treatment-resistant hypertension: diagnosis and management power over pressure
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Treatment-Resistant Hypertension:Diagnosis and Management
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Not all patients with uncontrolled hypertension are treatment resistant
Uncontrolled HypertensionIncludes patients who lack blood pressure (BP) control for any reason:1
• Inadequate treatment regimens• Poor adherence• Undetected secondary hypertension• True treatment resistance
1. Calhoun DA, et al. Circulation. 2008;117:e510-e526.2. Mancia G, et al. Eur Heart J. 2007;28:1462-1536.
Treatment-Resistant Hypertension • BP that remains above goal with maximum
tolerated doses of ≥3 antihypertensive medications* of different classes; ideally, 1 of the 3 agents should be a diuretic1,2
*Patients who require 4 antihypertensive agents to achieve BP control are also considered treatment resistant, according to some sources.1
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Black race
Excessive dietary salt ingestion
Who is at risk?
*Based on analyses of data from the Framingham Study and The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
Calhoun DA, et al. Circulation. 2008;117:e510-e526.
Obesity
High baseline blood pressure
Older age
Chronic kidney disease
Diabetes
Left ventricular hypertrophy
Female sex
Patient Characteristics Associated With Treatment-Resistant Hypertension*
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Which of these patients have treatment-resistant hypertension?
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Which of these patients have treatment-resistant hypertension?
Calhoun DA, et al. Circulation. 2008;117:e510-e526.
Treatment-resistant hypertension is a diagnosis of exclusion, requiring a systematic approach to evaluation and management
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The systematic approach to diagnosis begins with the definition…
• BP that remains above goal, in spite of…
*All medications should be titrated to the maximum in-label doses or until BP control is achieved, except in cases of intolerance, in which case treatments should be optimized to the maximum tolerated doses†Patients who require 4 antihypertensive agents to achieve BP control are also considered treatment resistant, according to some sources.1
1. Calhoun DA, et al. Circulation. 2008;117:e510-e526.2. Mancia G, et al. Eur Heart J. 2007;28:1462-1536.
Treatment-resistant hypertension is defined as:1,2
• compliance with maximum doses*… • of 3 antihypertensive medications†… • from different classes, ideally including a diuretic…BP Goal
• Reversible causes identified and addressed
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Treatment-resistant hypertension: a systematic approach to evaluation and management
Confirm Accuracy of BP Measurement
• Utilize correct BP measurement technique
• Rule out white-coat effect
Optimize Pharmacotherapy and Adherence
• Regimen of 3 drugs of different classes, including a diuretic
• Assess and improve adherence to the treatment regimen
• Intensify pharmacologic therapy
Address Lifestyle Barriers to BP Control
• Interfering substances• Dietary salt intake• Alcohol consumption • Obesity
Consider Referral to a Specialist
• Treatment for secondary causes of hypertension
• Hypertension specialist for intensive management of true treatment-resistant hypertension
Power Over Pressurewww.poweroverpressure.comMoser M, Setaro JF. N Engl J Med. 2006;355:385-392.
Treatment-resistant hypertension: a systematic approach to evaluation and management
Confirm Accuracy of BP Measurement
• Utilize correct BP measurement technique
• Rule out white-coat effect
Optimize Pharmacotherapy and Adherence
• Regimen of 3 drugs of different classes, including a diuretic
• Assess and improve adherence to the treatment regimen
• Intensify pharmacologic therapy
Address Lifestyle Barriers to BP Control
• Interfering substances• Dietary salt intake• Alcohol consumption • Obesity
Consider Referral to a Specialist
• Treatment for secondary causes of hypertension
• Hypertension specialist for intensive management of true treatment-resistant hypertension
Power Over Pressurewww.poweroverpressure.comMoser M, Setaro JF. N Engl J Med. 2006;355:385-392.
Technique is a common cause of pseudoresistance
• A cuff that is too small may cause an erroneously elevated reading1,2
– Properly sized cuff rule-of-thumb: the cuff’s air bladder should encircle at least 80% of the patient’s arm circumference
1. Makris A, et al. Int J Hypertens.2011:598694.2. Pickering T, et al. Hypertension. 2005;45:142-161.
• Allow patient to sit quietly for 5 minutes with the arm supported at heart level before the reading is taken1,2
– Patient should remove clothing that constricts upper arm2
– The average of 2 readings taken a minute apart should be recorded as the patient’s blood pressure1
– If BP is significantly different between the 2 arms, use the higher reading to guide treatment decisions2
Tips for obtaining accurate office BP readings
• Other factors that can effect BP readings include recent caffeine, nicotine, or alcohol consumption, full bladder, and background noise (including conversation)2
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Eliminating “white-coat” effect
• What Is It?– Elevated BP in physician’s office, but
significantly lower when measured at home1
• How Prevalent?– A recent Spanish study of 8,295 patients with
treatment-resistant hypertension found that 37.5% actually had office-resistant hypertension2• When to Suspect?
