Hypertension in childrenHypertension in children
F. Cachat
Pediatrics and Pediatric Nephrology
Vevey and Lausanne
Switzerland
Disease prevalence in childhood
Disease prevalence in childhood
• Congenital heart disease 1%
• Epilepsy 3-5%
• ADHD 3-5%
• Hypertension 4-5%
• Asthma 7%
• Obesity 18-25%
HTN is a major killer in adulthood
Some HTN originates in childhood
Many children with HTN during infancy will stillhave HTN as adults (blood pressure tracking)
PLANPLAN
• Definition
• Case presentation
• Physiology of hypertension in children (some aspects)
• Evaluation of the child with hypertension (some aspects)
• Management of the child with hypertension (some aspects)
• Conclusion
DefinitionsDefinitions
• Update on the 1996 and 1987 Task Force Report on
High Blood Pressure in Children and Adolescents:– 60’000 healthy children
– M/F: 50/50
– White: 56%, African-American: 29%, Spanish: 9%, Asian:
3%, Others: 3%
DefinitionsDefinitions
DefinitionsDefinitions
Classification of Hypertension in Childrenand Adolescents
Classification of Hypertension in Childrenand Adolescents
SBP or DBP Percentile
Normal <90th percentile
Prehypertension 90th percentile to <95th percentile, or if BP exceeds 120/80 mm Hg, even if below the 90th percentile up to <95th percentile
Stage 1 hypertension 95th percentile to the 99th percentile + 5 mm Hg
Stage 2 hypertension >99th percentile + 5 mm Hg
How to calculate the 95th percentile of BP for a child?How to calculate the 95th
percentile of BP for a child?
– Systolic BP (1-17 years)• 100 + (age in years x 2)
– Diastolic BP (1-10 years)• 60 + (age in years x 2)
– Diastolic BP (11-17 years)• 70 + (age in years)
Case presentationCase presentation
Case presentationsCase presentations
• Case 1: monogenic hypertension
• When a rare single genetic disease helps to understand the pathophysiology of HTN in children
• When HTN treatment benefits are obvious
• Case 2: obesity related hypertension
• A rising epidemic of HTN in children in the Western World• When HTN treatment benefits are less obvious (and treatment more
difficult)• Polygenic, multifactorial HTN
HTN
Sub-arachn.hemorrhage
BP 160/110 mm HgHx of surgically-corrected VUR
HTN
Sub-arachn.hemorrhage
BP 160/110 mm HgHx of surgically-corrected VUR
HTN
Sub-arachn.hemorrhage
BP 160/110 mm HgHx of surgically-corrected VUR
Premature death 36 years oldSub-arachn. hemorrhage
HTN
Sub-arachn.hemorrhage
BP 160/110 mm HgHx of surgically-corrected VUR
Premature death 36 years oldSub-arachn. hemorrhage
HTN
Sub-arachn.hemorrhage
BP 160/110 mm HgHx of surgically-corrected VUR
Premature death 36 years oldSub-arachn. hemorrhage
HTN
Sub-arachn.hemorrhage
BP 160/110 mm HgHx of surgically-corrected VUR
Premature death 36 years oldSub-arachn. hemorrhage
Physical examPhysical exam
• NORMAL except for confirmed severe asymptomatic HTN (discovered during routine school exam)
Laboratory valuesLaboratory values
• Plasma chemistries : Na 141 mmol/l, K 2.8 mmol/l, creatinine 71 mol/l, bicarbonates 27 mmol/l, BE + 3.2 mmol/l, glucose 5.3 mmol/l, calcium 2.37 mmol/l
• Urine chemistries : Na 113 mmol/l, K 75 mmol/l, no proteinuria, no glycosuria
• I123-Hippuran scintigraphy : normal, no scars
• Father’s plasma potassium : 3.2 mmol/l
Laboratory valuesLaboratory values
• Plasma renin activity: extremely low
• Plasma aldosterone: extremely high
• Plasma and urine cortisol : normal values
In summaryIn summary
• An autosomal dominant form of severe HTN
• With hypokalemia and alkalosis
• With very high aldosterone levels and suppressed renin activity
Na Intake
Kidneys
Urinary sodium
Renin
Blood volumeBlood pressure
Na and Cl transport
Aldosterone
ACTH
GRA
Congenital Adrenal hyperplasia
Deoxycorticosterone
Cortisol
Cortisone
ENaC(Liddle’ssyndrome)
Gordon syndrome
AME
Monogenic endocrine HTN
15-year-old boy
No past medical historyNo medicationFound by the pediatrician
to have sustained HTN 140/85 mm Hg
Extensive work-up negativeFamily history positive for
both parents having HTN
