Hyperaldosteronism

Importance: Hypertension, defined as office systolic blood pressure (SBP) 130 mm Hg or greater and/or diastolic blood pressure 80 mm Hg or greater, affects 43.9% of women and 49.5% of men in the US. Approximately 19.7% of patients treated for hypertension have apparent resistant hypertension (blood pressure ≥130/80 mm Hg) despite using 3 or more antihypertensive medications, preferably a renin-angiotensin system blocker, a calcium channel blocker, and a thiazide-type diuretic, at maximally tolerated doses.

Observations: Approximately 10% of patients treated for hypertension have true resistant hypertension confirmed with home or 24-hour ambulatory blood pressure monitoring to exclude white-coat hypertension (approximately 37.5% of apparent resistant hypertension) and after excluding medication nonadherence (approximately 50%) and secondary hypertension such as primary aldosteronism (approximately 5%-25%). Conditions associated with resistant hypertension include obesity, diabetes, chronic kidney disease, and sleep apnea. Resistant hypertension is associated with increased risk of cardiovascular death vs controlled blood pressure at 5 years to 10 years (absolute risk increase, 10.3% [95% CI, 8.7%-12.1%]). Lifestyle modifications for resistant hypertension include a low-sodium diet (<1500 mg/d), reducing or avoiding alcohol, 150 min/wk or more of aerobic exercise, and weight loss. Illicit drugs (eg, cocaine) and medications that increase blood pressure (eg, nonsteroid anti-inflammatory drugs, serotonin-norepinephrine reuptake inhibitors) should be avoided. Sleep apnea should be treated when diagnosis is confirmed. Pharmacologic optimization includes use of combination tablets of antihypertensives; intensifying diuretic therapy by using chlorthalidone; and sequential addition of antihypertensive medications using evidence-based algorithms. In a meta-analysis of 20 studies (9 randomized clinical trials [RCTs] and 11 observational studies [331 participants]), use of antihypertensive therapies that combine 2 to 3 medications into a single formulation reduced SBP by -3.99 mm Hg (95% CI, -7.92 to -0.07) vs equivalent doses given separately. For patients with apparent or true resistant hypertension who have an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or greater and a serum potassium level of 4.5 mmol/L or less, adding spironolactone (25-50 mg/d) compared with placebo lowers office SBP by -13.3 mm Hg (95% CI, -17.89 to -8.72 [4 RCTs]) and 24-hour ambulatory SBP by -8.46 mm Hg (95% CI, -12.54 to -4.38 [2 RCTs]) in a network meta-analysis of 24 RCTs (3485 patients with resistant hypertension). A meta-analysis of 10 RCTs (2478 participants) reported that compared with a sham procedure, catheter-based renal denervation, which disrupts the sympathetic nerves in the renal artery walls, decreased 24-hour ambulatory SBP by -4.4 mm Hg (95% CI, -6.1 to -2.7) and office SBP by -6.6 mm Hg (95% CI, -9.7 to -3.6).

Conclusions and relevance: True resistant hypertension affects 10% of patients treated for hypertension and is diagnosed after excluding white-coat hypertension, medication nonadherence, and secondary hypertension such as primary aldosteronism. First-line treatment includes lifestyle modifications, diuretic therapy with chlorthalidone, and combination tablets of antihypertensives. Spironolactone and renal denervation decrease blood pressure in patients with true resistant hypertension.

Author/s:

Michel Azizi, Wanpen Vongpatanasin, Naomi D L Fisher, Felix Mahfoud, Laurence Amar, Ajay J Kirtane

Screening for primary aldosteronism in primary care

Aubrey Delammermore — Thu, 30 Mar 2023 05:00:00 +0000

Date Added:

March 30, 2023

Journal/Publication:

Canadian Medical Association Journal

Publisher:

CMA Impact

Publication Date:

March 20, 2023

Issue:

Volume:

195

Pages:

E410

URL:

Screening for primary aldosteronism in primary care

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1503/cmaj.221466

Keywords

Hypokalemia

Aldosterone

primary aldosteronism

MeSH

Mineralocorticoid Receptor Antagonists

Aldosterone

Angiotensin-Converting Enzyme Inhibitors

A very concise review of the suspicion, detection, and management of hyperaldosteronism in patients with hypertension. James W. Mold, MD, MPH

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Primary aldosteronism (PA) is common among patients with hypokalemia and hypertension. Patients with PA are at an increased risk of chronic disease if undiagnosed or untreated. Expert consensus recommends screening for PA in high-risk populations. Most antihypertensive medications can be continued during the work-up for PA. An elevated aldosterone-to-renin ratio is suggestive of PA.

