Susanne Kuckuck^1,2,3, Mariëtte R. Boon^1,2, Robin Lengton^1,2, Erik J. Giltay⁴, Brenda W.J.H. Penninx⁵, Elisabeth F.C. van Rossum^1,2

¹ Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands, ² Obesity Center CGG, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands, ³ Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands, ⁴ Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands, s.kuckuck@erasmusmc.nl

Background: The striking link between Cushing’s syndrome, the metabolic syndrome (MetS), and cardiovascular disease (CVD) suggests that long-term exposure to high glucocorticoid levels catalyzes cardiometabolic deterioration. However, the association of subtle variations in
long-term biological stress with MetS and CVD remains poorly understood. Specifically, little is known about the role of age.

Methods: We investigated the cross-sectional association between long-term biological stress and cardiometabolic deterioration using data of 1541 participants (74.5% women, mean age=47.5 years +/-13.1SD, range 23-72 years) of the Netherlands Study of Depression and Anxiety (NESDA). Biological stress was measured as hair cortisol (HairF) and cortisone (HairE) levels (first 3 cm closest to the scalp). Outcomes included presence of MetS, number of MetS criteria, diastolic blood pressure, waist circumference, fasting glucose, HDL and triglyceride levels. We also performed stratified analyses for age groups (median split; <=49 years; >50 years) to investigate age differences in predicting MetS.

Results: HairF and HairE were positively associated with presence of MetS (OR=1.28; 95%CI: 1.12–1.47, and OR=1.35; 95%CI: 1.16–1.57, both p<0.001), as well as number of MetS criteria (p<0.05 and p<0.001, respectively), as well as triglyceride levels and waist circumference (all p<0.05). HairF, but not HairE, was negatively associated with HDL levels and positively associated with diastolic blood pressure (both p<0.05). Additionally, the relationships of HairF and HairE with presence of MetS were stronger among younger participants (OR=1.41 vs. OR=1.22 in younger vs. older participants, and OR=1.78 vs. OR=1.18 in younger vs. older participants, p for interaction=0.100, and <0.001, respectively).

Discussion/Conclusion: Long-term biological stress, as measured by HairF and HairE, is associated with the presence of MetS, especially among the younger population. Prospective studies need to evaluate the extent to which HairF and HairE can be used in addition to standard risk factors to predict future cardiometabolic deterioration.

Conflict of interest: All authors declare no conflict of interest

Funding: This work is funded by Stress in Action. The research project ‘Stress in Action’: www.stress-in-action.nl is financially supported by the Dutch Research Council and the Dutch Ministry of Education, Culture and Science (NWO gravitation grant number 024.005.010). EFCvR is also supported by a Vidi grant from the Netherlands Organization of Scientific Research NWO (grant number: 91716453) and funded by the Elisabeth Foundation.