Take The Stress Out of Pediatric Hypertension! Rasheda Amin, MD Division of Nephrology Pediatric Specialists of Virginia George Washington University

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1 Take The Stress Out of Pediatric Hypertension! Rasheda Amin, MD Division of Nephrology Pediatric Specialists of Virginia George Washington University

2 Disclosure I have no financial interests or relationships to disclose.

3 Objectives Pediatric HTN and Atherosclerosis Epidemiology Monitoring Definition Etiology Workup Management Complications Determine eligibility for participation in sports

4 Atherosclerosis Begins in Childhood

Cardiovascular Disease The Bogalusa Study: CVD risk factors in youth Autopsies in 204 young subjects (2-39y/o) fatty streaks in 50% & fibrous plaques in 20% (2-15 y/o) fatty streaks in 85% & fibrous

5 Cardiovascular Disease The Bogalusa Study: CVD risk factors in youth Autopsies in 204 young subjects (2-39y/o) fatty streaks in 50% & fibrous plaques in 20% (2-15 y/o) fatty streaks in 85% & fibrous plaques in 70% (21-39 y/o) Atherosclerotic changes were greater with increasing body mass index (BMI), blood pressure measurements, and levels of serum total cholesterol Risk factors for CVD tended to cluster. Berenson, NEJM, 1989

6 Prevalence of Hypertension in Children In the 1970s and1980s prevalence was 0.3% to 1.2% (Fixler, et al, Pediatrics 1979; Sinaiko et al, J Pediatr 1989) Now 5% of all children have HTN (Sorof et al, Pediatrics 2004) 3-24% of all children are pre-hypertensive Possibly due to growing population of obese children Obese children have 3X higher risk of HTN (Sorof & Daniels, Hypertension 2002) Are we underestimating prevalence?

7 Obesity Prevalence and Role in HTN Prevalence of obesity in 2-19 years olds remains high at 17% based on NHANES data. BP tables: 21% of this normative data comes from obese/ overweight children Obstructive sleep apnea common Dysfunctional adipocyte -> imbalance in expression of proand anti-inflammatory adipokines -> Hypertension Adipose Tissue Dysfunction: Macrophage infiltration Increased FFA Hyperleptinemia Adiponectin deficiency Increased resistin RAAS hormone secretion Mineralocorticoid stimulating factor RAAS Activation SNS Activation Oxidative stress and Inflammation Dorresteijn et al, Endothelial dysfunction Impaired pressure natriuresis Vascular hypertrophy

National High Blood Pressure Education Program Working Group on High

8 Current Guidelines The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents Published in Pediatrics, 2004

9 USPSTF Recommendations Evidence was insufficient to "assess the balance of benefits and harms of screening for primary hypertension in asymptomatic children and adolescents to prevent subsequent cardiovascular disease in childhood and adulthood (USPSTF 13) Immediate and strong reaction from ASPN and AHA issuing contradictory responses that continue to support routine BP measurement at well child visits

10 Monitoring of Blood Pressure When should blood pressure be measured Health maintenance visits ( 3y/o) Special populations < 3y/o premature/lbw neonates, or h/o CLD, Congenital HD, CKD, recurrent UTIs, transplant, malignancy, increased intracranial pressure, etc. Sports participation physicals Presentation with acute or chronic illness (if high, repeat when well)

Methods for BP Measurement Auscultation is the gold standard (since 1905) Normative data based on auscultation method Oscillometric (Dinamapp) device Measures mean

11 Methods for BP Measurement Auscultation is the gold standard (since 1905) Normative data based on auscultation method Oscillometric (Dinamapp) device Measures mean arterial BP and then calculates systolic and diastolic values Any high reading should be confirmed by auscultation Appropriate for ICU - trends Yury et al, Circulation. 1996

period (usually 24 hours) Masked or White coat HTN Wrist Blood

12 Methods for BP Measurement Ambulatory BP monitoring (ABPM) portable device worn by the patient to record BP over a specific period (usually 24 hours) Masked or White coat HTN Wrist Blood Pressure Monitors Not validated or recommended for BP monitoring in children

Measurement of Blood Pressure Sitting quietly~5 minutes Pulse should be normal Child should be seated with back and feet supported Infants supine position Appropriate cuff size Right arm

13 Measurement of Blood Pressure Sitting quietly~5 minutes Pulse should be normal Child should be seated with back and feet supported Infants supine position Appropriate cuff size Right arm preferable Position of arm extended, heart level, supported by solid surface Inflate to 20-30mmHg > normal Deflation rate (2-3mmHg/heartbeat) K 1 = systolic BP K 5 (disappearance) = diastolic BP

14 Technique is Important!

15 Case Tim, a 10-year-old boy with a history of intermittent asthma and ADHD, is seeing you for a WCC. He has no complaints. ROS is negative. Current medications: Methylphenidate once daily and albuterol inhaler PRN. Family history: HTN- Father and paternal grandfather. PE: Height: 140 cm (50%), Weight: 45 kg (95%),BMI: 23 (>95%) Temp: 37 C, HR: 85 bpm, BP: 124/82mmHg (automated) Physical exam is normal

