Transcript How to recognize the different faces of Hypertension

How to recognize the different
faces of Hypertension
Reena Kuriacose, MD. FACP.
March 26,2012
Disclosures
• No conflict of interest
• Not a specialist
• Statistical data varied
Resistant hypertension
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BP above goal in spite of > 3 anti HTN meds
All of these in optimal doses
Resistant HTN = Refractory HTN
Uncontrolled HTN = Resistant HTN
Inadequate Rx
Pseudo resistance
Pseudo resistance
• Attributed to other factors:
- Inaccurate measurement
- Poor adherence to Rx
- White coat syndrome 20-30%
(also more in resistant HTN: 37-44%)
• Suboptimal Rx: Only 18-27% uncontrolled get
Rx with at least 3 anti HTN meds
Difficult to control HTN
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Higher baseline
Left Ventricular Hypertrophy
Older age
Obesity- lifestyle and diet
AA race
Chronic kidney disease
Diabetes
Medications and herbal supplements
Resistant HTN
• Prevalence: Not known- 8.9-16%
• Pt with ≥ 3 BP meds
1994: 14% to 2004: 24%
• 5–20% HTN- specific underlying disorder
I. Intravascular volume
• ↑ Na  ↑ vascular vol  ↑ cardiac output
• Overtime  ↑ Peripheral resistance
• Non chloride Na salts have no effect on BP
• NaCl dependent HTN:
- Intrinsic renal disease: ↓ capacity to excrete Na
- ↑ Mineralocorticoid: ↑ tubular Na reabsorption
- ↑ Neural activity to kidney: ↑ tubular Na
reabsorption
ESRD 80% volume dependent and respond to dialysis
II. Autonomic Nervous System
• Adrenergic receptors:
α- activated by NE more than epinephrine
β- activated more by epinephrine than NE
• α₁ - vasoconstriction,↑ Renal Na reabsorption
• α₂ - inhibit NE release
• β₁ - ↑ rate and strength of cardiac contraction
↑ CO; ↑ renin release from kidney
• β₂ - vasodilatation
• Tachyphylaxis – sustained high levels of
catecholamines ↓ response
(orthostatic hypotension in pheo)
• C/c ↓ catecholamines  temporary
hypersensitivity to sympathetic stimuli
(clonidine withdrawal)
• Sympathetic outflow: ↑ Obesity and OSA
III. Renin-Angiotensin-Aldosterone
• Angiotensin II  Vasoconstriction
Atherosclerosis
• Aldosterone  Na retention
↓ NaCl in distal asc loop of Henle
↓ pr. In afferent renal arteriole
β₁ stimulation of renin secretion
Pharmacological blockade of
a. ACE receptor
b. Angiotensin II receptor
↓K ----------- ↓
Secondary Hypertension
• Severe or resistant hypertension
• An acute rise in BP developing in a patient
with previously stable values
• Malignant or accelerated hypertension
• < 30 years in non-obese, -ve FH, no other risk
factors
• >50 years
Secondary Hypertension
Resistant HTN with an identifiable cause:
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Primary Aldosteronism
Renal Artery Stenosis
Chronic Kidney Disease
OSA
Pheochromocytoma
Cushing’s Syndrome
Aortic Coarctation
Primary Aldosteronism
• 10 – 20% of resistant HTN
• Peak: 30–60 years
• Unexplained hypokalemia- 37%
> 50% Normokalemic @ presentation
Unprovoked hypokalemia : 40-50% primary
aldosteronism
• Renal Mag wasting  mild hypomagnesemia
Primary Aldosteronism
• ↑ Aldosterone  ↑ Na, ↓ Renin
 ↑ K excretion
• ↓ K  ↓ Aldosterone synthesis 
correct K before eval for hyperaldosteronism
Primary Aldosteronism
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Resistant hypertension
Spontaneous or thiazide-induced hypokalemia
Serum K <3.1 mmol/L
Incidentaloma
FH of primary hyperaldosteronism
Primary Aldosteronism
• Adrenal adenoma: 60–70%
Unilateral
< 3cm
• Unilateral/ bilateral adrenal hyperplasia
• Adrenal carcinoma or an ectopic malignancy
e.g., ovarian arrhenoblastoma- rare
Primary Aldosteronism
• PAC:PRA ratio (ratio ≥ 20:1)
• Plasma aldosterone concentration (PAC)
(>416 pmol/L) (>15 ng/dL))
• Sensitivity 90% , Specificity 91%
for aldosterone-producing adenoma
• Plasma renin activity (PRA) ↓
• 24 hr urine  Na excretion, Creatinine
clearance, aldosterone excretion
Primary Aldosteronism
• Medications that alter renin and aldosterone
levels:Diuretics (especially spironolactone)- should
