Hypertension Management of the “Difficult Patient” Clay A. Block, M.D. 12-6-2004 What is the “difficult patient”? The “Difficult Patient” Resistant Hypertension Intolerant of Multiple Medicines Definition of Hypertension Normal<= 120/80 Prehypertensive 120-139/80-89 Stage 1 Htn 140-159/90-99 Stage 2 Htn >= 160/100 Resistant Hypertension Failure to reach goal BP in a patient adhering to full doses of an appropriate three drug regimen that includes a diuretic What are the goals of therapy? <140/90 for patients without diabetes or renal disease – Most patients who achieve their systolic goal will also achieve their diastolic goal <130/80 for patients with diabetes or renal disease (JNC 7) What is the Benefit? Stroke Heart Incidence Reduction 35-40% Failure Reduction > 50% Myocardial 25% Infarction Reduction 20- What is the Benefit? Number Needed to Treat to Prevent 1 Death Over 10 Years by Lowering Systolic Pressure by 12 mmHg in Stage 1 Hypertension: 11 In the Presence of CV Disease or Target Organ Damage the NNT falls to 9 Approach to the Patient With Potentially Resistant Htn Review Diagnosis Review Goals Get on Same Page: – Most Patients Will Require Multiple Agents to Achieve Control – All Medicines Have Side Effects and Costs – Don’t Forget Lifestyle Modification and Nonpharmacologic Approaches Approach to Resistant Hypertension Establish “true resistance” – Measure BP accurately – Consider “White Coat Hypertension” – Consider “pseudoresistance” – Consider secondary causes Accurate BP Measurement “Persons should be seated quietly for 5 minutes with feet on the floor and the arm supported at heart level” Cuff must be appropriately sized (cuff bladder must encircle 80% of the arm) Check both arms and a leg (or palpate pulses carefully) Caffeine and Tobacco can transiently raise BP substantially Approach to Resistant Hypertension Establish “true resistance” – Measure BP accurately – Consider “White Coat Hypertension” (WCH) – Consider “pseudoresistance” – Consider secondary causes 'White-coat hypertension' needs attention Q.My doctor wants to start both me and my husband on blood-pressure pills, and his blood pressure is only 145/95. And my blood pressure is fine at home and only high in my doctor's office — isn't this just "white-coat hypertension"? We don't have headaches, tiredness, dizziness or anything – 2002 Honolulu Newspaper Column White Coat Hypertension 20-30% of Apparently Resistant Hypertension May be due to “White-Coat Hypertension” Patients with WCH have an increased risk of CV events and often have some degree of end organ damage Use home or ambulatory monitoring to sort out Home and Ambulatory BP Monitoring (ABPM) Often lower than office readings Useful to “calibrate” home monitors Nocturnal Dip (10-20% fall during the night) is physiologically important (Dippers vs. Non-Dippers) Can identify “windows of poor control” or windows of low BP and correlate with perceived symptoms Dippers vs. Non-Dippers More More More More More LVH silent cerebrovascular disease albuminuria progression of CKD CV mortality Additional Information From Ambulatory Monitoring Heart rate: For each 10% less reduction in heart rate, cardiovascular mortality increases by 30% (J Htn 16, 1335-1343, 1998) Increase in average 24 hour pulse pressure of >= 53 mmHg confers high risk Why and When ABPM Suspected Excessive Apparent Variability Drug Resistance Symptoms Episodes WCH Suggesting Hypotensive Explanation of ABPM plots An Example of “White Coat Hypertension” Approach to Resistant Hypertension Establish “true resistance” – Measure BP accurately – Consider “White Coat Hypertension” – Consider “pseudoresistance” – Consider secondary causes Pseudoresistance Pseudohypertension Non-adherence may account for up to 50% of resistant cases Inadequate Regimen – Especially inadequate diuretic component Interfering medicines and substances also need to be considered – – – – – NSAIDs Excessive Alcohol, Caffeine, or Tobacco Excessive Salt Intake Drugs of Abuse Oral contraceptives Critical Importance of Adequate Diuretic Therapy 23/32 patients referred