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Around-the-clock Ambulatory Blood Pressure Monitoring is Required to Properly Diagnose Resistant Hypertension and Assess Associated Vascular Risk

  • Ramón C. HermidaEmail author
  • Diana E. Ayala
  • María T. Ríos
  • José R. Fernández
  • Artemio Mojón
  • Michael H. Smolensky
Resistant Hypertension (E Pimenta, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Resistant Hypertension

Abstract

Diagnosis of resistant hypertension (RH) is currently based upon awake-time office blood pressure (BP). An increasing number of studies have documented abnormally elevated sleep-time BP in most RH patients, indicating that diagnosis of true RH cannot be determined solely by comparison of office BP with either patient awake-time BP self-measurements or awake-BP mean from ambulatory monitoring (ABPM), as is customary in the published literature. Moreover, the ABPM-determined sleep-time BP mean is an independent and stronger predictor of cardiovascular and cerebrovascular disease (CVD) risk than either daytime office/ABPM-derived awake or 24-hour means. Results of the recently completed MAPEC (Monitorización Ambulatoria para Predicción de Eventos Cardiovasculares) prospective outcomes study, which included a large cohort of RH patients, established that time of treatment relative to circadian rhythms constituted a critically important yet often neglected variable with respect to BP control. The study found that bedtime versus morning ingestion of the full dose of ≥1 BP-lowering medications resulted in both better therapeutic normalization of sleep-time BP and reduced CVD morbidity and mortality, including in RH patients. Accordingly, ABPM is highly recommended to properly diagnose and manage true RH, with a bedtime hypertension medication regimen as the therapeutic scheme of choice.

Keywords

Ambulatory blood pressure monitoring Asleep blood pressure Resistant hypertension Cardiovascular risk Bedtime hypertension chronotherapy 

Notes

Acknowledgments

Research was supported by unrestricted grants from Ministerio de Ciencia e Innovación, Spanish Government (SAF2009-7028-FEDER); Consellería de Economía e Industria, Xunta de Galicia (09CSA018322PR); Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia (CN2012/251); European Regional Development Fund (ERDF) and the Galician Regional Government under agreement for funding the Atlantic Research Center for Information and Communication Technologies (AtlantTIC); Spanish Government and the European Regional Development Fund (ERDF) under project TACTICA; and Vicerrectorado de Investigación, University of Vigo.