Conservative treatment/diet
No major changes in dietcontinues to eat saltyfood (salt sensitivity)
Pharmacological treatmentPoor compliance with
drug treatment (drug compliance)
Poor BP (and weight) improvement
PathophysiologyPathophysiology
Child at risk
Birth weight
Sex
Genetics
Adult with ± cardio-vascular risks
Physical activity
Job/social factorsWeightWeight gainObesityTruncal obesity
Food (fat, sodium) Smoking/environmental factors
Renal injury
Cardiac abnormality(coarctation of theAorta)
Endocrine abnormality
Programmeddeterminants Secondary
insults
Life style
Child at risk
Birth weight
Sex
Genetics
Adult with ± cardio-vascular risks
Physical activity
Job/social factorsWeightWeight gainObesityTruncal obesity
Food (fat, sodium) Smoking/environmental factors
Renal injury
Cardiac abnormality(coarctation of theAorta)
Endocrine abnormality
HTN
Sub-arachn.hemorrhage
BP 160/110 mm HgHx of surgically-corrected VUR
Premature death 36 years oldSub-arachn. hemorrhage
GRAAME
Liddle syndrome
Child at risk
Birth weight
Sex
Genetics
Adult with ± cardio-vascular risks
Physical activity
Job/social factorsWeightWeight gainObesityTruncal obesity
Food (fat, sodium) Smoking/environmental factors
Renal injury
Cardiac abnormality(coarctation of theAorta)
Endocrine abnormality
Relationship between blood pressure values and birth weightRelationship between blood pressure values and birth weightBarker DJP Schweiz Med Wochenschrift 1999;129:189-196Barker DJP Schweiz Med Wochenschrift 1999;129:189-196
f/u of BP in former premature infants with or without growth retardation in Lausanne (14-16
years)
f/u of BP in former premature infants with or without growth retardation in Lausanne (14-16
years)
Systolic BP (mm Hg) Diastolic BP (mm Hg)
Controls 123±11 71±5*
Premature infants**without growth retardation 129±13 86±9
Premature infants**with growth retardation 129±17 87±6
*P<0.0001 compared to premature with and without intrauterine growth retardation (unpaired t-test)Premature infants defined as 32 weeks gestational age
0%
5%
10%
15%
20%
<2.5 kg (270) 2.5-4.0 kg (3979) >4.0 kg (405)
% with elevated BP
at 12 y(at 1st visit)
16.7
10.616.711.2
Etude Chiolero-IUMSP
Relation between birth weight and blood pressure (systolic blood pressure)
Child at risk
Birth weight
Sex
Genetics
Adult with ± cardio-vascular risks
Physical activity
Job/social factorsWeightWeight gainObesityTruncal obesity
Food (fat, sodium) Smoking/environmental factors
Renal injury
Cardiac abnormality(coarctation of theAorta)
Endocrine abnormality
Background
• Obesity is increasingly frequent among children worldwide• There is a fear that obesity related conditions might
increase, such as hypertension • Few data on prevalence of hypertension among children,
especially in European countries• Most epidemiological studies assessed blood pressure (BP)
on one visit, hence BP was overestimated
Aims
• To assess prevalence of hypertension measured on up to three visits in a Swiss pediatric population
• To assess the relationship between hypertension, being overweight and other factors
Methods
• All children of the 6th grade of the schools of canton of Vaud (N=6873) were eligible and 5207 participated (76%).
• Weight, height, and blood pressure (BP) were measured.
• At initial visit, three BP readings were obtained with a clinically validated automated device.
Methods
• IOTF criteria for use for overweight/obesity.
• Elevated BP was defined for average of two last BP readings >95th sex-, age- and height specific percentiles (US reference).
• If BP was elevated at the initial visit, BP was measured on up to two additional separate visits.
• Hypertension is defined for elevated BP on the three visits (recommendation of NHBPEP)
10.5
12.4
4.0 3.72.3 2.0
0
5
10
15
1st visit 2nd visit 3rd visit
Boys Girls
Prevalence of elevated BP at each visit
Hypertension
Four fold decrease in the prevalence of elevated BP between 1st and 3rd visit
Probably lower prevalence than in US children (4-9%).
