, Agabiti-Rosei E, Algharably EAE, Azizi M, Benetos A, Borghi C, Hitij JB, Cifkova R, Coca A, Cornelissen V, Cruickshank JK, Cunha PG, Danser AHJ, Pinho RM, Delles C, Dominiczak AF, Dorobantu M, Doumas M, Fernández-Alfonso MS, Halimi JM, Járai Z, Jelaković B, Jordan J, Kuznetsova T, Laurent S, Lovic D, Lurbe E, Mahfoud F, Manolis A, Miglinas M, Narkiewicz K, Niiranen T, Palatini P, Parati G, Pathak A, Persu A, Polonia J, Redon J, Sarafidis P, Schmieder R, Spronck B, Stabouli S, Stergiou G, Taddei S, Thomopoulos C, Tomaszewski M, Van de Borne P, Wanner C, Weber T, Williams B, Zhang ZY, Kjeldsen SE. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens. 2023 Dec 1;41(12):1874-2071. https://doi.org/10.1097/HJH.0000000000003480.

Stergiou GS, Palatini P, Parati G, O’Brien E, Januszewicz A, Lurbe E, Persu A, Mancia G, Kreutz R; European Society of Hypertension Council and the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability. 2021 European Society of Hypertension practice guidelines for office and out-of-office blood pressure measurement. J Hypertens. 2021 Jul 1;39(7):1293-302. https://doi.org/10.1097/HJH.0000000000002843.

Perrone-Filardi P, Coca A, Galderisi M, Paolillo S, Alpendurada F, de Simone G, Donal E, Kahan T, Mancia G, Redon J, Schmieder R, Williams B, Agabiti-Rosei E. Noninvasive cardiovascular imaging for evaluating subclinical target organ damage in hypertensive patients: a consensus article from the European Association of Cardiovascular Imaging, the European Society of Cardiology Council on Hypertension and the European Society of Hypertension. J Hypertens. 2017 Sep;35(9):1727-41. https://doi.org/10.1097/HJH.0000000000001396.

Snell FD, Snell ST. Colorimetric method of analysis (1954). New York: Van Nostard; 153-155.

Kuchmenko O, Mkhytaryan L, Ievstratova I, Matova O, Vasylchenko V. The possibility of using citrulline as a new biochemical marker to evaluate the state of kidney under cardiovascular pathologies. Ukr J Nephr Dial. 2018;4(60):35-9. https://doi.org/10.31450/ukrjnd.4(60).2018.05.

Rath M, Müller I, Kropf P, Closs EI, Munder M. Metabolism via arginase or nitric oxide synthase: two competing arginine pathways in macrophages. Front Immunol. 2014 Oct 27;5:532. https://doi.org/10.3389/fimmu.2014.00532.

Mkhitaryan LS, Kuchmenko OB, Ievstratova IN, Lipkan NG, Vasylynchuk NM, Drobotko TF.Citrulline as a marker of the functional state of organs under pathological conditions.Ukrainian Journal of Cardiology. 2016;3:109-115. https: http://nbuv.gov.ua/UJRN/Ukzh_2016_3_14.

Thomas G, Felts J, Brecklin CS, Chen J, Drawz PE, Lustigova E, Mehta R, Miller ER 3rd, Sozio SM, Weir MR, Xie D, Wang X, Rahman M. Apparent Treatment-Resistant Hypertension Assessed by Office and Ambulatory Blood Pressure in Chronic Kidney Disease-A Report from the Chronic Renal Insufficiency Cohort Study. Kidney360. 2020 Aug;1(8):810-8. https://doi.org/10.34067/KID.0002072020.

Curis E, Nicolis I, Moinard C, Osowska S, Zerrouk N, Bénazeth S, Cynober L. Almost all about citrulline in mammals. Amino Acids. 2005 Aug;29(3):177-205. https://doi.org/10.1007/s00726-005-0235-4.

Ebinger JE, Kauko A; FinnGen; Bello NA, Cheng S, Niiranen T. Apparent treatment-resistant hypertension associated lifetime cardiovascular risk in a longitudinal national registry. Eur J Prev Cardiol. 2023 Aug 1;30(10):960-8. https://doi.org/10.1093/eurjpc/zwad066.

Kawel-Boehm N, Kronmal R, Eng J, Folsom A, Burke G, Carr JJ, Shea S, Lima JAC, Bluemke DA. Left Ventricular Mass at MRI and Long-term Risk of Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis (MESA). Radiology. 2019 Oct;293(1):107-14. https://doi.org/10.1148/radiol.2019182871.

King TF, McDermott JH. Endothelial progenitor cells and cardiovascular disease. J Stem Cells. 2014;9(2):93-106.

Daugherty SL, Powers JD, Magid DJ, Tavel HM, Masoudi FA, Margolis KL, O’Connor PJ, Selby JV, Ho PM. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation. 2012 Apr 3;125(13):1635-42. https://doi.org/10.1161/CIRCULATIONAHA.111.068064.

Chun KH, Lee CJ, Oh J, Lee SH, Kang SM, Kario K, Park S. Prevalence and prognosis of the 2018 vs 2008 AHA definitions of apparent treatment-resistant hypertension in high-risk hypertension patients. J Clin Hypertens (Greenwich). 2020 Nov;22(11):2093-102. https://doi.org/10.1111/jch.14043.

Khalfallah M, Elsheikh A, Eissa A, Elnagar B. Prevalence, Predictors, and Outcomes of Resistant Hypertension in Egyptian Population. Glob Heart. 2023 Jun 14;18(1):31. https://doi.org/10.5334/gh.1211.

Leiba A, Yekutiel N, Chodick G, Wortsman J, Angel-Korman A, Weinreb B. Resistant hypertension is associated with an increased cardiovascular risk compared to patients controlled on a similar multi-drug regimen. J Hum Hypertens. 2023 Jul;37(7):542-7. https://doi.org/10.1038/s41371-022-00749-y.

Holtrop J, Spiering W, Nathoe HM, De Borst GJ, Kappelle LJ, De Valk HW, Visseren FLJ, Westerink J; SMART Study Group. Apparent therapy-resistant hypertension as risk factor for the development of type 2 diabetes mellitus. J Hypertens. 2020 Jan;38(1):45-51. https://doi.org/10.1097/HJH.0000000000002227

Most read articles by the same author(s)