Focus on prevention, diagnosis and treatment of hypertension in children and adolescents

Italian Journal of Pediatrics

Simonetta Genovesi^1,12  Raffaele Virdis⁷  Mirella Strambi²  Loredana Simionato³  Patrizia Salice¹  Ettore Menghetti^1,11  Maria Chiara Matteucci⁵  Silvio Maringhini⁶  Mario Bianchetti⁹  Amalia Maria Ambruzzi⁴  Marco Giussani^1,10  Amedeo Spagnolo⁸ 

[1] Cardiologia Pediatrica UO Cardiologia Fondazione Policlinico Ca Granda IRCCS, Progetto CHild, Milan, Italy;Dipartimento di Pediatria, Ostetricia e Medicina della Riproduzione, Università di Siena, Siena, Italy;Pediatra di Famiglia, Progetto CHild, Milan, Italy;Pediatra-nutrizionista, Ospedale Pediatrico Bambino Gesù, Rome, Italy;Divisione di Nefrologia Pediatrica Ospedale Pediatrico Bambino Gesù, IRCCS, Società Italiana di Nefrologia Pediatrica, Rome, Italy;Unità Operativa Complessa Nefrologia Pediatrica, Ospedale dei Bambini “G. Di Cristina” A.R.N.A. S. “Civico, Di Cristina e Benefratelli”, Palermo, Italy;Dipartimento Età Evolutiva, Clinica Pediatrica, Università di Parma, Parma, Italy;ISFOL, Istituto per gli Affari Sociali, Rome, Italy;Department of Pediatrics, Mendrisio and Bellinzona Hospitals, Switzerland, and University of Bern, Switzerland, Bern, Switzerland;Pediatra di Famiglia, Progetto PAB (Pressione Arteriosa Bambino), Milan, Italy;Pediatra-nutrizionista, Università”La Sapienza”, Rome, Italy;Clinica Nefrologica e Dipartimento di Medicina Clinica e Prevenzione Università di Milano Bicocca. Progetto PAB (Pressione Arteriosa Bambino), Società Italiana Ipertensione Arteriosa, Milan, Italy

关键词: Salt intake;    Physical activity;    Prevention;    Overweight;    Obesity;    Hypertension;    Children;    Blood pressure;   

Others  :  825277
DOI  :  10.1186/1824-7288-39-20

 received in 2012-07-02, accepted in 2012-11-16,  发布年份 2013

【 摘 要 】

The European Society of Hypertension has recently published its recommendations on prevention, diagnosis and treatment of high blood pressure in children and adolescents. Taking this contribution as a starting point the Study Group of Hypertension of the Italian Society of Pediatrics together with the Italian Society of Hypertension has conducted a reappraisal of the most recent literature on this subject. The present review does not claim to be an exhaustive description of hypertension in the pediatric population but intends to provide Pediatricians with practical and updated indications in order to guide them in this often unappreciated problem.

This document pays particular attention to the primary hypertension which represents a growing problem in children and adolescents. Subjects at elevated risk of hypertension are those overweight, with low birth weight and presenting a family history of hypertension. However, also children who do not present these risk factors may have elevated blood pressure levels. In pediatric age diagnosis of hypertension or high normal blood pressure is made with repeated office blood pressure measurements that show values exceeding the reference values. Blood pressure should be monitored at least once a year with adequate methods and instrumentation and the observed values have to be interpreted according to the most updated nomograms that are adjusted for children’s gender, age and height. Currently other available methods such as ambulatory blood pressure monitoring and home blood pressure measurement are not yet adequately validated for use as diagnostic instruments. To diagnose primary hypertension it is necessary to exclude secondary forms. The probability of facing a secondary form of hypertension is inversely proportional to the child’s age and directly proportional to blood pressure levels. Medical history, clinical data and blood tests may guide the differential diagnosis of primary versus secondary forms. The prevention of high blood pressure is based on correct lifestyle and nutrition, starting from childhood age. The treatment of primary hypertension in children is almost exclusively dietary/behavioral and includes: a) reduction of overweight whenever present b) reduction of dietary sodium intake c) increase in physical activity. Pharmacological therapy will be needed rarely and only in specific cases.