Compliance with Ethics Guidelines

Conflict of Interest

Ramón C. Hermida, Diana E. Ayala, María T. Ríos, José R. Fernández, Artemio Mojón, and Michael H. Smolensky each declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206–52.PubMedCrossRefGoogle Scholar
  2. 2.
    Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension. 2008;51:1403–19.PubMedCrossRefGoogle Scholar
  3. 3.
    Fagard RH. Resistant hypertension. Heart. 2012;98:254–61.PubMedCrossRefGoogle Scholar
  4. 4.
    Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC 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). J Hypertens. 2013;31:1281–357.PubMedCrossRefGoogle Scholar
  5. 5.
    Cuspidi C, Macca G, Sampieri L, et al. High prevalence of cardiac and extracardiac target organ damage in refractory hypertension. J Hypertens. 2001;19:2063–70.PubMedCrossRefGoogle Scholar
  6. 6.
    Hernández del Rey R, Armanio P, Martín M, Sánchez P, Cárdenas P, Pardell H. Target organ damage and cardiovascular risk profile in resistant hypertension. Influence of the white coat effect. Blood Press Monit. 1998;3:331–7.Google Scholar
  7. 7.
    Redon J, Campos C, Narciso ML, Rodicio JL, Pascual JM, Ruilope LM. Prognostic value of ambulatory blood pressure monitoring in refractory hypertension. Hypertension. 1998;31:712–8.PubMedCrossRefGoogle Scholar
  8. 8.•
    Salles GF, Cardoso CR, Muxfeldt ES. Prognostic influence of office and ambulatory blood pressures in resistant hypertension. Arch Intern Med. 2008;168:2340–6. This study showed that higher nighttime BP was the strongest predictor of CVD morbidity and mortality in RH patients.PubMedCrossRefGoogle Scholar
  9. 9.••
    Ayala DE, Hermida RC, Mojón A, Fernández JR. Cardiovascular risk of resistant hypertension: dependence on treatment-time regimen of blood pressure-lowering medications. Chronobiol Int. 2013;30:340–52. This study documented: (i) bedtime- versus upon-awakening hypertension treatment significantly reduced CVD risk in patients with RH; and (ii) attenuation of the asleep SBP mean was an independent prognostic marker of reduced CVD risk, thus validating asleep BP as a novel therapeutic goal in RH.PubMedCrossRefGoogle Scholar
  10. 10.
    Perloff D, Sokolow M, Cowan R. The prognostic value of ambulatory blood pressures. JAMA. 1983;249:2792–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Verdecchia P, Porcellati C, Schillaci G, et al. Ambulatory blood pressure: an independent predictor of prognosis in essential hypertension. Hypertension. 1994;24:793–801.PubMedCrossRefGoogle Scholar
  12. 12.
    Clement DL, De Buyzere ML, De Bacquer DA, et al. Prognostic value of ambulatory blood-pressure recordings in patients with treated hypertension. N Engl J Med. 2003;348:2407–15.PubMedCrossRefGoogle Scholar
  13. 13.••
    Hermida RC, Ayala DE, Mojón A, Fernández JR. Decreasing sleep-time blood pressure determined by ambulatory monitoring reduces cardiovascular risk. J Am Coll Cardiol. 2011;58:1165–73. This report, derived from the MAPEC study showed for the very first time that attenuation of the asleep SBP mean, but not the awake BP mean or clinic BP measurements, was significantly associated with reduced CVD risk, thus validating asleep BP as a novel therapeutic goal.PubMedCrossRefGoogle Scholar
  14. 14.
    Minutolo R, Agarwal R, Borrelli S, et al. Prognostic role of ambulatory blood pressure measurement in patients with nondialysis chronic kidney disease. Arch Intern Med. 2011;171:1090–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Portaluppi F, Tiseo R, Smolensky MH, Hermida RC, Ayala DE, Fabbian F. Circadian rhythms and cardiovascular health. Sleep Med Rev. 2012;16:151–66.PubMedCrossRefGoogle Scholar
  16. 16.•
    Fabbian F, Smolensky MH, Tiseo R, Pala M, Manfredini R, Portaluppi F. Dipper and non-dipper blood pressure 24-hour patterns: circadian rhythm-dependent physiologic and pathophysiologic mechanisms. Chronobiol Int. 2013;30:17–30. This paper reviewed the underlying exogenous and endogenous mechansisms of 24-hour SBP and DBP patterning and helped to explain reported differences in effects of morning versus evening hypertension treatment strategies.PubMedCrossRefGoogle Scholar
  17. 17.
    Hermida RC, Fernández JR, Ayala DE, Mojón A, Alonso I, Smolensky M. Circadian rhythm of double (rate-pressure) product in healthy normotensive young subjects. Chronobiol Int. 2001;18:475–89.PubMedCrossRefGoogle Scholar
