Management of High Blood Pressure in Children and Adolescents: Recommendations of the European Society of Hypertension Empar Lurbe – Chairperson; Renata Cifkova; J Kennedy Cruickshank; Michael J Dillon; Isabel Ferreira; Cecilia Invitti; Tatiana Kuznetsova; Stephane Laurent – Ex officio; Giuseppe Mancia – Ex officio; Francisco Morales-Olivas; Wolfgang Rascher; Josep Redon; Franz Schaefer; Tomas Seeman; George Stergiou; Elke Wühl; Alberto Zanchetti

Hypertension in Children and Adolescents: Recommendations of the ESH Introduction and purpose Definition and classification Diagnostic evaluation Preventive measures Evidence for therapeutic management Therapeutic strategies Therapeutic approaches under special conditions Treatment of associated risk factors 9. Screening of secondary forms 10. Long-term follow-up 11. Future research 12. Implementation of guidelines 13. Bibliography Figures Tables Boxes

Introduction and Purpose (I) There is growing evidence that children and adolescents with mild BP elevation are much more common than was thought in the past Longitudinal studies have demonstrated that BP abnormalities in those age ranges do not infrequently translate into adult hypertension Hypertension in children and adolescents has gained ground in CV medicine thanks to the progress made in several areas of pathophysiological and clinical research

Introduction and Purpose (II) The remoteness of cardiovascular events from the BP values of many years before makes the relationship between those BP values and the events difficult to establish Large intervention studies are lacking, and therefore cannot provide hints about cutoffs for evidence-based recommendations Many of the classifications and recommendations in children are based on statistical considerations and are the result of assumptions or extrapolations from evidence obtained in adults

Characteristics of blood pressure Introduction and Purpose Characteristics of blood pressure Blood pressure increases during growth and maturation Adolescence is a fast growth period during which body mass and BP change rapidly Reference BP values over the last few decades have been referred to as ones specific for sex, age and/or height

Definition and classification SBP and/or DBP Percentile Normal <90th High-normal ≥ 90th to <95th ≥ 120/80 even if below 90th percentile in adolescents Stage 1 hypertension 95th percentile to the 99th percentile plus 5 mmHg Stage 2 hypertension >99th percentile plus 5 mmHg

Diagnostic algorithm of hypertension Definition and classification Diagnostic algorithm of hypertension SBP and/or DBP <P90th >P90th NORMOTENSION Repeated measurements <P90th P90-95th ≥P95th NORMOTENSION FOLLOW-UP HYPERTENSION Evaluation for etiology and organ damage Repeated measurements Figure 1

Blood pressure measurement Diagnostic evaluation Blood pressure measurement The recommended method is auscultatory Use K1 for systolic BP and K5 for diastolic BP If the oscillometric method is used, the monitor needs to be validated for this age group If hypertension is detected by the oscillometric method, it needs to be confirmed using the auscultatory method Use the appropriate cuff size according to arm width Children above 3 years of age who are seen in a medical setting should have their BP measured In younger children, BP should be measured under special circumstances that increase the risk for hypertension Box 1

Indications for 24-hour ABPM Diagnostic evaluation Indications for 24-hour ABPM During the process of diagnosis Confirm hypertension before starting antihypertensive drug treatment Type 1 diabetes Chronic kidney disease Renal, liver or heart transplant During antihypertensive drug treatment Evaluation of refractory hypertension Assessment of BP control in children with organ damage Symptoms of hypotension Clinical trials Other clinical conditions Autonomic dysfunction Suspicion of catecholamine-secreting tumours Box 2

Evaluation of organ damage Diagnostic evaluation Evaluation of organ damage Organ damage is common and LV hypertrophy is the most prominent type Echocardiography should be performed. Left Ventricular Hypertrophy is an indication to initiate or intensify antihypertensive therapy Microalbuminuria is recommended for routine clinical use Carotid intima-media thickness, arterial stiffness, retinal and CNS assessment are not recommended for routine clinical use

Evaluation for Secondary Hypertension Screening for secondary forms Evaluation for Secondary Hypertension Very young children with Stage 1 or Stage 2 hypertension Children or adolescents with Stage 2 hypertension Age-distribution of hypertension etiologies > 10 years Essential Hypertension Renal Parenchymal Disease Exogenous Hypertension (drugs) Endocrine Disorders Coarctation of the aorta Mendelian Genetic Disorders < 1 month Renal arterial thrombosis Congenital renal disease Umbilical canalization Bronchopulmonary dysplasia >1 month to <6 years Renal parenchymal disease Coarctation of the aorta Renovascular disease > 6 years to 10 years Renal parenchymal disease Renovascular disease Essential hypertension

