Abstract

BackgroundThe positive direct relation between stress and the development of cardiovascular disease has increasingly been recognized. However, the link between hypothalamic-pituitary-adrenal (HPA) dysregulation and subclinical cardiovascular disease has not been studied longitudinally. We investigated the relation of diurnal salivary cortisol, as a biological marker of stress levels, with progression of aortic stiffness over five years. MethodsA total of 3281 people (mean age 65.5) in the Whitehall II prospective study provided six saliva samples on a single weekday. We assessed the diurnal salivary cortisol using the daytime slope and bedtime level. Aortic stiffness was measured by carotid-femoral pulse wave velocity (PWV) at baseline (2007–2009) and five years later (2012–2013). Linear mixed models were used to estimate the association of diurnal salivary cortisol with baseline PWV and five-year longitudinal changes. ResultsDiurnal salivary cortisol were not associated with PWV at baseline. Among women but not men, a 1-SD shallower salivary cortisol slope at baseline was associated with a five-year increase in PWV (β = 0.199; 95% CI = 0.040, 0.358 m/s) and higher bedtime cortisol level (β = 0.208, 95% CI = 0.062, 0.354 m/s). ConclusionsDysregulation of the HPA axis measured using salivary cortisol (shallower slope, higher bedtime level) predicted the rate of progression of aortic stiffness among women.

Highlights

  • The positive direct relation between stress and the development of cardiovascular disease has increasingly been recognized in medical literature (Kivimaki and Steptoe, 2018)

  • We investigated the relation of diurnal salivary cortisol, as a bio­ logical marker of stress levels, with the progression of aortic stiffness over five years of follow-up, measured non-invasively by carotidfemoral pulse wave velocity (PWV) (Ben-Shlomo et al, 2014; Cifkova et al, 2019)

  • Our longitudinal analysis found that the rate of increase in PWV as a measure of aortic stiffness over five years was associated with the baseline diurnal pattern of salivary cortisol in women

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Summary

Introduction

The positive direct relation between stress and the development of cardiovascular disease has increasingly been recognized in medical literature (Kivimaki and Steptoe, 2018). The hypothesis that HPA axis dysregulation is linked to devel­ opment of cardiovascular disease implies that ‘stressed’ HPA func­ tioning predicts progression of arteriosclerosis in the general, healthy population (Kirschbaum and Hellhammer, 1989). Testing this direct stress hypothesis is a challenge and requires a sample of sufficient size to measure the circadian patterns of cortisol and the subsequent age-related changes in a subclinical measure of arteriosclerosis, such as aortic stiffness. Conclusions: Dysregulation of the HPA axis measured using salivary cortisol (shallower slope, higher bedtime level) predicted the rate of progression of aortic stiffness among women

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