  18. 18.
    Hermida RC, Calvo C, Ayala DE, Mojón A, López JE. Relationship between physical activity and blood pressure in dipper and nondipper hypertensive patients. J Hypertens. 2002;20:1097–104.PubMedCrossRefGoogle Scholar
  19. 19.
    Smolensky MH, Hermida RC, Castriotta RJ, Portaluppi F. Role of sleep-wake cycle on blood pressure circadian rhythms and hypertension. Sleep Med. 2007;8:668–80.PubMedCrossRefGoogle Scholar
  20. 20.••
    Hermida RC, Smolensky MH, Ayala DE, et al. 2013 ambulatory 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. These guidelines provide up-to-date recommendations for the proper use of ABPM to assess CVD risk and to guide therapeutic intervention, including in RH patients.PubMedCrossRefGoogle Scholar
  21. 21.
    Hermida RC, Ayala DE, Fernández JR, Mojón A. Sleep-time blood pressure: prognostic value and relevance as a therapeutic target for cardiovascular risk reduction. Chronobiol Int. 2013;30:68–86.PubMedCrossRefGoogle Scholar
  22. 22.
    Nakano S, Fukuda M, Hotta F, et al. Reversed circadian blood pressure rhythm is associated with occurrences of both fatal and nonfatal events in NIDDM subjects. Diabetes. 1998;47:1501–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Sturrock NDC, George E, Pound N, Stevenson J, Peck GM, Sowter H. Non-dipping circadian blood pressure and renal impairment are associated with increased mortality in diabetes mellitus. Diabet Med. 2000;17:360–4.PubMedCrossRefGoogle Scholar
  24. 24.
    Kario K, Pickering TG, Matsuo T, Hoshide S, Schwartz JE, Shimada K. Stroke prognosis and abnormal nocturnal blood pressure falls in older hypertensives. Hypertension. 2001;38:852–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Ohkubo T, Hozawa A, Yamaguchi J, et al. Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure: the Ohasama study. J Hypertens. 2002;20:2183–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Dolan E, Stanton A, Thijs L, et al. Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study. Hypertension. 2005;46:156–61.PubMedCrossRefGoogle Scholar
  27. 27.
    Ingelsson E, Bjorklund-Bodegard K, Lind L, Arnlov J, Sundstrom J. Diurnal blood pressure pattern and risk of congestive heart failure. JAMA. 2006;295:2859–66.PubMedCrossRefGoogle Scholar
  28. 28.
    Astrup AS, Nielsen FS, Rossing P, et al. Predictors of mortality in patients with type 2 diabetes with or without diabetic nephropathy: a follow-up study. J Hypertens. 2007;25:2479–85.PubMedCrossRefGoogle Scholar
  29. 29.
    Boggia J, Li Y, Thijs L, et al. Prognostic accuracy of day versus night ambulatory blood pressure: a cohort study. Lancet. 2007;370:1219–29.PubMedCrossRefGoogle Scholar
  30. 30.
    Brotman DJ, Davidson MB, Boumitri M, Vidt DG. Impaired diurnal blood pressure variation and all-cause mortality. Am J Hypertens. 2008;21:92–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Muxfeldt ES, Salles GF. Pulse pressure or dipping pattern: which one is a better cardiovascular risk marker in resistant hypertension? J Hypertens. 2008;26:878–84.PubMedCrossRefGoogle Scholar
  32. 32.
    Eguchi K, Pickering TG, Hoshide S, et al. Ambulatory blood pressure is a better marker than clinic blood pressure in predicting cardiovascular events in patients with/without type 2 diabetes. Am J Hypertens. 2008;21:443–50.PubMedCrossRefGoogle Scholar
  33. 33.
    Hermida RC, Ayala DE, Mojón A, Fernández JR. Blunted sleep-time relative blood pressure decline increases cardiovascular risk independent of blood pressure level—the “normotensive non-dipper” paradox. Chronobiol Int. 2013;30:87–98.PubMedCrossRefGoogle Scholar
  34. 34.
    Kikuya M, Ohkubo T, Asayama K, et al. Ambulatory blood pressure and 10-year risk of cardiovascular and noncardiovascular mortality. The Ohasama Study. Hypertension. 2005;45:240–5.PubMedCrossRefGoogle Scholar
  35. 35.
    Ben-Dov IZ, Kark JD, Ben-Ishay D, Mekler J, Ben-Arie L, Bursztyn M. Predictors of all-cause mortality in clinical ambulatory monitoring. Unique aspects of blood pressure during sleep. Hypertension. 2007;49:1235–41.PubMedCrossRefGoogle Scholar
  36. 36.
    Bouhanick B, Bongard V, Amar J, Bousquel S, Chamontin B. Prognostic value of nocturnal blood pressure and reverse-dipping status on the occurrence of cardiovascular events in hypertensive diabetic patients. Diabetes Metab. 2008;34:560–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Fagard RH, Celis H, Thijs L, et al. Daytime and nighttime blood pressure as predictors of death and cause-specific cardiovascular events in hypertension. Hypertension. 2008;51:55–61.PubMedCrossRefGoogle Scholar