【 授权许可】

   
2013 Spagnolo et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Blumenthal S, Epps RT, Heavenrich R, Lauer RM, Lieberman E, Mirkin B, Mitchell SC, Boyar Naito V, O'Hare D, McFate Smith W, Tarazi RC, Upson D: Report of the task force on blood pressure control in children. Pediatrics 1977, 59:797-820.
• [2]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, Wühl E, Zanchetti A: Management of high blood pressure in children and adolescents: recommendations of the European society of hypertension. J Hypertens 2009, 27:1719-1742.
• [3]Chen X, Wang Y: Tracking of blood pressure from childhood to adulthood: a systematic review and meta-regression analysis. Circulation 2008, 117:3171-3180.
• [4]National Hight Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents: The fourth report on the diagnosis, evaluation and treatment of high blood pressure in children and adolescents. Pediatrics 2004, 114:555-576.
• [5]Sorof JM, Lai D, Turner J, Poffenbarger T, Portman RJ: Overweight, ethnicity, and the prevalence of hypertension in school-aged children. Pediatrics 2004, 113:475-482.
• [6]Berenson GS, Wattigney WA, Webber LS: Epidemiology of hypertension from childhood to young adulthood in black, white, and Hispanic population samples. Public Health Rep 1996, 111(suppl 2):3-6.
• [7]Jung FF, Ingelfinger JR: Hypertension in childhood and adolescence. Pediatr Rev 1993, 14:169-179.
• [8]Robinson RF, Batisky DL, Hayes JR, Nahata MC, Mahan JD: Significance of heritability in primary and secondary pediatric hypertension. Am J Hypertens 2005, 18:917-921.
• [9]Flynn JT, Alderman MH: Characteristics of children with primary hypertension seen at a referral center. Pediatr Nephrol 2005, 20:961-966.
• [10]Martin RM, Ness AR, Gunnell D, Emmett P, Davey Smith G: ALSPAC study team. Does breast-feeding in infancy lower blood pressure in childhood? the Avon longitudinal study of parents and children (ALSPAC). Circulation 2004, 109:1259-1266.
• [11]Wilson AC, Forsyth JS, Greene SA, Irvine L, Hau C, Howie PW: Relation of infant diet to childhood health: seven year follow up of cohort of children in Dundee infant feeding study. BMJ 1998, 316:21-25.
• [12]Lawlor DA, Najman JM, Sterne J, Williams GM, Ebrahim S, Davey Smith G: Associations of parental, birth, and early life characteristics with systolic blood pressure at 5 years of age: findings from the mater-university study of pregnancy and its outcomes. Circulation 2004, 110:2417-2423.
• [13]Wühl E, Witte K, Soergel M, Mehls O, Schaefer F, German Working Group on Pediatric Hypertension: Distribution of 24-h ambulatory blood pressure in children: normalized reference values and role of body dimensions. J Hypertens 2002, 20:1995-2007.
• [14]Stergiou GS, Yiannes NG, Rarra VC, Panagiotakos DB: Home blood pressure normalcy in children and adolescents: the arsakeion school study. J Hypertens 2007, 25:1375-1379.
• [15]Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP: Prognostic implications of echocardiographically determined left ventricular mass in the Framingham heart study. N Engl J Med 1990, 322:1561-1566.
• [16]de Simone G, Devereux RB, Daniels SR, Koren MJ, Meyer RA, Laragh JH: Effect of growth on variability of left ventricular mass: assessment of allometric signals in adults and children and their capacity to predict cardiovascular risk. J Am Coll Cardiol 1995, 25:1056-1062.
• [17]Urbina EM, Gidding SS, Bao W, Pickoff AS, Berdusis K, Berenson GS: Effect of body size, ponderosity and blood pressure on left ventricular growth in children and young adult in the Bogalusa heart study. Circulation 1995, 91:2400-2406.
• [18]Burke GL, Arcilla RA, Culpepper WS, Webber LS, Chiang YK, Berenson GS: Blood pressure and echocardiographic measures in children: the Bogalusa heart study. Circulation 1987, 75:106-114.
• [19]Kavey RE, Kveselis DA, Atallah N, Smith FC: White coat hypertension in childhood: evidence for end-organ effect. J Pediatr 2007, 150:491-497.