– White-coat resistance may be present in patients with consistently elevated BP but no evidence of target organ damage3
• How to Screen?– Consider repeated at-home BP measurements to rule out white-
coat resistance3
– Where available, 24-hour ambulatory BP monitoring (ABPM) may be used for further diagnostic evaluation3
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1. Calhoun D, et al. Circulation. 2008;117;e510-e526. 2. de la Sierra A, et al. Hypertension. 2011;57:898-902. 3. Moser M, Setaro JF. N Engl J Med. 2006;355:385-392.
Automated BP measurement
Automated office BP measurement has several advantages1:• Minimizes potential for user error• Enables efficient collection of multiple BP readings• Reduces patient anxiety and aids in detection of white-coat effect
– Average of 5 BP readings taken 1 minute apart, while patient is alone in room, has been shown to approach average waking BP
Home BP measurement is a useful tool:• Average of as few as 6 readings may achieve similar accuracy for
measurement of true ambulatory BP as ABPM2
• May improve adherence to the treatment regimen3
• Affordable and accessible3,4
• Considerations:– Patients should be trained in proper BP measurement technique3,4
– Patients should utilize validated monitors to ensure accuracy (wrist or finger cuffs should be avoided)3,4
– Patients should bring new devices to clinic to confirm accuracy4
1. Myers M, et al. Hypertension. 2010;55:195-200.2. Chatellier G, et al. Am J Hypertens. 1996;9:644-652.
3. Parati G, et al. J Hypertens. 2008;26:1505-1526.4. Pickering TG, White WB. J Am Soc Hypertens. 2008;2:119-124.
Power Over Pressurewww.poweroverpressure.com
Treatment-resistant hypertension: a systematic approach to evaluation and management
Confirm Accuracy of BP Measurement
• Utilize correct BP measurement technique
• Rule out white-coat effect
Optimize Pharmacotherapy and Adherence
• Regimen of 3 drugs of different classes, including a diuretic
• Assess and improve adherence to the treatment regimen
• Intensify pharmacologic therapy
Address Lifestyle Barriers to BP Control
• Interfering substances• Dietary salt intake• Alcohol consumption • Obesity
Consider Referral to a Specialist
• Treatment for secondary causes of hypertension
• Hypertension specialist for intensive management of true treatment-resistant hypertension
Power Over Pressurewww.poweroverpressure.comMoser M, Setaro JF. N Engl J Med. 2006;355:385-392.
Poor adherence is a common cause of pseudoresistance
1. Van Wijk BLG, et al. J Hypertens. 2005;23:2101-2107.2. Moser M, Setaro JF. N Engl J Med. 2006;355:385-392.3. Calhoun DA, et al. Circulation. 2008;117:e510-e526.4. Hill M, et al. J Clin Hypertens. 2010;12:757-764.
• Within just 1 year, >1 in 3 patients had already discontinued their medication1
• After 10 years, almost 2 in 3 patients did not take their antihypertensive medications continuously1
39%Non-users
39%Continuous
users
22%Restarters
Percentage of patients utilizing antihypertensive agents at 10 years1
Signs of nonadherence2
• Missed office visits • Lack of physiological evidence of
therapy, such aso No change in BPo Absence of anticipated common side
effects
Check for suspected nonadherence by • Discussing medication use with
spouse or caregiver3
• Verifying prescription refills with the pharmacy
• Reviewing factors causing nonadherence and counseling patients on importance of therapy4
Power Over Pressurewww.poweroverpressure.com
Treatment-resistant hypertension: a systematic approach to evaluation and management
Confirm Accuracy of BP Measurement
• Utilize correct BP measurement technique
• Rule out white-coat effect
Optimize Pharmacotherapy and Adherence
• Regimen of 3 drugs of different classes, including a diuretic
• Assess and improve adherence to the treatment regimen
• Intensify pharmacologic therapy
Address Lifestyle Barriers to BP Control
• Interfering substances• Dietary salt intake• Alcohol consumption • Obesity
Consider Referral to a Specialist
• Treatment for secondary causes of hypertension
• Hypertension specialist for intensive management of true treatment-resistant hypertension
Power Over Pressurewww.poweroverpressure.comMoser M, Setaro JF. N Engl J Med. 2006;355:385-392.
Interfering substances may contribute to treatment resistanceUse of interfering substances• Certain medications or other drugs may cause elevated
BP or inhibit the effects of antihypertensive medications– Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2)
inhibitors – Sympathomimetic drugs (ephedra, phenylephrine, cocaine, amphetamines, etc)– Herbal supplements– Anabolic steroids– Appetite suppressants– Erythropoietin– Oral contraceptives
• Question patients about the use of interfering substances– If possible, discontinue use of these agents; otherwise, consider modifying
antihypertensive therapy
Calhoun DA, et al. Circulation. 2008;117:e510-e526.Moser M, Setaro JF. N Engl J Med. 2006;355:385-392.
