Apparent and true resistant hypertension: Why not the same?

Abstract

Resistant hypertension has been consistently defined as high blood pressure (BP) requiring four or more medications for treatment. Most definitions specify that one of the medications be a diuretic, if possible, and that all of the medications be prescribed at optimal or maximum tolerated doses. 1 While arbitrary in terms of the number of medications required, the definition has been very useful from clinical and research perspectives in terms of identifying a broad phenotype of antihypertensive treatment resistance that can benefit from special diagnostic considerations, such as increased testing for secondary causes of hypertension, and from utilization of targeted treatment options, such as preferential use of diuretics and mineralocorticoid receptor antagonists. More recently, a definition of severe resistant hypertension (systolic and diastolic BP >160/ 90 mm Hg) has been applied for testing of device-based approaches for suppression of sympathetic output, that is, renal nerve denervation and baroreflex activation. In addition, the definition has been of value in establishing criteria that clinicians can easily apply to identify patients that might benefit from being referred to a hypertension specialist. While the definition of resistant hypertension has been useful in facilitating successful research studies specific to this group of patients and by enhancing the clinical management of high-risk patients, it has always been recognized that the definition of resistant hypertension is overly broad by including patients who have been prescribed multiple antihypertensive agents, but whose BP remains uncontrolled not because of antihypertensive treatment failure but for a variety of other reasons. Hence use of the terms ‘‘true resistant hypertension’’ versus ‘‘apparent resistant hypertension,’’ with the latter referring to patients in whom common causes of poor BP control could not be excluded. These unassessed causes of lack of BP control include white coat effects, poor medication adherence, and undertreatment. Until recently, the degree to which these factors contributed to apparent treatment resistance was largely unknown. However, studies from a variety of investigators worldwide have begun to shed important quantitative insight into these confounding factors, allowing for better estimates of the prevalence of true resistant hypertension. In this edition of the Journal of the American Society of Hypertension, Grigoryan et al publish an analysis that is very impressive in having systematically quantified the degree of white coat hypertension, poor medication adherence, and undertreatment in a cohort of patients with apparent resistant hypertension. 2 The authors did a post-hoc evaluation of patients who had completed a randomized, multi-center study designed to assess clinical inertia and BP control. Overall, 69 patients with classically defined resistant hypertension, who had undergone 24-hour ambulatory BP monitoring and whose adherence with prescribed antihypertensive agents had been monitored by an electronic pill bottle monitoring system, were included in the evaluation. Of these subjects, 22% had controlled ambulatory BP levels, thus had white coat resistant hypertension, and 29% were non-adherent with their prescribed medications. The remaining 49% of patients were confirmed to have true resistant hypertension, based on having elevated ambulatory BP levels and having been adequately adherent with their medications.