Chronotherapy of arterial hypertension: current state of the issue

S.S. Boev, N.Yа. Dotsenko, I.A. Shekhunova, L.V. Gerasimenko


This article is a review of literature data on the clinical significance of chronotherapy for arterial hypertension in hypertensive patients. The chronotherapeutic approach to the treatment of arterial hypertension is given, which allows increasing the effectiveness of treatment taking into account the time of prescription of antihypertensive drugs. The results are presented of numerous studies on the possibility of reducing the risk of cardiovascular complications in the normalization of the daily rhythm of blood pressure.


arterial hypertension; chronotherapy; ambulatory blood pressure monitoring; review


Go A.S. Executive summary: heart disease and stroke statistics—2014 update a report from the American Heart Association / A.S. Go, D. Mozaffarian, V.L. Roger [et al.] // Circulation.- 2014.- Vol. 129(3). –Р. 399–410.

Mozaffarian D. American Heart Association Statistics Committee; Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association / D. Mozaffarian, E.J. Benjamin, A.S. Go [et al.] // Circulation.- 2016. - Vol.133. – Р. e38-e360.

Timmis A. Atlas Writing Group (2017) European Society of Cardiology: Cardiovascular Disease Statistics 2017/ A. Timmis, N. Townsend, C. Gale [et al.] // Eur. Heart J. - 2018. - Vol.39(7). - Р.508-579. doi: 10.1093/eurheartj/ehx628.

Muntner P. Potential U.S. Population Impact of the 2017 American College of Cardiology/American Heart Association High Blood Pressure Guideline / P. Muntner, R.M. Carey, S. Gidding [et al.] // J. Am. Coll. Cardiol. – 2018. - Vol.71. – Р. 109-118.

Reboussin D.M. Systematic Review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines / D.M. Reboussin, N.B. Allen, M.E. Griswold [et al.] // Hypertension. – 2018. - Vol.71(6). – Р.e116-e135. doi: 10.1161/HYP.0000000000000067.

John M. Flack The New ACC/AHA Hypertension Guidelines for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults /John M Flack, David Calhoun Ernesto, L. Schiffrin // American Journal of Hypertension. -2018. -Vol. 31. - Issue 2.- P. 133–135. DOI: 10.1093 / ajh / hpx207

Gorbunov VM, Fedorova EYu, Platonov EV. [Chronotherapy of arterial hypertension: current state of the problem]. Racional'naja Farmakoterapija v Kardiologii. 2017;13(5):706-715. Russian. DOI: 10.20996/1819-6446-2017-13-5-706-715

Olbinskaya LI, Khapaev BA. [Chronotherapeutic aspects of the use of various forms of nifedipine in hypertensive patients]. Kardiologija.2000;6:59-62. Russian.

Smolensky M.H. Administration-time-dependent effects of blood pressure-lowering medications: basis for the chronotherapy of hypertension / M.H. Smolensky, R.C. Hermida, Ayala D.E. [et al.] // Blood Press Monit. –2010. Vol.15. - Р.173-180. doi: 10.1097/MBP0b01 3e32833c7308.

Olbinskaya LI, Martynov AI, Khapaev BA. [Blood pressure monitoring in cardiology. М.: Russkij vrach, 1998. 99с. Russian.

Gapon LI, N.P. Shurkevich, A.S. Vetoshkin [et al.] [Blood pressure rhythms and heart rate in patients with arterial hypertension in the Far North]. Klinicheskaja medicina. 2006; 84, 2:39-44. Russian.

Gubin D.G. Activity, Sleep and Ambient Light Have aDifferent Impacton Circadian Blood Pressure, Heart Rate and Body Temperature Rhythms / D.G. Gubin, D. Weinert, S.V Rybina [et al.] // Chronobiology Int. - 2017. - Vol. 34(5). - Р. 632-649. doi: 10.1080/07420528.2017.1288632.

Gubin DG. Melatonin attenuates effects of light-at-night on systolic blood pressure and body temperature but does not affect diastolic blood pressure and heart rate circadian rhythms / D.G.Gubin, D.Weinert, S.V Solovieva // Chronobiology Int. - 2018. pending.

