Hypertension remains one of the primary causes of premature cardiovascular mortality representing a major independent risk factor.
The importance of ambulatory blood pressure monitoring in clinical evaluation of hypertensive patients, beyond diagnosis, is the identification of circadian dipping/non-dipping profile. The non-dipper pattern in hypertensive and normotensive patients is associated with significant target organ damage and worse outcomes, as an increased cardiovascular risk condition. Non-dipping pattern has been found to be associated with specific clinical conditions. Obesity, diabetes mellitus, metabolic syndrome, obstructive sleep apnea syndrome, chronic kidney disease, autonomic and baroreflex dysfunctions, salt sensitivity, hormonal changes, gender and age were extensively studied. Research efforts are focused on recognizing and exploring predictive markers of abnormal blood pressure circadian pattern. Previous studies acknowledge that red cell distribution width, mean platelet volume, fibrinogen level, C-reactive protein, serum uric acid and gamma-glutamyltransferase, are independently significant and positive associated to non-dipping pattern. Moreover, research on new biomarkers are conducted: Chitinase 3-Like-Protein 1, atrial and B-type natriuretic peptide, brain-derived neurotrophic factor, chemerin, sphingomyelin and the G972R polymorphism of the insulin receptor substrate-1 gene. This review summarizes the current knowledge of different clinical conditions and biomarkers associated with the non-dipper profile in hypertensive patients.
1. Mills KT, Bundy JD, Kelly TN, et al – Global disparities of hypertension prevalence and control a systematic analysis of population - based studies from 90 countries. Circulation. 2016;134(6):441-450.
2. Lloyd-Sherlock P, Beard J, Minicuci N, Ebrahim S, Chatterji S – Hypertension among older adults in low- and middle-income countries: prevalence, awareness and control. International Journal of Epidemiology, 2014;43(1):116-128.
3. Dorobantu M, Onciul S, Darabont R, et al – Arterial Hypertension Epidemiology: Romania among the Balkan Countries – Data from SEPHAR Surveys. Medicina Moderna. 2014;21(1):10-16.
4. Dorobantu M, Tautu OF, Dimulescu D, et al – Perspectives on hypertension's prevalence, treatment and control in a high cardiovascular risk East European country: data from the SEPHAR III survey. J Hypertens. 2017. doi:10.1097/HJH.0000000000001572. [Epub ahead of print]
5. Hermida RC, Smolensky MH, Ayala DE, Portaluppi F – Ambulatory blood pressure monitoring (ABPM) as the reference standard for diagnosis of hypertension and assessment of vascular risk in adults. Chronobiol Int. 2015;32(10):1329–1342.
6. 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;31:1281–1357.
7. Routledge FS, McFetridge-Durdle JA, Dean CR – Night-time blood pressure patterns and target organ damage: A review. Can J Cardiol. 2007;23(2):132-138.
8. Krzych LJ, Bochenek A – Blood pressure variability: epidemiological and clinical issues. Cardiol J. 2013;20(2):112–120.
9. Birkenhäger AM, van den Meiracker AH. – Causes and consequences of a non-dipping blood pressure profile. Neth J Med. 2007;65(4):127-131.
10. Dubielski Z, Zamojski M, Wiechecki B, et al. – The current state of knowledge about the dipping and non-dipping hypertension. Arterial Hypertension. 2016; 20(2):33–43.
11. Letizia C, Ferrari P, Cotesta D, et al. Ambulatory monitoring of blood pressure (AMBP) in patients with primary hyperparathyroidism. J Hum Hypertens 2005;19(11):901-916.
12. Krzyzanowska K, Schnack C, Mittermayer F, et al – High prevalence of abnormal circadian blood pressure regulation and impaired glucose tolerance in adults with hypopituitarism. Exp Clin Endocrinol Diabetes. 2005;113(8):430-434.
13. Pechanova O, Paulis L, Simko F – Peripheral and central effects of melatonin on blood pressure regulation. Int J Mol Sci 2014;15(10):17920–17937.
14. Pietrobelli DJ, Akopian M, Olivieri AO, et al – Altered circadian blood pressure profile in patients with active acromegaly. Relationship with left ventricular mass and hormonal values. J Hum Hypertens. 2001;15(9):601-605.
15. Covic A, Goldsmith DJ, Gusbeth-Tatomir P, et al – What added value does ambulatory blood pressure monitoring brings to the management of post renal transplantation hypertension? Rev Med Chir Soc Med Nat Iasi 2003;107(1):89-97.
16. Ohashi N, Isobe S, Ishigaki S, Suzuki T, Motoyama D, Sugiyama T, et al – The effects of unilateral nephrectomy on blood pressure and its circadian rhythm. Intern Med. 2016;55(23):3427–3433.
