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Resistant hypertension: epidemiology and risk factors

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Despite the possibilities of contemporary pharmacotherapy, more than 80% of hypertensive patients do not achieve target blood pressure levels. Besides the obvious reasons – poor adherence of patients to treatment and non-rational therapy, there are other objective risk factors of resistance. Three main modifiable causes of resistant hypertension, that are often underestimated, are considered: obesity, obstructive sleep apnea syndrome and primary hyperaldosteronism. Understanding these mechanisms of resistance and their diagnostic criteria can improve the results of resistant hypertension treatment.

About the Authors

I. E. Deneka
I.M. Sechenov First Moscow State Medical University
Russian Federation
Trubetskaya ul. 8-2, Moscow, 119991

A. A. Svetankova
I.M. Sechenov First Moscow State Medical University
Russian Federation
Trubetskaya ul. 8-2, Moscow, 119991

A. V. Rodionov
I.M. Sechenov First Moscow State Medical University
Russian Federation
Trubetskaya ul. 8-2, Moscow, 119991


1. Mathers C., Stevens G., Mascarenhas M. Global health risks: mortality and burden of disease attributable to selected major risks. Geneva, Switzerland: World Health Organization; 2009.

2. Kearney P.M., Whelton M., Reynolds K. et al. Global burden of hypertension: analysis of worldwide data. Lancet 2005; 365(9455): 217-23.

3. Oganov RG, Timofeev TN, Koltunov IE Epidemiology of arterial hypertension in Russia. the federal monitoring results of 2003-2010. Kardiovaskulyarnaya Terapiya i Profilaktika 2011; 10 (1): 9-13. In Russian (Оганов Р. Г., Тимофеева Т. Н., Колтунов И. Е. Эпидемиология артериальной гипертонии в России. Результаты федерального мониторинга 2003-2010 гг. Кардиоваскулярная Терапия и Профилактика 2011; 10(1): 9-13).

4. Shlyakhto E., ed. Resistant hypertension. St. Petersburg: Nauka; 2011. In Russian (Шляхто Е.В., ред. Резистентная артериальная гипертензия. СПб.: Наука; 2011).

5. Boytsov SA, Balanova JA, Shalnova SA.Arterial hypertension among people aged25-64: prevalence, awareness,treatment and control.According to studies essay. Kardiovaskulyarnaya Terapiya i Profilaktika 2014; 14 (4): 4-14. In Russian (Бойцов С.А., Баланова Ю.А., Шальнова С.А. Артериальная гипертония среди лиц 25-64 лет: распространенность, осведомленность, лечение и контроль. По материалам исследования ЭССЕ. Кардиоваскулярная Терапия и Профилактика 2014; 14(4): 4-14).

6. Calhoun D. A, 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. Circulation 2008; 117(25): e510-26.

7. Mancia G., Fagard R., Narkiewicz K, et al. ESH-ESC Task Force on the Management of Arterial Hypertension. 2013 ESH-ESC Practice Guidelines forthe Management of ArterialHypertension: ESH-ESC Task Force on the Management of Arterial Hypertension. Eur Heart J 2013; 34(28): 2159-219.

8. Mancia G., Laurent S., Agabiti-Rosei E. et al. European Society of Hypertension. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J Hypertension 2009; 27(11): 2121-58.

9. Chazova IE, Fomin VV, Razuvaeva MA, Vigdorchik AV. Resistance and uncontrolled hypertension: the problem of the XXI century. Farmateka 2011; 5: 8-13. In Russian (Чазова И.Е., Фомин В.В., Разуваева М.А., Вигдорчик А.В. Резистентная и неконтролируемая артериальная гипертензия: проблема XXI века. Фарматека 2011; 5: 8-13).

10. Shalnova SA. Problems of treatment of hypertension. Kardiovaskulyarnaya Terapiya i Profilaktika 2003; 3: 17-21. In Russian (Шальнова С.А. Проблемы лечения артериальной гипертонии. Кардиоваскулярная Терапия и Профилактика 2003; 3: 17-21).

11. Pimenta E., Calhoun D. A. Resistant Hypertension: Incidence, Prevalence, and Prognosis. Circulation 2012; 125(13): 1594-96.

12. Roberie D.R., Elliott W.J. What is the prevalence of resistant hypertension in the United States. Curr Opin Cardiol 2012; 27(4): 386-91.

13. AmericanHeart Association. Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation 2005; 113(6): 898-918.

14. Daugherty S.L., Powers J.D., Magid D.J. et al. Incidence and prognosis ofresistant hypertension in hypertensive patients. Circulation 2012; 125(13): 1635-42.

