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Slide 2 Resistant Hypertension Slide 3 Outline 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 Slide 4 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 7:160/100 Slide 5 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 toSlide 6 Risk Factors Associated with Resistant Hypertension 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 Slide 7 Secondary or Identifiable Causes of Resistant Hypertension Common Obstructive sleep apnea Renal parenchymal disease Primary aldosteronism Renal artery stenosis Uncommon Pheochromocytoma Cushings disease Hyperparathyroidism Aortic coarctation Intracranial tumor Slide 8 Primary Aldosteronism Common in patients with resistant hypertension Studies of resistant hypertension showing prevalence between 17 to 23%(1,5,10,11,12) Circulating aldosterone levels positively correlate with incident, resistant, and obesity- and obstructive sleep apnea-related hypertension, as well as impaired LV function The Endocrine Society in their 2008 Clinical Practice Guideline(6) regarding Primary Aldosteronism recommend screening the following patient groups: 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 Slide 9 More on primary aldosteronism 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) 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. 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) Slide 10 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 Slide 11 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 mens Slide 12 Inadequate diuretic therapy Inadequate doses of anti-hypertensives Noncompliance with prescribed BP meds Use of the following classes of drugs: 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 Drug induced causes of resistant hypertension Slide 13 Screening for Secondary/Identifiable Causes of HTN Chronic kidney disease Estimated GFR Coarctation of the aorta Measure leg pressure, CT angiography Cushing syndrome, chronic steroid RX History/dexamethasone suppression Drug-induced/related History; drug screening Pheochromocytoma 24-hour urinary metanephrine,normetanephrine Primary aldosteronism 24-hour urinary aldosterone level or aldosterone/renin activity ratio Renovascular hypertension Doppler flow study; magnetic resonance angiography Sleep apnea Sleep study with O 2 saturation Thyroid/parathyroid disease TSH; serum Slide 14 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 Slide 15 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.orghttp://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 http://www.jbc.org/cigi/doi/10.1074/jbc.R109.025049 4.Aldosterone Receptor Antagonists Circulation. 2010; 121: 934-939 Slide 16 Resources 5.Hyperaldosteronism Among Black and White Subjects With Resistant Hypertension HTN. 2002; 40: 892-896 6. Case Detection, Diagnos i s, 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 Slide 17 Slide 18 Slide 19