Abstract
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.
References
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):797–820
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 114:555–576
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 114:664–669
Fixler DE, Laird WP, Fitzgerald V, Stead S, Adams R (1979) Hypertension screening in schools: results of the Dallas study. Pediatrics 63:32–36
Sorof JM, Lai D, Turner J, Poffenbarger T, Portman RJ (2004) Overweight, ethnicity, and the prevalence of hypertension in school-aged children. Pediatrics 113:475–482
McNiece KL, Poffenbarger TS, Turner JL, Franco KD, Sorof JM, Portman RJ (2007) Prevalence of hypertension and pre-hypertension among adolescents. J Pediatr 150:640–644
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 116:1488–1496
Muntner P, He J, Cutler JA, Wildman RP, Whelton PK (2004) Trends in blood pressure among children and adolescents. JAMA 291:2107–2113
Boneparth A, Flynn JT (2009) Evaluation and treatment of hypertension in general pediatric practice. Clin Pediatr (Phila) 48:44–49
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–e8
Flynn JT (2011) Management of hypertension in the young: role of antihypertensive medications. J Cardiovasc Pharmacol 58:111–120
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 27:1719–1742
Hornsby JL, Mongan PF, Taylor AT, Treiber FA (1991) ‘White coat’ hypertension in children. J Fam Pract 33:617–623
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 122:1177–1181
Sorof JM, Portman RJ (2000) White coat hypertension in children with elevated casual blood pressure. J Pediatr 137:493–497
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 360:1903–1913
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 42:1206–1252
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 97:1907–1911
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 111:61–66
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 113:328–333
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 361:1639–1650
Flynn JT, Daniels SR (2006) Pharmacologic treatment of hypertension in children and adolescents. J Pediatr 149:746–754
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 29:2484–2490
Blowey DL (2012) Update on the pharmacologic treatment of hypertension in pediatrics. J Clin Hypertens (Greenwich) 14:383–387
Simonetti GD, Rizzi M, Donadini R, Bianchetti MG (2007) Effects of antihypertensive drugs on blood pressure and proteinuria in childhood. J Hypertens 25:2370–2376
Woroniecki RP, Flynn JT (2005) How are hypertensive children evaluated and managed? A survey of North American pediatric nephrologists. Pediatr Nephrol 20:791–797
Batisky DL (2012) What is the optimal first-line agent in children requiring antihypertensive medication? Curr Hypertens Rep 14:603–607
Prichard BN, Cruickshank JM, Graham BR (2001) Beta-adrenergic blocking drugs in the treatment of hypertension. Blood Press 10:366–386
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 60:444–450
Garovic V, Textor SC (2005) Renovascular hypertension: current concepts. Semin Nephrol 25:261–271
Garovic VD, Textor SC (2005) Renovascular hypertension and ischemic nephropathy. Circulation 112:1362–1374
Johansson M, Friberg P (2000) Role of the sympathetic nervous system in human renovascular hypertension. Curr Hypertens Rep 2:319–326
Kenny D, Hijazi ZM (2011) Coarctation of the aorta: from fetal life to adulthood. Cardiol J 18:487–495
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 312:1224–1228
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 51:742–749
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 160:434–440
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 334:13–18
Iseki K, Ikemiya Y, Iseki C, Takishita S (2003) Proteinuria and the risk of developing end-stage renal disease. Kidney Int 63:1468–1474
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 11:461–467
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 334:939–945
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 349:1857–1863
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 135:73–87
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 52:631–637
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 60:43–50
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:S213–256
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 http://www.cdc.gov/nchs/data/databriefs/db82.pdf. Accessed 1 February 2013
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 49:13–21
Valdes Pizarro J, Royo-Bordonada MA (2012) Prevalence of childhood obesity in Spain: National Health Survey 2006–2007. Nutr Hosp 27:154–160
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 24:929–938
Midha T, Nath B, Kumari R, Rao YK, Pandey U (2012) Childhood obesity in India: a meta-analysis. Indian J Pediatr 79:945–948
Wang Y, Lobstein T (2006) Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes 1:11–25
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 43:1817–1822
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 287:356–359
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 31:587–589
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) 15:14–33
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 26:831–843
Caballero AE (2003) Endothelial dysfunction in obesity and insulin resistance: a road to diabetes and heart disease. Obes Res 11:1278–1289
Allcock DM, Sowers JR (2010) Best strategies for hypertension management in type 2 diabetes and obesity. Curr Diab Rep 10:139–144
Prabhakar SS (2013) Inhibition of renin–angiotensin system: implications for diabetes control and prevention. J Investig Med 61:551–557
Sharma AM (2008) Does it matter how blood pressure is lowered in patients with metabolic risk factors? J Am Soc Hypertens 2:S23–S29
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 10:93–96
Mancia G, Grassi G, Zanchetti A (2006) New-onset diabetes and antihypertensive drugs. J Hypertens 24:3–10
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 24:1164–1180
Laragh J (2001) Laragh’s lessons in pathophysiology and clinical pearls for treating hypertension. Am J Hypertens 14:837–854
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 22:792–801
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 23:1014–1022
Alderman MH, Cohen HW, Sealey JE, Laragh JH (2010) Pressor responses to antihypertensive drug types. Am J Hypertens 23:1031–1037
Maron BJ, Zipes DP (2005) Introduction: eligibility recommendations for competitive athletes with cardiovascular abnormalities-general considerations. J Am Coll Cardiol 45:1318–1321
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 61:1–162
Goulet C, Valois P, Buist A, Cote M (2010) Predictors of the use of performance-enhancing substances by young athletes. Clin J Sport Med 20:243–248
Fagard RH (2007) Athletes with systemic hypertension. Cardiol Clin 25:441–448
Van Baak MA (1988) Beta-adrenoreceptor blockade and exercise. An update. Sports Med 5:209–225
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 25:169–177
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 18:35–43
Vehaskari VM (2009) Heritable forms of hypertension. Pediatr Nephrol 24:1929–1937
Simonetti GD, Mohaupt MG, Bianchetti MG (2012) Monogenic forms of hypertension. Eur J Pediatr 171:1433–1439
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Ferguson, M.A., Flynn, J.T. Rational use of antihypertensive medications in children. Pediatr Nephrol 29, 979–988 (2014). https://doi.org/10.1007/s00467-013-2510-z
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DOI: https://doi.org/10.1007/s00467-013-2510-z