15. Wolf-Maier K., Cooper R. S., Kramer H. et al. Hypertension treatment and control in five European countries, Canada, and the United States. J Hypertension 2004; 43(1): 7-10.

16. De la SierraA., Segura J., Banegas J.R. et al. Clinicalfeatures of 8295 patientswith resistant hypertension classified on the basis of ambulatory blood pressure monitoring.Hypertension 2011; 57(5): 898-902.

17. Fagard R.H. Resistant hypertension. Heart 2012; 98(3): 254-61.

18. Frolich E.D. Classification of resistant hypertension. Hypertension 1988; 11(3): 67-70.

19. Rossi G. P., Seccia T. M., Maniero T. M. et al. Drug-related hypertension and resistance to antihypertensive treatment: a call for action. J Hypertens 2011; 29(12): 2295-309.

20. Cruz-Gonzalez I.,Corral E., Sánchez-LedesmaM. et al.Association between -T786C NOS3polymorphism and resistant hypertension: a prospective cohort study. BMC Cardiovasc Disord 2009; 9: 35.

21. Roberie D.R., Elliott W.J. What is the prevalence of resistant hypertension in the United States. Curr Opin Cardiol 2012; 27(4): 386-91.

22. Jordan J., Yumuk V., Schlaich M. et al. Joint statement of the European Association for the study of obesity and the European Society of Hypertension: obesity and difficult to treat arterial hypertension. J Hypertens 2012; 30: 1047-55.

23. Aucott L., Poobalan A., Smith W.C. et al. Effects of weight loss in overweight/obese individuals and long-term hypertension outcomes: a systematic review. Hypertension 2005; 45(6): 1035-41.

24. Dimeo F., Pagonas N., Seibert F. et al. Aerobic exercise reduces blood pressure in resistant hypertension. Hypertension 2012; 60(3): 653-8.

25. Poirier P., Giles T.D., Bray G.A., et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation 2006; 113(6): 898-918.

26. Massiera F., Bloch-Faure M., CeilerD. et al.Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation. FASEB J 2001; 15(14): 2727-9.

27. Sarzani R., Salvi F.,Dessì-Fulgheri P. et al. Renin-angiotensin system, natriuretic peptides, obesity, metabolic syndrome, and hypertension: an integrated view in humans.JHypertens 2008; 26(5): 831-43.

28. Pivovarova O., Gögebakan Ö., Klöting N. et al. Insulin up-regulates natriuretic peptide clearance receptor expression in the subcutaneous fat depot in obese subjects: a missing link between CVD risk and obesity? J Clin Endocrinol Metab 2012; 97(5): E731-9.

29. Bordicchia M., LiuD.,Amri E.Z. et al. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. J Clin Invest 2012; 122(3): 1022-36.

30. Pieterse C., Schutte A.E., Mels C. et al. Carotid cross-sectional wall area is significantly associated with serum leptin levels, independent of body mass index: the SABPA study.Hypertens Res 2012; 30: 130.

31. Pieter M., Jansen I., Jan A. H. et al. Drug Mechanisms to Help in Managing Resistant Hypertension in Obesity. Curr Hypertens Rep 2010; 12(4): 220-5.

32. LiebW., Pencina M.J., Lanier K.J. et al.Association of parental obesity with concentrations of select systemic biomarkers in nonobese offspring: the Framingham Heart Study. Diabetes 2009; 58(1): 134-7.

33. Machowska A., Juszczak K., Novak P. et al. The natriuretic peptide neurohormonal system modulation by vasopeptidase inhibitors-the novel therapeutical approach of hypertension treatment. Folia Med Cracov 2009; 50(3-4): 35-42.

34. Calhoun D. A. Obstructive Sleep Apnea and Hypertension. Cur Hypertens Rep 2010; 12: 189-95.

35. Sydney B., Montesi M.D., Ednan K. et al. Biomarkers of sleep apnea. Chest 2012; 142(1): 239-45.

36. Ruttanaumpawan P., Nopmaneejumruslers C., Logan A.G. et al. Association between refractory hypertension and obstructive sleep apnea. Journal of Hypertension 2009; 27(7): 1439-45.

37. Marin J. M., Agusti A., Villar I. et al. Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA 2012; 307: 2169-76.

38. Barbe F., Duran-Cantolla J., Sanchez-de-la-Torre M. et al. Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a randomized controlled trial. JAMA 2012; 307: 2161-8.

