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Resistant and Secondary Hypertension Oliver Z. Graham, MD “Hypertension Specialist” Department of Internal Medicine What I am going to talk about Why BP control is important Initial workup of newly diagnosed HTN Secondary hypertension Sleep apnea Primary Hyperaldosteronism Renal Artery Stenosis White coat HTN Tips for improving adherence Resistant hypertension and diuretic use Benefits of Lowering BP Antihypertensive therapy has been associated with: 35-40% reduction in stroke 20-25% reduction in MI 50% reduction in heart failure Treating HTN – A Clear Reduction in MORTALITY If patient with BP 140-159/90-99, (and other cardiac RF) achieving a 12 mm Hg decrease in SBP over 10 years will prevent one death for every 11 patients treated!! In the presence of CVD or target-organ damage, same tx will prevent one death for every 9 patients treated!! % Reduction In Relative Risk Diabetes: Tight Glucose vs Tight BP Control and CV Outcomes in UKPDS 0 Stroke DM Deaths Any Diabetic Endpoint Microvascular Complications 5% -10 10% 12% -20 24% * -30 32% * -40 -50 32% *P <0.05 compared to tight glucose control 44% * Tight Glucose Control (Average HA1c 7.9 vs 7.0) Bakris GL, et al. Am J Kidney Dis. 2000;36(3):646-661. Reprinted by permission, Harcourt Inc. 37% * Tight BP Control (Average 154/87 vs 144/82) Slide Source HypertensionOnline www.hypertensiononline.org www.hypertensiononline.org A Case Study… A 55 year old Hispanic man comes to your clinic for a first visit. He recently immigrated from Mexico several years ago, he was on some medications for blood pressure previously but has not taken anything for several years. PE 5’ 8” 190 pounds BP 172/105 HR 82 What are you looking for on PE? What kind of screening labs do you order? New Hypertensive Patient – The Physical Examination Test accuracy of reading (check cuff size, check other arm, repeat office reading or home reading) “fundoscopic evaluation” Thorough exam heart/lung/JVP Auscultate for abdominal bruit (renal artery stenosis?) Femoral pulses (coarctation?) LE edema Diagnosis of HTN: Initial Workup The “cheap screening for secondary hypertension” labs: Creatinine Sodium, Potassium (hyperaldosteronism) U/A (nephrotic syndrome, nephritic syndrome) Calcium (secondary hyperparathyroidism) CBC (polycythemia) UTox (CCRMC special) Consider TSH (both hyper and hypothyroidism associated with hypertension) Diagnosis of HTN: Initial Workup The “Cardiovascular Risk” labs: EKG (get as baseline + evaluate for LVH, prior MI) Lipid panel Fasting glucose Back to case study…. Repeat SBP 182/96, Obese (BMI 35). CV/lungs WNL. No abd bruit. No edema. Na 141 K 4.2 Creat 1.2 U/A neg, except 30 protein. Spot urine protein 0.14 g/24 hours. EKG – LVH. CBC, Calcium, TSH, WNL. Utox neg. Fasting Glucose 145, HA1c 8.1 Would you do a secondary HTN workup? If so, what would you focus on? Risk factors for secondary hypertension Poor response to therapy An acute rise of BP over a previously stable value Confirmed onset of hypertension before 20 or after 50 years (need accurate hx) Age < 30 in non-obese, non-black patients with a negative family hx Stage 3 HTN (>180/110) Prevalence of Secondary Causes of Hypertension COMMON (prevalence) RARE (prevalence) Sleep Apnea (? Really Common ?) Renal Disease (1-8%) Pheochromocytoma (<0.5%) Hyperaldosteronism (1.5-15%) Renal Artery Stenosis (3-4%) Cushing’s Syndrome (0.5%) Thyroid disease (1-3%) Carcinoid Syndrome Coarctation of Aorta (<1%) Acromegaly Hypercalcemia Obstructive Sleep Apnea In one study, 83% of those with resistant HTN had sleep apnea Intervention Studies (using CPAP in pts with sleep apnea + resistant HTN): Two studies show decrease SBP 10-15 Other studies showed little or no reduction after CPAP administration BOTTOM LINE: Reasonable to screen those with resistant hypertension, especially if with risk factors (obesity, daytime somulence, apnea history) Primary Hyperaldosteronism and Hypertension Primary hyperaldo – excessive secretion aldosterone from tumor or Hyperplasia salt retention increase blood pressure Primary Hyperaldosteronism May be present in 1.5 - 15% those with resistant hypertension Etiologies Clinical features Hypokalemia (although normal K in 30%) Adrenal adenoma Bilateral adrenal hyperplasia Hypernatremia Metabolic alkalosis Workup – AM plasma renin and aldosterone levels, go to Uptodate Hypertension and renal artery stenosis less blood flow Decreased blood to kidney kidney “senses” diminished BP Activation renin/angiotension system vasoconstriction Aldosterone secretion salt retention Renal Artery Stenosis – Etiologies Fibromuscular dysplasia (young women) Atherosclerotic (HTN/DM/lipids/FH etc) Suspect in resistant hypertension and: Elevation Cr with admin ACE/ARB Unilateral small kidney on imaging Abdominal bruit Repeated episodes flash pulmonary edema Acute rise in BP over previously stable value Renal Artery Stenosis and Resistant HTN – Does Dx/Intervention matter? RAS from fibromuscular dysplasia responds well to angioplasty (HTN improved in 20-80%) RAS from atherosclerosis: sustained response to intervention “unusual” (lesions usually too diffuse) NEJM study: 106 pts