Daily hassles and cortisol suppression following low-dose dexamethasone suppression test are independently associated with cardiovascular disease

Objective: Chronic stress is linked to cardiometabolic diseases through increased glucocorticoid exposure, but the impact of daily life stress on glucocorticoid regulation and cardiometabolic health remains underexplored. This study investigated these associations. Design This is a cross-sectional analysis of participants from the Netherlands Study of Depression and Anxiety (NESDA) without psychiatric diagnosis in the prior 6 months. Methods: We included 870 participants (64.7% female, median age 47.0 years). Daily life stress was assessed using the Daily Hassles Questionnaire (DHQ). Salivary cortisol was analyzed for 1-h awakening cortisol (4 time points), evening cortisol, and slope. Also an overnight 0.5 mg dexamethasone suppression test was performed. Associations between DHQ, glucocorticoid measures, and cardiometabolic health were studied using logistic and linear regressions. Results: After multivariable adjustment, each standard deviation (SD) increase in DHQ score was associated with 1.38 times (95% confidence interval [CI] 1.07; 1.77) higher odds of cardiovascular disease (CVD), but not diabetes, metabolic syndrome, or obesity. Higher DHQ scores were also associated with higher evening cortisol levels. In addition, each SD increase in cortisol suppression ratio was associated with 1.36 times (95% CI 1.08; 1.72) higher odds of CVD, but not diabetes, metabolic syndrome, or obesity. No interactions between DHQ and glucocorticoid measures on CVD were observed. Conclusion: A higher cortisol suppression ratio, indicative of increased glucocorticoid sensitivity, and increased daily hassles were both independently associated with having CVD. The absence of interaction suggests they influence CVD through separate pathways, highlighting the need for further research to better understand stress mechanisms and identify “stress profiles” most closely linked to cardiometabolic diseases.