Characterization of Resistant HypertensionAssociation Between Resistant Hypertension, Aldosterone, and Persistent Intravascular Volume Expansion

Vascular Biology and Hypertension Program, University of Alabama at Birmingham, 933 19th St S, Community Health Services Bldg 115, Birmingham, AL 35294, USA.
Archives of internal medicine (Impact Factor: 17.33). 06/2008; 168(11):1159-64. DOI: 10.1001/archinte.168.11.1159
Source: PubMed


Resistant hypertension is a common clinical problem and greatly increases the risk of target organ damage.
We evaluated the characteristics of 279 consecutive patients with resistant hypertension (uncontrolled despite the use of 3 antihypertensive agents) and 53 control subjects (with normotension or hypertension controlled by using <or=2 antihypertensive medications). Participants were prospectively examined for plasma aldosterone concentration, plasma renin activity, aldosterone to renin ratio, brain-type natriuretic peptide, atrial natriuretic peptide, and 24-hour urinary aldosterone (UAldo), cortisol, sodium, and potassium values while adhering to a routine diet.
Plasma aldosterone (P < .001), aldosterone to renin ratio (P < .001), 24-hour UAldo (P = .02), brain-type natriuretic peptide (P = .007), and atrial natriuretic peptide (P = .001) values were higher and plasma renin activity (P = .02) and serum potassium (P < .001) values were lower in patients with resistant hypertension vs controls. Of patients with resistant hypertension, men had significantly higher plasma aldosterone (P = .003), aldosterone to renin ratio (P = .02), 24-hour UAldo (P < .001), and urinary cortisol (P < .001) values than women. In univariate linear regression analysis, body mass index (P = .01), serum potassium (P < .001), urinary cortisol (P < .001), urinary sodium (P = .02), and urinary potassium (P < .001) values were correlated with 24-hour UAldo levels. Serum potassium (P = .001), urinary potassium (P < .001), and urinary sodium (P = .03) levels were predictors of 24-hour UAldo levels in multivariate modeling.
Aldosterone levels are higher and there is evidence of intravascular volume expansion (higher brain-type and atrial natriuretic peptide levels) in patients with resistant hypertension vs controls. These differences are most pronounced in men. A significant correlation between 24-hour urinary aldosterone levels and cortisol excretion suggests that a common stimulus, such as corticotropin, may underlie the aldosterone excess in patients with resistant hypertension.

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Available from: Inmaculada B Aban, Sep 18, 2014
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    • "Increased sympathetic tone implies the following physiological changes (Figure 1): (1) Intermittent hypoxia due to apnea and hypopnea triggers an excess of sympathetic activity by the activation of the carotid chemoreceptors; it leads to direct vasoconstriction and the subsequent stimulation of the renin-angiotensin-aldosterone system (RAAS) as well as increased levels of endothelin and angiotensin II. Activation of the renin-angiotensin axis produces fluid retention due to sodium reabsorption; it seems to lead to edema in the peripharyngeal walls, which predisposes to upper airway obstruction [18] [19]. "

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    • "Primary hyperaldosteronism presents in approximately 20% of patients with resistant hypertension.[29] In general, plasma renin activity (PRA) is very low or undetectable in patients with primary aldosteronism. "
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    ABSTRACT: Resistant hypertension in adolescents is increasing in frequency and is increasingly recognized as having significant short- and long-term health consequences. It may be seen in up to 30% of all hypertensive patients cared for. Adolescents with resistant hypertension are at higher cardiovascular (CV) risk due to a long history of severe hypertension complicated by other CV risk factors such as obesity. Common causes of resistant hypertension include primary aldosteronism, sleep apnea, diabetes and chronic kidney disease. Careful blood pressure (BP) measurement and thorough evaluation of patients with sustained BP elevation should make a possible early diagnosis of resistant hypertension. Successful treatment requires identification and reversal of life-style factors contributing to treatment resistant and diagnosis and appropriate treatment of causes of hypertension. Improved pharmacologic therapies may offer the potential for preventing or at least ameliorating early CV disease. This review highlights these and other important issues in the evaluation and management of adolescents with resistant hypertension and provides practical guidance to the practitioners involved in caring for such patients.
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    • "A further diuretic agent successfully tested in RH patients is spironolactone based on the finding that plasma aldosterone levels are higher in RH that in those with controlled hypertension [64]. Recently, ASPIRANT study, a randomized, controlled, double-blind study evaluated the antihypertensive effects of spironolactone in 117 patients with RH. "
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    ABSTRACT: Resistant hypertension (RH) is defined as blood pressure (BP) that remains above the target of less than 140/90 mmHg in the general population and 130/80 mmHg in people with diabetes mellitus or chronic kidney disease (CKD) in spite of the use of at least three full-dose antihypertensive drugs including a diuretic or as BP that reaches the target by means of four or more drugs. In CKD, RH is a common condition due to a combination of factors including sodium retention, increased activity of the renin-angiotensin system, and enhanced activity of the sympathetic nervous system. Before defining the hypertensive patient as resistant it is mandatory to exclude the so-called "pseudoresistance." This condition, which refers to the apparent failure to reach BP target in spite of an appropriate antihypertensive treatment, is mainly caused by white coat hypertension that is prevalent (30%) in CKD patients. Recently we have demonstrated that "true" RH represents an independent risk factor for renal and cardiovascular outcomes in CKD patients.
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