Investigation of hypertensive child

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Investigation of hypertensive child
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Case 1.

• 11-yrs old girl admitted because of severe
  headache, nausea, vomiting and nuchal rigidity.
  At admission she was somnolent and her BP was
  240/146 mm Hg HR 98/min. CSF fluid contained
  blood.
• Retinal exam optic disk oedema, foci of retinal
  hemorrhages.
• Laboratory results normal
• ECHO left ventricular hypertrophy
• Abdominal ultrasonography hypoplastic right
  kidney, hypoplastic aorta, stenosis of left renal
  artery
• Arteriography
• subarachnoid hemorrhage, aneurysm of right brain
  connecting artery
• aortic hypoplasia with amputation on the level of
  renal arteries,
• right kidney supplied by collateral circulation.

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Case 1.

• BP measurement, clinical and retinal exam -
  diagnosis of hypertension and its severity
  (emergency hypertension).
• Ultrasonography, arteriography diagnosis of
  etiology of hypertension.
• ECHO, retinal exam, arteriography - estimation of
  extent of target organ damage.
• Etiological diagnosis middle-aortic syndrome,
  renal artery stenosis

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Case 2.

• 14-yrs old girl, diagnosed because of headache.
• Body mass 95kg (gt97cc ), height 172 cm (gt90cc.),
  BMI32,4 (4,3 SD), R/R 160/100- 150/90 mmHg
• Perinatal history 2850g/52cm/Apgar 10 points
• Typical breakfast 2 large cakes
• Limited physical activity because of recurrent
  upper respiratory tract infections
• ABPM sBPIndex 1,16 dBPIndex 0,97
• Retinal exam narrowing of retinal arteries and
  positive Gunn sign
• ECHO normal
• Doppler ultrasonography normal

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Case 2 contd.
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Case 3.

• 16-yrs old boy presented with episodic HT (116/64
  170/80 mm Hg) and episodes of hypotension.
• Basal laboratory investigation normal
• Abdominal ultrasonography tumor in aortic
  bifurcation
• Retinal exam - Ie in KW score
• Left ventricular hypertrophy
• Urinary catecholamine excretion
• Vanilinmandelic acid 18.7mg/d (n)
• Adrenaline 46.6mg/d (n 1,7
  22,4)
• Noradrenaline - 1184mg/d (n lt85,5)
  
• Dopamine 132,7µg/d (n lt434)

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Case 3 contd.
Molecular diagnosis mutation in SDHD
subunit Diagnosis benign paraganglioma
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Investigation of hypertensive child.

• 3 children with arterial hypertension, 3
  different diagnostic investigations.
• Do all hypertensive children need the same
  investigative approach ?

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Key points in investigative approach to
hypertensive child.

• To diagnose
• To classify (to estimate severity)
• To establish etiology

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Confirm diagnosis
Classify
Establish etiology
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What is hypertension in childhood and adolescence
?

• Practical definition used in adult medicine a
  level of blood pressure above which recognizable
  morbidity occurs.
• Formal pediatric definition an average of 3 BP
  (SBP and/or DBP) readings exceeding the 95th
  percentile for age, gender and height.
• Formal definition of arterial hypertension in
  childhood is based on statistical criteria and
  not on cardiovascular risk.

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Analysis of causes of sustained hypertension
Dillon M in Pediatric Hypertensioned. Portman
RJ, Sorof JM, Ingelfinger JR, 2004
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Arterial hypertension in childhood
Secondary hypertension (90-95)
Primary hypertension (5-10)
gt 14 yrs of age gt 50
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Renal disease is dominant cause of secondary
hypertension Wyszynska T et al. Acta Pediatr 1992
More in hospitals with cardiac surgery facility
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3 steps of diagnostic evaluation of hypertensive
child.
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Step 1 basic diagnostic evaluation.

• Physical examination
• Anthropometrical evaluation BMI, WHR, skinfolds
• Skin
• Head
• Extremities
• Eyes
• Neck
• Lungs
• Heart
• Abdomen
• Genitalia
• Neurologic evaluation

• Family history CV disease, diabetes, renal
  disease
• Personal history neonatal history, chronic
  disease, medications, symptoms, substance abuse,
  contraceptives,

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Step 1 basic diagnostic evaluation.
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Step 1 basic investigative procedures.