• [20]Richey PA, Disessa TG, Hastings MC, Somes GW, Alpert BS, Jones DP: Ambulatory blood pressure and increased left ventricular mass in children at risk for hypertension. J Pediatr 2008, 152:343-348.
• [21]Joyce JJ, Dickson PI, Qi N, Noble JE, Raj JU, Baylen BG: Normal right and left ventricular mass development during early infancy. Am J Cardiol 2004, 93:797-801.
• [22]Koren MJ, Ulin RJ, Koren AT, Laragh JH, Devereux RB: Left ventricular mass change during treatment and outcome in patients with essential hypertension. Am J Hypertens 2002, 15:1021-1028.
• [23]Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N: Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986, 57:450-458.
• [24]Daniels SR, Kimball TR, Morrison JA, Khoury P, Meyer RA: Indexing left ventricular mass to account for differences in body size in children and adolescents without cardiovascular disease. Am J Cardiol 1995, 76:699-701.
• [25]Khoury PR, Mitsnefes M, Daniels SR, Kimball TR: Age-specific reference intervals for indexed left ventricular mass in children. J Am Soc Echocardiogr 2009, 22:709-714.
• [26]Sorof JM, Alexandrov AV, Cardwell NG, Portman RJ: Carotid intima-media thickness and left ventricular hypertrophy in children with elevated blood pressure. Pediatrics 2003, 111:61-66.
• [27]Sorof JM, Alexandrov AV, Garami Z, Turner JL, Grafe RE, Lai D, Portman RJ: Carotid ultrasonography for detection of vascular abnormalities in hypertensive children. Pediatr Nephrol 2003, 18:1020-1024.
• [28]Litwin M, Trelewicz J, Wawer Z, Antoniewicz J, Wierzbicka A, Rajszys P, Grenda R: Intima-media thickness and arterial elasticity in hypertensive children: controlled study. Pediatr Nephrol 2004, 19:767-774.
• [29]Lande MB, Carson LN, Roy J: Effects of childhood primary hypertension on carotid intima media thickness: a matched controlled study. Hypertension 2006, 48:40-44.
• [30]Jarvisalo MJ, Jartti L, Nanoto-Salonen K, Irjala K, Ronnemaa T, Hartiala JJ, Celermajer DS, Raitakari OT: Increased aortic intima-media thickness: a marker of preclinical atherosclerosis in high risk children. Circulation 2001, 104:2943-2947.
• [31]Jourdan C, Whul E, Litwin M, Fahr K, Trelewicz J, Jobs K: Normative values for intima-media thickness and distensibility of large arteries in healthy adolescents. J Hypertens 2005, 23:1707-1715.
• [32]Litwin M, Niemirska A, Sladowska-Kozlowska J, Wierzbicka A, Janas R, Wawer ZT, Wisniewski A, Feber J: Regression of target organ damage in children and adolescents with primary hypertension. Pediatr Nephrol 2010, 25:2489-2499.
• [33]Wingen AM, Fabian-Bach C, Schaefer F, Mehls O: Randomised multicentre study of low-protein diet on the progression of chronic renal failure in children. European Study Group of Nutritional treatment of Chronic Renal Failure in Childhood. Lancet 1997, 349:1117-1123.
• [34]The Escape Trial Group: Strict blood-pressure control and progression of renal failure in children. NEJM 2009, 361:1639-1650.
• [35]Genovesi S, Pieruzzi F, Giussani M, Tono V, Stella A, Porta A, Pagani M, Lucini D: Analysis of heart period and arterial pressure variability in childhood hypertension: key role of baroreflex impairment. Hypertension 2008, 51:1289-1294.
• [36]Daniels SR, Lipman MJ, Burke MJ, Loggie JM: The prevalence of retinal vascular abnormalities in children and adolescents with essential hypertension. Am J Ophthalmol 1991, 111:205-208.
• [37]Mitchell P, Cheung N, de Haseth K, Taylor B, Rochtchina E, Wang JJ: Blood pressure and retinal arteriolar narrowing in children. Hypertension 2007, 49:1156-1162.
• [38]Calvetta A, Martino S, von Vigier RO, Schmidtko J, Fossali E, Bianchetti MG: "What goes up must immediately come down!" which indication for short-acting nifedipine in children with arterial hypertension? Pediatr Nephrol 2003, 18:1-2.