Губин Д. Г., Вайнерт Д., Соловьева С. В., Дуров А. М. Роль активности, сна и внешней освещенности в суточной динамике артериального давления / Д.Г. Губин, Д. Вайнерт, С.В Соловьева [и др.] // Медицинский алфавит. 2018. - Том 1. - № 3. - Артериальная гипертензия. - С. 20-23.

Hermida RC. Circadian variation of blood pressure: the basis for the chronotherapy of hypertension / R.C. Hermida, D.E. Ayala, F. Portaluppi //Adv Drug Deliv Rev. – 2007. - Vol. 59. – Р. 904-922. DOI:10,1016/ j.addr.2006.08.003

Salles G.F. Prognostic effect of the nocturnal blood pressure fall in hypertensive patients: the ambulatory blood pressure collaboration in patients with hypertension (ABC-H) meta-analysis. / GF Salles, G Reboldi, RH Fagard [et al.] // Hypertension. – 2016. - Vol.67(4). – Р. 693–700. DOI:10,1161 / HYPERTENSIONAHA.115.06981

Ermiş N. Comparison of left atrial volume and function in non-dipper versus dipper hypertensives: a real-time three-dimensional echocardiography study. / N. Ermiş, Y.Ö. Otlu, A. Afşin [et al.] // TheAnatolian journal of cardiology. – 2016. - Vol.16(6). - Р. 428–433. doi:[10.14744/AnatolJCardiol.2015.6569].

Acar G. Comparison of left atrial mechanical function in nondipper versus dipper hypertensive patients: a speckle tracking study / G. Açar, М. Bulut, К. Arslan [et al.] // Echocardiography. – 2013. - Vol.30(2). - Р.164–170. DOI:10,1111 / echo.12023.

Tadic M. Circadian blood pressure pattern and right ventricular and right atrial mechanics: a two- and three-dimensional echocardiographic study / M. Tadic, C. Cuspidi, B. Pencic [et al.] // J Am Soc Hypertens. – 2014. - Vol.8(1). : Р.45–53. DOI:

Liu M. Non-dipping is a potent predictor of cardiovascular mortality and is associated with autonomic dysfunction in haemodialysis patients / M. Liu, H. Takahashi, Y. Morita [et al.] // Nephrol Dial Transplant. – 2003. - Vol.18(3). – Р.563–569. DOI: org/10.1093/ndt/18.3.563

Timio M. “Non-dipper” hypertensive patients and progressive renal insufficiency: a 3-year longitudinal study / M. Timio, S. Venanzi, S. Lolli [et al.] // Clin Nephrol. – 1995. - Vol.43(6). – Р.382–387.

Ukkola O. Non-dipping pattern in ambulatory blood pressure monitoring is associated with metabolic abnormalities in a random sample of middle-aged subjects / O. Ukkola, R-L. Vasunta, Y.A. Kesäniemi // Hypertens Res. – 2009. - Vol.32(11). - Р.1022–1027. DOI:10,1038 / hr.2009.137.

Wang C. Reversed dipper blood-pressure pattern is closely related to severe renal and cardiovascular damage in patients with chronic kidney disease / C. Wang, J. Zhang, X. Liu [et al.] // PLoS One. – 2013. - Vol.8(2). – Р.e55419. doi:[10.1371/journal.pone.0055419].

Yan B. Blood pressure reverse-dipping is associated with early formation of carotid plaque in senior hypertensive patients./ B. Yan, L. Peng, D. Han [et al.] // Medicine (Baltimore). – 2015. - Vol.94(10). – Р.e604. doi:[10.1097/MD.0000000000000604]

Yan B. Reverse-dipper pattern of blood pressure may predict lacunar infarction in patients with essential hypertension / B. Yan, L. Peng, Q. Dong [et al.] // Eur J Neurol. – 2015. - Vol.22(6). – Р.1022–1025. DOI:10.1111/ene.12659

Kario K. Risers and extreme-dippers of nocturnal blood pressure in hypertension: antihypertensive strategy for nocturnal blood pressure. / K. Kario , K. Shimada // Clin Exp Hypertens. - 2004. - Vol.26(2). - Р.177-189.

Schillaci G. Antihypertensive Drug Treatment and Circadian Blood Pressure Rhythm: A Review of the Role of Chronotherapy in Hypertension / G. Schillaci, F. Battista, L. Settimi [et al.] // Current Pharmaceutical Design. - 2015. - Vol.21. - Р.756-772. doi: 10.2174/138161282066614102413001 325.