• Urinalysis and urine culture
• Peripheral blood hematology screen, electrolytes
  (including bicarbonates), creatinine, BUN, uric
  acid, glucose, lipids (cholesterol, HDL, LDL, TG)
• Abdominal ultrasonography with Doppler flow
• Infants transcranial ultrasonography
• Retinal exam
• ECHO with LVM measurement (carotid IMT ?)
• 4-th Task Force guidelines do not recommend
  renal Doppler flow evaluation in all pts.

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Step 2 full work-up

• Voiding cystourethrography in selected cases
• Isotopic renoscintography (captopril test)
• Urine (plasma) catecholamines
• Plasma renin and aldosterone
• Urinary steroid profile
• Fasting glycemia and insulinemia and/or OGTT
• Metabolites of vitamin D3, fT3, fT4, TSH and
  thyroid sonography - in selected cases

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Step 3 selected investigations in selected
patients needing diagnosis and/or who are
resistant to hypotensive treatment

• To diagnose renovascular hypertension
• Renal angioCT and/or MRI
• Classic arteriography
• To diagnose adrenal pathology and/or
  pheochromocytoma/paraganglioma
• Adrenal CT and/or MRI
• MIBG scintigraphy and/or octreotide scintigraphy
• Scintandren scintigraphy
• Dexamathasone test
• To diagnose monogenic hypertension
• Molecular diagnosis
• Other, special tests (i.e.angioMRI/angioCT of
  basal brain arteries)

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Investigation of hypertensive child

• Investigative procedures in detail pro and cons

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Diagnosis of HT Classification CV risk Target
organ damage Co-morbidity
Etiological diagnosis CV risk Co-morbi- dity
Evaluation of treatment eficacy
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Investigative procedures of step 1 is patient
truly hypertensive ?

• Guidelines
• ABPM suspicion of white coat HT, need for
  additional informations (BP load, dipping
  pattern).

• Comment
• ABPM in every older child with confirmed HT.
• Interpretation of ABPM in infants and small
  children may be difficult and may lead to
  overdiagnosis of HT.

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Investigative procedures of step 1.Usefulness of
ABPM.
Graves J, Althaf MM Pediatr Nephrol 2006 in press
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Investigative procedures of step 1.ABPM
normative values.

• Soergel M et al. J Pediatr 1997 130 178-184
• Wühl E et al. J Hypertens 2002 20 1995-2007

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Investigative procedures of step 1. ABPM
parameters to analysis.

• Daytime, nighttime, 24h
• MBP
• SBP
• DBP (?)
• Dipping pattern
• Blood pressure load

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Investigative procedures of step 1.ABPM.

• SBP load
• 20
• 25
• 30
• 40 or
• 50 ?
• Sorof J et al.. J Pediatr 2000 137 493-497
• Lurbe e et al. J Pediatr 2004 144 7-16
• Graves J, Althaf MM Pediatr Nephrol 2006 in
  press

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Investigative procedures of step 1. ABPM.

• Hypertension confirmed
• by 3 measurements

White-coat hypertension
ABPM
Hypertension
Dipping status SBP load
Swinford RD, Portman RJ in Pediatric
Hypertension, ed. Portman RJ, Sorof JM,
Ingelfinger JR, 2004
Periodic ABPM
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Investigative procedures of step
1. Classification and assessment of severity of
hypertension.
NHBPEP Pediatrics 2004 114 555-576
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Criteria to diagnose primary hypertension in
childhood.

• Primary criterion
• Exclusion of a known secondary cause of
  hypertension

• Secondary criteria
• Abnormal response to mental stress
• Family history of primary hypertension
• Evidence of end-organ damage

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Key point in investigative approach to
hypertensive child.

• Very young children, children with stage 2 HT and
  children with clinical signs that suggest
  systemic conditions and/or intermediate phenotype
  typical for secondary HT should be evaluated more
  completely than adolescents with stage 1 HT.

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Investigative procedures of step 1. Etiology and
comorbid conditions.

• Guidelines recommendations
• All children with hypertension
• Renal function, urine culture, complete
  peripheral blood count, lipids, fasting glycemia,
  renal ultrasonography, echocardiography, retinal
  exam.

• Comment
• Cost-effective screening investigation useful for
  further management of overweight adolescent with
  stage 1 HT, positive familial history and no
  target organ damage.
• Limited possibility to describe intermediate
  phenotype, to diagnose secondary HT and to treat
  according to intermediate phenotype.

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Investigative procedures of step 2. Etiology.

• Guidelines
• Plasma renin activity (only) young children in
  stage 1 HT, older children with stage 2 HT,
  positive family history of severe hypertension.