• [39]Patel HP, Mitsnefes M: Advances in the pathogenesis and management of hypertensive crisis. Curr Opin Pediatr 2005, 17:210-214.
• [40]Constantine E, Merritt C: Hypertensive emergencies in children: identification and management of dangerously high blood pressure. Minerva Pediatr 2009, 61(2):175-184.
• [41]Constantine E, Linakis J: The assessment and management of hypertensive emergencies and urgencies in children. Pediatr Emerg Care 2005, 21:391-396.
• [42]Chiolero A, Bovet P, Paradis G, Paccaud F: Has blood pressure increased in children in response to the obesity epidemic? Pediatrics 2007, 119:544-553.
• [43]Eriksson JG, Forsén T, Tuomilehto J, Osmond C, Barker DJ: Early growth and coronary heart disease in later life: longitudinal study. BMJ 2001, 322:949-953.
• [44]Kaijser M, Bonamy AK, Akre O, Cnattingius S, Granath F, Norman M, Ekbom A: Perinatal risk factors for ischemic heart disease: disentangling the roles of birth weight and preterm birth. Circulation 2008, 22:405-410.
• [45]Huxley R, Neil A, Collins R: Unravelling the fetal origins hypothesis: is there really an inverse association between birthweight and subsequent blood pressure? Lancet 2002, 360:659-665.
• [46]Barker DJ: Fetal programming of coronary heart disease. Trends Endocrinol Metab 2002, 13:364-368.
• [47]Bubb KJ, Cock ML, Black MJ, Dodic M, Boon WM, Parkington HC, Harding R, Tare M: Intrauterine growth restriction delays cardiomyocyte maturation and alters coronary artery function in the fetal sheep. J Physiol 2007, 578:871-881.
• [48]Bahtiyar MO, Copel JA: Cardiac changes in the intrauterine growth—restricted fetus. Semin Perinatol 2008, 32:190-193.
• [49]Vedrburg BO, Jaddoe VW, Wladimiroff JW, Hofman A, Witteman JC, Steegers EA: Fetal hemodynamic adaptive changes related to intrauterine growth: the generation R. Study Circulation 2008, 117:649-659.
• [50]Rolland-Cachera MF, Deheeger M, Maillot M, Bellisle F: Early adiposity rebound: causes and consequences for obesity in children and adults. Int J Obes 2006, 30(Suppl 4):S11-S17.
• [51]Torrance B, McGuire KA, Lewanczuk R, McGavock J: Overweight, physical activity and high blood pressure in children: a review of the literature. Vasc Health Risk Manag 2007, 3:139-149.
• [52]Genovesi S, Antolini L, Giussani M, Pieruzzi F, Galbiati S, Valsecchi MG, Brambilla P, Stella A: Usefulness of waist circumference for the identification of childhood hypertension. J Hypertens 2008, 26:1563-1570.
• [53]Brambilla P, Pozzobon G, Pietrobelli A: Physical activity as the main therapeutic tool for metabolic syndrome in childhood. Int J Ob 2011, 35(1):16-28.
• [54]Pescatello LS, Franklin BA, Fagard R, Farquhar WB, Kelley GA, Ray CA: American college of sports medicine position stand. Exercise and hypertension. Med Sci Sports Exerc 2004, 36:533-553.
• [55]Cutler JA, Roccella EJ: Salt reduction for preventing hypertension and cardiovascular disease: a population approach should include children. Hypertension 2006, 48:818-819.
• [56]Mu JJ, Liu ZQ, Liang YM, Yang DY, Zhu DJ, Wang ZX: Reduction of blood pressure with calcium and potassium supplementation in children with salt sensitivity: a 2-year double blinded placebo-controller trial. J Hum Hyperten 2005, 19:479-483.
• [57]Beratis NG, Panagoulias D, Varvarigou A: Increased blood pressure in neonates and infants whose mothers smoked during pregnancy. J Pediatr 1996, 128:806-812.
• [58]Cohen G, Jeffery H, Lagercrantz H, Katz-Salamon M: Long-term reprogramming of cardiovascular function in infants of active smokers. Hypertension 2010, 55:722-728.
• [59]Pijanowska M, Zajaczkowska M: Passive smoking and patterns of 24-hour ambulatory blood pressure in healthy children. Pol Merkur Lekarski 2004, 16:320-322.
• [60]Schwandt P, Haas GM, Liepold E: Lifestyle and cardiovascular risk factors in 2001 child–parent pairs: the PEP family heart study. Atherosclerosis 2010, 213:642-648.