39. Gonçalves S. C., Martinez D., Gus M. et al. Obstructive sleep apnea and resistant hypertension: a case control study. Chest 2007; 132: 1858-62.

40. Peppard P.E., Young T., Palta M. et al. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000; 342: 1378-84.

41. Demede M., Pandey A., Zizi F. et al. Resistant hypertension and obstructive sleep apnea in the primarycare setting. Int J Hypertens 2011;2011:340929.

42. Rajagopalan N. Obstructive sleep apnea: not just a sleep disorder. Journal of postgraduate medicine 2011; 57(2): 168-75.

43. Krasinska B., Miazga A., Cofta S. et al. Effect of eplerenone on the severity of obstructive sleep apnea and arterial stiffness in patients with resistant arterial hypertension. Pol Arch Med Wewn 2016; 126(5): 330-9.

44. Cereda CW, Tamisier R, Manconi M, et al. Endothelial dysfunction and arterial stiffness in ischemic stroke: the role of sleep-disordered breathing. Stroke 2013; 44:1175.

45. Vein AM, Eligulashvili TS, Polouektov MG. Sleep apnea and other breathing disorders associated with sleep: clinical features, diagnosis and treatment. Moscow: Eidos Media; 2002. In Russian (Вейн А.М., Елигулашвили Т.С., Полуэктов М.Г. Синдром апноэ во сне и другие расстройства дыхания, связанные со сном: клиника, диагностика и лечение. Москва: Эйдос Медиа; 2002).

46. Funder J.W., Carey R.M., Fardella C. et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline.J Clin Endocrinol Metab 2008; 63: 3266-81.

47. Douma S., Petidis K., Doumas M. et al. Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study. Lancet 2008; 371: 1921-26.

48. Chazova IE, Fomin VV, Razuvaeva MA, Vigdorchik AV, on behalf of the researchers. Register resistant hypertension - ResistantHypertension arterial (REGATTA) research program. Consilium Medicum 2009; 11 (10): 5-9. In Russian (Чазова И.Е., Фомин В.В., Разуваева М.А., Вигдорчик А.В. от имени исследователей. Регистр резистентной артериальной гипертонии – Резистентная Гипертония АрТериАльная (РЕГАТА): программа исследования. Consilium Medicum 2009; 11(10): 5-9).

49. Kaplan N.M. The current epidemic of primary aldosteronism: causes and consequences . J Hypertens 2004; 22(5): 863-9.

50. Sabbadin C., Fallo F. Hyperaldosteronism: Screening and Diagnostic Tests. High Blood Press Cardiovasc Prev 2016; 23(2): 69-72.

51. Funder J. W., Carey R. M., Fardella C. et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrin Metab 2008; 93(9): 3266-81.

52. Stowasser M., Gordon R.D., Gunasekera T.G. et al. High rate of detection of primary aldosteronism, including surgically treatable forms, after‘non-selective’ screening of hypertensive patients.JHypertens 2003; 21(11): 2149-57.

53. Baranova EI OO Bolshakova, Berkovich OA Blockade of aldosterone. The new strategy of treatment of resistant hypertension. Arterial'naya Gipertenziya 2008; 14 (3): 203-10. In Russian (Баранова Е.И., Большакова О.О., Беркович О.А. Блокада альдостерона. Новая стратегия лечения резистентной артериальной гипертензии. Артериальная Гипертензия 2008; 14(3): 203-10).

54. Pisoni R., Acelajado M.C., Calhoun D.A. et al. Long-term effects of aldosterone blockade in resistant hypertension associated with chronic kidney disease. J Hum Hypertens 2012; 26(8): 502-6.

55. Kumar N., Calhoun D.A., Dudenbostel T. Management of patients with resistant hypertension: current treatment options. Integr Blood Press Control 2013; 22(6): 139-51.

56. Narayan H., Webb D.J. New Evidence Supporting the Use of Mineralocorticoid Receptor Blockers in Drug-Resistant Hypertension. Curr Hypertens Rep 2016; 18(5): 34.

57. Nishizaka M.K., Zaman M.A., Calhoun D.A. Efficacy of low-dose spironolactone in subjects with resistant hypertension. Am J Hypertens 2003; 16(11 Pt 1): 925-30.

58. Chapman N., Dobson J., Wilson S. et al. Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension 2007; 49: 839-45.


For citation:

Deneka I.E., Svetankova A.A., Rodionov A.V. Resistant hypertension: epidemiology and risk factors. Rational Pharmacotherapy in Cardiology. 2016;12(4):459-464. (In Russ.)

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