Increased arterial stiffness and atherosclerosis in patients with nonfunctioning adrenal incidentaloma

Nonfunctioning adrenal incidentalomas (NFAIs) are typically considered benign and hormonally inactive, yet emerging evidence suggests a potential association with increased cardiovascular risk. This study aimed to evaluate whether NFAIs are independently associated with vascular damage, assessed through arterial stiffness and carotid Doppler ultrasound. In this observational study, we prospectively enrolled outpatients undergoing evaluation for suspected secondary hypertension at the Arterial Hypertension and Cardiovascular Endocrinology Laboratory of the University of Turin. Patients with NFAI were compared to individuals with essential hypertension and normal adrenal imaging. Cardiometabolic and hemodynamic parameters, including augmentation index (AIx), pulse wave velocity, carotid intima-media thickness, and plaque presence, were assessed. A total of 25 patients with NFAI and 165 controls were included. Univariate analysis revealed a worse cardiometabolic profile in NFAI patients. In multivariable models, NFAI was independently associated with increased arterial stiffness: AIx P2/P1 (EC 1.097, 95% CI 1.016-1.185; p = 0.019), AIx AP/PP (EC 1.133, 95% CI 1.043-1.232; p = 0.004), and AIx@HR75 (EC 1.073, 95% CI 1.004-1.147; p = 0.039). Pulse wave velocity was also significantly higher in the NFAI group (EC 2.144, 95% CI 1.021-4.502; p = 0.044). Furthermore, NFAI was associated with increased odds of having carotid intima-media thickness ≥0.9 mm (OR 3.312, 95% CI 1.011-10.855; p = 0.048), independent of other confounders. This is the first study to demonstrate that NFAI is independently associated with increased arterial stiffness and early vascular remodeling. These findings support the need for systematic cardiovascular risk assessment in patients with NFAI, even in the absence of overt hormonal activity. This graphical abstract illustrates the findings of a cross-sectional study comparing 25 patients with nonfunctioning adrenal incidentaloma (NFAI) to 165 controls with essential hypertension. All participants underwent a comprehensive cardiometabolic and vascular evaluation, including pulse wave analysis (PWA), pulse wave velocity (PWV), and carotid Doppler ultrasound. Compared to controls, patients with NFAI displayed increased arterial stiffness-demonstrated by higher augmentation index (AIx) and PWV values-as well as a higher prevalence of carotid intimamedia thickness (cIMT) ≥0.9 mm. These vascular alterations occurred despite the absence of overt hormonal hypersecretion. The results support the interpretation of NFAI as a potential marker of early vascular remodeling and advocate for systematic cardiovascular risk assessment in these patients.