Results
High prevalence of overweight, relatively low compared to other regions of Europe
Underestimation as some overweight/obese children did not participate
Results
Boys GirlsN 2621 2586Mean age (SD) [range], year 12.3 (0.5) 12.3 (0.5)
[10.1-14.9] [10.3-14.8]BMI categories (IOTF*) (SE), % No excess weight 85.0 (0.7) 87.6 (0.6) Overweight (not obese) 13.3 (0.7) 10.7 (0.6) Obese 1.8 (0.3) 1.7 (0.3) Overweight or obese 15.0 (0.7) 12.4 (0.6)
BP strongly relates to BMI
The association between BP and BMI is independent of age and height
Blood pressure and body mass index
Girls
0
20
40
60
80
100
120
140
160
10 20 30 40
Diastolic Systolic
Boys
0
20
40
60
80
100
120
140
160
10 20 30 40
Diastolic Systolic
BP (mmHg)
BMI (kg/m2)
Results
1.7 1.22.0
3.8
14.9
0
5
10
15
20
<25th 25th-74th 75th-84th 85th-94th >=95th
BMI percentile (CDC)
Hyp
ert
en
sio
n (
%)
Results Prevalence of hypertension according to BMI category
ConclusionConclusion
1) Prevalence of overweight and obesity in children aged 12 years old was high but relatively low compared to other regions of Europe
2) Prevalence of hypertension was highly dependent on the number of visits at which BP was measured
3) HTN prevalence was low, and increased with increase in BMI
Evaluation of HTN in childrenEvaluation of HTN in children
History taking
Child at risk
Birth weight
Sex
Genetics
Adult with ± cardio-vascular risks
Physical activity
Job/social factorsWeightWeight gainObesityTruncal obesity
Food (fat, sodium) Smoking/environmental factors
Renal injury
Cardiac abnormality(coarctation of theAorta)
Endocrine abnormality
Physical exam
Child at risk
Birth weight
Sex
Genetics
Adult with ± cardio-vascular risks
Physical activity
Job/social factorsWeightWeight gainObesityTruncal obesity
Food (fat, sodium) Smoking/environmental factors
Renal injury
Cardiac abnormality(coarctation of theAorta)
Endocrine abnormality
Cushing syndrome
Henoch-Schoenlein purpura
Lab investigations
Child at risk
Birth weight
Sex
Genetics
Adult with ± cardio-vascular risks
Physical activity
Job/social factorsWeightWeight gainObesityTruncal obesity
Food (fat, sodium) Smoking/environmental factors
Renal injury
Cardiac abnormality(coarctation of theAorta)
Endocrine abnormality
ChildrenChildren
Secondary causesSecondary causesRenal causes Renal causes (78%)(78%)
Reno-vascular causes Reno-vascular causes (12%)(12%)
Coarctation Aorta Coarctation Aorta (2%)(2%)
Other causes Other causes (endocrine(endocrinecauses, phaeo) (8%)causes, phaeo) (8%)
(Essential HTN)(Essential HTN)
AdultsAdults
Essential HTN
(Secondary causes)
AgeAge
Frequency
Measurement of blood pressure in children
Measurement of blood pressure in children
BP measurement : cuff choiceBP measurement : cuff choice
Cuff too narrow Good-sized cuff
BP measurement : cuff choiceBP measurement : cuff choice
American Family Physician 2006; 7(9)
40%40% of the circumference of the circumferenceoror
2/32/3 of the arm lengt of the arm lengt
≥ ≥ 80%80% of the arm circumference of the arm circumference
BP measurement : cuff choiceBP measurement : cuff choice
BP measurement methodsBP measurement methods
• BP measurement in the office
• ABPM
• Self-blood pressure monitoring at home
BP measurement in the officeBP measurement in the office
• Most commonly used• Always obtain at least 3 values to diagnose
sustained hypertension• White coat hypertension:
– Innocent bystander (?)
– Adults data makes the f/u of white coat hypertension mandatory, no data in children
Single office BP measureSingle office BP measure
• Is there any difference between arm and wrist cuff?
