Transcript Resistant Hypertension

Resistant Hypertension
Outline
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Definition
Prevalence
Risk Factors
Secondary / Identifiable Causes HTN
– Elaboration on primary aldosteronism
• Treatment
– Assessing accurately
– Evaluate lifestyle factors
– Minimize interfering drugs
– If appropriate, screen for secondary causes
– Medications
Definition
• Blood pressure greater than goal in spite of concurrent use of
3 optimally dosed medications, with one of the medications
being a diuretic.
• Controlled blood pressure requiring 4 or more medications to
do so.
• Normal blood pressure per JNC 7: <120 /80
• Goal for diabetic patients per the ADA and JNC 7: < 130/80
• Classification of Blood Pressure for Adults per JNC 7
– Prehypertension
– Stage 1 HTN
– Stage 2 HTN
120-139/80-89
140-159/90-99
> 160/100
Prevalence
• Actual prevalence unknown
• Cross-sectional studies and hypertension outcome studies suggest that it
is not uncommon
• National Health and Nutrition Examination Survey (NHANES)(8)
– 53% controlled < 140/90
– 37% with CKD controlled to < 130/80
– 25% with DM controlled to <130/80
• Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack
Trial (ALLHAT)(13)
– After 5 yr f/u, 34% uncontrolled on an average of 2 medications
Risk Factors Associated with Resistant Hypertension
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Older age
High baseline blood pressure
Obesity
Excessive dietary salt ingestion
Excessive alcohol ingestion
Chronic kidney disease
Diabetes
Left ventricular hypertrophy
Black race
Female sex
Residence in southeastern United States
Inadequate diuretic therapy
Use of certain drugs: NSAIDS, sympathomimetics, oral contraceptives,
cyclosporine and tacrolimus, stimulants, ephedra, ma haung, bitter orange,
licorice
Secondary or Identifiable Causes of Resistant Hypertension
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Obstructive sleep apnea
Renal parenchymal disease
Primary aldosteronism
Renal artery stenosis
• Uncommon
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Pheochromocytoma
Cushing’s disease
Hyperparathyroidism
Aortic coarctation
Intracranial tumor
Primary Aldosteronism
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Common in patients with resistant hypertension
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Studies of resistant hypertension showing prevalence between 17 to
23%(1,5,10,11,12)
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Circulating aldosterone levels positively correlate with incident, resistant, and
obesity- and obstructive sleep apnea-related hypertension, as well as impaired
LV function
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The Endocrine Society in their 2008 Clinical Practice Guideline(6) regarding
Primary Aldosteronism recommend screening the following patient groups:
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JNC 7 Stage 2 HTN, ie BP > 160/100
Resistant HTN
HTN with either spontaneous or diuretic-induced hypokalemia
HTN with adrenal incidentaloma
HTN with family history of early-onset HTN or CVA at < 40 yr age
More on primary aldosteronism
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How aldosterone effects blood pressure
– Acts on renal cortical collecting ducts via mineralocortocoid receptor which increases
expression of the sodium/potassium ATPase, resulting in reabsorption of sodium and
excretion of potassium
– Non-genomically activates the amiloride-sensitive epithelial sodium channel (ENaC) in cortical
collecting duct resulting in reabsorption of sodium and excretion of potassium (insulin does
this as well)
– Hypokalemia induces hypertension (14)
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Several studies demonstrating reduced systolic and diastolic blood pressures
with use of spironolactone, eplerenone, and amiloride (2,4)
– One study showing reduction of systolic and diastolic blood pressures by 25 and 12 mm Hg ,
respectively.