be discontinued 4 weeks before
ACE inhibitors, ARBs, β -blockers, Clonidine
• Calcium channel and α-receptor blockers can
be used
Primary Aldosteronism
• Confirmed by demonstrating : - Failure to suppress plasma aldosterone to
isotonic saline
- Failure to suppress aldosterone to
oral NaCl load/ fludrocortisone/ captopril
Primary Aldosteronism
• High-resolution CT (90%) or MRI scanning
• Bilateral adrenal venous sampling for plasma
aldosterone
(sensitivity 95% and specificity 100%)
Primary Aldosteronism
• Hyperplasia- Aldosterone receptor antagonist
• Pts not willing for surgery  Medical Rx
(avoid extensive w/u)
Renal Artery Stenosis
• Atherosclerotic disease: 2/3 – older males
OR
• Fibromuscular dysplasia: 1/3- younger females
• Renal artery stenosis:
1–2% of hypertensive patients
10-45% of refractory HTN
• Prevalence 60% in >70 years
Renal Artery Stenosis
• < 20; > 50 years
• HTN is resistant to ≥ 3 drugs
• Epigastric / renal artery bruits
• ↓ Renal perfusion pr → ↑ renin
(over time secondary renal damage)
Renal Artery Stenosis
• Atherosclerotic disease of the aorta or
peripheral arteries:
- 15–25% of patients with symptomatic PVD
in legs renal artery stenosis
• Abrupt deterioration in kidney function (30%)
after administration of ACE inhibitors
• Episodes of pulmonary edema are associated
with abrupt surges in BP
Renal Artery Stenosis
• BP meds can effectively control BP in many
patients with renovascular HTN
• Screening is not recommended unless plan is
to intervene if a significant stenotic lesion is
found:
* Failure of medical therapy to control BP
* Intolerance to medical Rx
* Progressive renal failure
* Young pt- to avoid life long Rx
Renal Artery Stenosis
• No ideal screening test for renal vascular HTN
• Magnetic resonance angiographyatherosclerotic
• Spiral CT with CT angiography
• Duplex Doppler ultrasonography- operator
dependant
• Renal arteriography, the definitive diagnostic
test (suspicion is sufficiently high )
---------------------------------------* Renal insufficiency limits use of contrasts
OSA
• OSA seen in 71-85 % of resistant HTN referred
for sleep study
• 45% OSA without HTN develop HTN in 4 years
• Blunted/ No ↓ in nighttime BP
• >50% OSA  HTN (independent of obesity)
OSA
• Screen if:
Obesity + snoring + daytime sleepiness
• CPAP (> 5.6 hr/night) Decreases both
systolic and diastolic hypertension
Pheochromocytoma
• < 0.1% of all patients with hypertension
• < 0.3% of Secondary hypertension
• Incidence: 2-3/ million / yr
autopsy: 250–1300/ million
• Episodic HTN(90%)
HA (80%)
Diaphoresis (70%)
Palpitation (60%)
Anxiety (50%)
Tremor (40%)
• 90% in adrenals; 98% in Abdomen
Pheochromocytoma
• Hyperglycemia 35%
• ↑ RBC
• ↑ Ca
• Leukocytosis
• Occa ↑ ESR
• PRA may be ↑ ed by catecholamines
• Meds: Tricyclic antidepressants, Antidopaminergic
agents, Metoclopramide, and Naloxone- can ppt
HTNsive crisis
Pheochromocytoma
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Plasma fractionated free metanephrines
Used in high risk pts- FH or personal h/o pheo
Sensitivity - 96% ; Specificity - 85%
N levels = end of w/u
• ↑ levels - Physical or emotional stress
Sleep apnea
MAO inhibitors,levodopa
Pheochromocytoma
• 24-hour urinary collection for catecholamines and
metanephrines
- Sensitivity - 87.5% ; Specificity of 99.7%
- 2.2 mcg of total metanephrine /mg creatinine
> 135 mcg total catecholamines /gm creatinine
- Total u. metanephrine >1300mcg/24hr
• Lab values varies- Slightly +ve tests not significant
• 2-3 times above Normal
• VMA is not required
Pheochromocytoma
• Noncontrast CT - followed by CT with nonionic
contrast
• MRI scanning
• CT/ MRI - sensitivity ~ 90% for adrenal
pheochromocytoma
• Less sensitive - recurrent tumors, metastases, and
extra-adrenal paragangliomas
• I¹³¹ metaiodobenzyl guanidine if CT/MRI -ve
Cushing’s syndrome
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80% of spontaneous Cushing syndrome HTN
↑ WBC > 11,000/mm3
Hyperglycemia
Hypokalemic metabolic alkalosis :
Cortisol renal mineralocorticoid receptor.
