Pediatric Nephrology

, Volume 29, Issue 6, pp 979–988

Rational use of antihypertensive medications in children

Educational Review


Hypertension has traditionally been regarded as an uncommon diagnosis in childhood and adolescence; however, there is compelling evidence to suggest that its prevalence is on the rise, particularly in those with obesity. As a result, pediatricians increasingly are asked to evaluate and manage patients with elevated blood pressure. An increased emphasis on conducting drug trials in children over the last 15 years has yielded important advances with respect to evidence-based data regarding the efficacy and safety of antihypertensive medications in children and adolescents. Unfortunately, data to definitively guide selection of initial agents is lacking. This article will present guidelines for the appropriate use of antihypertensive medications in the pediatric population, including the rational approach to selecting an appropriate medication with respect to pathophysiology, putative benefit, and likelihood for side effects.


Hypertension Primary hypertension Renal artery stenosis Renin Obesity Chronic kidney disease Athlete 


  1. 1.
    Blumenthal S, Epps RP, Heavenrich R, Lauer RM, Lieberman E, Mirkin B, Mitchell SC, Boyar Naito V, O’Hare D, McFate Smith W, Tarazi RC, Upson D (1977) Report of the task force on blood pressure control in children. Pediatrics 59(I-II):797–820Google Scholar
  2. 2.
    National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:555–576CrossRefGoogle Scholar
  3. 3.
    Sinaiko AR, Gomez-Marin O, Prineas RJ (1989) Prevalence of “significant” hypertension in junior high school-aged children: the Children and Adolescent Blood Pressure Program. J Pediatr 114:664–669PubMedCrossRefGoogle Scholar
  4. 4.
    Fixler DE, Laird WP, Fitzgerald V, Stead S, Adams R (1979) Hypertension screening in schools: results of the Dallas study. Pediatrics 63:32–36PubMedGoogle Scholar
  5. 5.
    Sorof JM, Lai D, Turner J, Poffenbarger T, Portman RJ (2004) Overweight, ethnicity, and the prevalence of hypertension in school-aged children. Pediatrics 113:475–482PubMedCrossRefGoogle Scholar
  6. 6.
    McNiece KL, Poffenbarger TS, Turner JL, Franco KD, Sorof JM, Portman RJ (2007) Prevalence of hypertension and pre-hypertension among adolescents. J Pediatr 150:640–644PubMedCrossRefGoogle Scholar
  7. 7.
    Din-Dzietham R, Liu Y, Bielo MV, Shamsa F (2007) High blood pressure trends in children and adolescents in national surveys, 1963 to 2002. Circulation 116:1488–1496PubMedCrossRefGoogle Scholar
  8. 8.
    Muntner P, He J, Cutler JA, Wildman RP, Whelton PK (2004) Trends in blood pressure among children and adolescents. JAMA 291:2107–2113PubMedCrossRefGoogle Scholar
  9. 9.
    Boneparth A, Flynn JT (2009) Evaluation and treatment of hypertension in general pediatric practice. Clin Pediatr (Phila) 48:44–49CrossRefGoogle Scholar
  10. 10.
    Yoon EY, Cohn L, Rocchini A, Kershaw D, Freed G, Ascione F, Clark S (2012) Antihypertensive prescribing patterns for adolescents with primary hypertension. Pediatrics 129:e1–e8PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Flynn JT (2011) Management of hypertension in the young: role of antihypertensive medications. J Cardiovasc Pharmacol 58:111–120PubMedCrossRefGoogle Scholar
  12. 12.
    Lurbe E, Cifkova R, Cruickshank JK, Dillon MJ, Ferreira I, Invitti C, Kuznetsova T, Laurent S, Mancia G, Morales-Olivas F, Rascher W, Redon J, Schaefer F, Seeman T, Stergiou G, Wuhl E, Zanchetti A (2009) Management of high blood pressure in children and adolescents: recommendations of the European Society of Hypertension. J Hypertens 27:1719–1742PubMedCrossRefGoogle Scholar
