In the past, the terms resistant hypertension and refractory hypertension were both used to describe patients with difficult-to-treat hypertension.1 Recently, however, each term has become more defined and the differences between them have become more evident. The definition of resistant hypertension is uncontrolled blood pressure (>140/90 mmHg) despite the use of at least three antihypertensive medications, including a diuretic. Refractory hypertension, on the other hand, is considered a phenotype of antihypertensive treatment failure and occurs in patients with uncontrolled blood pressure despite the use of at least five antihypertensive medications, including a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist.

While resistant hypertension has been found to affect approximately 10-20% of treated hypertensive patients, refractory hypertension is less common and affects about 5% of patients with uncontrolled resistant hypertension.1 Although these conditions were once thought to be relatively similar, resistant and refractory hypertension not only affect different patient populations, but are also associated with different comorbidities and prognoses. Features of resistant and refractory hypertension are summarized in Table 1.

There are various causes associated with resistant and refractory hypertension.1 Apparent resistant hypertension is a term used to describe resistant hypertension having not accounted for causes of “pseudoresistance”. Common causes of pseudoresistance include inaccurate blood pressure readings, noncompliance to medications, undertreatment of a patient, and the white coat effect. Unfortunately, research has found that approximately 50% of the cases of apparent resistant hypertension are actually caused by pseudoresistance. Although difficult, eliminating causes of pseudoresistance would allow for a better determination of the prevalence of true resistant hypertension. Table 2 summarizes causes of pseudoresistance.

There is a lack of data determining the extent to which medication noncompliance, the white coat effect, and inaccurate blood pressure readings contribute to apparent refractory hypertension.1 However, it is believed that these causes of pseudorefractory hypertension are just as common as in the cases of pseudoresistant hypertension. Because, by definition, patients with refractory hypertension are taking at least 5 antihypertensive medications with different mechanisms of action, undertreatment of a patient should not contribute as a cause of refractory hypertension.

The mechanisms that attribute to the development of resistant and refractory hypertension vary significantly.1 Generally, excess intravascular fluid retention is thought to be the main cause of resistant hypertension. There are several attributing factors to fluid retention in patients. These include increasing age, obesity, presence of chronic kidney disease or hyperaldosteronism, African-American race, and excessive sodium intake.