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  1. HypertensionManagement of the “Difficult Patient” Clay A. Block, M.D. 12-6-2004

  2. What is the “difficult patient”?

  3. The “Difficult Patient” • Resistant Hypertension • Intolerant of Multiple Medicines

  4. Definition of Hypertension • Normal<= 120/80 • Prehypertensive 120-139/80-89 • Stage 1 Htn 140-159/90-99 • Stage 2 Htn >= 160/100

  5. Resistant Hypertension • Failure to reach goal BP in a patient adhering to full doses of an appropriate three drug regimen that includes a diuretic

  6. 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)

  7. What is the Benefit? • Stroke Incidence Reduction 35-40% • Heart Failure Reduction > 50% • Myocardial Infarction Reduction 20-25%

  8. 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

  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

  10. Approach to Resistant Hypertension • Establish “true resistance” • Measure BP accurately • Consider “White Coat Hypertension” • Consider “pseudoresistance” • Consider secondary causes

  11. 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

  12. Approach to Resistant Hypertension • Establish “true resistance” • Measure BP accurately • Consider “White Coat Hypertension” (WCH) • Consider “pseudoresistance” • Consider secondary causes

  13. '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

  14. 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

  15. 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

  16. Dippers vs. Non-Dippers • More LVH • More silent cerebrovascular disease • More albuminuria • More progression of CKD • More CV mortality

  17. 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

  18. Why and When ABPM • Suspected WCH • Excessive Variability • Apparent Drug Resistance • Symptoms Suggesting Hypotensive Episodes

  19. Explanation of ABPM plots

  20. An Example of “White Coat Hypertension”

  21. Approach to Resistant Hypertension • Establish “true resistance” • Measure BP accurately • Consider “White Coat Hypertension” • Consider “pseudoresistance” • Consider secondary causes

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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

  28. 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

  29. 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

  30. Approach to Resistant Hypertension • Establish “true resistance” • Measure BP accurately • Consider “White Coat Hypertension” • Consider “pseudoresistance” • Consider secondary causes

  31. Important Secondary Causes of Hypertension • Obstructive Sleep Apnea • Obesity (Metabolic Syndrome) • Endocrinopathies • Hyperaldosteronism, thyroid problems, pheochromocytoma • Kidney Disease • Renal Insufficiency and Renal Artery Stenosis

  32. All Htn Nieto JAMA 2000 CAD Shafer Card 1999 Drug Resistant Htn Logan J Htn 2001 Stroke or TIA Basetti Sleep, 1999 CHF Javaheri Circ 1999

  33. 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)

  34. 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

  35. Table 1. Forms of primary aldosteronism

  36. Table 2. Prevalence of unrecognized primary aldosteronism in patients with hypertension

  37. Renal Artery Stenosis

  38. Associations of Clinical Characteristics with Renal Artery Stenosis Krijnen, P. et. al. Ann Intern Med 1998;129:705-711

  39. 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

  40. 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 gadolinium-enhanced MRA are superior to the other studied diagnostic tests for the detection of renalarterystenosis. 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 gadolinium-enhanced MRA could be included in our meta-analysis, further research is recommended.

  41. 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

  42. 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

  43. 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

  44. November 2003 • Volume 42 • Number 5 Controversies in nephrologyStable patients with atherosclerotic renal artery stenosis should be treated first with medical management