  13. 13.
    Hornsby JL, Mongan PF, Taylor AT, Treiber FA (1991) ‘White coat’ hypertension in children. J Fam Pract 33:617–623PubMedGoogle Scholar
  14. 14.
    Swartz SJ, Srivaths PR, Croix B, Feig DI (2008) Cost-effectiveness of ambulatory blood pressure monitoring in the initial evaluation of hypertension in children. Pediatrics 122:1177–1181PubMedCrossRefGoogle Scholar
  15. 15.
    Sorof JM, Portman RJ (2000) White coat hypertension in children with elevated casual blood pressure. J Pediatr 137:493–497PubMedCrossRefGoogle Scholar
  16. 16.
    Lewington S, Clarke R, Qizilbash N, Peto R, Collins R (2002) Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 360:1903–1913PubMedCrossRefGoogle Scholar
  17. 17.
    Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ (2003) Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 42:1206–1252PubMedCrossRefGoogle Scholar
  18. 18.
    Daniels SR, Loggie JM, Khoury P, Kimball TR (1998) Left ventricular geometry and severe left ventricular hypertrophy in children and adolescents with essential hypertension. Circulation 97:1907–1911PubMedCrossRefGoogle Scholar
  19. 19.
    Sorof JM, Alexandrov AV, Cardwell G, Portman RJ (2003) Carotid artery intimal-medial thickness and left ventricular hypertrophy in children with elevated blood pressure. Pediatrics 111:61–66PubMedCrossRefGoogle Scholar
  20. 20.
    Hanevold C, Waller J, Daniels S, Portman R, Sorof J (2004) The effects of obesity, gender, and ethnic group on left ventricular hypertrophy and geometry in hypertensive children: a collaborative study of the International Pediatric Hypertension Association. Pediatrics 113:328–333PubMedCrossRefGoogle Scholar
  21. 21.
    Wuhl E, Trivelli A, Picca S, Litwin M, Peco-Antic A, Zurowska A, Testa S, Jankauskiene A, Emre S, Caldas-Afonso A, Anarat A, Niaudet P, Mir S, Bakkaloglu A, Enke B, Montini G, Wingen AM, Sallay P, Jeck N, Berg U, Caliskan S, Wygoda S, Hohbach-Hohenfellner K, Dusek J, Urasinski T, Arbeiter K, Neuhaus T, Gellermann J, Drozdz D, Fischbach M, Moller K, Wigger M, Peruzzi L, Mehls O, Schaefer F (2009) Strict blood-pressure control and progression of renal failure in children. N Engl J Med 361:1639–1650PubMedCrossRefGoogle Scholar
  22. 22.
    Flynn JT, Daniels SR (2006) Pharmacologic treatment of hypertension in children and adolescents. J Pediatr 149:746–754PubMedCrossRefGoogle Scholar
  23. 23.
    Schaefer F, Litwin M, Zachwieja J, Zurowska A, Turi S, Grosso A, Pezous N, Kadwa M (2011) Efficacy and safety of valsartan compared to enalapril in hypertensive children: a 12-week, randomized, double-blind, parallel-group study. J Hypertens 29:2484–2490PubMedCrossRefGoogle Scholar
  24. 24.
    Blowey DL (2012) Update on the pharmacologic treatment of hypertension in pediatrics. J Clin Hypertens (Greenwich) 14:383–387CrossRefGoogle Scholar
  25. 25.
    Simonetti GD, Rizzi M, Donadini R, Bianchetti MG (2007) Effects of antihypertensive drugs on blood pressure and proteinuria in childhood. J Hypertens 25:2370–2376PubMedCrossRefGoogle Scholar
  26. 26.
    Woroniecki RP, Flynn JT (2005) How are hypertensive children evaluated and managed? A survey of North American pediatric nephrologists. Pediatr Nephrol 20:791–797PubMedCrossRefGoogle Scholar
  27. 27.
    Batisky DL (2012) What is the optimal first-line agent in children requiring antihypertensive medication? Curr Hypertens Rep 14:603–607PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Prichard BN, Cruickshank JM, Graham BR (2001) Beta-adrenergic blocking drugs in the treatment of hypertension. Blood Press 10:366–386PubMedCrossRefGoogle Scholar
