1. How to recognize the different faces of Hypertension
Reena Kuriacose, MD. FACP.
March 26,2012

2. Disclosures No conflict of interest Not a specialist
Statistical data varied

3. Resistant hypertension
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

4. 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

5. Difficult to control HTN
Higher baseline
Left Ventricular Hypertrophy
Older age
Obesity- lifestyle and diet
AA race
Chronic kidney disease
Diabetes
Medications and herbal supplements

6. Resistant HTN Prevalence: Not known- 8.9-16% Pt with ≥ 3 BP meds
1994: 14% to 2004: 24%
5–20% HTN- specific underlying disorder

8. I. Intravascular volume
↑ Na  ↑ vascular vol  ↑ cardiac output
Overtime  ↑ Peripheral resistance
Non chloride Na salts have no effect on BP

9. 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

10. 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

11. 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

12. III. Renin-Angiotensin-Aldosterone
Angiotensin II  Vasoconstriction
Atherosclerosis
Aldosterone  Na retention

13. ↓ NaCl in distal asc loop of Henle ↓ pr
↓ 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  ↓

15. 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

16. Secondary Hypertension
Resistant HTN with an identifiable cause:
Primary Aldosteronism
Renal Artery Stenosis
Chronic Kidney Disease
OSA
Pheochromocytoma
Cushing’s Syndrome
Aortic Coarctation

17. Primary Aldosteronism
10 – 20% of resistant HTN
Peak: 30–60 years
Unexplained hypokalemia- 37%
> 50% presentation
Unprovoked hypokalemia : 40-50% primary
aldosteronism
Renal Mag wasting  mild hypomagnesemia

18. Primary Aldosteronism
↑ Aldosterone  ↑ Na, ↓ Renin
 ↑ K excretion
↓ K  ↓ Aldosterone synthesis 
correct K before eval for hyperaldosteronism

19. Primary Aldosteronism
Resistant hypertension
Spontaneous or thiazide-induced hypokalemia
Serum K <3.1 mmol/L
Incidentaloma
FH of primary hyperaldosteronism

20. Primary Aldosteronism
Adrenal adenoma: 60–70%
Unilateral
< 3cm
Unilateral/ bilateral adrenal hyperplasia
Adrenal carcinoma or an ectopic malignancy e.g., ovarian arrhenoblastoma- rare

21. 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

22. 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

23. Primary Aldosteronism
Confirmed by demonstrating : -
- Failure to suppress plasma aldosterone to
isotonic saline
- Failure to suppress aldosterone to
oral NaCl load/ fludrocortisone/ captopril

24. Primary Aldosteronism
High-resolution CT (90%) or MRI scanning
Bilateral adrenal venous sampling for plasma
aldosterone
(sensitivity 95% and specificity 100%)

25. Primary Aldosteronism
Hyperplasia- Aldosterone receptor antagonist
Pts not willing for surgery  Medical Rx
(avoid extensive w/u)

27. 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

28. 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)

29. 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

30. 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

31. Renal Artery Stenosis No ideal screening test for renal vascular HTN
Magnetic resonance angiography atherosclerotic
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

33. 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)

34. OSA Screen if: Obesity + snoring + daytime sleepiness
CPAP (> 5.6 hr/night) Decreases both
systolic and diastolic hypertension

35. 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

36. Pheochromocytoma Hyperglycemia 35% • Leukocytosis ↑ RBC • Occa ↑ ESR
PRA may be ↑ ed by catecholamines
Meds: Tricyclic antidepressants, Antidopaminergic agents, Metoclopramide, and Naloxone- can ppt HTNsive crisis

37. Pheochromocytoma 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

38. Pheochromocytoma 24-hour urinary collection for catecholamines and
metanephrines
- Sensitivity % ; 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

39. Pheochromocytoma Noncontrast CT - followed by CT with nonionic
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

41. Cushing’s syndrome 80% of spontaneous Cushing syndrome HTN
↑ WBC > 11,000/mm3
Hyperglycemia
Hypokalemic metabolic alkalosis :
Cortisol renal mineralocorticoid receptor.

42. 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

43. 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

44. Cushing’s syndrome Tests for diagnosis:
- 24 hr Urinary free cortisol level
- 1mg dexamethasone suppression test
- Evening serum and salivary cortisol level

45. 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

46. Cushing’s syndrome Dexamethasone suppression test:
1 pm  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

47. 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)

48. Cushing’s syndrome Confirmation: - Low dose Dexa suppression test:
Dexa 0.5mg q6hrX 48hrs
- Cortisol > 55.2nmol/L (2 µg/dL)  Cushing
syndrome

49. Etiology of Cushing’s To differentiate ACTH dependant vs ACTH
independent
Plasma or serum ACTH:
< 5pg/mL = adrenal tumor
> pg/mL = pituitary or ectopic ACTH-
secreting tumors.

50. Etiology of Cushing’s To differentiate Pituitary ACTH vs ectopic ACTH:
- 8mg Dexamethasone suppression 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

51. 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

53. Coarctation of Aorta 1-8/1000 live births
30 % Subsequent HTN after surgical correction
Less severe lesions diagnosed in young
adulthood

54. 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

55. 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