17. Kario K, Eguchi K, Nakagawa Y, Motai K, Shimada K – Relationship between extreme dippers and orthostatic hypertension in elderly hypertensive patients. Hypertension. 1998;31(1):77-82.
18. Briasoulis A, Silver A, Yano Y, Bakris GL – Orthostatic hypotension associated with baroreceptor dysfunction: treatment approaches. J Clin Hypertens (Greenwich). 2014;16:141–148.
19. Mellman TA, Brown DD, Jenifer ES, Hipolito MM, Randall OS – Posttraumatic stress disorder and nocturnal blood pressure dipping in young adult African Americans. Psychosom Med. 2009;71(6): 627–630.
20. Huang Y, Mai W, Hu Y, et al – Poor sleep quality, stress status, and sympathetic nervous system activation in nondipping hypertension. Blood Press Monit. 2011;16(3):117–123.
21. Xuan AP – Investigate damages in target organs in two groups of patients who have dipper and non-dipper hypertension. J Hypertens. 2011;29:e11.
22. Nesukay H, Polenova N, Titov E – Ambulatory blood pressure monitoring (ABPM) and myocardium deformation parameters in patients with hypertension. J Hypertens. 2016;34:e122-e123.
23. Sousa F, Neves J, Ferreira R, et al. – In hypertension the change from a non-dipper to a dipper pattern is associated with a better cardiovascular prognosis than the persistence within the non-dipper pattern. J Hypertens. 2015;33(1):e6.
24. Crippa G, Zabzuni D, Cassi A, Bravi E – Effect of bedtime dosing of barnidipine hydrochloride in non-dipper hypertensive patients with obstructive sleep apnoea not treated with continuous positive airway pressure. Eur Rev Med Pharmacol Sci. 2016;20(2):339-344.
25. Kario K, Nariyama J, Kido H, et al – Effect of a novel calcium channel blocker on abnormal nocturnal blood pressure in hypertensive patients. J Clin Hypertens (Greenwich). 2013;15(7):465-472.
26. Esler M. The sympathetic system and hypertension. Am J Hypertens. 2000;13:99S–105S.
27. Dauphinot V, Gosse P, Kossovsky M, et al – Autonomic nervous system activity is independently associated with the risk of shift in the non-dipper blood pressure pattern. Hypertens Res. 2010;33:1032–1037.
28. Quijada SG, Sáez MC, Gutiérrez CD, et al – Factores cardiovasculares y hormonales asociados a la falta de descenso nocturno de la presión arterial en sujetos mayores de 55 años. Rev Clin Esp. 2002;202(5):264-268.
29. Grassi G, Seravalle G, Quarti-Trevano F, et al – Adrenergic, metabolic, and reflex abnormalities in reverse and extreme dipper hypertensives. Hypertension. 2008;52:925-931.
30. Voichanski S, Grossman C, Leibowitz A, et al – Orthostatic hypotension is associated with nocturnal change in systolic blood pressure. Am J Hypertens. 2012;25(2):159-164.
31. Alquadan KF, Singhania G, Koratala A, Eja AA – Office orthostatic blood pressure measurements and ambulatory blood pressure monitoring in the prediction of autonomic dysfunction. Clin Hypertens. 2017;23:3.
32. Hossain P, Kawar B, El Nahas M – Obesity and diabetes in the developing world – a growing challenge. N Engl J Med 2007;356(3):213–215.
33. Faulkner JL, Bruder-Nascimento T, Belin de Chantemèle EJ – The regulation of aldosterone secretion by leptin: implications in obesity-related cardiovascular disease. Curr Opin Nephrol Hypertens. 2017;doi:10.1097/MNH.0000000000000384. [Epub ahead of print]
34. Ruano M, Silvestre V, Castro R, et al – Morbid obesity, hypertensive disease and the renin-angiotensin-aldosterone axis. Obes Surg 2005;15:670–676.
35. Westcott KV, Huang BS, Leenen FH – Brain renin-angiotensin-aldosterone system and ventricular remodelling after myocardial infarct: a review. Can J Physiol Pharmacol. 2009;87:979–988.
37. de Courten M, Zimmet P, Hodge A. et al – Hyperleptinaemia: the missing link in the metabolic syndrome? Diabet Med. 1997;14:200–208.
38. Kang YS – Obesity associated hypertension: new insights into mechanism. Electrolyte Blood Press. 2013;11:46–52.
39. Kanbay M, Turgut F, Uyar ME, et al – Causes and mechanisms of nondipping hypertension. Clin Exp Hypertens. 2008;30:585–597.
40. 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(1-2):17–30
41. Ayukusuma AR, Rohman MS, Lukitasari M et al – No difference of serum IL-6 level among dipper and non dipper hypertensive patients. J Hypertens. 2015; doi: 10.1097/01.hjh.0000469858.46811.f4
42. Duggal A, Bal BS, Singh N – Study of dipping and non-dipping patterns in patients of type 2 diabetes mellitus with hypertension and its association with microalbuminuria. Ann Int Med Den Res. 2017;3(2):20-24.
