Diurnal cortisol features with cardiovascular disease in hypertensive patients: a cohort study

The hypothalamic-pituitary-adrenal (HPA) axis may be associated with cardiovascular disease (CVD) and the effects of diurnal cortisol features on future CVD remain unclear among patients with hypertension. This study aimed to evaluate the association between diurnal cortisol features and CVD in patients with hypertension.Participants with cortisol rhythm test at baseline in Urumqi Research on Sleep Apnea and Hypertension (UROSAH) in 2011-2013 were enrolled and followed up till 2021. Incident events included coronary heart disease, stroke, and heart failure. Cox proportional hazards model was used to evaluate the relationship between diurnal cortisol features and incident CVD. Sex-specific and sensitivity analyses were also performed.In total, 2305 hypertensive participants comprised the current analytical sample. During a median follow-up of 7.2 years and 16374.9 person-years, there were 242 incident CVD cases. Multivariable Cox regression showed that steep diurnal cortisol slope (DCS) was significantly associated with decreased CVD risk (per s.d., hazard ratio (HR) = 0.86, 95% CI: 0.77-0.96, P = 0.011). Midnight cortisol was positively associated with an increased CVD risk (per s.d., HR = 1.24, 95% CI: 1.08-1.42, P = 0.002). Comparable results were observed in the sensitivity analyses. Neither midnight cortisol nor DCS was associated with incident CVD in the female subgroup.Flatter DCS and higher midnight cortisol levels are associated with an increased risk of CVD in patients with hypertension, especially in men. The detection of diurnal cortisol rhythm may help identify patients with hypertension at high risk of CVD.