Hyperaldosteronism Among Black and White Subjects With Resistant Hypertension

Calhoun, David A.; Nishizaka, Mari K.; Zaman, Mohammad A.; Thakkar, Roopal; Weissmann, Paula

doi:10.1161/01.hyp.0000040261.30455.b6

Cited by 658 publications

(363 citation statements)

References 20 publications

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“…In patients with PA, plasma aldosterone is inappropriately high for circulating levels of plasma renin and is not normalized by dietary or drug treatments that suppress the renin-angiotensin system (RAS) (1)(2)(3)(4)(5). Thus, in PA, neither volume expansion induced by dietary sodium loading nor the use of antihypertensive agents that either antagonize the angiotensin type 1 (AT 1 ) receptor (angiotensin receptor blockers) or block the generation of angiotensin II (Ang II) (angiotensin-converting enzyme inhibitors) remediates aldosterone excess (6).…”

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confidence: 99%

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TASK channel deletion in mice causes primary hyperaldosteronism

Davies¹,

Hu²,

Guagliardo³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

172

166

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When inappropriate for salt status, the mineralocorticoid aldosterone induces cardiac and renal injury. Autonomous overproduction of aldosterone from the adrenal zona glomerulosa (ZG) is also the most frequent cause of secondary hypertension. Yet, the etiology of nontumorigenic primary hyperaldosteronism caused by bilateral idiopathic hyperaldosteronism remains unknown. Here, we show that genetic deletion of TWIK-related acid-sensitive K (TASK)-1 and TASK-3 channels removes an important background K current that results in a marked depolarization of ZG cell membrane potential. Although TASK channel deletion mice (TASK −/− ) adjust urinary Na excretion and aldosterone production to match Na intake, they produce more aldosterone than control mice across the range of Na intake. Overproduction of aldosterone is not the result of enhanced activity of the renin–angiotensin system because circulating renin concentrations remain either unchanged or lower than those of control mice at each level of Na intake. In addition, TASK −/− mice fail to suppress aldosterone production in response to dietary Na loading. Autonomous aldosterone production is also demonstrated by the failure of an angiotensin type 1 receptor blocker, candesartan, to normalize aldosterone production to control levels in TASK −/− mice. Thus, TASK −/− channel knockout mice exhibit the hallmarks of primary hyperaldosteronism. Our studies establish an animal model of nontumorigenic primary hyperaldosteronism and identify TASK channels as a possible therapeutic target for primary hyperaldosteronism.

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confidence: 99%

“…Strikingly, among patients that are resistant to combination antihypertensive therapy, the prevalence of PA is estimated to be Ϸ20% worldwide (3,6,7). The incidence of PA increases with the severity of hypertension, and among resistant hypertensives, mineralocorticoid receptor blockade is of broad benefit (8)(9)(10).…”

mentioning

confidence: 99%

TASK channel deletion in mice causes primary hyperaldosteronism

Davies¹,

Hu²,

Guagliardo³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

172

166

View full text Add to dashboard Cite

show abstract

“…Up to 20% of patients consecutively referred to a hypertension clinic for aTRH were diagnosed with primary hyperaldosteronism based on suppressed renin activity and high 24-hour urinary aldosterone excretion. 20 Aldosterone is produced in the adrenal glands in response to local and systemic angiotensin II and serum potassium concentrations. It binds MRs found in the CLINICAL SUMMARY Apparent treatment resistant hypertension is common and increasing in prevalence.…”

Section: Volume Expansionmentioning

confidence: 99%

Apparent Treatment-Resistant Hypertension and Chronic Kidney Disease: Another Cardiovascular-Renal Syndrome?

