Study details
The new study ran a post hoc analysis on data collected in five independent studies run at centers in four U.S. locations: Birmingham, Ala.; Boston; Charlottesville, Va.; and Salt Lake City. The studies included a total of 1,846 adults, mostly patients with hypertension of varying severity but also several hundred normotensive people. Data on 24-hour sodium excretion during an oral sodium suppression test were available for all participants, and the researchers excluded 831 people with an “inadequate” sodium balance of less than 190 mmol based on this metric, leaving a study population of 1,015. The researchers acknowledged the limitation that the study participants were not representative of the U.S. population.
The analysis included 289 normotensive people not on any blood pressure–lowering medications, and 239 fit the definition of having suppressed renin. The adjusted prevalence of aldosteronism at the level of at least 12 mcg excreted in a 24-hour urine specimen was 11% among all 289 normotensive subjects and 12% among the 239 with suppressed renin. When the definition of aldosteronism loosened to at least 10 mcg excreted during 24 hours the adjusted prevalence of excess aldosterone among normotensives increased to 19% among the entire group and 20% among those with suppressed renin. This finding may have identified a primordial phase of nascent hypertension that needs further study but may eventually provide a new scenario for intervention. “If a normotensive person has compliant arteries and healthy kidneys they can handle the excess salt and volume load of PA,” but when compensatory mechanisms start falling short through aging or other deteriorations, then blood pressure starts to rise, suggested Dr. Vaidya.
Whom to screen for aldosteronism and how
While several experts agreed these findings added to an existing and growing literature showing that PA is common and needs greater diagnostic attention, they differed on what this may mean for the specifics of screening and diagnosis, especially at the primary care level.
“Our results showed more explicitly that excess aldosterone exists on a broad severity spectrum and can’t be regarded as a categorical diagnosis that a patient either has or does not have. The hard part is figuring out where we should begin interventions,” said Dr. Vaidya.
Dr. William F. Young Jr.
“This publication will hopefully increase clinician awareness of this common and treatable form of hypertension. All people with high blood pressure should be tested at least once for PA,” commented William F. Young Jr., MD, professor and chair of endocrinology at the Mayo Clinic in Rochester, Minn. “Diagnosis of PA provides clinicians with a unique opportunity in medicine, to provide either surgical cure or targeted pharmacotherapy. It’s been frustrating to me to see patients not tested for PA when first diagnosed with hypertension, but only after they developed irreversible chronic kidney disease,” he said in an interview. Dr. Young cited statistics that only about 2% of patients diagnosed with treatment-resistant hypertension are assessed for PA, and only about 3% of patients with hypertension and concomitant hyperkalemia. “Primary care physicians don’t think about PA and don’t test for PA,” he lamented.
The new study “is very convincing, and confirms and extends the findings of several other groups that previously reported the high prevalence of PA among patients with hypertension,” commented Dr. Stowasser. Despite this accumulating evidence, uptake of testing for PA, usually starting with spot measurement of renin and aldosterone to obtain an ARR, has “remained dismally low” among primary care and specialist physicians in Australia, the United States, Europe, and elsewhere, he added.
One stumbling block may be the complexity, or at least perceived complexity, of screening by an ARR and follow-up steps as recommended in a 2016 guideline issued by the Endocrine Society and endorsed by several international medical societies including the American Heart Association, Dr. Carey said. Dr. Funder chaired the task force that wrote the 2016 Endocrine Society PA guideline, and the eight-member task force included Dr. Carey, Dr. Stowasser, and Dr. Young.
The new study highlights what its authors cited as a limitation of the ARR for screening. When set at the frequently used ratio threshold of 30 ng/dL/ng/mL per hour to identify likely cases of PA, the crude PA prevalence rates corresponding to this threshold were 4% in treated stage 1 hypertensives, 10% in treated stage 2 patients, and 7% in those with resistant hypertension, substantially below the adjusted PA prevalence rates calculated by applying different criteria for excess aldosterone. In addition to missing clinically meaningful cases, the ARR may also underachieve at a functional level, Dr. Carey suggested.
“We note the difficulty with point assessment of ARR, but that’s what we have at the moment. We’ll look for other ways to identify patients with excessive aldosterone production,” he said. “We need to design a [diagnostic] pathway that’s easily doable by primary care physicians. Right now it’s pretty complicated. Part of the reason why primary care physicians often don’t screen for PA is the pathway is too complicated. We need to simplify it.”
In his editorial, Dr. Funder wrote that “much of the present guideline needs to be jettisoned, and radically reconstructed recommendations should be developed.”
One answer may be to apply a less stringent ARR threshold for further work-up. Dr. Stowasser’s program in Brisbane, as well as some other groups worldwide, use an ARR of at least 20 ng/dL as an indication of possible PA. “If you lower the cutoff to 20 [ng/dL], and ignore the plasma aldosterone level, then the ARR should pick up the great majority of patients with PA,” he said.
Another controversial aspect is whether aldosterone detection should be screened by 24-hour urine collection or by spot testing. In his editorial, Dr. Funder called spot testing “useless” and “misleading,” but Dr. Vaidya acknowledged that the 24-hour collection used in his current study is “not practical” for widespread use. Despite that, the Mayo Clinic in Rochester has focused on 24-hour urine collected “for more than 4 decades,” said Dr. Young, even though “a morning blood sample remains a simple screening test” that will catch “more than 95% of patients with PA” when combined with a plasma aldosterone threshold of 10 ng/dL. Dr. Stowasser noted that “patients don’t like” 24-hour collection, and not infrequently muck up collection” by forgetting to collect their entire 1-day output. Regardless of its shortcomings, 24-hour urine has the advantage of greater precision and accuracy than spot measurement, and using it on newly diagnosed hypertensive patients who also show renin suppression may be a viable approach, Dr. Carey suggested.
Regardless of exactly how guidelines for assessing aldosterone in hypertensive patients change, prospects seem ripe for some sort of revision and for greater participation and buy-in by primary care physicians than in the past. Dr. Carey, who also served as vice-chair of the American College of Cardiology and American Heart Association Task Force that wrote the most current U.S. guideline for managing hypertension, said it was too soon to revise that document, but the time had come to revise the Endocrine Society’s 2016 guideline for diagnosing and treating PA and to hash out the revision “in partnership” with one or more primary care societies. He also highlighted that publishing the current study in a high-profile primary care journal was an intentional effort to reach a large segment of the primary care community.
The new report “has the potential to change the current state of inertia” over wider PA diagnosis and targeted treatment “by being published in a widely read, major international journal,” commented Dr. Stowasser.
Dr. Vaidya has been a consultant to Catalys Pacific, Corcept Therapeutics, HRA Pharma, Orphagen, and Selenity Therapeutics. None of the other report coauthors had commercial disclosures, including Dr. Carey. Dr. Funder, Dr. Stowasser, and Dr. Young had no disclosures.
SOURCE: Brown JM et al. Ann Int Med. 2020 May 25. doi: 10.7326/M20-0065.