  38. 38.
    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;28:2036–45.PubMedCrossRefGoogle Scholar
  39. 39.
    Hermida RC, Ayala DE, Mojón A, Fernández JR. Sleep-time blood pressure as a therapeutic target for cardiovascular risk reduction in type 2 diabetes. Am J Hypertens. 2012;25:325–34.PubMedCrossRefGoogle Scholar
  40. 40.
    Hermida RC, Ayala DE, Mojón A, Fernández JR. Sleep-time blood pressure and the prognostic value of isolated-office and masked hypertension. Am J Hypertens. 2012;25:297–305.PubMedCrossRefGoogle Scholar
  41. 41.
    Muxfeldt ES, Cardoso CR, Salles GF. Prognostic value of nocturnal blood pressure reduction in resistant hypertension. Arch Intern Med. 2009;169:874–80.PubMedCrossRefGoogle Scholar
  42. 42.
    Pierdomenico SD, Lapenna D, Bucci A, et al. Cardiovascular outcome in treated hypertensive patients with responder, masked, false resistant, and true resistant hypertension. Am J Hypertens. 2005;18:1422–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Hermida RC. Ambulatory blood pressure monitoring in the prediction of cardiovascular events and effects of chronotherapy: rationale and design of the MAPEC study. Chronobiol Int. 2007;24:749–75.PubMedCrossRefGoogle Scholar
  44. 44.••
    Hermida RC, Ayala DE, Mojón A, Fernández JR. Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study. Chronobiol Int. 2010;27:1629–51. The MAPEC study is the first and only prospective trial investigating the association among prognostic ABPM parameters, CVD risk, and time-specified hypertension treatment strategy. Results indicated that routine ingestion of the full daily dose of ≥1 BP-lowering medications at bedtime, compared to ingestion of all medications upon awakening, resulted in significantly lower adjusted HR of total and major CVD events.PubMedCrossRefGoogle Scholar
  45. 45.
    Hermida RC, Ayala DE, Mojón A, Fernández JR. Influence of time of day of blood pressure-lowering treatment on cardiovascular risk in hypertensive patients with type 2 diabetes. Diabetes Care. 2011;34:1270–6.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Hermida RC, Ayala DE, Mojón A, Fernández JR. Bedtime dosing of antihypertensive medications reduces cardiovascular risk in CKD. J Am Soc Nephrol. 2011;22:2313–21.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Hermida RC, Ayala DE, Mojón A, Fernández JR. Cardiovascular risk of essential hypertension: influence of class, number, and treatment-time regimen of hypertension medications. Chronobiol Int. 2013;30:315–27.PubMedCrossRefGoogle Scholar
  48. 48.
    Hermida RC, Ayala DE, Mojón A, Fernández JR. Role of time-of-day of hypertension treatment on the J-shaped relationship between blood pressure and cardiovascular risk. Chronobiol Int. 2013;30:328–39.PubMedCrossRefGoogle Scholar
  49. 49.
    Hermida RC, Ayala DE, Fontao MJ, Mojón A, Fernández JR. Ambulatory blood pressure monitoring: Importance of sampling rate and duration—48 versus 24 hours—on the accurate assessment of cardiovascular risk. Chronobiol Int. 2013;30:55–67.PubMedCrossRefGoogle Scholar
  50. 50.
    Gustavsen PH, Hoegholm A, Bang LE, Kristensen KS. White coat hypertension is a cardiovascular risk factor: a 10-year follow-up study. J Hum Hypertens. 2003;17:811–7.PubMedCrossRefGoogle Scholar
  51. 51.
    Ohkubo T, Kikuya M, Metoki H, et al. Prognosis of “masked” hypertension and “white-coat” hypertension detected by 24-h ambulatory blood pressure monitoring. 10-year follow-up from the Ohasama study. J Am Coll Cardiol. 2005;46:508–15.PubMedCrossRefGoogle Scholar
  52. 52.
    Verdecchia P, Roboldi GP, Angeli F, et al. Short- and long-term incidence of stroke in white-coat hypertension. Hypertension. 2005;45:203–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Fagard RH, Cornelissen VA. Incidence of cardiovascular events in white-coat, masked and sustained hypertension versus true normotension: a meta-analysis. J Hypertens. 2007;25:2193–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Bobrie G, Clerson P, Ménard J, Postel-Vinay N, Chatellier G, Plouin PF. Masked hypertension: a systematic review. J Hypertens. 2008;26:1715–25.PubMedCrossRefGoogle Scholar
  55. 55.