Case According to the BP tables published in the Fourth Report by the National High Blood Pressure Education Program Working Group on High Blood Pressure in

16 Case According to the BP tables published in the Fourth Report by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents, the BP norms for a child of this age, gender, and height percentile are as follows: 50%: 102/61 90%: 116/76 95%: 120/80 99%: 127/88 124/82mmHg

17 BP Norms Gender, Age & Height

18 Definitions: Pediatric vs Adult

19 Severe Hypertension Hypertensive emergency: Severe symptomatic elevation in BP with evidence of potentially life threatening symptoms or acute target organ damage brain (seizures, increased intracranial pressure), eyes (papilledema, retinal hemorrhages, exudates), heart (heart failure), and kidneys (renal insufficiency). Hypertensive urgency: Severe elevation in BP without severe symptoms or evidence of acute target organ damage

20 BP Measurement Frequency Recommendations Frequency of BP Measurement Normal Prehypertension Stage 1 hypertension Stage 2 hypertension Recheck at next scheduled physical examination. Recheck in 6 months. Recheck in 1 2 weeks or sooner if the patient is symptomatic; if BP is persistently elevated on two additional occasions, evaluate or refer to source of care within 1 month. Evaluate or refer to source of care within 1 week or immediately if the patient is symptomatic.

21 Case Repeat Tim s BP by manual auscultation 126/84 mm Hg; one minute later it s 116/84 mm Hg; average BP of 121/84 BP is between 120/80 and 132/93 (the 95% and 99%+5 mm Hg) He is asymptomatic Have him return weekly on two more occasions. Manual BPs confirm he has sustained BPs 95% and < 99%+5 mm Hg Diagnosis: Stage 1 Hypertension

22 Etiology of HTN in Children Primary or Essential Hypertension Most common form of HTN and is a diagnosis of exclusion Common in all ages except infants More frequent in: African American children Family history of HTN Overweight or obese Secondary Hypertension For all age groups, renal parenchymal or renovascular causes together account for ~60-90% of secondary causes More frequent in: Younger children Children with a greater degree of BP increase at the time of initial diagnosis (Portman 2005, Brady 2009)

23 (Brady 2009) Age Based Etiology of HTN Age Etiology First year of life Secondary (99%) Coarctation of aorta, Renovascular, Renal parenchymal disease, Miscellaneous, Neoplasia, Endocrine years of age Secondary (70%-85%) Renal parenchymal disease, Coarctation of aorta, Reflux nephropathy, Renovascular, Neoplasia, Endocrine, Miscellaneous. Primary/ Essential (15%-30%) years of age Primary/ Essential (85%-95%) Secondary (5%-15%)

24 (Trachtman, 2014) Secondary Hypertension

25 Initial Workup of Hypertension History Physical Exam Laboratory studies Imaging Cardiac Studies Target Organ Damage

26 Clinical Assessment of a Child with Hypertension History Symptoms suggestive of endocrine etiology (weight loss, sweating, flushing) History of prematurity and/or placement of umbilical artery/vein catheter; neonatal course; birth weight History of UTI Symptoms of Obstructive Sleep Apnea Medications including steroids, decongestant/cold prep, OCP, stimulants, βadrenergic agonists, etc. Family history of HTN, early cardiovascular or cerebrovascular events, ESRD Diet (caffeine, salt intake) Smoking/drinking/recreational drugs Physical Activity

27 Clinical Assessment of a Child with Hypertension Important Physical Exam Elements Four extremity pulses and BP Moon facies, truncal obesity, buffalo hump Retinopathy Thyromegaly Skin lesions (café-au-lait spots, neurofibromas, adenoma sebaceum, striae, hirsutism, butterfly rash, purpura) Evidence of CHF Abdominal mass or bruits Edema Ambiguous genitilia in infants

28 Laboratory Studies Basic metabolic panel (electrolytes, BUN, HCO3, creatinine) Urinalysis, urine culture CBC to rule our anemia which could be consistent with CKD Fasting lipids and glucose Thyroid function tests Plasma renin activity and serum aldosterone level Drug screen (in high risk individuals)

29 Imaging, Cardiac & Other Tests Imaging: Renal ultrasound with Doppler examination of the renal vasculature Echocardiography including measurement of LVMI Renal arteriography: severe HTN or failure to control Other Tests: Retinal Exam: severe cases Assessment of catecholamines Polysomnography ABPM

30 Ambulatory BP Monitoring Target Population Suspected white-coat or masked HTN When other information on BP pattern is needed mean daily BP during the day, night and over 24 hours degree of nocturnal dipping BP load (%readings >95%) Correlates better than office BP with CV complications (e.g. LVH)

31 Diagnostic Algorithm for HTN Rodrigues-Cruz, 2011

32 Case Tim s Initial workup Normal electrolytes, renal function, thyroid and lipid profiles and urinalysis Normal renal Doppler ultrasound Echocardiography normal LVMI Normal retinal exam Diagnosis Primary HTN which is asymptomatic No evidence of end organ damage Management Lifestyle modifications

