Does hyperaldosteronism drive increased salt-sensitive BP in women?

Salt-sensitive blood pressure (SSBP), aldosterone response to angiotensin II, and aldosterone/plasma renin activity (PRA) ratios are all greater in women than in men, suggests a study. However, men show higher levels of basal aldosterone and its secretagogues.

In the total population, men and women had the same 24-h urine aldosterone levels. However, when stratified into subsets, normotensive women and those aged <51 years had higher urine aldosterone levels than men.

“These results suggest increased aldosterone production is the mechanism responsible for the SSBP in women but only in those younger than 51 [years of age],” the investigators said.

This study included 363 women and 483 men from the HyperPATH cohort and examined the potential underlying mechanism for observed sex difference in aldosterone production.

The findings revealed greater SSBP, greater aldosterone and vasculature response to angiotensin II, and higher upright aldosterone/PRA in women. On the other hand, men on both restricted- and liberal-salt diets demonstrated greater basal levels of supine aldosterone, PRA levels, and other secretagogues. [J Clin Endocrinol Metab 2025;110:2623-2630]

When assessing overall production using 24-h urine aldosterone, no difference in sex was noted regardless of salt intake except when assessed in subsets. Normotensive women exhibited higher urine aldosterone than men, while women vs men aged <51 years also showed greater levels.

“Similar 24-h urine aldosterone levels in women and men do not support the concept that relative hyper-aldosterone is the mechanism for sex difference in SSBP,” the investigators said. “The data also suggest that the SSBP in women, in some cases, may be benign since it is secondary to a BP reduction on the restricted-salt diet, not an increase on the liberal-salt diet.”

Hyper-aldosterone state

Available data in HyperPATH are lacking to determine whether women are at greater risk than men for being in a relative hyperaldosterone state.

“Since men have higher ALDO level supine than women, if the individual's predominant daily status is supine, then, the men would have higher daily aldosterone levels,” the investigators said. “Contrariwise, since the aldosterone levels in women are higher in response to angiotensin II stimulation if the individual is upright and active, then women would have higher daily aldosterone levels.”

Results for the 24-h urine aldosterone levels suggest that neither women nor men had a relative hyper-aldosterone state daily, except when stratifying them into subsets.

The subset findings indicate that a younger woman, theoretically in reproductive age, has a higher likelihood of being in a hyper-aldosterone state.

“It is interesting to speculate if these results are related to the physiological needs of pregnancy,” the investigators said.

“In a healthy pregnancy, plasma volume expansion and the increasing demands of a growing fetoplacental unit require an increase in renal blood flow (∼50-percent increase), increased sodium retention, and increased RAAS activation,” they added.

“However, although angiotensin II levels increase in pregnancy, aldosterone levels increase disproportionally to PRA and thereby play a substantial role in the sodium retention required for the late stages of foetal growth,” according to the investigators. [Hypertension 2023;80:268‐278]

Overall, these findings suggest that women have greater odds of having SSBP than men, but they are not more likely to have increased daily aldosterone production than men, unless they are younger than 51 years of age.

“Therefore, if the physician identifies a woman younger than 51 with SSBP and hypertension, likely the treatment of choice would be a mineralocorticoid receptor antagonist or potentially an aldosterone synthase inhibitor,” the investigators said. [N Engl J Med 2022;388:395‐405]