• [61]Genovesi S, Antolini L, Giussani M, Brambilla P, Barbieri V, Galbiati S, Mastriani S, Sala V, Valsecchi MG, Stella A: Hypertension, prehypertension, and transient elevated blood pressure in children: association with weight excess and waist circumference. Am J Hypertens 2010, 23:756-761.
• [62]Lande MB, Meagher CC, Fisher SG, Belani P, Wang H, Rashid M: Left ventricular mass index in children with white coat hypertension. J Pediatr 2008, 153:50-54.
• [63]Menghetti E: La pressione arteriosa nel primo anno di vita: normalità e patologia. Parma: Cristoforetti Ed; 1981.
• [64]Flynn JT: Neonatal hypertension: diagnosis and management. Pediatr Nephrol 2000, 14:332-341.
• [65]Pollini I: Ipertensione arteriosa nei bambini, negli adolescenti e nei giovani. Ital Heart J 2000, 1(Suppl 5):83-86.
• [66]Loirat C: Hypertension artérielle du nouveau né. Arch Fr Pediatr 1988, 45:287-294.
• [67]Menghetti E: Manuale di Neonatologia. First edition. : Società Ed Universo Roma; 2008:141.
• [68]Arar MY, Hogg RJ, Arant BS Jr, Seikaly MG: Etiology of sustained hypertension in children in the southwestern united states. Pediatr Nephrol 1994, 8:186-189.
• [69]Lieberman E: Hypertension in childhood and adolescence. In Clinical hypertension. 5th edition. Edited by Kaplan N. Baltimore: Williams and Wilkins; 1990:407-433.
• [70]Dillon MJ: Secondary forms of hypertension in children. In Pediatric hypertension. Edited by Portman RJ, Sorof JM, Ingelfinger JR. Totowa: Humana Press; 2004:159-179.
• [71]Lurbe E, Redon J: Secondary hypertension in children and adolescents. In Secondary hypertension. Edited by Mansoor GA. Totowa: Humana Press; 2004:279-306.
• [72]Ardissino G, Bianchetti M, Braga M, Calzolari A, Dacco V, Fossali E, Ghiglia S, Orsi A, Pollini I, Sforzini C, Salice P: Progetto child. Recommendations on hypertension in childhood, the CHild project. Ital Heart J Suppl 2004, 5:398-412.
• [73]Kavey RW, Daniels SR, Lauer RM, Atkins DL, Hayman LL, Taubert K: American heart association guidelines for primary prevention of atherosclerotic cardiovascular disease beginning in childhood. Circulation 2003, 107:1562-1566.
• [74]Williams CL, Hayman LL, Daniels SR, Robinson TN, Steinberger J, Paridon S, Bazzarre T: Cardiovascular health in childhood. A statement for health professionals from the committee in atherosclerosis, hypertension, and obesity in the young (AHOY) of the council on cardiovascular disease in the young, American hearth association. Circulation 2002, 106:143-160.
• [75]Hayman LL, Meininger JC, Daniels SR, Mc Crindle BW, Helden L, Dennison BA, Steinberger J, Williams CL: Primary prevention of cardiovascular disease in nursing practice: focus on children and youth. A scientific statement from the American heart association committee on atherosclerosis, hypertension, and obesity in youth of the council on cardiovascular disease in the young, council on cardiovascular nursing, council on epidemiology and prevention, council on nutrition, physical activity and metabolism. Circulation 2007, 116:344-357.
• [76]McGavock JM, Torrance B, McGuire KA, Wozny P, Lewanczuk RZ: The relationship between weight gain and blood pressure in children and adolescents. Am J Hypertens 2007, 20:1038-1044.
• [77]Genovesi S, Giussani M, Pieruzzi F, Vigorita F, Arcovio C, Cavuto S, Stella A: Results of blood pressure screening in a population of school-aged children in the province of Milan: role of overweight. J Hypertens 2005, 23:493-497.
• [78]Cole TJ, Bellizzi MC, Flegal KM, Dietz WH: Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 2000, 320:1240-1243.
• [79]Società Italiana di Nutrizione Umanahttp://www.sinu.it/larn/tab_rias.asp webcite
• [80]Gidding SS, Dennison BA, Birch LL, Daniels SR, Gilman MW, Lichtenstein AH, Rattay KT, Steinberger J, Stettler N, Van Horn L: Dietary recommendation for children and adolescents. Circulation 2005, 112:2061-2075.
