Coronary Endothelial Dysfunction Is Associated With Major Depressive Disorder in Men With Chest Pain and Nonobstructive Coronary Artery Disease

Background: Studies have demonstrated an association between endothelial dysfunction and major depressive disorder (MDD). However, the link between coronary endothelial dysfunction (CED) and an incident diagnosis of MDD across sexes is unclear. Methods: Patients with nonobstructive coronary artery disease (stenosis <40%) underwent an invasive assessment of CED. Macrovascular CED was defined as a percentage change in coronary diameter in response to acetylcholine of ≤-10% compared with baseline. Microvascular CED was defined as a percentage change in coronary blood flow in response to acetylcholine of ≤-50% compared with baseline. In the period after the index procedure, patients were followed up for developing a diagnosis of MDD, and logistic regression was performed to assess the association between baseline CED and incident MDD. Results: In total, 2280 patients underwent invasive testing for CED. A total of 516 patients (23%) underwent an evaluation for MDD at a date after the index procedure (mean±SD age, 53±12 years; 72% women). A total of 160 (31%) were diagnosed with MDD. The percentage change in coronary diameter in response to acetylcholine was lower in those diagnosed with MDD in all patients (-10.8% versus -5.3%; P=0.008), and in men (-19.0% versus -4.8%; P=0.001). In men, a higher proportion of those with macrovascular CED were diagnosed with MDD compared with those not diagnosed with MDD (59% versus 38%; P=0.035). In multivariable analyses, macrovascular CED was associated with MDD in men (odds ratio: 2.99 [95% CI, 1.26-7.45]; P=0.015). Conclusions: Macrovascular CED is significantly associated with incident MDD in men with nonobstructive coronary artery disease. Endothelial dysfunction in the coronary arteries could thus be a helpful biomarker to identify patients at risk of MDD.