Refractory hypertension: an important clinical phenotype.

C alhoun et al 1 in this edition of the journal report on an important clinical phenotype: refractory hypertension. They provide important information on the prevalence, risk factors, and comorbidities for refractory hypertension in a large observational study, including adults from across the United States. 2 They note that 0.5% of the patients receiving antihy-pertensive treatment and 3.6% of the individuals with resistant hypertension had refractory hypertension. These observations are of great importance and provide key evidence that true antihypertensive treatment failure is uncommon. Moreover, the observations also help us appreciate the paradox that with an increasing number of medications needed to treat hyperten-sion, there is an association with greater proclivity for refrac-tory hypertension. In their study, they note that patients of African descent, and those with albuminuria and diabetes mellitus, were more likely to have refractory hypertension, even after multivariable adjustment. Moreover, individuals with refractory hyperten-sion had a much higher 10-year Framingham coronary heart disease and stroke risk score than those without. This observation underscores the importance of hypertension as a major risk factor for promoting cardiovascular disease. So what is the cause of refractory hypertension? Is it simply noncompliance, or are there biological factors? Are African descent and chronic kidney disease important underlying factors? Is this related to insufficient use or dose of diuretics or abnormal hormonal pathways? The investigators monitored the blood pressure in the patient's home and assessed medication adherence using the 4-item Morisky Medication Adherence Scale that is a validated measure of medication adherence. On the basis of their data, we conclude that noncompliance was not a factor. Other studies have suggested that patients with resistant hypertension exhibit high medication compliance. In a large study using data from Kaiser Permanente Southern California Health System, 93% of patients with resistant hypertensive had ≥80% of days covered with medication use based on prescription refill rates. 3 The fact that blood pressure was measured in the patient's home is of some interest. This might eliminate some of the white-coat effect and could provide a more valid measure of blood pressure load. More studies now indicate that home readings or ambulatory blood pressure readings are of value in predicting kidney disease progression, especially in patients with kidney disease. 4 However, no 24-hour ambulatory measures were taken to distinguish between white-coat and masked hypertension. What about biological factors? In a prior study, Acelajado et al 5 noted that individuals with …