Treatment-Resistant Hypertension: Diagnosis and Management

Treatment-Resistant Hypertension:Diagnosis and Management

Power Over Pressurewww.poweroverpressure.com

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


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*


Which of these patients have treatment-resistant hypertension?


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


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


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


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


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 measurementAutomated 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.


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


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.


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


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 activity Aerobic activity >30 min/day, most days of the week 4-9 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.


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


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


Treatment-Resistant Hypertension: Diagnosis and Management

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