One in Three Hypertensive Patients Has an Elevated Aldosterone-to-Renin Ratio

Yael Waknine

September 20, 2004

Sept. 20, 2004 — An elevated aldosterone-to-renin ratio (ARR) characterizes one in three hypertensive patients and screening should be extended to all hypertensive patients, according to the results of a cross-sectional population study published in the September issue of the Journal of Clinical Endocrinology and Metabolism.

"In recent years, growing evidence has consistently supported the view that arterial hypertension due to primary aldosteronism is much more frequent than was previously suspected," writes Oliviero Olivieri, MD, from the Department of Clinical and Experimental Medicine at the University of Verona in Italy, and colleagues. "This change in the estimated prevalence has been mainly due to the widespread use of the [ARR] as a screening test."

According to the authors, ARR detects inappropriately high aldosterone secretion for the degree of renin-angiotensin system activation. Most affected patients are normokalemic and clinically indistinguishable from patients with essential hypertension.

"In addition to its screening function, ARR elevation has been reported to be a useful predictor of patient susceptibility to spironolactone treatment regardless of the established diagnosis of primary aldosteronism," the authors note.

To determine the prevalence of hypertension associated with ARR, the investigators reviewed the medical data of 1,348 subjects aged 35 to 74 years randomly selected from the population register of a health district in Italy and agreeable to a physician appointment within four weeks. The demographic features of the group were similar to that of the district population with respect to age, sex, socioeconomic level, and educational status.

Hypertensive subjects (n = 412, 30.5% of total) with a systolic blood pressure (BP) higher than 140 mm Hg or diastolic BP higher than 90 mm Hg, or taking therapy for previously diagnosed hypertension were included in the study.

A four-week washout period ensued during which no hypotensive drugs were allowed, with the exception of verapamil or alpha-blockers if necessary. At four weeks, direct active plasma aldosterone and renin were assayed in 287 subjects (response rate, 70%) after having remained at least two hours in the upright position. Aldosteronism was defined as a minimal aldosterone to active renin ratio (AARR) of 32 pg/mL, equivalent to an ARR of 50 ng/dL/ng/mLxh.

The assayed group showed demographic features similar to those of the nonassayed group with respect to sex, systolic and diastolic BP, body mass index greater than 30 kg/m 2, and educational status.

Results showed that an elevated AARR (higher than 32 pg/mL) was observed in 32.4% of the hypertensive population. The prevalence of elevated AARR increased with age (ages 35-44, 15%; ages 45-54, 29%) but remained constant in those aged 55 years and older (ages 55-64, 65-74, 38%). Prevalence was also higher in women compared with men (64.9% women, 35.1% men).

"[T]he study does not allow us to quantify the prevalence of primary aldosteronism, but only that of an elevated ARR," the authors write, noting that no confirmatory tests were performed.

However, potentially relevant healthcare implications of the study results should be taken into account. "The first is probably the need to extend AARR screening to all hypertensive patients," the authors write, adding that subjects suffered no adverse events from the required washout period and that a diagnosis of aldosteronism may offer a possible cure for accompanying hypertension.

In addition, "[A]n elevated AARR may serve as a guide for targeting drug therapy in hypertensive patients independently of the established diagnosis of aldosteronism," the authors add. "Once validated by controlled trials and adequately extended to all sensitive patients, this approach should prove highly cost-effective in terms of cardiovascular prevention and public health, taking into consideration the low cost of spironolactone treatment."

The authors report no pertinent financial disclosures.

John W. Funder, MD, from Prince Henry's Institute of Medical Research in Clayton, Australia, agrees. "[I]nappropirate levels of aldosterone may be of pathogenetic importance in essential hypertension, as recently suggested by longitudinal analyses of patients in the Framingham study," he writes in a related editorial.

"Given the very low cost of spironolactone, the eventual availability of more selective mineralocorticoid receptor antagonists like eplerenone, and the minimal risk of hyperkalemia when such agents are titrated to effect, it would now seem possible to make a case for the use of mineralocorticoid receptor blockade in hypertension across the board," Dr. Funder concludes.

J Clin Endocrinol Metab. 2004;89:4219-4220, 4221-4226

Reviewed by Michael W. Smith, MD