Resistant hypertension: Diagnostic strategies and management
ABSTRACTBlood pressure that remains above target levels despite drug therapy is an increasingly common problem. The evaluation of resistant hypertension includes confirming blood pressure measurements with an automated device that works without the clinician present and with 24-hour ambulatory monitoring; assessing for target-organ damage; and determining if kidney disease is present or if the hypertension is secondary to another condition. The goal of management should be to optimize drug therapy by using different classes of appropriate drugs.
KEY POINTS
- Resistant hypertension is arbitrarily divided into two categories: apparent resistance (pseudoresistant hypertension) and true resistance. Apparent resistance is much more common.
- Common causes of true resistant hypertension are volume overload, excessive alcohol use, some drugs (eg, nonsteroidal anti-inflammatory drugs), and some over-the-counter supplements.
- Volume overload commonly results from excess sodium intake, kidney disease, or a counterregulatory response to arterial vasodilation.
- To address volume overload, an appropriate diuretic at an adequate dosage is a cornerstone of therapy, along with potassium supplementation.
- Hospitalization may be needed to monitor drug intake if poor compliance is suspected.
Poor control of blood pressure is one of the most common risk factors for death worldwide, responsible for 62% of cases of cerebral vascular disease and 49% of cases of ischemic heart disease as well as 7.1 million deaths annually. As our population ages and the prevalence of obesity, diabetes, and chronic kidney disease increases, resistant hypertension will be seen more often in general practice.
Using a case study, this article will provide a strategy for diagnosing and treating resistant hypertension.
CASE: A WOMAN WITH LONG-STANDING HIGH BLOOD PRESSURE
A 37-year-old woman was referred for help with managing difficult-to-control hypertension. She had been diagnosed with hypertension at age 32, and it was well controlled until about 2 years ago. Various combinations of antihypertensive drugs had been tried, and a search for a cause of secondary hypertension revealed no clues.
On examination, her blood pressure averaged 212/124 mm Hg, and her heart rate was 109 beats per minute. Her medications were:
- Amlodipine (Norvasc), a calcium channel blocker, 10 mg once daily
- Valsartan (Diovan), an angiotensin II receptor antagonist, 160 mg once daily
- Carvedilol (Coreg), a beta-blocker, 25 mg twice daily
- Labetalol (Normodyne), a beta-blocker, 400 mg three times daily
- Clonidine (Catapres), a sympatholytic agent, 0.05 mg three times daily
- Doxazosin (Cardura), a peripheral alpha-blocker, 16 mg once daily
- Xylometazoline (Xylomet), an alpha agonist nasal spray for nasal congestion.
She had previously been taking spironolactone (Aldactone), hydralazine (Apresoline), and hydrochlorothiazide, but they were discontinued because of adverse effects.
Does this patient have resistant hypertension? How should her condition be managed?
RESISTANT HYPERTENSION DEFINED
The seventh Joint National Committee and the American Heart Association define resistant hypertension as an office blood pressure above the appropriate goal of therapy (< 140/90 mm Hg for most patients, and < 130/80 mm Hg for those with ischemic heart disease, diabetes, or renal insufficiency) despite the use of three or more antihypertensive drugs from different classes at full dosages, one of which is a diuretic.1,2
In this definition, the number of antihypertensive drugs required is arbitrary. More importantly, the concept of resistant hypertension is focused on identifying patients who may have a reversible cause of hypertension, as well as those who could benefit from special diagnostic or therapeutic intervention because of persistently high blood pressure.
This definition does not apply to patients who have recently been diagnosed with hypertension.
Resistant hypertension is not synonymous with uncontrolled hypertension, which includes all cases of hypertension that is not optimally controlled despite treatment, including apparent resistance (ie, pseudoresistance) and true resistance (defined below).
COMMON, BUT ITS PREVALENCE IS HARD TO PINPOINT
The prevalence of resistant hypertension is unknown because of inadequate sample sizes in published studies. However, it is common and is likely to become more common with the aging of the population and with the increasing prevalence of obesity, diabetes mellitus, and chronic kidney disease.
In small studies, the prevalence of resistance in hypertensive patients ranged from 5% in general medical practice to more than 50% in nephrology clinics. In the National Health and Nutrition Examination Survey in 2003 to 2004, only 58% of people being treated for hypertension had achieved blood pressure levels lower than 140/90 mm Hg,3 and the control rate in those with diabetes mellitus or chronic kidney disease was less than 40%.4
Isolated systolic hypertension—elevated systolic pressure with normal diastolic pressure—increases in prevalence with age in those with treated, uncontrolled hypertension. It accounted for 29.1% of cases of treated, uncontrolled hypertension in patients ages 25 to 44, 66.1% of cases in patients ages 45 to 64, and 87.6% of cases in patients age 65 and older.5
Even in clinical trials, in which one would expect excellent control of hypertension, rates of control ranged from 45% to 82%.6–10
APPARENT RESISTANCE VS TRUE RESISTANCE
Resistant hypertension can be divided arbitrarily into two broad categories: apparent resistance and true resistance, with the prevalence of apparent resistance being considerably higher. Each broad category has a long list of possible causes; most are readily identifiable in the course of a thorough history and physical examination and routine laboratory testing. If resistance to therapy persists, referral to a hypertension specialist is a logical next step.
Detecting pseudoresistance
Causes of apparent resistance include improper technique in measuring blood pressure, such as not having the patient rest before measurement, allowing the patient to have coffee or to smoke just before measurement, or not positioning the patient’s arm at the level of the heart during measurement.
Many elderly patients have calcified arteries that are hard to compress, leading to erroneously high systolic blood pressure measurements, a situation called pseudohypertension and a cause of pseudoresistance. The only way to measure blood pressure accurately in such cases is intra-arterially. These patients often do not have target-organ disease, which would be expected with high systolic pressure.
The white-coat phenomenon is another common cause of apparent resistance. It is defined as persistently elevated clinic or office blood pressure (> 140/90 mm Hg), together with normal daytime ambulatory blood pressure (the “white-coat effect” is the difference between those blood pressures).
Finally, poor patient adherence to treatment is estimated to account for 40% of cases of resistant hypertension.4,5,11 Poor adherence is difficult to prove because patients often claim they are compliant, but certain clues are indicative. For example, patients taking a diuretic should have increased uric acid levels, so normal uric acid levels in a patient on a diuretic could be a clue that he or she is not taking the medication. If poor adherence is suspected, patients should be admitted to the hospital to take the medications under close observation.