43. Tartan Z, Uyarel H, Kasikcioglu H, et al – Metabolic syndrome as a predictor of non-dipping hypertension. Tohoku J Exp Med. 2006;210:57–66.
44. Tutal E, Sayın B, Ertugrul DT, et al – Is there a link between hyperuricemia, morning blood pressure surge, and non-dipping blood pressure pattern in metabolic syndrome patients? Int J Nephrol Renovasc Dis. 2013;6:71–77.
45. Karaagac K, Tenekecioglu E, Yontar OC, et al – Effect of non-dipper and dipper blood pressure patterns on Tp-Te interval and Tp-Te/QT ratio in patients with metabolic syndrome. Int J Clin Exp Med. 2014;7(5):1397-1403.
46. Karaagac K, Vatansever F, Tenekecioglu E, et al – The relationship between non-dipper blood pressure and thoracic aortic diameter in metabolic syndrome. Eurasian J Med. 2014;46:120-125.
47. Ma Y, Sun S, Peng CK, Fang Y, Thomas RJ – Ambulatory blood pressure monitoring in chinese patients with obstructive sleep apnea. J Clin Sleep Med. 2017;13(3):433–439.
48. Suzuki M, Guilleminault C, Otsuka K, Shiomi T – Blood pressure “dipping” and “non-dipping” in obstructive sleep apnea syndrome patients. Sleep. 1996;19(5):382–387
49. Nabe B, Lies A, Pankow W, Kohl FV, Lohmann FW – Determinants of circadian blood pressure rhythm and blood pressure variability in obstructive sleep apnoea. J Sleep Res. 1995;4(S1):97–101
50. Wolf J, Hering D, Narkiewicz K – Non-dipping pattern of hypertension and obstructive sleep apnea syndrome. Hypertens Res. 2010;33(9):867–871.
51. de Paula Soares CF, Cavichio L, Cahali MB – Lateral pharyngoplasty reduces nocturnal blood pressure in patients with obstructive sleep apnea. Laryngoscope. 2014;124:311–316.
52. Routledge FS, McFetridge-Durdle JA, Dean CR – Stress, menopausal status and nocturnal blood pressure dipping patterns among hypertensive women. Can J Cardiol. 2009;25(6):e157-e163.
53. Refaie WR, Refaie E, Abd El Hady N, et al – Cardiovascular changes in dipper and nondipper hypertension in perimenopausal women (time-dependent effects of antihypertensives). Egypt J Int Med. 2012;24(2):37-42.
54. Iqbal A, Figenschau Y, Jorde R – Blood pressure in relation to serum thyrotropin: The Tromsø study. J Hum Hypertens. 2006;20:932–936
55. Canbolat IP, Belen E, Bayyigit A, et al – Evaluation of Daily Blood Pressure Alteration in Subclinical Hypothyroidism. Acta Cardiol Sin. 2017;33(5): 489–494.
56. Kanbay M, Turgut F, Karakurt F, et al – Relation between serum thyroid hormone and ‘nondipper’ circadian blood pressure variability. Kidney Blood Press Res. 2007; 30(6): 416–420.
57. Kanbay M, Isik B, Akcay A et al – Relation between serum calcium, phosphate, parathyroid hormone and ‘nondipper’ circadian blood pressure variability profile in patients with normal renal function. Am J Nephrol. 2007;27(5):516–521.
58. Velasquez MT, Beddhu S, Nobakht E, Rahman M, Raj DS – Ambulatory blood pressure in chronic kidney disease: ready for prime time? Kidney Int Rep. 2016;1(2):94–104.
59. Fedecostante M, Spannella F, Cola G, et al – Chronic kidney disease is characterized by “double trouble” higher pulse pressure plus night-time systolic blood pressure and more severe cardiac damage. PLoS One 2014;9(1):e86155.
60. Lurbe E, Redon J, Kesani A, et al – Increase in nocturnal blood pressure and progression to microalbuminuria in type 1 diabetes. N Engl J Med. 2002;347(11):797–805.
61. Sezer S, Karakan S, Çolak T, Haberal M – Nocturnal nondipping hypertension is related to dyslipidemia and increased renal resistivity index in renal transplant patients. Transplant Proc. 2011;43(2):530–532.
62. Wadei HM, Amer H, Griffin MD, Taler SJ, Stegall MD, Textor SC. Abnormal circadian blood pressure pattern 1-year after kidney transplantation is associated with subsequent lower glomerular filtration rate in recipients without rejection. J Am Soc Hypertens. 2011;5(1):39-47.
63. Choudhary L, Gupta P, Gupta A, et al – 24 hour ambulatory blood pressure monitoring and left ventricular ejection fraction-prognostic markers in chronic kidney disease. Int J Adv Med. 2016;3(2):402-408.
