Urinary cortisol and cardiovascular events in women vs. men: The multi-ethnic study of atherosclerosis

Research suggests that women experience greater cardiovascular ischemic effects from stress than men. Visceral adiposity is an endocrine tissue that differs by sex and interacts with stress hormones. We hypothesized that urinary cortisol would be associated with increased cardiovascular events and change in coronary artery calcium score (CAC) in women, and these relationships would vary by central obesity. In the Multi-Ethnic Study of Atherosclerosis Stress Ancillary study, cortisol was quantified by 12-h overnight urine collection. Central obesity was estimated by waist-hip ratio (WHR). Multivariable Cox models estimated the relationship between cortisol and cardiovascular events and assessed for moderation by WHR. The relationship between cortisol and change in CAC Agatston score was assessed by Tobit regression models. 918 patients were analyzed with median follow up of 11 years. There was no association between urinary cortisol and cardiovascular events in the cohort. However, in individuals with below median WHR, higher urinary cortisol levels (upper tertile) were associated with higher cardiovascular event rates in the full cohort, women, and men, but not in groups with above median WHR. There was significant moderation by WHR in women, but not men, whereby the association between elevated cortisol and increased cardiovascular events diminished as WHR increased. Urinary cortisol was associated with increased change in CAC in women (P = 0.003) but not men, without moderation by WHR. Our study highlights associations between cortisol and subclinical atherosclerosis in women, and moderation of the relationship between cortisol and cardiovascular events by central obesity in both genders.