for management of “resistant hypertension” had evidence of expanded extracellular volume by nuclear study – None had clinical evidence of expanded extracellular volume – All were already on diuretic therapy Am J Med Sci 1989; 298: 361-365 Critical Importance of Adequate Diuretic Therapy Control improved in patients treated with potent thiazide diuretics (indapamide, metolazone, or larger doses of hctz, etc.) or given multiple daily doses of loop diuretics Patients with co-existent renal disease may require more intensive diuretic therapy Pseudohypertension Calcification of the arteries resulting in failure of the BP cuff to compress and occlude flow Suspect if: – severe hypertension by cuff but no end organ injury – Antihypertensive rx results in sx of Hypoperfusion/hypotension without measurable hypotension – Pipe stem calcification on x-ray Pseudohypertension Osler’s Maneuver (the radial artery remains palpable due to calcification and thickening despite inflation of cuff above systolic pressure) – Poorly reproducible “Dynamap”-like devices may be more accurate in this setting Direct Intra-arterial measurement is the only definitive way to establish the diagnosis, but this is uncommonly done The Importance of Adherence Only 1/2 to 2/3 of patients take at least 75% of prescribed antihypertensive medicines – Of those taking < 75%, only 37% achieved BP goal – Of those taking >= 75%, 81% achieved goal Arch Int Med 1987; 147:1393-1396 The Importance of Adherence In a more recent BMJ study, the same rate of adherence was found in both responsive and resistant patients (82%) BMJ 2001; 323:142 Techniques to Improve Adherence Education of the patient – Increases awareness but less effect on behavior Minimize the number of pills – Combination pills (acei/diuretic, arb/diuretic, arb/ca-blocker, etc.) Increase the frequency of visits – Use of care managers Approach to Resistant Hypertension Establish “true resistance” – Measure BP accurately – Consider “White Coat Hypertension” – Consider “pseudoresistance” – Consider secondary causes Important Secondary Causes of Hypertension Obstructive Sleep Apnea Obesity (Metabolic Syndrome) Endocrinopathies – Hyperaldosteronism, thyroid problems, pheochromocytoma Kidney Disease – Renal Insufficiency and Renal Artery Stenosis Drug Resistant Htn Logan J Htn 2001 Stroke or TIA Basetti Sleep, 1999 CHF Javaheri Circ 1999 All Htn Nieto JAMA 2000 CAD Shafer Card 1999 Sleep Apnea and Hypertension Clear dose response between severity of OSA and the incidence of hypertension – May relate to the “Non-dipping” Clear improvement in hypertension of approximately 10mmHg with effective CPAP therapy (and no effect with ineffective CPAP) Obesity and the Metabolic Syndrome According to the Framingham Heart Study, 65-78% of the risk for hypertension can be related to obesity Obesity is linked to: – OSA – Insulin resistance – Resistance to antihypertensive effect of medicines – Activation of the RAAS and the SNS Table 1. Forms of primary aldosteronism Aldosterone-producing adenoma (APA) Bilateral idiopathic hyperplasia (IHA) Primary (unilateral) adrenal hyperplasia Aldosterone-producing adrenocortical carcinoma Familial hyperaldosteronism (FH) Glucocorticoid-remediable aldosteronism (FH type I) FH type II (APA or IHA) Table 2. Prevalence of unrecognized primary aldosteronism in patients with hypertension Author (Ref.) Country No. screened Prevalenc e Gordon et al. (21 ) Australia 199 8.5% Kumar et al. (22 ) India 103 8.7% Kreze et al. (23 ) Slovakia 115 13.0% Lim et al. (24 ) United Kingdom 465 9.2% Loh et al. (25 ) Singapore 350 4.6% Fardella et al. (26 ) Chile 305 9.5% Schwartz et al. (27 ) United States 117 12.0% Rossi et al. (10 ) Italy 1,046 6.3% Renal Artery Stenosis Associations of Clinical Characteristics with Renal Artery Stenosis Krijnen, P. et. al. Ann Intern Med 1998;129:705-711 Diagnosis of Renal Artery Stenosis Clinical Features – Severe hypertension, resistance, flash pulmonary edema, cad/cvd/pvod, abdominal bruits, hypokalemia, high renin level, marked clinical response to angiotensin blockade, ARF