Author/s:

Dubrofsky, L., Hundemer, G. L.

The Unrecognized Prevalence of Primary Aldosteronism

John Bayhi — Tue, 26 May 2020 21:01:14 +0000

Date Added:

May 26, 2020

Journal/Publication:

Annals of Internal Medicine

Publisher:

American College of Physicians

Publication Date:

May 26, 2020

Volume:

Online ahead of print

URL:

The Unrecognized Prevalence of Primary Aldosteronism

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.7326/M20-0065

Keywords

primary aldosteronism

hypertension

cardiovascular disease

PMID (1):

32449886

MeSH

Essential Hypertension

Cross-Sectional Studies

prevalence

cardiovascular diseases

Hyperaldosteronism

hypertension

Hypoakalemia

Blood Pressure Determination

Academic Medical Centers

Potassium

Sodium

This study suggests (confirming what Dr. David Kem at OU has long taught) that primary aldosteronism is much more common than generally thought, occurring in as many as 11% of people with normal BP and 22% of those with hard to control HTN. Usual diagnostic tests aren’t very accurate. We should probably be using spironolactone more often. James W. Mold, MD, MPH

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Background:

Primary aldosteronism is a nonsuppressible renin-independent aldosterone production that causes hypertension and cardiovascular disease.

Objective:

To characterize the prevalence of nonsuppressible renin-independent aldosterone production, as well as biochemically overt primary aldosteronism, in relation to blood pressure.

Design:

Cross-sectional study.

Setting:

4 U.S. academic medical centers.

Participants:

Participants with normotension (n = 289), stage 1 hypertension (n = 115), stage 2 hypertension (n = 203), and resistant hypertension (n = 408).

Measurements:

Participants completed an oral sodium suppression test, regardless of aldosterone or renin levels, as a confirmatory diagnostic for primary aldosteronism and to quantify the magnitude of renin-independent aldosterone production. Urinary aldosterone was measured in participants in high sodium balance with suppressed renin activity. Biochemically overt primary aldosteronism was diagnosed when urinary aldosterone levels were higher than 12 µg/24 h.

Results:

Every blood pressure category had a continuum of renin-independent aldosterone production, where greater severity of production was associated with higher blood pressure, kaliuresis, and lower serum potassium levels. Mean adjusted levels of urinary aldosterone were 6.5 µg/24 h (95% CI, 5.2 to 7.7 µg/24 h) in normotension, 7.3 µg/24 h (CI, 5.6 to 8.9 µg/24 h) in stage 1 hypertension, 9.5 µg/24 h (CI, 8.2 to 10.8 µg/24 h) in stage 2 hypertension, and 14.6 µg/24 h (CI, 12.9 to 16.2 µg/24 h) in resistant hypertension; corresponding adjusted prevalence estimates for biochemically overt primary aldosteronism were 11.3% (CI, 5.9% to 16.8%), 15.7% (CI, 8.6% to 22.9%), 21.6% (CI, 16.1% to 27.0%), and 22.0% (CI, 17.2% to 26.8%). The aldosterone–renin ratio had poor sensitivity and negative predictive value for detecting biochemically overt primary aldosteronism.

Limitation:

Prevalence estimates rely on arbitrary and conventional thresholds, and the study population may not represent nationwide demographics.

Conclusion:

The prevalence of primary aldosteronism is high and largely unrecognized. Beyond this categorical definition of primary aldosteronism, there is a prevalent continuum of renin-independent aldosterone production that parallels the severity of hypertension. These findings redefine the primary aldosteronism syndrome and implicate it in the pathogenesis of “essential” hypertension.

Primary Funding Source:

National Institutes of Health.

Author/s:

Brown, JM, Siddiqui, M, Calhoun, DA, Carey, RM, Hopkins, PN, Williams, GH, Vaidya, A