Rethinking Resistant Hypertension

Abstract

Resistant hypertension is common and known to be a risk factor for cardiovascular events, including stroke, myocardial infarction, heart failure, and cardiovascular mortality, as well as adverse renal events, including chronic kidney disease and end-stage kidney disease. This review will discuss the definition of resistant hypertension as well as the most recent evidence regarding its diagnosis, evaluation, and management. The issue of medication non-adherence and its association with apparent treatment-resistant hypertension will be addressed. Non-pharmacological interventions for the treatment of resistant hypertension will be reviewed. Particular emphasis will be placed on pharmacological interventions, highlighting the role of mineralocorticoid receptor antagonists and sodium-glucose cotransporter-2 inhibitors and device therapy, including renal denervation, baroreceptor activation or modulation, and central arteriovenous fistula creation.

Sustained Activation of CLR/RAMP Receptors by Gel-Forming Agonists

“…It has been estimated that 10–15% of the hypertensive population in developed countries met the strict definition of RHTN [ 123 , 124 , 125 , 126 ]). RHTN is an important risk factor for cardiovascular and renal events, including stroke, myocardial infarction, heart failure, chronic and end-stage kidney disease as well as cardiovascular mortality [ 40 ]. Although antihypertensive treatment options have increased from just three classes in 1970 to over 11 classes now [ 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 ], physicians are with difficulties achieving controlled blood pressure in these patients.…”

“…In addition, the CLR/RAMP3 system has been shown to be essential for regulating normal lymphatic vessel functions [ 35 ]. Because these peptides exhibit potent cardioprotective, neuroprotective, and renoprotective effects in a variety of disease models [ 24 , 25 , 36 , 37 , 38 , 39 ], CLR/RAMP receptors are considered valid targets for ameliorating endothelial dysfunction-associated diseases such as treatment-resistant hypertension (RHTN), preeclampsia, and secondary lymphedema [ 40 ]. However, due to the lack of stable analogs, the utility of CLR/RAMP receptor agonists for disease treatment remains to be vetted.…”

Approaches in Managing Resistant Hypertension: A Review

“…The prevalence of RH using these criteria is ≈10%. In contrast, Canadian guidelines have recommended BP levels above the target based on comorbidities and projected cardiovascular risk for defining RH patients [ 21 ]. These patients should have been on three or more anti-hypertensive drugs at optimal doses, with one of those agents preferably being a diuretic [ 21 ].…”

Advances in Renal Denervation in the Treatment of Hypertension

“…Although various types of antihypertensive drugs and agents are available as treatment options, they do not result in a satisfactory rate of attainment of optimal BP decrease [2,4,5]. Resistant hypertension (RH) is usually defined by BP remaining above guidelinespecified targets despite the use of three or more antihypertensive agents at optimal or maximally tolerated doses, preferably with one of those agents being a diuretic [1][2][3]6]. The management of RH involves both nonpharmacological and pharmacological strategies.…”

“…With the development of research on hypertension therapy, interventional or device therapy has become a novel option for patients. Nonpharmacological strategies to decrease BP include renal denervation (RDN), central arteriovenous fistula creation, baroreceptor activation or modulation therapy, and lumbar sympathectomy [6]. RDN is a new interventional technique that modulates the sympathetic nerve fibers surrounding the renal artery, thereby decreasing sympathetic nerve excitability and consequently BP.…”