Henskens L.H. Different classifications of nocturnal blood pressure dipping affect the prevalence of dippers and non-dippers and the relation with target-organ damage / L.H. Henskens, A.A. Kroon, R.J. van Oostenbrugge [et al.] // J Hypertens. – 2008. - Vol. 26 - Р.691-698. doi:10.1097/HJH.0b013e3282f4225f

Van Ittersum F.J. Analysis of twenty-four-hour ambulatory blood pressure monitoring: what time period to assess blood pressures during waking and sleeping? / F.J.Van Ittersum, R.G. Ijzerman, C.D. Stehouwer A. // J Hypertens. - 1995. - Vol.13. - Р.1053-1058.

Kario K. Morning Surge in Blood Pressure and Cardiovascular Risk. Evidence and Perspectives / K. Kario // Hypertension. - 2010. - Vol.56. -Р. :765 -773. doi: 10.1161/HYPERTENSIONAHA.1 10.1 571 49

Kario K. Clinician's Manual on Early Morning Risk Management in Hypertension // K. Kario London: Science Press, 2004. - 68p.

O'Brien E. European Society of Hypertension position paper on ambulatory blood pressure monitoring. / E. O'Brien, G. Parati, G. Stergiou [et al.] // Journal of Hypertension. – 2013. - Vol.31. –Р.1731-1768. doi: 10.1097/HJH.0b013e328363e964.

Hoshide S. Ethnic differences in the degree of morning blood pressure. Surge and in its determinants between Japanese and European hypertensive subjects data from the ARTEMIS Study / S. Hoshide, K. Kario, la Sierra [et al.] // Hypertension. 2015. - Vol.66(4). – Р. 750-756. doi: 10.1161 /HYPERTENSIONAHA.1 1 5.05958.

Hermida RC, Ayala DE, Fernändez JR [et al.]. Bedtime Blood Pressure Chronotherapy Significantly Improves Hypertension Management. Heart Failure Clinics. 2017;13(4):759–777. DOI:10.1016/j.hfc.2017.05.010

Roush G.C. Evening dosing of antihypertensive therapy to reduce cardiovascular events: a third type of evidence based on a systematic review and meta-analysis of randomized trials / G.C. Roush, J. Fapohunda, J.B. Kostis // J Clin Hypertens (Greenwich). – 2014. - Vol.16(8). – Р.561–568. DOI: 10,1111 / jch.12354

Hermida R.C. Bedtime ingestion of hypertension medications reduces of new-onset type 2 diabetes: a randomized controlled trial / R.C.Hermida, D.E. Ayala, A. Mojon [et al.] // Diabetologia. – 2015. - Vol.59(2). - Р.395- 405. doi: 10.1007/s001 25-01 5-3749-7

Hermida R.C. Chronotherapy with conventional blood pressure medications improves management of hypertension and reduces cardiovascular and stroke risks / R.C. Hermida, E.A. Diana, M.H. Smolensky [et al.] // Hypertens Res. – 2016. - Vol.39(5). – Р. 277-292. doi: 1 0.1038/hr.201 5.1 42.

Neldam S. Early combination therapy with telmisartan plus amlodipine for rapid achievement of blood pressure goals / S. Neldam, B. Dahlof, W. Oigman [et al.] // Int J Clin Pract. - 2013. - Vol.67(9). - Р. 843-852. doi: 10.1111/ijcp.12180.

Chobanian A.V. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. / A.V. Chobanian, G.L. Bakris, H.R. Black [et al.] // Hypertension. – 2003. – Vol.42(6). – Р. 1206–1252. DOI: 10,1161 / 01.HYP.0000107251.49515.c2

Mancia G. 2007 Guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) / G. Mancia, G. De Backer, A. Dominiczak [et al.] / J Hypertens. - 2007. - Vol.25(6). - Р.1105-1187. DOI:10,1097 / HJH.0b013e3281fc975a.

Law M.R. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials / M.R. Law, N.J. Wald, J.K. Morris [et al.] / BMJ. – 2003. - Vol.326(7404). – Р.1427. DOI:10.1136/bmj.326.7404.1427.

Saini S.D. Effect of medication dosing frequency on adherence in chronic diseases / S.D. Saini, P. Schoenfeld, K. Kaulback [et al.] // Am J Manag Care. - 2009. - Vol.15(6). - Р.e22–33.