Power Over Pressurewww.poweroverpressure.com
Patient factors may contribute to treatment resistance
Calhoun DA, et al. Circulation. 2008;117:e510-e526.Moser M, Setaro JF. N Engl J Med. 2006;355:385-392.
Modifiable lifestyle factors
• High sodium intake (urinary sodium excretion >150
mmol/day) may contribute to treatment-resistant
hypertension both by increasing BP directly and by
blunting the BP-lowering effect of antihypertensive drugs– Elderly patients, black patients, and patients with chronic kidney disease may
be more sensitive to salt intake
• Excessive alcohol intake of >3-4 drinks
per day may also contribute to treatment-
resistant hypertension
• Obesity is associated with more severe hypertension,
requirement for increased number of antihypertensive
medications, and increased likelihood of never achieving
BP control– It is estimated that >40% of patients with treatment-resistant hypertension are
obese
Obesity
Excessive dietary salt ingestion
Excessive alcohol ingestion
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What to expect: lifestyle modification effects on BP
Chobanian AV, et al. JAMA. 2003;289:2560-2572.Blumenthal JA, et al. Arch Intern Med. 2000;160:1947-1958.Table courtesy of Hypertension Online. http://www.hypertensiononline.org/slides2/slide01.cfm?tk=24&dpg=5. Accessed April 27, 2012
Modifications* RecommendationApproximate
SBP Reduction
Reduce weight Maintain normal body weight
(BMI of 18.5-24.9 kg/m2)3-20 mm Hg
Adopt DASH dietRich in fruit, vegetables, and low-fat
dairy; reduced saturated and total fat content
8-14 mm Hg
Reduce dietary sodium <100 mmol (2.4 g)/day 2-8 mm Hg
Increase physical activityAerobic activity >30 min/day,
most days of the week4-9 mm Hg
Moderate alcohol consumption
Men: ≤2 drinks/dayWomen: ≤1 drink/day
2-4 mm Hg
*Combining 2 of these modifications may or may not have an additive effect on blood pressure reduction. SBP = systolic blood pressure; BMI = body mass index; DASH = Dietary Approaches to Stop Hypertension.
Power Over Pressurewww.poweroverpressure.com
Treatment-resistant hypertension: a systematic approach to evaluation and management
Confirm Accuracy of BP Measurement
• Utilize correct BP measurement technique
• Rule out white-coat effect
Optimize Pharmacotherapy and Adherence
• Regimen of 3 drugs of different classes, including a diuretic
• Assess and improve adherence to the treatment regimen
• Intensify pharmacologic therapy
Address Lifestyle Barriers to BP Control
• Interfering substances• Dietary salt intake• Alcohol consumption • Obesity
Consider Referral to a Specialist
• Treatment for secondary causes of hypertension
• Hypertension specialist for intensive management of true treatment-resistant hypertension
Power Over Pressurewww.poweroverpressure.comMoser M, Setaro JF. N Engl J Med. 2006;355:385-392.
Difficult-to-control hypertension may be due to underlying conditions• A number of medical conditions may
contribute to hypertension
• Patients should be screened for these disorders if suggestive findings are identified upon history taking, physical exam, or basic laboratory testing
• Patients with treatment-resistant hypertension and a secondary cause will rarely achieve BP control until the underlying cause is treated*
• Consider consultation with a hypertension specialist for evaluation of secondary causes of hypertension
*Many patients with renal artery stenosis or aldosteronism may achieve BP control without diagnosis of the underlying condition.Calhoun DA, et al. Circulation. 2008;117:e510-e526.Moser M, Setaro JF. N Engl J Med. 2006;355:385-392.Kaplan NM, Victor R. Kaplan's Clinical Hypertension. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2010.
Secondary Cause Est Prevalence (%)
Renal artery disease 3.0-4.0
Aldosteronism 1.5-15.0 (higher in recent series)
Renal parenchymal disease 1.0-8.0 (depends on Cr level)
Hyperthyroidism or hypothyroidism
1.0-3.0
Coarctation of the aorta <1.0
Cushing’s syndrome <0.5
Pheochromocytoma <0.5
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Summary: diagnosis and management of treatment-resistant hypertension
• Identify and reverse “pseudoresistance”– Confirm proper measurement technique– Exclude “white-coat” effect– Assess adherence to treatment regimen
• Identify and reverse factors contributing to true resistance– Interfering substances– Modifiable lifestyle factors
• Obesity• Excessive sodium intake• Excessive alcohol intake
• Identify and, if possible, reverse causes of secondary hypertension– Consider consultation with a hypertension specialist for evaluation of
secondary causes of hypertension
The diagnosis and management of true treatment-resistant hypertension is accomplished through a process of exclusion
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