Vemulapalli

Tyson

Svetkey

2014

Advances in Chronic Kidney Disease

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To identify patients at increased risk of cardiovascular (CV) outcomes, apparent treatment-resistant hypertension (aTRH) is defined as having a blood pressure above goal despite the use of 3 or more antihypertensive therapies of different classes at maximally tolerated doses, ideally including a diuretic. Recent epidemiologic studies in selected populations estimated the prevalence of aTRH as 10% to 15% among patients with hypertension and that aTRH is associated with elevated risk of CV and renal outcomes. Additionally, aTRH and CKD are associated. Although the pathogenesis of aTRH is multifactorial, the kidney is believed to play a significant role. Increased volume expansion, aldosterone concentration, mineralocorticoid receptor activity, arterial stiffness, and sympathetic nervous system activity are central to the pathogenesis of aTRH and are targets of therapies. Although diuretics form the basis of therapy in aTRH, pathophysiologic and clinical data suggest an important role for aldosterone antagonism. Interventional techniques, such as renal denervation and carotid baroreceptor activation, modulate the sympathetic nervous system and are currently in phase III trials for the treatment of aTRH. These technologies are as yet unproven and have not been investigated in relationship to CV outcomes or in patients with CKD.

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“…Renovascular disease is prevalent in approximately 20% of those with hypertension resistant to combinations of two antihypertensive medications (13). In addition to renal causes, adrenal hypertension is being recognized with increasing frequency -20% in one small series of resistant hypertensive patients (14). Aldosterone not only stimulates sodium retention, but as recently reviewed by Duprez (15), it also leads to increased arterial stiffness, endothelial dysfunction and central effects with impaired baroreflex function.…”

Section: Abstract: Hypertension; Resistant Hypertensionmentioning

confidence: 99%

Resistant hypertension

Tobe

Lewanczuk

2009

Canadian Journal of Cardiology

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R esistant hypertension is defined by a lack of response to therapy with three or more medications and is evidence of a more severe stage of hypertension, with over a fourfold greater risk of cardiovascular events compared with hypertensive patients achieving blood pressure targets (1). The Joint National Committee's recommendations on high blood pressure (2) define resistant hypertension as "the failure to reach goal blood pressure despite full doses of an appropriate 3 drug regimen including diuretics". The European Society of Hypertension definition (3) is "hypertension resistant or refractory to lifestyle measures and at least three medications, including a diuretic to lower blood pressure to target". These definitions are reasonable and would then be modified by the urgency to treat based on the actual stage of blood pressure, with higher stages indicating greater urgency to achieve control. The Canadian Hypertension Education Program (CHEP) has not developed a recommendation specific to resistant hypertension because of the lack of randomized controlled trials specific to treating the condition. Etiology and PathoPhysiologyThe main categories to consider for patients with resistant hypertension are presented in Table 1. Longstanding uncontrolled hypertension leading to resistant hypertension is most often the result of a drug regimen lacking a diuretic, or insufficient antihypertensive classes and dosages (4). Epstein (5) has described the common clinical characteristics of patients with resistant hypertension. These include obesity, diabetes, chronic kidney disease, black race, female sex and left ventricular hypertrophy. To these, Pickering (6) has added older age, and reviewed the literature associating each characteristic with arterial stiffness -a major component of arterial blood pressure. High blood pressure itself causes arterial stiffness and, if uncontrolled over time, it likely also leads to resistance to therapy. Conversely, there are anecdotal reports that over time (months to years), after blood pressure is brought to target, the dosage and number of antihypertensive agents can be reduced. Resistant hypertension may also be secondary to other medical conditions, most often chronic kidney disease or primary hyperaldosteronism as well as renovascular disease and obstructive sleep apnea (7). Low potassium and target organ damage, including albuminuria, retinopathy and left ventricular hypertrophy, were more frequent in those found to have true resistant hypertension compared with those with white coat hypertension (8).Nonadherence to therapy may be a much more common cause of resistant hypertension than appreciated, as reviewed by Park and Campese (9), who make the distinction between apparent resistance from lack of patient adherence as well as ineffective physician prescribing, versus true resistance. Clues to patient nonadherence are gathered by a careful patient history including a review of prescription refills. Other patient behaviours may lead to resistant hypertension. This includes taki...

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Hyperaldosteronism Among Black and White Subjects With Resistant Hypertension

Cited by 658 publications

References 20 publications

TASK channel deletion in mice causes primary hyperaldosteronism

TASK channel deletion in mice causes primary hyperaldosteronism

Apparent Treatment-Resistant Hypertension and Chronic Kidney Disease: Another Cardiovascular-Renal Syndrome?

Resistant hypertension

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