    Angeli F, Reboldi G, Verdecchia P. Masked hypertension: evaluation, prognosis, and treatment. Am J Hypertens. 2010;23:941–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Pierdomenico SD, Cuccurullo F. Prognostic value of white-coat and masked hypertension diagnosed by ambulatory monitoring in initially untreated subjects: an updated meta-analysis. Am J Hypertens. 2011;24:52–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Mezzetti A, Pierdomenico SD, Costantini F, et al. White-coat resistant hypertension. Am J Hypertens. 1997;10:1302–7.PubMedCrossRefGoogle Scholar
  58. 58.
    Brown MA, Buddle ML, Martin A. Is resistant hypertension really resistant? Am J Hypertens. 2001;14:1263–9.PubMedCrossRefGoogle Scholar
  59. 59.
    Veglio F, Rabbia F, Riva P, et al. Ambulatory blood pressure monitoring and clinical characteristics of the true and white-coat resistant hypertension. Clin Exp Hypertens. 2001;23:203–11.PubMedCrossRefGoogle Scholar
  60. 60.
    Muxfeldt ES, Bloch KV, Nogueira AR, Salles GF. Twenty-four hour ambulatory blood pressure monitoring pattern of resistant hypertension. Blood Press Monit. 2003;8:181–5.PubMedCrossRefGoogle Scholar
  61. 61.
    de la Sierra A, Segura J, Banegas JR, et al. Clinical features of 8295 patients with resistant hypertension classified on the basis of ambulatory blood pressure monitoring. Hypertension. 2011;57:898–902.PubMedCrossRefGoogle Scholar
  62. 62.
    Brambilla G, Bombelli M, Seravalle G, et al. Prevalence and clinical characteristics of patients with true resistant hypertension in central and Eastern Europe: data from the BP-CARE study. J Hypertens. 2013;31:2018–24.PubMedCrossRefGoogle Scholar
  63. 63.
    Muxfeldt ES, Salles GF. How to use ambulatory blood pressure monitoring in resistant hypertension. Hypertens Res. 2013;36:385–9.PubMedCrossRefGoogle Scholar
  64. 64.
    Ríos MT, Domínguez-Sardiña M, Ayala DE, et al. Prevalence and clinical characteristics of isolated-office and true resistant hypertension determined by ambulatory blood pressure monitoring. Chronobiol Int. 2013;30:207–20.PubMedCrossRefGoogle Scholar
  65. 65.
    Ayala DE, Moyá A, Crespo JJ, et al. Circadian pattern of ambulatory blood pressure in hypertensive patients with and without type 2 diabetes. Chronobiol Int. 2013;30:99–115.PubMedCrossRefGoogle Scholar
  66. 66.
    Crespo JJ, Piñeiro L, Otero A, et al. Administration-time-dependent effects of hypertension treatment on ambulatory blood pressure in patients with chronic kidney disease. Chronobiol Int. 2013;30:159–75.PubMedCrossRefGoogle Scholar
  67. 67.••
    Hermida RC, Ríos MT, Crespo JJ, et al. Treatment-time regimen of hypertension medications significantly affects ambulatory blood pressure and clinical characteristics of patients with resistant hypertensions. Chronobiol Int. 2013;30:192–206. This paper is a comprehensive review of the advanatages of the bedtime treatment strategy over the traditional morning-time regimen as a means of controlling ambulatory BP of patients labeled as resistant to therapy.PubMedCrossRefGoogle Scholar
  68. 68.
    Mojón A, Ayala DE, Piñeiro L, et al. Comparison of ambulatory blood pressure parameters of hypertensive patients with and without chronic kidney disease. Chronobiol Int. 2013;30:145–58.PubMedCrossRefGoogle Scholar
  69. 69.
    Moyá A, Crespo JJ, Ayala DE, et al. Effects of time-of-day of hypertension treatment on ambulatory blood pressure and clinical characteristics of patients with type 2 diabetes. Chronobiol Int. 2013;30:116–31.PubMedCrossRefGoogle Scholar
  70. 70.
    Friedman O, Logan AG. Nocturnal blood pressure profiles among normotensive, controlled hypertensive and refractory hypertensive subjects. Can J Cardiol. 2009;25:e312–6.PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Crespo C, Fernández JR, Aboy M, Mojón A. Clinical application of a novel automatic algorithm for actigraphy-based activity and rest period identification to accurately determine awake and asleep ambulatory blood pressure parameters and cardiovascular risk. Chronobiol Int. 2013;30:43–54.PubMedCrossRefGoogle Scholar
  72. 72.
    Bruguerolle B, Lemmer B. Recent advances in chronopharmacokinetics: methodological problems. Life Sci. 1993;52:1809–24.PubMedCrossRefGoogle Scholar
  73. 73.
    Gupta SK, Yih BM, Atkinson L, Longstreth J. The effect of food, time of dosing and body composition on the pharmacokinetics and pharmacodynamics of verapamil and norverapamil. J Clin Pharmacol. 1995;35:1083–93.PubMedCrossRefGoogle Scholar
