BACKGROUND Stress is considered a modifiable risk factor for cardiovascular disease. Scalp hair analysis is a tool to assess long-term exposure to the stress hormone cortisol. We aimed to determine the association between hair cortisol concentrations (HCC) and clinical characteristics in patients with structural heart disease. Additionally, we investigated potential predictors for longitudinal change in HCC. METHODS The study consisted of 261 patients with structural heart disease from a randomized controlled trial of mindfulness training. One sample of scalp hair was used to determine HCC both at baseline and at 12-week follow-up. In 151 patients, HCC was available (mean age: 41.3 years, range 18-65). We investigated the association between HCC at baseline and several physiological measures (BMI, blood pressure, heart rate, respiratory rate, 6-minute walk test), as well as psychological parameters (physical and mental component summary measures (SF-36), emotional distress (HADS), and perceived stress). Additionally, we used these clinical parameters to predict HCC change over time. RESULTS The median HCC was 22.3 pg/mg of hair (23.5 interquartile range). In multivariable linear regression analyses, an association was observed between log-transformed HCC and BMI (β 0.171, p=0.037), respiratory rate (β 0.194, p=0.016), and the physical summary score (β -0.163, p=0.054). Independent predictors of log-transformed HCC change after 12 weeks were mental summary score (β -0.200, p=0.019) and diastolic blood pressure (β -0.171, p=0.049). CONCLUSIONS In patients with structural heart disease a positive association exists between HCC and BMI. Mental health status may predict a change in long-term cortisol over time.