Hermida R.C., Ayala D.E., Mojón A. Decreasing sleep time blood pressure determined by ambulatory monitoring reduces cardiovascular risk / R.C. Hermida, D.E. Ayala, A. Mojón // J Am Coll Cardiol. - 2011. - Vol.58. – Р.1165-1173.

Hermida R.C. Sleep-time blood pressure: prognostic value and relevance as a therapeutic target for cardiovascular risk reduction / R.C. Hermida, D.E. Ayala, J.R. Fernández [et al.] // Chronobiol Int. – 2013. - Vol.30. - Р.68-86. doi: 10.3109/07420528.2012.702581.

Minutolo R. Prognostic role of ambulatory blood pressure measurement in patients with nondialysis chronic kidney disease / R. Minutolo, R. Agarwal, S. Borrelli [et al.] // Arch Intern Med. - 2011. - Vol.171. - Р.1090-1098. DOI:10,1001 / archinternmed.2011.230

Roush G.C. Prognostic impact from clinic, daytime, and nighttime systolic blood pressure in 9 cohorts on 13,844 patients with hypertension / G.C. Roush, R.H. Fagard, G.F. Salles [et al.] /J Hypertens. - 2014. - Vol.32. -Р.2332-2340. DOI:10.1097/HJH.0000000000000355.

Ben-Dov I.Z. Predictors of all cause mortality in clinical ambulatory monitoring. Unique aspects of blood pressure during sleep / I.Z. Ben-Dov, J.D. Kark, D. Ben-Ishay [et al.] // Hypertension. - 2007. - Vol.49. – Р.1235-1241. DOI: 10.1161/HYPERTENSIONAHA.107.087262

Fagard R.H. Daytime and nighttime blood pressure as predictors of death and cause-specific cardiovascular events in hypertension / R.H. Fagard, H. Celis, L. Thijs [et al.] // Hypertension. - 2008. - Vol.51. - Р. 55-61. DOI:10,1161 / HYPERTENSIONAHA.107.100727

Fan HQ, Li Y, Thijs L. [et al.] Prognostic value of isolated nocturnal hypertension on ambulatory measurement in 8711 individuals from 10 populations. J Hypertens. 2010; 28:2036-2045. DOI: 10.1097/HJH.0b013e32833b49fe.

Hermida RC, Diana Ayala E, José Fernández R. [et al.] Hypertension: New perspective on its definition and clinical management by bedtime therapy substantially reduces cardiovascular disease risk. European Journal of Clinical investigation. 2018; 48(5): e12909. doi: 10.1111/eci.12909.

Hermida RC, Ayala DE, Mojón A. [et al.] Influence of time of day of blood pressure lowering treatment on cardiovascular risk in hypertensive patients with type 2 diabetes. Diabetes Care. 2011;34:1270-1276. DOI:10,2337 / dc11-0297.

Hermida RC, Ayala DE, Mojón A. [et al.] Bedtime dosing of antihypertensive medications reduces cardiovascular risk in CKD. J Am Soc Nephrol. 2011;22: 2313-2321. DOI:10,1681 / ASN.2011040361.

Ayala DE, Hermida RC, Mojón A. [et al.] Cardiovascular risk of resistant hypertension: dependence on treatment time regimen of blood pressure lowering medications. Chronobiol Int. 2013;30: 340-352. DOI:10,3109 / 07420528.2012.701455

Hermida RC, Smolensky MH, Ayala DE. [et al.] 2013 Аmbulatory blood pressure monitoring recommendations for the diagnosis of adult hypertension, assessment of cardiovascular and other hypertension associated risk, and attainment of therapeutic goals. Joint recommendations from the International Society for Chronobiology (ISC), American Association of Medical Chronobiology and Chronotherapeutics (AAMCC), Spanish Society of Applied Chronobiology, Chronotherapy, and Vascular Risk (SECAC), Spanish Society of Atherosclerosis (SEA), and Romanian Society of Internal Medicine (RSIM). Chronobiol Int. 2013;30:355-410. DOI:10.1016/j.arteri.2013.03.002

Hermida RC, Smolensky MH, Ayala DE. [et al.]Ambulatory blood pressure monitoring (ABPM) as the reference standard for diagnosis of hypertension and assessment of vascular risk in adults. Chronobiol Int. 2015;32:1329-1342. DOI: 10,3109 / 07420528.2015.1113804

American Diabetes Association. Standards of medical care in diabetes – 2012 // Diabetes Care. 2012;35(l1):S11-S63. doi: [10.2337/dc12-s011]

Rydén L, Grant PJ. [et al.] ESC guidelines on diabetes, prediabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2013; 34: 3035-3087. DOI:10,1093 / eurheartj / eht108.

