how to recognize the different faces of hypertension reena kuriacose, md. facp. march 26,2012
TRANSCRIPT
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
• 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
• 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 secretionPharmacological 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 HypertensionResistant HTN with an identifiable cause:
1. Primary Aldosteronism2. Renal Artery Stenosis3. Chronic Kidney Disease4. OSA5. Pheochromocytoma6. Cushing’s Syndrome7. 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
• 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 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
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% • Leukocytosis• ↑ RBC • Occa ↑ ESR• ↑ Ca
• PRA may be ↑ ed by catecholamines
• Meds: Tricyclic antidepressants, Antidopaminergic agents, Metoclopramide, and Naloxone- can ppt HTNsive crisis
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
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• 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 ACTH- secreting 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
