Importance of Hypercortisolism in BP Control, Cardiovascular Risk and in Patients With Difficult‐to‐Control Hypertension: An Overview for Primary Care Physicians

AIMS: Hypertension remains one of the most prevalent and consequential modifiable cardiovascular risk factors worldwide, affecting approximately 1.28 billion adults globally and nearly half of the United States population. Despite the availability of effective therapies, optimal blood pressure control is achieved in fewer than one in four patients, contributing substantially to the burden of myocardial infarction, stroke, heart failure, chronic kidney disease and cognitive decline. Resistant hypertension, defined as blood pressure remaining above goal despite three maximally tolerated antihypertensive agents including a diuretic or requiring four or more agents to achieve control, affects a meaningful proportion of hypertensive patients and carries a disproportionately elevated risk of end-organ damage and adverse cardiovascular events. MATERIALS AND METHODS: In this review, we sought to describe how hypercortisolism has historically been underrecognized and under screened as a secondary cause of resistant hypertension, in part due to the perception that overt Cushing's syndrome is rare. However, emerging evidence is challenging this assumption. RESULTS: The CATALYST study demonstrated a 24% prevalence of endogenous hypercortisolism amongst patients with difficult-to-control type 2 diabetes and a 37% prevalence in those requiring three or more antihypertensive medications. Treatment with the glucocorticoid receptor antagonist mifepristone resulted in improvements in glycemic control and body weight, providing hypothesis generating evidence that hypercortisolism may be a relevant, as opposed to an incidental, contributor to cardiometabolic dysregulation. The MOMENTUM registry prospectively evaluated the prevalence of endogenous hypercortisolism specifically in patients with resistant hypertension and found that hypercortisolism was present in 27.3% of this cohort of patients. Primary care providers occupy a central role in the recognition, initial workup and coordinated management of hypertension, including appropriate screening for secondary causes. CONCLUSIONS: Awareness of hypercortisolism as an underdiagnosed driver of treatment-resistant hypertension represents an important and potentially treatable opportunity to improve outcomes at the primary care level.