  29. 29.
    Bullo M, Tschumi S, Bucher BS, Bianchetti MG, Simonetti GD (2012) Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists: a systematic review. Hypertension 60:444–450PubMedCrossRefGoogle Scholar
  30. 30.
    Garovic V, Textor SC (2005) Renovascular hypertension: current concepts. Semin Nephrol 25:261–271PubMedCrossRefGoogle Scholar
  31. 31.
    Garovic VD, Textor SC (2005) Renovascular hypertension and ischemic nephropathy. Circulation 112:1362–1374PubMedCrossRefGoogle Scholar
  32. 32.
    Johansson M, Friberg P (2000) Role of the sympathetic nervous system in human renovascular hypertension. Curr Hypertens Rep 2:319–326PubMedCrossRefGoogle Scholar
  33. 33.
    Kenny D, Hijazi ZM (2011) Coarctation of the aorta: from fetal life to adulthood. Cardiol J 18:487–495PubMedCrossRefGoogle Scholar
  34. 34.
    Gidding SS, Rocchini AP, Beekman R, Szpunar CA, Moorehead C, Behrendt D, Rosenthal A (1985) Therapeutic effect of propranolol on paradoxical hypertension after repair of coarctation of the aorta. N Engl J Med 312:1224–1228PubMedCrossRefGoogle Scholar
  35. 35.
    Brili S, Tousoulis D, Antoniades C, Vasiliadou C, Karali M, Papageorgiou N, Ioakeimidis N, Marinou K, Stefanadi E, Stefanadis C (2008) Effects of ramipril on endothelial function and the expression of proinflammatory cytokines and adhesion molecules in young normotensive subjects with successfully repaired coarctation of aorta: a randomized cross-over study. J Am Coll Cardiol 51:742–749PubMedCrossRefGoogle Scholar
  36. 36.
    Flynn JT, Pierce CB, Miller ER 3rd, Charleston J, Samuels JA, Kupferman J, Furth SL, Warady BA (2012) Reliability of resting blood pressure measurement and classification using an oscillometric device in children with chronic kidney disease. J Pediatr 160:434–440PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Klag MJ, Whelton PK, Randall BL, Neaton JD, Brancati FL, Ford CE, Shulman NB, Stamler J (1996) Blood pressure and end-stage renal disease in men. N Engl J Med 334:13–18PubMedCrossRefGoogle Scholar
  38. 38.
    Iseki K, Ikemiya Y, Iseki C, Takishita S (2003) Proteinuria and the risk of developing end-stage renal disease. Kidney Int 63:1468–1474PubMedCrossRefGoogle Scholar
  39. 39.
    Locatelli F, Marcelli D, Comelli M, Alberti D, Graziani G, Buccianti G, Redaelli B, Giangrande A (1996) Proteinuria and blood pressure as causal components of progression to end-stage renal failure. Northern Italian Cooperative Study Group. Nephrol Dial Transplant 11:461–467PubMedCrossRefGoogle Scholar
  40. 40.
    Maschio G, Alberti D, Janin G, Locatelli F, Mann JF, Motolese M, Ponticelli C, Ritz E, Zucchelli P (1996) Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. N Engl J Med 334:939–945PubMedCrossRefGoogle Scholar
  41. 41.
    The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia) (1997) Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 349:1857–1863Google Scholar
  42. 42.
    Jafar TH, Schmid CH, Landa M, Giatras I, Toto R, Remuzzi G, Maschio G, Brenner BM, Kamper A, Zucchelli P, Becker G, Himmelmann A, Bannister K, Landais P, Shahinfar S, de Jong PE, de Zeeuw D, Lau J, Levey AS (2001) Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data. Ann Intern Med 135:73–87PubMedCrossRefGoogle Scholar
  43. 43.
    Flynn JT, Mitsnefes M, Pierce C, Cole SR, Parekh RS, Furth SL, Warady BA (2008) Blood pressure in children with chronic kidney disease: a report from the Chronic Kidney Disease in Children study. Hypertension 52:631–637PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Samuels J, Ng D, Flynn JT, Mitsnefes M, Poffenbarger T, Warady BA, Furth S (2012) Ambulatory blood pressure patterns in children with chronic kidney disease. Hypertension 60:43–50PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents (2011) Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics 128 Suppl 5:S213–256Google Scholar