  74. 74.
    Labrecque G, Beauchamp D. Rhythms and pharmacokinetics. In: Redfern P, editor. Chronotherapeutics. London: Pharmaceutical Press; 2003. p. 75–110.Google Scholar
  75. 75.
    Okyar A, Dressler C, Hanafy A, Baktir G, Lemmer B, Spahn-Langguth H. Circadian variations in exsorptive transport: in-situ intestinal perfusion data and in-vivo relevance. Chronobiol Int. 2012;29:443–53.PubMedCrossRefGoogle Scholar
  76. 76.
    Smolensky MH, Siegel RA, Haus E, Hermida RC, Portaluppi F. Biological rhythms, drug delivery, and chronotherapeutics. In: Siepmann J, Siegel RA, Rathbone MJ, editors. Fundamentals and applications of controlled release drug delivery. Heildelberg: Springer-Verlag; 2012. p. 359–443.CrossRefGoogle Scholar
  77. 77.
    Hermida RC, Ayala DE, Fernández JR, Portaluppi F, Fabbian F, Smolensky MH. Circadian rhythms in blood pressure regulation and optimization of hypertension treatment with ACE inhibitor and ARB medications. Am J Hypertens. 2011;24:383–91.PubMedCrossRefGoogle Scholar
  78. 78.
    Hermida RC, Ayala DE, Fernández JR, et al. Administration-time-differences in effects of hypertension medications on ambulatory blood pressure regulation. Chronobiol Int. 2013;30:280–314.PubMedCrossRefGoogle Scholar
  79. 79.
    Hermida RC, Ayala DE, Smolensky MH, et al. Chronotherapeutics of conventional blood pressure-lowering medications: simple, low-cost means of improving management and treatment outcomes of hypertensive-related disorders. Curr Hypertens Rep. 2014;16:412.PubMedCrossRefGoogle Scholar
  80. 80.
    Cugini P. The treatability of refractory or resistant hypertension by personalized antihypertensive chronotherapy based on ambulatory monitoring of the arterial pressure. Recenti Prog Med. 1996;87:51–7.PubMedGoogle Scholar
  81. 81.
    Hermida RC, Ayala DE, Calvo C, et al. Effects of the time of day of antihypertensive treatment on the ambulatory blood pressure pattern of patients with resistant hypertension. Hypertension. 2005;46:1053–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Hermida RC, Ayala DE, Fernández JR, Calvo C. Chronotherapy improves blood pressure control and reverts the nondipper pattern in patients with resistant hypertension. Hypertension. 2008;51:69–76.PubMedCrossRefGoogle Scholar
  83. 83.
    Hermida RC, Ayala DE, Mojón A, Fernández JR. Effects of time of antihypertensive treatment on ambulatory blood pressure and clinical characteristics of subjects with resistant hypertension. Am J Hypertens. 2010;23:432–9.PubMedCrossRefGoogle Scholar
  84. 84.
    Almirall J, Comas L, Martínez-Ocaña JC, Roca S, Arnau A. Effects of chronotherapy on blood pressure control in non-dipper patients with refractory hypertension. Nephrol Dial Transplant. 2012;27:1855–9.PubMedCrossRefGoogle Scholar
  85. 85.
    Degaute JP, Van de Borne P, Kerkhofs M, Dramaix M, Linkowski P. Does non-invasive ambulatory blood pressure monitoring disturb sleep? J Hypertens. 1992;10:879–85.PubMedGoogle Scholar
  86. 86.
    Musso NR, Vergassola C, Barone C, Lotti G. Ambulatory blood pressure monitoring: how reproducible is it? Am J Hypertens. 1997;10:936–9.PubMedCrossRefGoogle Scholar
  87. 87.
    Mochizuki Y, Okutani M, Donfeng Y, Iwasaki H, Takusagawa M, Kohno I, et al. Limited reproducibility of circadian variation in blood pressure dippers and nondippers. Am J Hypertens. 1998;11:403–9.PubMedCrossRefGoogle Scholar
  88. 88.
    James GD, Pickering TG, Yee LS, Harshfield GA, Riva S, Laragh JH. The reproducibility of average, ambulatory, home, and clinical pressures. Hypertension. 1988;11:545–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Ramón C. Hermida
    • 1
    • 4
    Email author
  • Diana E. Ayala
    • 1
  • María T. Ríos
    • 1
    • 2
  • José R. Fernández
    • 1
  • Artemio Mojón
    • 1
  • Michael H. Smolensky
    • 3
  1. 1.Bioengineering & Chronobiology Laboratories, Atlantic Research Center for Information and Communication Technologies (AtlantTIC)University of VigoVigoSpain
  2. 2.Centro de Salud de A Doblada, Estructura de Gestión Integrada de VigoServicio Galego de Saúde (SERGAS)VigoSpain
  3. 3.Cockrell School of Engineering, Department of Biomedical EngineeringThe University of Texas at AustinAustinUSA
  4. 4.Bioengineering and Chronobiology LabsE.I. TelecomunicaciónVigoSpain

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