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2 studies underscore high CV risk in primary aldosteronism, despite treatment
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Patients with primary aldosteronism have markedly increased risk for cardiovascular and cerebrovascular events, including stroke and coronary artery disease, compared with those with essential hypertension, and that risk persists even with mineralocorticoid antagonist therapy, according to two analyses published in The Lancet Diabetes & Endocrinology.
The association was independent from blood pressure level, age and sex, suggesting that aldosterone can induce CV effects through mechanisms that are at least partly independent of its effects on BP, according to the researchers.
In a systematic review and meta-analysis, Silvia Monticone, MD, of the division of internal medicine and hypertension unit at the University of Turin, Italy, and colleagues analyzed data from 31 studies conducted through February comparing patients with primary aldosteronism (n = 3,838; mean age, 53 years; 28% women) and patients with essential hypertension (n = 9,284; mean age, 53 years; 32% women). Researchers assessed the association between primary aldosteronism and incidence of stroke and CAD (coprimary endpoints) and secondary endpoints that included the prevalence of atrial fibrillation, heart failure, metabolic syndrome and diabetes.
The cohorts were followed for a mean of 8.8 years.
Compared with patients diagnosed with essential hypertension, six studies found that patients with primary aldosteronism had a higher incidence of stroke (OR = 2.58; 95% CI, 1.93-3.45), consistently across both matched and unmatched studies. In eight studies assessing risk for CAD, patients with primary aldosteronism also showed a higher risk vs. those with essential hypertension (OR = 1.77; 95% CI, 1.1-2.83). Patients with primary aldosteronism also saw an increased risk for both atrial fibrillation (OR = 3.52; 95% CI, 2.06-5.99) and heart failure (OR = 2.05; 95% CI, 1.11-3.78) compared with those who had essential hypertension. There were no between-group differences for patients with aldosterone-producing adenomas or bilateral adrenal hyperplasia, according to researchers.
Patients with primary aldosteronism also had increased risks for diabetes, metabolic syndrome and left ventricular hypertrophy compared with those who had essential hypertension.
“These data strongly highlight the importance of an early diagnosis of primary aldosteronism, of the early initiation of specific treatment, and of promoting strategies to improve the dramatically low diagnostic rate of this condition,” Monticone and colleagues wrote. “Specific treatment appears to reverse the cardiovascular risk excess.”
In a second analysis, Gregory L. Hundemer, MD, of the division of renal medicine at Brigham and Women’s Hospital in Boston, and colleagues assessed registry data from 602 patients with primary aldosteronism without a previous CV event who were prescribed mineralocorticoid antagonist therapy, and 41,853 patients with essential hypertension without a previous CV event, matched by decade at age of study entry to the primary aldosteronism study population. Primary outcome was an incident CV event, including myocardial infarction, coronary revascularization, hospital admission with congestive heart failure or stroke; secondary outcomes were incident atrial fibrillation, diabetes and death.
Researchers found that patients with primary aldosteronism treated with mineralocorticoid antagonist therapy had double the unadjusted incidence of composite CV events vs. those with essential hypertension (56.3 vs. 26.6 events per 1,000 person-years; P < .0001). The adjusted HR for incident composite CV events was 1.91 (95% CI, 1.63-2.25), with each individual component associated with higher risk, according to the researchers. These patients similarly had a higher risk for death and developing incident atrial fibrillation and diabetes compared with those with essential hypertension.
Researchers also found that the excess risk for CV events and mortality was limited to patients whose plasma renin activity remained suppressed at less than 1 µg/L per hour on mineralocorticoid antagonist therapy compared with those with essential hypertension, whereas patients treated with a higher mineralocorticoid receptor antagonist dose and who had unsuppressed renin levels had no excess risk. The findings led researchers to suggest a more aggressive and multifaceted approach to medical therapy.
“Targeting a rise in plasma renin activity as a biomarker for adequate [mineralocorticoid antagonist] blockade might serve as an important clinical benchmark in treatment of primary aldosteronism with [mineralocorticoid] antagonists,” Hundemer and colleagues wrote.
In a commentary accompanying the two studies, John W. Funder, MD, PhD, FRACP, FRCP, senior fellow at the Hudson Institute of Medical Research and a professor in the department of medicine at Monash University in Australia, noted that, in Hundemer and colleagues’ study, the recommendation to increase mineralocorticoid receptor antagonist dose as optimal therapy is “fraught with danger in terms of noncompliance” and does not consider the physiology of renin suppression.
“The counter-suggestion to increasing [mineralocorticoid receptor] antagonist therapy would then be salt restriction, if necessary coupled with amiloride or triamterene as saluretics,” Funder wrote. “It takes about 6 weeks to accommodate to a low-salt diet, but for patients with primary aldosteronism who have a suppressed renin on a [mineralocorticoid receptor] antagonist, it would raise the renin levels into the same range as people with essential hypertension.”
Funder called primary aldosteronism a major public health problem and said all patients presenting with hypertension should have plasma renin levels measured.
“If plasma renin activity is less than 1 µg/L per hour (or plasma renin concentration equivalently suppressed), they should proceed straight to screening for primary aldosteronism,” Funder wrote. – by Regina Schaffer
Disclosures: One of the study authors reports he receives grants and personal fees from Allena Pharmaceuticals, AstraZeneca and other fees from UpToDate.
References:
Monticone S, et al. Lancet Diabetes Endocrinol. 2017;doi:10.1016/s2213-8587(17)30319-4.
Hundemer GL, et al. Lancet Diabetes Endocrinol. 2017;doi:10.1016/s2213-8587(17)30367-4.
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