64. Dziwura J, Bińczak-Kuleta A, Miazgowski T, et al – The associations between G972R polymorphism of the IRS-1 gene, insulin resistance, salt sensitivity and non-dipper hypertension. Hypertens Res. 2011;34:1082–1086.
65. Uzu T, Ishikawa K, Fujii T, et al. – Sodium restriction shifts circadian rhythm of blood pressure from nondipper to dipper in essential hypertension. Circulation, 1997;96:1859–1862.
66. Campese VM, Romoff MS, Levitan D, et al. – Abnormal relationship between sodium intake and sympathetic nervous system activity in salt-sensitive patients with essential hypertension. Kidney Int. 1982;21:371–378.
67. Piepoli MF, Hoes AW, Agewall S, et al – 2016 European Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2016;37:2315-2381.
68. Chen Y, Liu JH, Zhen Z, et al. – Assessment of left ventricular function and peripheral vascular arterial stiffness in patients with dipper and non-dipper hypertension. J Investig Med. 2017; pii: jim-2017-000513
69. Mahabala C, Kamath P, Bhaskaran U, et al – Antihypertensive therapy: nocturnal dippers and nondippers. Do we treat them differently? Vasc Health Risk Manag. 2013;9:125–133.
70. Kario K, Schwartz JE, Pickering TG - Changes of nocturnal blood pressure dipping status in hypertensives by nighttime dosing of alpha-adrenergic blocker, doxazosin: results from the HALT study. Hypertension. 2000;35(3):787-794.
71. Wang C, Ye Y, Liu C, et al – Evening versus morning dosing regimen drug therapy for chronic kidney disease patients with hypertension in blood pressure patterns: a systematic review and meta-analysis. Intern Med J. 2017;47(8):900-906.
72. Wang C, Zhang J, Liu X, et al – Effect of Valsartan with bedtime dosing on chronic kidney disease patients with nondipping blood pressure pattern. J Clin Hypertens (Greenwich). 2013;15(1):48-54.
73. Fukuda M, Kimura G. Salt sensitivity and nondippers in chronic kidney disease. Curr Hypertens Rep. 2012;14(5):382-387.
74. Tosu AR, Demir S, Selcuk M, et al – Comparison of inflammatory markers in non-dipper hypertension vs. dipper hypertension and in normotensive individuals: uric acid, C-reactive protein and red blood cell distribution width readings. Postepy Kardiologii Interwencyjnej. 2014;10(2):98–103.
75. Buyukkaya E, Erayman A, Karakas E, et al – Relation of red cell distribution width with dipper and non-dipper hypertension. Medicinski Glasnik. 2016;13(2):75-81.
76. Kaya MG, Yarlioglues M, Gunebakmaz O, et al. – Platelet activation and inflammatory response in patients with non-dipper hypertension. Atherosclerosis. 2010;209(1):278-282.
77. Ortakoyluoglu A, Boz B, Sitki DO, et al – The association of serum gamma-glutamyl transpeptidase level and other laboratory parameters with blood pressure in hypertensive patients under ambulatory blood pressure monitoring. Ther Clin Risk Manag. 2016;12:1395-1401.
78. Tabara Y, Igaseb M, Mikia T, et al – B-type natriuretic peptide is a determinant of the nocturnal increase in blood pressure independently of arterial hypertrophy and hypoxia. J Hypertens. 2016;34:2393-2401.
79. Bakirci EM, Degirmenci H, Hamur H, et al. – New inflammatory markers for prediction of non-dipper blood pressure pattern in patients with essential hypertension: Serum YKL-40/Chitinase 3-like protein 1 levels and echocardiographic epicardial adipose tissue thickness. Clin Exp Hypertens. 2015;37:1–6.
80. Ji Q, Cheng G, Ma N, et al – Circulating Th1, Th2, and Th17 levels in hypertensive patients. Dis Markers. 2017; 7146290
81. Kadoya M, Koyama H, Kanzaki A, et al – Plasma brain-derived neurotrophic factor and reverse dipping pattern of nocturnal blood pressure in patients with cardiovascular risk factors. PLoS One. 2014;9(8): e105977.
82. Meric M, Soylu K, Avci B, et al – Evaluation of plasma chemerin levels in patients with non-dipper blood pressure patterns. Med Sci Monit. 2014;20:698–705.
83. Zheng H, Xie X, Xie N, Xu H, et al – Sphingomyelin levels in nondipper and dipper hypertensive patients. Exp Ther Med. 2014;7:599-603.
84. Cayli M, Gur M, Elbasan Z, et al – High-Sensitivity Cardiac Troponin T Predicts Nondipper Hypertension in Newly Diagnosed Hypertensive Patients. J Clin Hypertens (Greenwich). 2013;15(10):731-736.