33 Who Needs Urgent Management? Symptomatic or acutely ill children should be immediately treated Severe, symptomatic hypertension should be treated with intravenous antihypertensive drugs Hydralazine Labetalol Nicardipine Nitroprusside Esmolol

34 Non-pharmacologic Management Aerobic exercise (30-45min) daily Weight reduction if indicated DASH (Dietary Approaches to Stop HTN) Diet Salt reduction (< g/d) Potassium and Calcium intake Cessation of smoking Yoga/meditation Physical activity with increased HR for minutes, 3-4x/wk can lead to a demonstrable drop in BP Loss of lbs is sufficient to achieve a meaningful reduction in BP (NHBEP 2004, Brady 2009,Trachtman 2011)

35 Pharmacologic Management The 2004 NHBPEP guidelines for pharmacological therapy Symptomatic HTN (e.g. headache, seizures, visual disturbances, etc) Stage 2 HTN Persistent Stage 1 HTN (without evidence of TOD) after a trial of 4-6 months of non-pharmacologic therapy Hypertensive target-organ damage, most often LVH Pre HTN or Stage 1 HTN with other risk factors / comorbidities such as dyslipidemia, CKD or DM Stage 1 HTN with family history of premature CVD

36 Class Examples Major Side Effects Comments Calcium Chanel Blockers Amlodipine Flushing, edema, headache, gingival hyperplasia Well tolerated Sports -ok ACE-I ARB Enalapril Lisinopril Losartan Cough, loss of taste, hyperkalemia angioedema Monitor K and RF Do not use in pregnancy/bl RAS Beta blockers Alpha & Beta blockers Atenolol Metoprolol Labetolol Bronchospasm, CHF, depression, masking of hypoglycemia, orthostasis Migraine Monitor HR Do not use in patients with CHF/ asthma/dm Diuretics HCTZ Furosemide Spironolactone Electrolyte abnorm, Hyperglycemia, nephrocalcinosis, gynaecomastia Care in athletes Monitor lytes Good adjuvants Central alpha agonists Clonidine Sedation, withdrawl Dry mouth Rebound HTN if stopped abruptly

37 Pharmacologic Therapy Choose an agent based on pathophysiology Begin with the lowest dose of an agent Titrate up to maximal dose as needed Add agents sequentially Aim for fewest medication side effects Aim for most patient compliance

38 Goal of Therapy Reduction of BP to <95th percentile, unless concurrent conditions are present. In that case, BP should be lowered to <90th percentile. Severe, symptomatic hypertension should be treated with intravenous antihypertensive drugs. Preventing end organ damage including vascular changes, cardiac damage and renal effects.

39 What are the Complications of Pediatric HTN? There is evidence that childhood HTN leads to adult HTN Target organ damage (TOD) Cardiovascular Left Ventricular Hypertrophy Prevalence of LVH in hypertensive children 25 to 70% No longitudinal studies in children Renal Proteinuria (No studies) Retinal Changes Neurocognitive

40 Left Ventricular Hypertrophy Echocardiographic assessment of left ventricular mass should be performed at diagnosis of hypertension and periodically thereafter. The presence of LVH is an indication to initiate or intensify antihypertensive therapy.

41 Elevated BP and Cognitive Function in Children & Adolescents NHANES III Data 6-16y 5077 children Prevalence SHTN 3.4%, DHTN 1.6% Groups: BP > or 90%ile Wechsler Intelligence Scale for Children, Wide Range Achievement Test, Revised Lande, 2003

42 Elevated BP and Cognitive Function in Children & Adolescents Lande, 2003

43 AAP: Sports Participation Athletes with significant hypertension may compete as long as no target organ damage or heart disease Office BP check needed for follow-up q 2 months With severe hypertension (uncontrolled stage 2), sports and highly static activities need to be restricted until BP well controlled Cardiovascular conditioning may continue Healthy lifestyle choices need to be encouraged Demorest et al. Pediatrics 2010

44 Sports Participation Dynamic Versus Static Exercise: Dynamic - intramuscular force not greatly increased; BP and MAP increases but dbp and tpr falls Static - large intramuscular forces but little change in muscle length or joint motion; sbp, MAP, dbp all rise significantly and tpr does not change

45 Classification of sports based on combined static and dynamic components MaxO2: maximal oxygen uptake MVC: Maximal voluntary contraction

46 HTN: New developments Updated guideline for the evaluation of elevated blood pressure in children and adolescents Sponsored by the American Academy of Pediatrics Multidisciplinary committee Increased CVD risk with pre-hypertension? Need for lower BP thresholds to decrease CVD risk? SHIP-AHOY The Population project -> investigate BP thresholds for development of hypertensive target organ damage (TOD) The Clinical Project -> characterize the ambulatory BP and metabolic phenotype best predicting TOD. The Basic Project -> investigate epigenetic changes that influence the development of TOD in youth with HTN.

47 The End Thank You!

Dr Doris M. W Kinuthia

Dr Doris M. W Kinuthia Objectives Normal blood pressures in children Measurement of blood pressure in children Aetiology of Hypertension in children Evaluation of children with hypertension Treatment of