Clinical features of resistant hypertension are described, and the importance of several risk factors undergoing clinical investigation and reappraisal are considered in this review.
True resistant hypertension must be distinguished from apparent resistant hypertension, of which important causes include medication nonadherence, illicit drug use, and alcoholism. Ambulatory blood pressure monitoring should be considered to rule out white coat hypertension. The pathogenesis is multifactorial, but the 2 pivotal factors include volume excess and the myriad effects of aldosterone. Aldosterone increases vascular tone because of endothelial dysfunction and enhances the pressor response to catecholamines. It also plays a crucial role in vascular remodeling of small and large arteries. Aldosterone also promotes collagen synthesis, which leads to increased arterial stiffness and elevation of blood pressure. Because aldosterone has been demonstrated to modulate baroreflex resetting, in cases of severe hypertension, there would be fewer compensatory mechanisms available to offset the blood pressure elevation.
Resistant hypertension is a common medical disorder encountered by all clinicians. Demographic trends, including the aging of our adult population and the increasing prevalence of obesity, indicate that resistant hypertension will become even more common. The past few years have witnessed increased clinical and investigative attention to this disease entity that informs an appropriate clinical management.
Moreover, clinical studies have focused increasingly on the overriding importance of aldosterone and mineralocorticoid signaling in the pathogenesis and maintenance of resistant hypertension. This review will focus on the clinical features of resistant hypertension and consider the importance of several risk factors undergoing reappraisal and clinical investigation, as well as the pivotal pathogenic role of aldosterone in both promoting and sustaining resistant hypertension.
Definition
Resistant hypertension is defined as failure to attain the goal blood pressure of <140/90 mm Hg despite adherence to 3 different antihypertensive medications at reasonable dosages, one of which must be a diuretic. For patients with diabetes or renal failure (defined as a serum creatinine >1.5 mg/dL or 133 μmol/L and/or proteinuria >300 mg in 24 hours), the definition is modified as a failure to reach a goal blood pressure of <135/85 mm Hg with the stated criteria.
Scope of the Problem
Increased Cardiovascular/Renal Morbidity and Mortality
Hypertension is a major independent risk factor for cardiovascular disease and mortality, and patients with resistant hypertension represent a more severe subset with an even greater increased cardiovascular risk compared with patients without resistant hypertension. Compared with patients with controlled hypertension, patients with resistant hypertension develop greater target end-organ damage, including increased left ventricular hypertrophy, retinal changes, and microalbuminuria. Consequently, these translate into an enhanced overall long-term cardiovascular risk.
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-Murray Epstein, MD, Daniel A. Duprez, MD, PhD
This article originally appeared in the July 2016 issue of The American Journal of Medicine.