• Comment
• Plasma renin activity plasma aldosterone
  urinary Na excretion. Estimation of only PRA can
  not diagnose hyperaldosteronism state.

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Plasma renin activity as marker of intermediate
phenotype
PRA
PRA ?
PRA ?

• Malignant HT
• Renovascular HT
• Primary reninism
• Neurogenic
• Renoparenchymal

Plasma aldosterone
high
low
1. Primary hyperaldosteronism (hyperplasia,
adenoma, carcinoma) 2. Familial
hyperaldosteronism - type I (FH1) - GRA -
type II (FH2)
1. CAH (block of 11ß hydroxylase or 17a
hydroxylase) 2. Liddle syndrome 3. AME
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Investigative procedures of step 2. Etiology.

• Guidelines
• Plasma and urine steroids young children with
  stage 1, other pts with stage 2.
• Plasma and urinary catecholamines young
  children with stage 1, other pts with stage 2.

• Comment
• Limited possibility to estimate full urinary
  steroid profile. Enables to diagnose blocks in
  steroid synthesis, to precise intermediate
  phenotype. Except rare cases it does not increase
  effectiveness of treatment.
• In practice urinary excretion of catecholamines
  and theirs metabolites. Interpretation may be
  difficult in case of slight increase of
  catecholamines excretion in adolescents.
• Influence of diet and drugs.

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Investigative procedures of step 2. Etiology and
comorbid conditions.

• Comment
• Primary hypertension in obese pts can be treated
  as distinct form of hypertension
  obesity-related hypertension. High percentage of
  insulin resistance is an argument for OGTT and
  full work-up towards diagnosis of metabolic
  syndrome in obese pts. However, insulin
  resistance and metabolic syndrome is not limited
  only to obese pts.
• Should insuline be measured also ?
• Should OGTT be performed in all pts with primary
  HT ?

• Guidelines
• Fasting glucose in all pts, overweigth children
  with prehypertension, pts with chronic kidney
  disease.
• OGTT in obese pts.

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Investigative procedures of step 2. Etiology.

• Guidelines
• Polysomnography suspicion of sleep apnoe.
• Drug screen.

• Comment
• Useful but may be performed only in few centers.
• Useful in practice.

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Investigative procedures of step 1 and 2. Imaging
studies.

• Comment
• Doppler flow ultrasonography all hypertensive
  pts.
• Scintigraphy (with captopril) in children with
  suspicion of kidney disease and/or abnormal
  ultrasonography or renal Doppler flow.
• Angio-CT (3D) and/or classic arteriography if
  strong suspicion of renovascular HT and/or
  resistant hypertension.

• Guidelines
• Renovascular imaging Doppler flow, renal
  scintigraphy, angio-CT, angio-MRI, classic
  arteriography young children with stage 1 HT,
  older children with stage 2 HT.

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Investigative procedures of step 2. Etiology.

• Vascular imaging of other arterial systems.
• Comment
• non-invasive imaging and classic arteriography
  visualize stenosis of aorta (coarctation, middle
  aortic syndrome), visceral, intracranial arteries
  and abberant course of brain arterial vessells
  what may be a cause of hypertension.

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Assessment of target organ damage what to
assess ?

• Guidelines
• Measurement of left ventricular mass all
  hypertensive children and children with
  pre-hypertension and cardiovascular risk factors.
  

• Comment
• Standardized conditions of LVM measurement.
• Known referential values.
• Paediatric or adult criteria ?

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Assessment of left ventricular mass.

• LVM measurement according to ASE guidelines and
  Deveraux formula.
• Indexation to m2 of BSA.
• Recommended indexation according to deSimone
• (m of height2.7)
• NHBPEP Pediatrics 2004 114 555-576

• 0.8(1.04(IVSdLVPWdLVEDd)3-LVEDd3)0.6

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Left ventricular hypertrophy.Paediatric criteria
vs adult criteria.

• Adult criteria
• LVM associated with increased morbidity in adults
  with HT gt 51g/m of height2.7

• Paediatric criteria
• LVM gt 95th percentile
• gt 38.6 g/m2.7
• or
• gt 84.2 g/m2 for girls
• gt 103 g/m2 for boys

(gt99th percentile for children and adolescents)

• Daniels SR et al.. Am J Cardiol 1995 76 699-701
• deSimone G et al.. J Am Coll Cardiol 1992 20
  1251-1260

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Assessment of target organ damage retinal
arteriolopathy.