Cushing’s syndrome
• 40% of cases are due to Cushing "disease,“
• ACTH hypersecretion by the pituitary- benign
pituitary adenoma (98% in ant pituitary)
• 10% nonpituitary ACTH-secreting neoplasms
(eg small cell lung Ca) 
↑ K & ↑ pigmentation
• 15% ACTH source that cannot be initially
located
Cushing’s syndrome
• 30% of cases- autonomous secretion of
cortisol by the adrenals 
independently of ACTH
• Benign adrenal adenomas (small) cortisol
• Adrenocortical carcinomas (large)  cortisol
+ androgens
Cushing’s syndrome
• Tests for diagnosis:
- 24 hr Urinary free cortisol level
- 1mg dexamethasone suppression test
- Evening serum and salivary cortisol level
Cushing’s syndrome
• Urine Cortisol:
- 24-hour urine collection
>3-4 times upper limit (>200 µg/24hr)
3 N urine free cortisol – excludes
• ↑ Free Urine cortisol: high fluid intake; preg,
Carbamazepine and fenofibrate
Cushing’s syndrome
• Dexamethasone suppression test:
1 mg @11 pm  cortisol @ 8 am;
a cortisol level < 5 mcg/dL or < 2 mcg/dL
• Phenytoin, Phenobarbital, Primidone, Rifampin,
Estrogens (preg / OC) - lack of dexamethasone
suppressibility false +ve
• 8% of pituitary Cushing disease- also have
suppression
Cushing’s syndrome
• Midnight serum cortisol level > 7.5 mcg/dL:
- Same time zone for at least 3 days
- Fasting for at least 3 hours
- Indwelling IV line
• Late-night salivary cortisol test: consistently
> 0.25 mcg/dL (7.0 nmol/L)
Cushing’s syndrome
• Confirmation:
- Low dose Dexa suppression test:
Dexa 0.5mg q6hrX 48hrs
- Cortisol > 55.2nmol/L (2 µg/dL)  Cushing
syndrome
Etiology of Cushing’s
• To differentiate ACTH dependant vs ACTH
independent
• Plasma or serum ACTH:
< 5pg/mL = adrenal tumor
> 10-20 pg/mL = pituitary or ectopic ACTHsecreting tumors.
Etiology of Cushing’s
• To differentiate Pituitary ACTH vs ectopic ACTH:
- 8mg Dexamethasone suppression test @ 11pm:
OR
- 48-hr Dexamethasone suppression test: 2mg q 6hr X
8 doses
- Cortisol suppression <50% of baseline =
Pituitary ACTH
- Sensitivity 80%; Specificity 70-80%
- ↓ of 90% in U free cortisol  ~ 100% specific
for ant pit disease
Cushing’s syndrome
• MRI of the pituitary- pituitary lesion ~ 50%
• Selective catheterization of the inferior
petrosal sinus veins +/- CRH adm
• CT scan: chest (lungs, thymus) abdomen
(pancreas, adrenals)- 60% lesions found
• 111In-octreotide (OCT, somatostatin receptor
scintigraphy) scan: occult tumors
• Non-ACTH-dependent Cushing syndrome- CT
scan of the adrenals
Coarctation of Aorta
• 1-8/1000 live births
• 30 % Subsequent HTN after surgical correction
• Less severe lesions diagnosed in young
adulthood
Coarctation of Aorta
• Diminished and delayed femoral pulses
• Systolic pr gradient b/w R arm and legs / L arm
• Blowing systolic murmur - posterior L
interscapular areas
• Chest x-ray and transesophageal
echocardiography
Other causes:
• Renal: Polycystic kidney disease, Renin
secretory tr, obstructive uropathy
• Adrenal: 17α hydroxylase defi, 11β hydroxylase
dehydrogenase defi
• Preeclampsia/ Eclampsia
• Neuro: psycogenic, polyneuritis, a/c ↑ICP
• Hyperthyroidism (systolic HTN)
Hypothyroidism (Mild diastolic HTN)
↑ Ca, acromegaly
• Mendelian forms