Hidden Hormone Condition May Be Driving Hard-to-Treat High Blood Pressure

Endogenous hypercortisolism was identified in more than a quarter of patients with resistant hypertension, according to findings presented at the American College of Cardiology Annual Scientific Session (ACC.26).

Results from the screening portion of the MOMENTUM trial suggest the condition may be a substantially more common and under-recognized driver of treatment-resistant hypertension than current clinical practice assumes.

“Resistant hypertension increases the risk of cardiovascular events like heart attacks, strokes and heart failure, as well as kidney damage,” said Deepak L. Bhatt, M.D., M.P.H., director of Mount Sinai Fuster Heart Hospital, and Valentin Fuster, M.D., Ph.D., professor of cardiovascular medicine at the Icahn School of Medicine at Mount Sinai. “MOMENTUM shows that hypercortisolism contributes to resistant hypertension in over a quarter of patients and that screening for hypercortisolism in these challenging-to-treat patients may help physicians provide more personalized care.”

MOMENTUM Study Design and Testing Methodology

MOMENTUM was a prospective, multicenter observational study conducted at 50 U.S. sites. Eligible participants were adults aged 18 years or older with resistant hypertension defined by American Heart Association criteria: systolic blood pressure of 130 mm Hg or greater despite use of three or more antihypertensive medication classes, including a diuretic at maximally tolerated doses, or use of four or more medications from different classes regardless of blood pressure level.

A total of 1,086 patients were screened.

Each participant was evaluated for hypercortisolism using the 1-milligram overnight dexamethasone suppression test (DST), with hypercortisolism defined as a post-DST cortisol level greater than 1.8 micrograms per deciliter in the setting of adequate dexamethasone levels of 140 nanograms per deciliter or higher.

Key exclusion criteria were designed to minimize false-positive results and included white-coat hypertension, confirmed nonadherence to antihypertensive medications, systemic glucocorticoid exposure, impaired renal function, acute illness, severe untreated sleep apnea and oral contraceptive use.

The primary end point was the prevalence of hypercortisolism. Secondary end points included clinical and laboratory characteristics associated with hypercortisolism, markers of primary aldosteronism, prevalence of cortisol-aldosterone co-secretion and sex-based differences in frequency.

Hypercortisolism Identified in 27% of Screened Patients

Results presented at ACC.26 indicated 297 of the 1,086 patients screened, or 27.3%, met the study definition for hypercortisolism. Among the subset of participants with hemoglobin A1c of 7.5% or higher who were taking three or more antihypertensive medications, the prevalence rose to 32.6%, the company reported.

According to investigators, the MOMENTUM results, if replicated, may support broader screening with the standardized DST in resistant hypertension workups.

The MOMENTUM findings should be interpreted in the context of several limitations. As an industry-sponsored observational prevalence study, the results reflect provider-referred patients at specialty sites and may not represent the broader resistant hypertension population. The DST, while standardized, can produce false positives, and the study exclusion criteria aimed to minimize but not eliminate this risk.

The results come on the heels of the CATALYST trial, which was a two-part trial funded by Corcept Therapeutics. In the first half of the CATALYST trial, investigators found hypercortisolism in 23.8% of the 1,057 patients screened with difficult-to-control Type 2 diabetes. In the second half, treatment with mifepristone significantly reduced A1c by 1.32% compared with placebo and improved weight management over 24 weeks.

“It is now clear that hypercortisolism is more common than previously assumed in patients whose hypertension and diabetes don’t respond to standard-of-care treatments,” said Bill Guyer, Pharm.D., chief development officer at Corcept Therapeutics. “We are grateful to the investigators and patients who have participated in this research and hope that the findings will provide critical information to support increased screening for hypercortisolism, more accurate diagnoses and improved treatment options.”

This article was originally published on HCPLive.