Blood pressure reactivity in adultsLausanne Study
Blood pressure reactivity in adultsLausanne Study
Single office BP measurementSingle office BP measurement
ABPMABPM
Most commonly usedmethod to confirm
HTN
Prognostic factor of “dipping”
Abnormal ABPM linkedto left ventricular
hypertrophy
Self-measurement of BP at homeSelf-measurement of BP at home
• Advantages: • Greater numbers of readings• Avoidance of the white-coat syndrome• Absence of observer bias• Increased compliance with anti-hypertensive therapy
• Reference values• Derived from population studies• In adults:
– Mean + 2 SD: 137/89 mm Hg
– 95th percentile: 135/86 mm Hg
Treatment of HTN in childrenTreatment of HTN in children
When to treat HTN in children?When to treat HTN in children?
S/D BP Measure Non-pharm. pharm. treatm.
Normal < P90 No measure none none
Pre-HTN P90-95 or f/u 6 months low salt diet none unless > 120/80 physical act. CKD or
diabetes or cardiac disease
When to treat HTN in children?When to treat HTN in children?
TA S/D Measure Non-pharm. Pharmacol ttt
Stage I HTN P95-99 f/u within diet none unless+ 5 mmHg 2 weeks physical activity organ damage
or symptomatic
Stage II HTN > P99 referral diet yes+ 5 mmHg physical activity
Pharmacologic managementPharmacologic management
• Pharmacological approach will allow to control:
– hormonal aspect of BP (IEC or ARBs)– Vascular reactivity (arterial and venous) (calcium
channel blockers or peripheral -blockers)– Cardiac output (-blockers)– SNC sympathetic activity (central -agonists)
Why to treat, does it make a difference?
Why to treat, does it make a difference?
• Outcome difficult to assess in children:
• Rare complications during childhood
• Classic complications (stroke, heart failure, blindness) occur (very) late
• Notable exception of children with CKD and HTN:
Mortality in children with CKDMortality in children with CKD
Death rate per 100,000
0
10
100
1000
10000
0-14 15-19 20-30
Age (years)
Adapted from Parekh et al, J Pediatr, 2002
Dialysis
Transplant
General Population
Black White
• CrCl< 75ml/min/1.73m 2
• HTN: >95 th % (Task Force)•Normotensive: n=1987 (52%)•Hypertensive: n=1874 (48%)
• Endpoint:
– CrClby 10 ml/min/1.73m2
– Renal replacement therapy
Non-HypertensionHypertension
% P
RO
GR
ES
SIO
N T
O E
SR
D/C
R.C
L. D
RO
P 1
0
0
20
40
60
80
100
MONTHS
0 12 24 36
P<0.001
Mitsnefes et al, J Am Soc Nephrol 2003
NAPRTCS CRI Database:NAPRTCS CRI Database:
58%
49%
Morbidity in children with CKDMorbidity in children with CKD
ConclusionsConclusions
• BP measurement must be done routinely in all children, as soon as possible, at least for the first time when the child in 3 years old, or earlier in children with associated risk factors for HTN
• The vast majority of children with HTN are asymptomatic until their BP is significantly high with potential target organ damage
ConclusionsConclusions
ConclusionsConclusions
• Younger children (< 10 years old) often (always) have secondary HTN
• One single abnormal BP value must always be confirmed, either at the office (first), or with ABPM and/or self-monitored blood pressure at home
ConclusionsConclusions
• Non-pharmacologic treatment must be started in every child with HTN
• Pharmacologic treatment will be reserved for children with target organ damage or severe HTN
What we knowWhat we know
• HTN exists in infancy
• In selected cases (monogenic HTN, severe symptomatic HTN) treatment benefits are obvious
• Treatment of HTN should not only rely on mere BP readings but also on associated risk factors such as obesity, diabetes, renal failure, microalbuminuria, metabolic syndrome, family history or end-organ damage
What we do not knowWhat we do not know
• What is the best way of measuring BP in children ? (office? Self blood pressure monitoring? ABPM?)
• What is the relationship between pediatric HTN and later adult morbidity/mortality in a non selected population?
• What is the role of biomarkers such as microalbuminuria?
ReferencesReferences
• Hypertension in children. Leonard G Feld. Butterworth-Heinemann Ed. Boston, 1997;233p.
• Excellent review, short, global approach and management of the child with HTN
• Hypertension: pathophysiology, diagnosis and management. Laragh JH, Brenner BM. Raven Press, New-York, 1990, 2 volumes.
• One (the) reference in adult HTN medicine
• The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004;114:555-576
• Last recommendations from the AAP regarding investigation and management of HTN in children. The pediatric reference
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