Results of a cross-sectional study published in Annals of Internal Medicine suggest primary aldosteronism may be a more common driver of hypertension than previously believed.
Jenifer M. Brown, MD, of Brigham and Women’s Hospital, Boston, along with colleagues from the University of Alabama, University of Utah, and the University of Virginia, found evidence of overt primary aldosteronism in 22% of a cohort of patients with resistant hypertension.
The researchers recruited 289 normotensive volunteers (<130/80 mmHg), 115 persons with untreated stage 1 hypertension (130-139/80-89 mmHg) , and 203 with untreated state 2 hypertension (≥ 140/90 mm Hg). In addition, they enrolled 408 patients with treated, resistant hypertension who were kept in their own category. The participants were middle-age and roughly three of four normotensive, stage 1 and stage 2 participants were white, but in the uncontrolled hypertension group most were black (59.3%). The percent of women varied by group: 50.9% in the normotensive group, 29.6% in the stage 1 group, 38.9% in the stage 2 group and 40.4% in the treated, uncontrolled group. In general, those with treated, uncontrolled hypertension were more likely to be “older, had higher body mass index, and were more predominantly black and diabetic.”
Among the treated, uncontrolled group 82.8% were taking an ACE or ARB, 71.6% a calcium channel blocker, 75.6% thiazide diuretic, and 62.0% β/αβ-blocker.
“Participants were required to have complete data for aldosterone and renin activity, as well as a 24-hour rate of urinary sodium excretion reflective of high sodium balance (≥190 mmol/24 h),” they wrote. “Renin-independent aldosterone production was then assessed among those with suppression of renin activity (<1.0 μg/L per hour seated or <0.6 μg/L per hour supine). Participants with 24-hour urinary sodium excretion less than 190 mmol were excluded because physiologic aldosterone suppressibility could not be adequately assessed.”
Brown and colleagues observed a continuum of renin-independent aldosterone production as blood pressure increased.
“The adjusted prevalence of biochemically overt primary aldosteronism ranged from 11.3% (95% CI, 5.9%-16.8%) in normotension to 22.0% (CI, 17.2%-26.8%) in resistant hypertension. This prevalence could be substantially modulated with the application of more liberal or conservative diagnostic thresholds. Among the subset of participants with suppressed renin activity in high sodium balance, the prevalence of biochemically overt primary aldosteronism was further enriched,” they noted.
But of concern was fact that the aldosterone-renin-ratio (ARR), which is commonly used for screening, was found to have poor sensitivity and negative predictive value among participants confirmed to have biochemically overt primary aldosteronism, thus limiting the value of ARR, Brown and colleagues wrote.
“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. By applying established diagnostic thresholds to this continuum, we found the estimated prevalence of primary aldosteronism to be much higher than conventionally considered in every blood pressure category, providing a stark contrast to the fact that primary aldosteronism is currently rarely diagnosed, even among high-risk populations with resistant hypertension or hypokalemia,” they wrote.
Brown et al listed several “practical clinical implications” of their findings:
- Forget the classic stereotype —primary aldosteronism can be detected in normokalemic hypertensive individuals across all blood pressure ranges, including normotensive blood pressure so more screening is needed.
- ARR is not the most reliable tool for screening.
- Suppressed renin is “a biomarker that identifies patients who are more likely to have primary aldosteronism and may especially benefit from mineralocorticoid receptor antagonists. For these patients, clinicians should first strongly emphasize the importance of dietary sodium restriction, not only as a general intervention to improve blood pressure but also as a targeted maneuver to minimize the fuel that feeds primary aldosteronism pathophysiology.”
The authors acknowledged that the study findings are limited by use of conventional thresholds to develop prevalence estimates and by the fact that the population may not “represent nationwide demographics.”
In an editorial, John W. Funder, MD, PhD, of the Hudson Institute of Medical Research, Wandin East, Victoria, Australia wrote that “Brown and colleagues sound a call to arms and start the process of bringing the management of primary aldosteronism into the 21st century. For this, the authors deserve congratulations, thanks, and unstinting praise.”
But Funder notes that putting this information into clinical practice is likely to be difficult. He pointed out that in “Germany and the United Kingdom, only 1 in 1,000 hypertensive patients is ever screened for primary aldosteronism (Reincke M, Brown M. Personal communication.). This reflects the reluctance of primary care physicians—or others treating hypertensive patients—to refer them for investigation, given the taxing nature of the current work-up and the possible expense of adrenal venous sampling. Instead, physicians just try to control blood pressure. One in 1,000 is an appallingly low capture rate, and the risk profile for patients without appropriate levels of targeted therapy is at least 3 times higher than that for patients with essential hypertension matched on age, sex, and blood pressure. Much of the present guideline needs to be jettisoned, and radically reconstructed recommendations should be developed to guide clinicians treating hypertensive patients.”
Be aware that this cross-sectional analysis suggests that primary aldosteronism may be a more common cause of hypertension than previously believed.
Note that this analysis suggests that use of ARR may not be a reliable screening tool for primary aldosteronism.
Peggy Peck, Editor-in-Chief, BreakingMED™
Brown reported grants from the National Heart, Lung, and Blood Institute.
Funder had no disclosures.
Cat ID: 6
Topic ID: 74,6,730,6,192,916