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Recommended screening test is a morning plasma aldosterone/renin activity
ratio, with a high (abnormal) ratio being 20 to 30 or greater when aldosterone
reported in nanograms/dl and renin activity in nanograms/ml/hour. (1,6)
Therapeutic Approach to Resistant Hypertension
• Accurate assessment of blood pressure
– Proper technique: sitting 5 minutes with back supported, arm at heart level, air bladder
encircling at least 80% of arm, measure in both arms (and in a leg at least once), take at
least two measurements separated by one minute and average, and do this at least
twice
• Exclude white coat HTN
• Consider pseudohypertension
Evaluate Lifestyle Factors
• Obesity
• Excessive salt use
– AHA recommends use of 2.3 gram of sodium a day or less (= 100 meq of sodium)
– DASH low sodium diet
• Excessive alcohol use
– Limit for men is 24 ounces beer or 10 ounces wine or 3 ounces of 80 proof liquor/day
– Limit for women is half of men’s
Drug –induced causes of resistant hypertension
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Inadequate diuretic therapy
Inadequate doses of anti-hypertensives
Noncompliance with prescribed BP meds
Use of the following classes of drugs:
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NSAIDS, including ASA and acetominophen
Cocaine, amphetamines
Sympathomimetics (decongestents, anorectics)
Oral contraceptive hormones
Cyclosporine and tacrolimus
Erythropoietin
Licorice (included in chewing tobacco)
Herbs such as ma haung, ephedra, bitter orange
Screening for Secondary/Identifiable Causes of HTN
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Chronic kidney disease
Estimated GFR
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Coarctation of the aorta
Measure leg pressure, CT angiography
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Cushing syndrome, chronic steroid RX
Drug-induced/related
Pheochromocytoma
History/dexamethasone suppression
History; drug screening
24-hour urinary
metanephrine,normetanephrine
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Primary aldosteronism
24-hour urinary aldosterone level or
aldosterone/renin activity ratio
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Renovascular hypertension
Sleep apnea
Doppler flow study; magnetic resonance angiography
Sleep study with O2 saturation
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Thyroid/parathyroid disease
TSH; serum
Medications
• General principle: combine agents of different mechanisms
– Little data assessing the efficacy of specific combinations of 3 or more drugs
• Need to consider co-morbid conditions when choosing agents, eg. CHF,
DM, albuminuria, ischemic heart disease, LVH
• Notes from JNC 7 and AHA Scientific Statement re: Resistant HTN
– Chlorthalidone should be preferentially used as opposed to hydrochlorothiazide
– In patients with eGFR < 60 ml/min or CHF, may need to use loop diuretic
– Spironolactone, eplerenone, and amiloride all have studies showing good effects, but
unable to use in patient with serum K+ > 5.0 or serum Creatinine men > 2.5 or in women
>2.0
– In regards to LVH, order of preference is diuretics, ACEi, dihydropine CCB, and BB
– Labetolol, having both beta and alpha blocking properties, is sometimes more effective
than selective beta only blockers
Resources
1.
Resistant Hypertension: Diagnosis, Evaluation, and Treatment. A
Scientific Statement From the American Heart Association Professional
Education Committee of the Council for High Blood Pressure Research.
Published online Apr 7, 2008, located at http://hyper.ahajournals.org
2.
Seventh Report of the Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure.
HTN. 2003; 42: 1206-1252
3.
Enac, Hormones, and HTN.
Published online May 11, 2010, located at
http://www.jbc.org/cigi/doi/10.1074/jbc.R109.025049
4.
Aldosterone Receptor Antagonists
Circulation. 2010; 121: 934-939
Resources
5.
Hyperaldosteronism Among Black and White Subjects With Resistant Hypertension
HTN. 2002; 40: 892-896
6. Case Detection, Diagnosis, and Treatment of Patients with Primary Aldosteronism: An
Endocrine Society Clinical Practice Guideline
Journal of Clinical Endocrinology & Metabolism 2008. 93; 3266-3281
7.
Nishizaka MK Am J Hypertension 2003; 16: 925-930
8.
NHANES. Trends in Prevalence, Awareness, Treatment and Control of HTN in the US,
1988-2000. JAMA 2003; 290: 199-206
9.
J. Clinical Hypertension 2002; 4: 393-404
10. Am J Kidney Dis. 2001; 37: 699-705
11. J Hypertension 2004; 22: 2217-2226
12. J Am Coll Cardiol 2006; 48: 2293-2300
13. ALLHAT. JAMA. 2002; 288: 2981-2997
14. Curr Hypertens Rep . 2008; 10: 496-503