  46. 46.
    Ogden CL, Carroll MD, Kit BK, Flegal KM (2012) Prevalence of obesity in the United States, 2009–2010. NCHS data brief, no. 82. National Center for Health Statistics, Hyattsville, MD. Available at Accessed 1 February 2013
  47. 47.
    Lazzeri G, Rossi S, Pammolli A, Pilato V, Pozzi T, Giacchi MV (2008) Underweight and overweight among children and adolescents in Tuscany (Italy). Prevalence and short-term trends. J Prev Med Hyg 49:13–21PubMedGoogle Scholar
  48. 48.
    Valdes Pizarro J, Royo-Bordonada MA (2012) Prevalence of childhood obesity in Spain: National Health Survey 2006–2007. Nutr Hosp 27:154–160PubMedGoogle Scholar
  49. 49.
    Kollias A, Skliros E, Stergiou GS, Leotsakos N, Saridi M, Garifallos D (2011) Obesity and associated cardiovascular risk factors among schoolchildren in Greece: a cross-sectional study and review of the literature. J Pediatr Endocrinol Metab 24:929–938PubMedCrossRefGoogle Scholar
  50. 50.
    Midha T, Nath B, Kumari R, Rao YK, Pandey U (2012) Childhood obesity in India: a meta-analysis. Indian J Pediatr 79:945–948PubMedCrossRefGoogle Scholar
  51. 51.
    Wang Y, Lobstein T (2006) Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes 1:11–25PubMedCrossRefGoogle Scholar
  52. 52.
    Schillaci G, Pirro M, Vaudo G, Gemelli F, Marchesi S, Porcellati C, Mannarino E (2004) Prognostic value of the metabolic syndrome in essential hypertension. J Am Coll Cardiol 43:1817–1822PubMedCrossRefGoogle Scholar
  53. 53.
    Ford ES, Giles WH, Dietz WH (2002) Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 287:356–359PubMedCrossRefGoogle Scholar
  54. 54.
    Ford ES, Li C, Zhao G, Pearson WS, Mokdad AH (2008) Prevalence of the metabolic syndrome among U.S. adolescents using the definition from the International Diabetes Federation. Diabetes Care 31:587–589PubMedCrossRefGoogle Scholar
  55. 55.
    Landsberg L, Aronne LJ, Beilin LJ, Burke V, Igel LI, Lloyd-Jones D, Sowers J (2013) Obesity-related hypertension: pathogenesis, cardiovascular risk, and treatment: a position paper of the obesity society and the American Society of Hypertension. J Clin Hypertens (Greenwich) 15:14–33CrossRefGoogle Scholar
  56. 56.
    Sarzani R, Salvi F, Dessi-Fulgheri P, Rappelli A (2008) Renin–angiotensin system, natriuretic peptides, obesity, metabolic syndrome, and hypertension: an integrated view in humans. J Hypertens 26:831–843PubMedCrossRefGoogle Scholar
  57. 57.
    Caballero AE (2003) Endothelial dysfunction in obesity and insulin resistance: a road to diabetes and heart disease. Obes Res 11:1278–1289PubMedCrossRefGoogle Scholar
  58. 58.
    Allcock DM, Sowers JR (2010) Best strategies for hypertension management in type 2 diabetes and obesity. Curr Diab Rep 10:139–144PubMedCrossRefGoogle Scholar
  59. 59.
    Prabhakar SS (2013) Inhibition of renin–angiotensin system: implications for diabetes control and prevention. J Investig Med 61:551–557PubMedGoogle Scholar
  60. 60.
    Sharma AM (2008) Does it matter how blood pressure is lowered in patients with metabolic risk factors? J Am Soc Hypertens 2:S23–S29PubMedCrossRefGoogle Scholar
  61. 61.
    Murakami K, Wada J, Ogawa D, Horiguchi CS, Miyoshi T, Sasaki M, Uchida HA, Nakamura Y, Makino H (2013) The effects of telmisartan treatment on the abdominal fat depot in patients with metabolic syndrome and essential hypertension: Abdominal fat Depot Intervention Program of Okayama (ADIPO). Diab Vasc Dis Res 10:93–96PubMedCrossRefGoogle Scholar
