Hypertension Closely Tied to Aldosterone Levels

People with hypertension may also have an underrecognized hormonal issue — primary aldosteronism, researchers reported.

In a cross-sectional study of more than 1,800 adults, urinary aldosterone levels were closely linked with hypertension, according to Anand Vaidya, MD, of Brigham and Women’s Hospital in Boston, and colleagues.

Specifically, higher stages of hypertension — including resistant hypertension — were positively correlated across the spectrum of urinary aldosterone levels:

• Normotension: urinary aldosterone 6.5 μg/24 h (95% CI 5.2-7.7 μg/24 h)
• Stage 1 hypertension: 7.3 μg/24 h (95% CI 5.6-8.9 μg/24 h)
• Stage 2 hypertension: 9.5 μg/24 h (95% CI 8.2-10.8 μg/24 h)
• Resistant hypertension: 14.6 μg/24 h (95% CI 12.9-16.2 μg/24 h)

“Most hypertension is considered idiopathic, and the approach for antihypertensive treatment is rarely directed toward a primary underlying mechanism,” the authors wrote in Annals of Internal Medicine.

They explained that “Primary aldosteronism is caused by renin-independent aldosterone production, wherein aldosterone is produced despite the suppression of renin and angiotensin II and is not adequately suppressed by sodium loading or extracellular volume expansion.”

The authors also noted that although “primary aldosteronism is often considered an uncommon cause of hypertension, it is frequently identified when hypertensive persons undergo systematic screening for a high [aldosterone-renin ratio] and aldosterone level.”

A total of 1,846 individuals were included in the analysis: 1,015 of whom had a urinary sodium excretion rate of at least 190 mmol/24 h. Among this subset, 289 were considered normotensive and untreated, while 115 and 203 had untreated stage 1 and stage 2 hypertension, respectively. The remaining 408 individuals had resistant hypertension that was being treated with an antihypertensive agent.

The researchers also identified that 24-hour rates of urinary aldosterone excretion spanned quite a range, from below the threshold of detection to well exceeding the diagnostic threshold for primary aldosteronism of 12 μg per 24 hours.

However, the authors highlighted that “the magnitude of renin-independent aldosterone production was progressively higher across blood pressure categories, regardless of this arbitrary designation [of primary aldosteronism].”

Among normotensive individuals, there was an 11.3% (95% CI 5.9%-16.8%) adjusted prevalence for biochemically overt primary aldosteronism, versus a prevalence rate of 22% (95% CI 17.2%-26.8%) among those with resistant hypertension. “This prevalence could be substantially modulated with the application of more liberal or conservative diagnostic thresholds,” the group pointed out.

They also found that the sensitivity and negative predictive value of the aldosterone-renin ratio (ARR) was “poor” among those that were confirmed to have primary aldosteronism, which thus “highlights the limitations of this diagnostic ratio in screening for — and excluding — true cases of primary aldosteronism,” they stated.

Instead, they said that using this “conventional approach” of using a high ARR and circulating aldosterone level to screen for primary aldosteronism likely leads to underdiagnosis, and may subsequently be underrecognized as a main cause of hypertension.

Vaidya’s group also noted that among the subset of individuals with resistant hypertension — in which there was a very high pretest probability of having primary aldosteronism — only 24.5% of the confirmed case patients had a serum aldosterone level under 10 ng/dL, which they highlighted is below a threshold where primary aldosteronism “is almost never entertained.”

“These findings indicate a highly prevalent pathologic continuum of renin-independent aldosteronism that extends, or redefines, the classic concept of primary aldosteronism as a ‘secondary’ cause of hypertension,” they concluded.

Study limitations were the fact that prevalence estimates relied on “arbitrary and conventional thresholds,” according to the authors. Also, the study population may not have represented nationwide demographics.

In an accompanying editorial, John Funder, MD, PhD, of the Hudson Institute of Medical Research in Victoria, Australia called this study a “game changer.” He said the main takeaway of this study is that “the single spot measurement of plasma aldosterone concentration, which clinicians have used for decades to screen for primary aldosteronism, is not merely useless but actually misleading.”

Funder pointed out that among the 210 normotensive individuals in the study, 29 surpassed the urinary aldosterone excretion threshold of 12 μg/24 h, but only six of these 29 individuals tested positive for primary aldosteronism on conventional spot screening of plasma aldosterone concentration.

Overall, the researchers suggested a shift in viewing primary aldosteronism from a rare condition, instead to a relatively common occurrence across a “broad severity spectrum” that may be a primary cause of hypertension.