Shimamoto K., Ando K, Fujita T. [et al.] The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH2014). Hypertens Res. 2014;.37:253-390. DOI:10.1038/hr.2014.20.

Chiang CE, Wang TD, Ueng KC. [et al.] 2015 guidelines of the Taiwan Society of Cardiology and the Taiwan Hypertension Society for the Management of Hypertension. J Chin Med Assoc. 2015; 78:1-47. DOI:10,1016 / j.jcma.2014.11.005

Callaway E, Ledford H. Medicine Nobel awarded for work on circadian clocks. Nature. 2017;550:18. DOI:10.1038/nature.2017.22736.

Martino TA, Young ME. Influence of the cardiomyocyte circadian clock on cardiac physiology and pathophysiology. J Biol Rhythms. 2015;30:183-205. DOI:10,1177 / 0748730415575246

Gamble KL, Berry R. [et al.] Circadian clock control of endocrine factors. Nat Rev Endocrinol. 2014; 10:466-475. DOI:10,1038 / nrendo.2014.78.

Scheer FA, Hu K, Evoniuk H. [et al.] Impact of the human circadian system, exercise, and their interaction on cardiovascular function. Proceedings of the National Academy of Sciences. 2010;107: 20541-20546. doi:[10.1073/pnas.1006749107].

Paschos GK, Fitz Gerald GA. Circadian clocks and metabolism: implications for microbiome and aging. Trends Genet. 2017;33:760-769. doi: 10.1016/j.tig.2017.07.010.

Natesh R, Schwager SL, Evans HR Structural details on the binding of antihypertensive drugs captopril and enalaprilat to human testicular angiotensin I-converting enzyme. Biochemistry. 2004; 43(27):8718–8724. DOI:10,1021 / bi049480n

Baraldo M. The influence of circadian rhythms on the kinetics of drugs in humans. Expert Opin Drug Metab Toxicol. 2008;4(2):175-192. DOI:10.1517/17425255.4.2.175

Martino TA, Tata N., Simpson JA. [et al.] The primary benefits of angiotensin-converting enzyme inhibition on cardiac remodeling occur during sleep time in murine pressure overload hypertrophy. J Am Coll Cardiol. 2011;57: 2020-2028. DOI: 10.3389/fphar.2015.00077.

Zhang R. A circadian gene expression atlas in mammals: implications for biology and medicine / R. Zhang, N.F. Lahens, H.I. Ballance // Proc Natl Acad Sci U S A. - 2014. - Vol.111(45). - Р.16219-16224. DOI:10,1073 / pnas.1408886111.

Morris CJ, Purvis TE, Mistretta J.Circadian misalignment increases C-reactive protein and blood pressure in chronic shift workers. J Biol Rhythm. 2017; 32(2): 154-164. DOI:10,1177 / 0748730417697537

Tsimakouridze EV, Alibhai FJ, Martino TA. Therapeutic applications of circadian rhythms for the cardiovascular system. Front Pharmacol. 2015; 6:77. (DOI:10.3389/fphar.2015.00077.

Carter BL, Chrischilles EA, Rosenthal G. [et al.] Efficacy and safety of nighttime dosing of antihypertensive: review of the literature and design of a pragmatic clinical trial. J Clin Hypertens (Greenwich). 2014;16:115-121. doi: 10.1111 /jch.1 2238.

Rorie DA, Rogers A, Mackenzie IS. [et al.] Methods of a large prospective, randomized, open-label, blinded end-point study comparing morning versus evening dosing in hypertensive patients: the Treatment In Morning versus Evening (TIME) study. BMJ Open. 2016;.6(2): 1 -10. doi: 10.1136/bmjopen- 2015-010313.

Copyright (c) 2019 HYPERTENSION

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.


© Publishing House Zaslavsky, 1997-2018


   Seo анализ сайта