FAQ
Resistant hypertension: summary of the American Heart Association’s scientific statement
Introduction
The American Heart Association (AHA) recently published a scientific statement on the diagnosis, evaluation, and treatment of resistant hypertension. Blood pressure that remains above goal despite the concurrent use of 3 or more antihypertensive agents from different classes is the definition of resistant hypertension. Although the exact prevalence of resistant hypertension is unknown, it is common. Similarly, the prognosis of patients with resistant hypertension has not been specifically evaluated. Patient characteristics associated with resistant hypertension include: /b>>older age, high baseline blood pressure, obesity, excessive dietary sodium intake, chronic kidney disease, diabetes, left ventricular hypertrophy, being African-American, female gender, and residence in the southeastern United States. Resistant hypertension is almost always associated with more than one etiology. Treatment should focus on identifying and reversing any pertinent lifestyle factors and secondary causes of resistant hypertension and using effective multi-drug regimens. Ideally, optimal doses should be utilized and one of the classes should be a diuretic. This review will focus on the nonpharmacological and pharmacological treatment recommendations for resistant hypertension. Clinicians are encouraged to review the full update at http://hyper.ahajournals.org.
Pseudoresistance
Factors possibly affecting blood pressure control despite use of several antihypertensives include poor blood pressure technique, lack of medication adherence, and the white-coat phenomenon. Measuring blood pressure before letting the patient sit quietly and using too small of a blood pressure cuff are 2 common mistakes in technique that can result in falsely elevated blood pressure readings. Lack of compliance with antihypertensive therapy is a major reason for poor blood pressure control. Approximately 40% of newly diagnosed hypertensive patients discontinue their blood pressure lowering medication(s) within the first year of treatment. Simplifying regimens as much as possible can maximize adherence. This can include using once-daily combination products to reduce the number of pills and frequency of administration. Frequent clinic visits and recording home blood pressure readings have also been demonstrated to enhance adherence. Twenty to 30% of patients with resistant hypertension have a component of white-coat hypertension. These patients tend to have less cardiovascular risk and less severe target organ damage. Patients who have consistently higher in-office blood pressure readings compared to out-of-office measurements, have persistent signs of overtreatment, or have chronically high office blood pressure values but lack target organ damage should have 24-hour ambulatory blood pressure monitoring performed with a mean daytime ambulatory blood pressure goal of <135/85 mm Hg.
Secondary Causes of Hypertension
Several medications can interfere with blood pressure control and contribute to treatment resistance. These medications include nonsteroidal anti-inflammatory agents (including aspirin), cyclooxygenase (COX)-2 inhibitors, sympathomimetic agents (decongestants, diet pills, cocaine), stimulants (methylphenidate, dextroamphetamine, amphetamine, methamphetamine, modafinil), glucocorticoids, alcohol, oral contraceptives, cyclosporine, erythropoietin, natural licorice, and some herbal compounds (ephedra, ma huang). Whenever possible, these medications should be avoided or withdrawn in patients with resistant hypertension. Common medical causes of resistant hypertension (secondary hypertension) include obstructive sleep apnea, renal parenchymal disease, primary aldosteronism, and renal artery stenosis. Less common secondary causes include pheochromocytoma, Cushing’s disease, hyperparathyroidism, aortic coarctation, and intracranial tumor. Whenever possible, treatment should focus on the specific disorder contributing to resistant hypertension.
Nonpharmacological Treatment
Patients with resistant hypertension who are overweight or obese should be encouraged to lose weight. A cited study found that a sustained 10 kg weight loss resulted in an average 6 mm Hg reduction in systolic blood pressure and a 4.6 mm Hg reduction in diastolic blood pressure. Although not specifically evaluated in resistant hypertension, dietary salt restrictions of <100 mEq sodium/24-hours is recommended. Sodium restrictions have resulted in reductions in systolic and diastolic blood pressure of 5 to 10 mm Hg and 2 to 6 mm Hg, respectively. Alcohol should also be limited, and should not exceed 2 drinks (1 ounce of ethanol) per day for men and 1 drink per day for women or lighter-weight persons. Patients should also be encouraged to increase physical activity with a recommendation to exercise for a minimum of 30 minutes on most days of the week. The DASH (Dietary Approaches to Stop Hypertension) diet, which is rich in fresh fruit and vegetables, high in low-fat dietary products, potassium, magnesium, and calcium, and low in total saturated fats, is also recommended.
Pharmacological Treatment
Underuse of diuretic therapy is a common finding in patients with resistant hypertension. Volume expansion is a frequent phenomenon that contributes to treatment resistance. Therefore, a diuretic is essential in the management of resistant hypertension. A long-acting thiazide diuretic is preferred in most individuals. Chlorthalidone is preferred over hydrochlorothiazide in patients with resistant hypertension based on superior efficacy in a head-to-head trial. Patients with a creatinine clearance <30 mL/minute may require a loop diuretic. Several studies have confirmed the benefit of 2 medication combination therapy, especially when one of the agents is a thiazide diuretic. However, there is little data evaluating the efficacy of specific combinations of 3 or more antihypertensives. Combinations of 3 or more agents should be individualized and take into account prior benefit, history of adverse events, concomitant disease processes, and patient financial limitations.
A triple drug regimen of an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), calcium channel blocker, and a thiazide diuretic is effective and well tolerated. Aldosterone antagonists have also shown benefit as add-on therapy in patients with resistant hypertension. Because of their dual sites of action, alpha-beta antagonists may be more effective antihypertensives compared to beta-antagonists. Central acting agents and vasodilators are effective but have a high incidence of adverse effects. The combination of an ACE inhibitor and an ARB or dihydropyridine and non-dihydropyridine calcium channel blocker has been reported to have additive antihypertensive effects compared to monotherapy. However, these combinations are not recommended over using agents from distinctly different classes. Improved mean 24-hour blood pressure control was achieved when at least one of the antihypertensives was taken at bedtime. It has also been documented that patients with uncontrolled hypertension benefit from referral to a hypertension specialist. Finally, it is acknowledged that resistant hypertension has not been adequately studied, and trials assessing the efficacy of specific multidrug combinations are needed to better guide therapy.
Reference
Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension. 2008;51:000-000 (published ahead of print).