Life style recommendations to reduce high BP values Preventive measures Life style recommendations to reduce high BP values GOAL Maintain or achieve BMI <85th GENERAL RECOMMENDATIONS Moderate to vigorous physical aerobic activity 40 minutes, 3-5 days/week and avoid more than 2 hours daily of sedentary activities Avoid intake of excess sugar, excess soft drinks, saturated fat and salt and recommend fruits, vegetables and grain products Implement the behavioural changes (physical activity and diet) tailored to individual and family characteristics Involve the parents/family as partners in the behavioural change process Provide educational support and materials Establish realistic goals Develop a health-promoting reward system Competitive sports participation should be limited only in the presence of uncontrolled stage 2 hypertension Box 6

When to initiate antihypertensive treatment Evidence for therapeutic management When to initiate antihypertensive treatment Life threatening hypertension High-normal BP Hypertension One or more of the following conditions: Symptomatic Secondary Organ damage Diabetes NO YES Nonpharmacological treatment Pharmacological treatment Figure 3

Blood pressure targets Evidence for therapeutic management Blood pressure targets In general BP <90th age, sex and height specific percentile Chronic kidney disease BP <75th percentile in children without proteinuria and <50th percentile in cases of proteinuria 24-hour ABP strongly recommended. Goals: <75th percentile in children without proteinuria and <50th percentile in cases of proteinuria

How to initiate antihypertensive treatment Therapeutic strategies How to initiate antihypertensive treatment Particular conditions Stage 2 Chronic kidney disease Secondary All hypertensives Monotherapy (low dose 4-8 w) No response Monotherapy (full dose) No response Switch drug Side effects No response Combination therapy

Therapeutic strategies Antihypertensive agents with efficacy and safety studies in children and adolescents Class Efficacy studies Diuretics Clorthalidone, HCZT b-blockers Atenolol, Metoprolol, Propanolol CCB Amlodipine, Felodipne, Isradipine ACEi Captopril, Enalapril, Fosinopril, Lisinopril, Quinapril, Ramipril ARB Candesartan, Irbesartan, Losartan, Valsartan

Long-term follow-up Long-term follow-up Initial frequent follow up visits to monitor BP control, organ damage Side effects of treatment Other reversible risk factors Once BP stable and in target range, frequency of visits can be reduced Home monitoring of BP or 24 hour ABPM can facilitate follow up assessments Dependent on the underlying cause of hypertension, further investigative procedures may be indicated to monitor success of surgical intervention or medical treatment

Future research Future research Develop accurate non-mercury sphygmomanometer for auscultatory BP measurement and oscillometric BP Reference values for office, home and ambulatory BP based on a European pediatric population Increase knowledge in the use of out-of-office BP measurements Collect information about early organ damage to refine risk stratification and use the information to set intermediate objectives during treatment Box 10

Future research Future research Conduct controlled studies with antihypertensive drugs in order to improve knowledge about specific benefits and disadvantages of BP lowering agents and establish adequate doses Conduct large, long term randomized therapeutic trials using onset of organ damage to obtain information about when to initiate antihypertensive drug treatment and about BP goals Box 10

Implementation of Guidelines Implementation guidelines Implementation of Guidelines Joint efforts should be started so as to promptly implement the guidelines Synergistic actions at various levels (learned societies, expert committees, GPs, pediatricians, nurses and other healthcare providers, school, parents and policy makers) should be encouraged to participate The role of learned Societies, particularly ESH, is crucial for spreading the guidelines and the acceptance by National Hypertension Societies and Leagues Active support of research is necessary in order to gain knowledge helpful to future developments in the field, so studies that are recommended should be promptly initiated

Hypertension in Children and Adolescents: Recommendations of the European Society of Hypertension Renata Cifkova, Prague J Kennedy Cruickshank, Manchester Michael J Dillon, London Isabel Ferreira, Maastricht Cecilia Invitti, Milan Tatiana Kuznetsova, Leuven Stephane Laurent, Paris - Ex officio Empar Lurbe, Valencia – Chair Giuseppe Mancia, Milan - Ex officio Francisco Morales-Olivas, Valencia Wolfgang Rascher, Erlangen Josep Redon, Valencia Franz Schaefer, Heidelberg Tomas Seeman, Prague George Stergiou, Athens Elke Wühl, Heidelberg Alberto Zanchetti, Milan