randomized to angioplasty vs med tx. No difference in BP control or renal insufficiency noted at 1 year No good studies using angioplasty + stents Complications from intervention include atheroembolism dialysis Renal Artery Stenosis and Resistant HTN – Does Dx/Intervention matter? BOTTOM LINE: If you suspect RAS, people who may benefit from intervention: Young women (may have dysplasia) Suspicion for atherosclerotic RAS + any of the following: 1) HTN not responsive to treatment, esp if severely elevated over stable value 2) Progressive renal failure 3) Repeated episodes flash pulmonary edema 4) Age < 60 Workup: At our institution, order MRA Screening for the rare stuff – Reasonable to go by Hx/PE Pheochromocytoma Paroxysmal elevations in BP, HA, Palpitations, sweating Cushings disease Moon facies, central obesity, striae, inc glucose Coarctation of aorta Hypertension in arms but not legs, decreased femoral pulse, abnl murmur/bruits Acromegaly Looks like they have acromegaly Height: 5’11” Weight: 129 My BMI, circa 1991: 17 Back to our patient… His blood pressure is 182/96. How many agents would you start him on? “The Rule of 10’s” Each BP med will reduce SBP by about 10 mmHg Per JNC recommendations: If BP > 20/10 of goal, consider initial treatment with TWO agents (one should probably be diuretic) Case continued So you start the patient on lisinopril 10 mg daily + HCTZ 25 daily When should you check his potassium and creatinine? Recommended intervals for Monitoring Creatinine/K in ACE/ARB tx After initiation or change of ACE/ARB dose After dose is stable GFR > 60 4-12 weeks GFR 30-59 2-4 weeks GFR < 30 <2 weeks 6-12 months 3-6 months 1-3 months Back to our patient… A sleep study was ordered given the patient’s obesity. He comes back for followup, and is on HCTZ 25 daily, Lisinopril 20 daily. His BP in office is 174/96 What are some other features that may be contributing to the patient’s hypertension? White Coat Hypertension May be responsible for 30% those with resistant hypertension Appears that BP values obtained at home correlate better with target organ involvement If a consideration – have patient check BP at home, have therapy target those values Medication Adherence – Possibly helpful tips Appropriately educate patient/family about benefits of good BP control Have patient check BP at home periodically and bring in logbook Use “Rule of 10’s” to guide expectations patient: “You will likely need 2 or more meds to get your BP under control” Tell Medication Adherence – Possibly helpful tips on prescription: “take 1 tablet daily to get blood pressure less than 140/90” Write Use fixed-dose combinations Benazepril/HCTZ combo on both CCHP and MediCal formularies Other things that can increase Blood Pressure Medications NSAIDS (inc SBP by approx 4 mmHg) Cocaine, Amphetamines Phenylephrine Anabolic Steroids Erythropoietin Oral Contraceptives Excessive EtOH (>3-4 drinks/day) High Salt Diet Obesity Another patient comes in…. A 65 YO woman is seen in your clinic for f/u of longstanding HTN. She is on HCTZ 12.5 mg, Toprol XL 200 mg daily, amlodipine 10 daily, lisinopril 40 daily. Her BP is 162/94. Creat 1.4 (GFR 45), no protienuria. Utox neg. She emphatically states that she takes her medications as directed. What is your next step in managing her HTN? Diuretics – Cornerstone of HTN therapy Most patients with resistant hypertension have inappropriate sodium/fluid retention EFFECTIVE DIURETIC THERAPY ESSENTIAL for HTN control 60% of those with resistant HTN improve BP by add/increasing diuretic therapy What is the proper HCTZ dose? In uncomplicated patients without resistant HTN or renal disease, no real benefit in HTN control with increase from 12.5 vs 25/50 daily Those with resistant HTN and normal renal function – may need increase in HCTZ 12.5 25 50 What about resistant HTN with GFR < 50? HCTZ may not be not effective Options: 1. Substitiute another thiazide: Metolazone 2.5 – 10 daily 2. Substitute for loop diuretic: Lasix 20-80 BID or Bumex 0.5-2 BID (Dosed BID because of short half life) Toresemide 2.5 – 5 daily (longer half life, more expensive) Resistant HTN and Diuretics Spirinolactone for Resistant Hypertension Study patients with uncontrolled HTN and on 4 agents were given spirinolactone 12.550 mg daily Avg BP reduction at 6 months: 25/12 (!!) Degree of antihypertensive benefit similar in subjects with and without primary hyperaldosteronism **Follow K very closely, esp in renal failure Probably avoid in Creatinine > 2 My bullet points… Blood pressure control is a worthwhile endeavor and improves mortality more than most other stuff you do in clinic Strongly consider sleep apnea screening in hypertensive patients Think of primary hyperaldosteronism in those with hypertension and low K Renal artery stenosis relatively common, but unclear if invasive procedures work My bullet points, continued “Rule of 10’s” guideline helpful for guidance tx OK to follow home BPs if patient with white coat HTN Try combination medication and writing BP goals on prescription to improve adherence If patient has resistant hypertension, ensure s/he is on proper diuretic dose HCTZ may not work at GFR < 50 Spirinolactone may be really great