• Guidelines
• Retinal exam in children with pre-hypertension
  and cardiovascular risk factors and in all
  hypertensive children.

• Comment
• Important diagnostic tool. The result enables to
  decide about treatment in hypertensive urgency
  and emergency.
• Potential interpretational problems in pts with
  pre-hypertension or in stage 1 and 1-st grade
  changes according to K-W score.

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Assessment of target organ damage retinal
arteriolopathy.

• Keith-Wagener classification (classic)
• I. Arteriolar narrowing
• II. Diffuse arteriolar narrowing, arteriovenous
  nicking (Gunn sign)
• III. As above foci of hemorrhage and exudate
• IV. As above optic nerve oedema

• Clinical classification
• Diffuse arteriolar narrowing and/or Gunn sign
• Foci of hemorrhage, exudate, optic nerve oedema

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Assessment of target organ damage retinal
arteriolopathy. Standardized, digital measurement
of diameter of retinal arteries.
Wong TY, Mitchell P N Eng J Med 2004 351 2310-7
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Assessment of target organ damage arteriopathy.

• Easy to perform.
• Possible measurement of elastic properties of
  carotid artery.
• Correlates with left ventricular mass and
  biochemical risk factors.
• Sorof J et al.. Pediatrics 2003
• Litwin M et al. Pediatr Nephrol 2006

• carotid IMT

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Assessment of target organ damage arteriopathy.

• HDI ultrasonography.
• Intima-media thickness complex (IMT).
• Common carotid artery (elastic type artery).
• Superficial femoral artery (muscular type
  artery).
• Possible measurement of elastic properties of
  carotid artery.
• Normative data for children and adolescents has
  been published recently
• Jourdan C et al. J Hypertens 2005, 53 1707-1715

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Assessment of target organ damage
microalbuminuria.

• Microalbuminuria still not accepted as marker of
  target organ damage in children.

• Microalbuminuria is accepted marker in adults.
• Normative values in children are similar to adult
  values.

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Follow-up investigation.Case 1 two months later.

• 120/80 mm Hg
• Retinal exam - arterial narrowing
• ECHO LVMI 41.9g/m2.7 (after next 6 months ?
  35.2g m2.7)
• Right kidney length 98 mm, Vmax 26 cm/s RI 0.50,
  (after next 6 mts 67 mm)
• Left kidney length 101mm, Vmax 152 cm/s RI 0.66
• Treatment labetalol enalapril spironolactone
  amlodipine

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Follow-up investigation. Case 2 12 months
later.
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Follow-up investigation.

• Extent of investigative procedures at follow-up
  depends on
• diagnosis,
• presence of target organ damage
• management
• Treatment efficacy
• casual BP, home BP, ABPM, imaging studies,
  hormonal tests
• Regression/progression of target organ damage
• ECHO, retinal exam, cIMT, microalbuminuria
• Total cardiovascular risk
• as above biochemical cardiovascular risk factors

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Resistant hypertension
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Resistant hypertension
Diagnostic re-evaluation additional tests
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Resistant hypertension

• 14-teen years old boy with stage 2 HT, target
  organ damage (LVH, microalbuminuria, Io KW,
  cardiac ischemia) and high-renin activity.
• Thorough diagnostic evaluation including all
  biochemical tests and non-invasive vascular
  imaging was negative and primary hypertension was
  diagnosed.
• Treatment with 5 hypotensive drugs (CCA, BB,
  ACEi, diuretic, rilmenidine) was unsuccesful.
• Resistant hypertension was diagnosed.

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Resistant hypertension

• During re-evaluation consultation brain vessel
  imaging was proposed.
• Both brain angioCT and angio NMR revealed
  compression of brain stem blood pressure control
  centers.
• After addition of losartan normotension was
  achieved.
• After 2 months normotension was maintained with 3
  drugs (AT1B, ACEi, rilmenidine).

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Key points.

• Treatment efficacy in case of primary
  hypertension is lower than in secondary
  hypertension.
• However, primary hypertension in childhood rarely
  leads to severe target organ damage and patients
  do not need to use more than 2 hypotensives.
• Patient with resistant hypertension and with
  severe target organ damage needs futher
  (re-)evaluation towards cause.

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Diagnosis of HT Classification CV risk Target
organ damage Co-morbidity
Etiological diagnosis CV risk Co-morbi- dity
Evaluation of treatment efficacy