• [81]Krebs NF, Himes JH, Jacobson D, Nicklas TA, Guilday P, Styne D: Assessment of child and adolescent overweight and obesity. Pediatrics 2007, 120:S193-S228.
• [82]He FJ, Mac Gregor GA: Importance of salt in determining blood pressure in children: meta-analysis of controlled trials. Hypertension 2006, 48:861-869.
• [83]Società Italiana di Nutrizione Umanahttp://www.sinu.it/larn/mineral1.asp#SODIO webcite
• [84]Council on Sport Medicine and Fitness and Council on School Health Active Healthy Living: Prevention of childhood obesity through increased physical activity. Pediatrics 2006, 117:1834-1842.
• [85]Campbell KJ, Hesketh KD: Strategies which aim to positively impact on weight, physical activity, diet and sedentary behaviours in children from zero to five years. A systematic review of the literature. Obes Rev 2007, 8:327-338.
• [86]Società Italiana di Pediatria, Indagine Adolescenti 2008. http://www.sip.it/index/index/atom/1455 webcite
• [87]Wiecha JL, Sobol AM, Peterson KE, Gortmaker SL: Household television access: associations with screen time, reading and homework among youth. Ambul Pediatr 2001, 1:244-251.
• [88]Martinez-Gomez D, Tucker J, Heelan KA, Welk GL, Eisenmann JC: Associations between sedentary behavior and blood pressure in young children. Arch Pediatr Adolesc Med 2009, 163:724-730.
• [89]Jackson DM, Djafarian K, Stewart J, Speakman JR: Increased television viewing is associated with elevated body fatness but not with lower total energy expenditure in children. Am J Nutr 2009, 89:1031-1036.
• [90]Wells T, Frame V, Soffer B, Shaw W, Zhang Z, Herrera P, Shahinfar S: Enalapril pediatric hypertension collaborative study group. A double-blind, placebo-controlled, dose–response study of the effectiveness and safety of enalapril for children with hypertension. J Clin Pharmacol 2002, 42:870-880.
• [91]Li JS, Berezny K, Kilaru R, Hazan L, Portman R, Hogg R, Jenkins RD, Kamani P, Cottril CM, Mattoo TK, Zharkova L, Kozlova L, Weisman I, Deichman D, Califf RM: Is the extrapolated adult dose of Fosinopril safe and effective in treating hypertensive children? Hypertension 2004, 44:289-293.
• [92]Soffer B, Zhang Z, Miller K, Vogt BA, Shahinfar S: A double-blind, placebo-controlled, dose–response study of the effectiveness and safety of Lisinopril for children with hypertension. Am J Hypertens 2003, 16:795-800.
• [93]Simonetti G, Rizzi M, Donadini R, Bianchetti MG: Effects of antihypertensive drugs on blood pressure and proteinuria in childhood. J Hypertens 2007, 25:2370-2376.
• [94]Simonetti GD, von Vigier RO, Konrad M, Rizzi M, Fossali E, Bianchetti MG: Candesartan cilexetil in children with hypertension or proteinuria: preliminary data. Pediatr Nephrol 2006, 21:1480-1482.
• [95]Flynn JT, Meyers KE, Neto JP, De Paula Meneses R, Zurowska A, Bagga A, Mattheyse L, Shi V, Gupte J, Solar-Yohay S, Han G: Pediatric valsartan study group. Efficacy and safety of the angiotensin receptor blocker valsartan in children with hypertension aged 1 to 5 years. Hypertension 2008, 52:222-228.
• [96]Falkner B, Lowenthal DT, Affrime MB: The pharmacodynamic effectiveness of metoprolol in adolescent hypertension. Pediatr Pharmacol (New York) 1982, 2:49-55.
• [97]Flynn JT, Pasko DA: Calcium channel blockers: pharmacology and place in therapy of pediatric hypertension. Pediatr Nephrol 2000, 15:302-316.
• [98]Bachmann H: Propranolol versus chlorthalidone: a prospective therapeutic trial in children with chronic hypertension. Helv Paediatr Acta 1984, 39:55-61.
• [99]Wühl E, Mehls O, Schaefer F, ESCAPE Trial Group: Antihypertensive and antiproteinuric efficacy of ramipril in children with chronic renal failure. Kidney Int 2004, 66:768-776.
• [100]Gartenmann AC, Fossali E, von Vigier RO, Simonetti GD, Schmidtko J, Edefonti A, Bianchetti MG: Better renoprotective effect of angiotensin II antagonist compared to dihydropyridine calcium channel blocker in childhood. Kidney Int 2003, 64:1450-1454.