  62. 62.
    Mancia G, Grassi G, Zanchetti A (2006) New-onset diabetes and antihypertensive drugs. J Hypertens 24:3–10PubMedCrossRefGoogle Scholar
  63. 63.
    Laragh JH, Sealey JE (2011) The plasma renin test reveals the contribution of body sodium-volume content (V) and renin-angiotensin (R) vasoconstriction to long-term blood pressure. Am J Hypertens 24:1164–1180PubMedCrossRefGoogle Scholar
  64. 64.
    Laragh J (2001) Laragh’s lessons in pathophysiology and clinical pearls for treating hypertension. Am J Hypertens 14:837–854PubMedCrossRefGoogle Scholar
  65. 65.
    Egan BM, Basile JN, Rehman SU, Davis PB, Grob CH 3rd, Riehle JF, Walters CA, Lackland DT, Merali C, Sealey JE, Laragh JH (2009) Plasma Renin test-guided drug treatment algorithm for correcting patients with treated but uncontrolled hypertension: a randomized controlled trial. Am J Hypertens 22:792–801PubMedCrossRefGoogle Scholar
  66. 66.
    Turner ST, Schwartz GL, Chapman AB, Beitelshees AL, Gums JG, Cooper-DeHoff RM, Boerwinkle E, Johnson JA, Bailey KR (2010) Plasma renin activity predicts blood pressure responses to beta-blocker and thiazide diuretic as monotherapy and add-on therapy for hypertension. Am J Hypertens 23:1014–1022PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Alderman MH, Cohen HW, Sealey JE, Laragh JH (2010) Pressor responses to antihypertensive drug types. Am J Hypertens 23:1031–1037PubMedCrossRefGoogle Scholar
  68. 68.
    Maron BJ, Zipes DP (2005) Introduction: eligibility recommendations for competitive athletes with cardiovascular abnormalities-general considerations. J Am Coll Cardiol 45:1318–1321PubMedCrossRefGoogle Scholar
  69. 69.
    Eaton DK, Kann L, Kinchen S, Shanklin S, Flint KH, Hawkins J, Harris WA, Lowry R, McManus T, Chyen D, Whittle L, Lim C, Wechsler H (2012) Youth risk behavior surveillance - United States, 2011. MMWR Surveill Summ 61:1–162PubMedGoogle Scholar
  70. 70.
    Goulet C, Valois P, Buist A, Cote M (2010) Predictors of the use of performance-enhancing substances by young athletes. Clin J Sport Med 20:243–248PubMedCrossRefGoogle Scholar
  71. 71.
    Fagard RH (2007) Athletes with systemic hypertension. Cardiol Clin 25:441–448PubMedCrossRefGoogle Scholar
  72. 72.
    Van Baak MA (1988) Beta-adrenoreceptor blockade and exercise. An update. Sports Med 5:209–225PubMedCrossRefGoogle Scholar
  73. 73.
    Van Baak MA, Koene FMM, Verstappen FTJ (1988) Exercise hemodynamics and maximal exercise capacity during beta-adrenoreceptor blockade in normotensive and hypertensive subjects. Br J Clin Pharmacol 25:169–177PubMedCentralPubMedCrossRefGoogle Scholar
  74. 74.
    Vanhees L, Defoor JG, Schepers D, Lijnen P, Peeters BY, Lacante PH, Fagard RH (2000) Effect of bisoprolol and atenolol on endurance exercise capacity in healthy men. J Hypertens 18:35–43PubMedCrossRefGoogle Scholar
  75. 75.
    Vehaskari VM (2009) Heritable forms of hypertension. Pediatr Nephrol 24:1929–1937PubMedCentralPubMedCrossRefGoogle Scholar
  76. 76.
    Simonetti GD, Mohaupt MG, Bianchetti MG (2012) Monogenic forms of hypertension. Eur J Pediatr 171:1433–1439PubMedCrossRefGoogle Scholar

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© IPNA 2013

Authors and Affiliations

  1. 1.Division of Nephrology, Boston Children’s Hospital, Department of Pediatrics Harvard Medical SchoolBoston Children’s HospitalBostonUSA
  2. 2.Division of Nephrology, Seattle Children’s Hospital, Department of PediatricsUniversity of Washington School of MedicineSeattleUSA

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