Imaging Options – Duplex ultrasound, MRA, CT angiography Diagnostic Tests for Renal Artery Stenosis in Patients Suspected of Having Renovascular Hypertension: A Meta-Analysis G. Boudewijn C. Vasbinder, MD; Patricia J. Nelemans, MD, PhD; Alfons G.H. Kessels, MD, MSc; Abraham A. Kroon, MD, PhD; Peter W. de Leeuw, MD, PhD; and Jos M.A. van Engelshoven, MD, PhD 18 September 2001 | Volume 135 Issue 6 | Pages 401-411 Our meta-analysis indicates that CTA and gadoliniumenhanced MRA are superior to the other studied diagnostic tests for the detection of renal artery stenosis. Careful selection based on clinical evaluation, which can increase the pretest probability to 20% to 40%, is a prerequisite for cost-effective use of these tests in the work-up strategy for patients with possible renovascular hypertension Because only a limited number of published studies on CTA and gadoliniumenhanced MRA could be included in our meta-analysis, further research is recommended. What is the definition of RAS? Stenosis is considered >=50% luminal narrowing Clinically relevant (also called “critical”) stenosis is not well defined (50-70% by some pharmacologic studies vs. 80% by renal vein renin Response to intervention does not correlate well with pre or post treatment degree of stenosis What is the natural history of RAS? RAS is part of a systemic disease that effects the entire vascular tree and both kidneys Patients are at greater risk for CV events than of ESRD Angiographic progression occurs in 49% and occlusion occurs 14% Renal atrophy over two years was 11.7% vs. 20.8% for stenoses <60% and >=60% respectively Goals of Management of RAS Prevention of clinical events such as stroke, MI, chf, or renal failure Surrogate markers or goals are: – Improvement or normalization of BP – Restoration of renal artery patency November 2003 • Volume 42 • Number 5 Controversies in nephrology Stable patients with atherosclerotic renal artery stenosis should be treated first with medical management Medical Therapy vs. Revascularization Medical therapies such as antihypertensives, antiplatelet agents and lipid lowering agents will not restore patency, may or may not improve BP, but have proven efficacy in the reduction of CV events and death Renal artery revascularization can restore patency, has at best a modest effect on BP , and has no clearly documented effect in the prevention of renal failure or CV events The Role for Inhibition of the RAAS 108 patients at high risk for severe RAS were treated with ACEI with diuretics – 44 with bilateral stenosis – 29 with a solitary functioning kidney – 20 with unilateral stenosis 57 developed >=20% rise in creatinine between 4 days and 4 weeks (about half early) – All recovered to baseline after stopping the ACEI – KI 1998; 53:986-993 Predictors of Poor Response to Revascularization Elevated Resistive Indices that are indicative of glomerulosclerosis and interstitial fibrosis Advancing Age Small kidney size Complications of renal artery revascularization Serious complications excluding hematomas occurred in 11% of renal artery stent procedures 9.5% incidence of clinical atheroembolic events ~5% incidence of ARF 5 fatalities in a meta-analysis of 644 patients Role for Revascularization Resistant hypertension Patients intolerant of ACEI or ARB with severe hypertension (more than 20% increase in serum creatinine) Patients with rapidly declining renal function (1/3 may benefit) Recurrent or intractable pulmonary edema Summary Establish Dx, risks and benefits Eliminate interference and optimize lifestyle, adherence and regimen Consider secondary causes See frequently and modify regimen References The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure European Society of Hypertension Newsletter 2003; 4, No. 15 Minireview: Primary Aldosteronism-Changing Concepts in Diagnosis and Treatment. Endo 144(6):2208-2213 Obesity, Sleep Apnea, and Hypertension. Hypertension Dec 2003:1067-1074 Clinical Usefulness of Ambulatory Blood Pressure Monitoring. J Am Soc Neph 15: S30-S33, 2004 Mayo Clinic Proceedings March 2000. 278-284
