Susanne Kuckuck^1,2,3, Nina van Gerwen³, Robin Lengton^1,2, Maryam Kavousi³, Mariëtte R. Boon^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 Epidemiology and Biostatistics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
4. Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands
5. Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

Introduction: Higher hair cortisol and cortisone levels, reflecting long-term biological stress, show strong cross-sectional links with cardiometabolic diseases and predict the onset of cardiovascular disease. However, little is known about the association of hair glucocorticoid levels and longitudinal trajectories of cardiometabolic health parameters.

Methods: We investigated longitudinal associations between baseline hair cortisol and cortisone levels and cardiometabolic outcome variables at baseline, 3-year and 7-year follow-up using data of 1,231 participants (72.3% women) of the Netherlands Study of Depression and Anxiety (NESDA). Outcomes included levels of diastolic blood pressure, fasting glucose, triglyceride, and high-density lipoprotein (HDL) cholesterol levels and waist circumference. Analyses were performed using linear-mixed models, adjusted for age, sex, educational level, hair washing frequency, smoking, physical activity, alcohol consumption, mental health status and medication use.

Results: Hair glucocorticoid levels were associated with higher waist circumference and triglyceride levels across time points. In addition, hair glucocorticoid levels were associated with higher blood pressure at 7-year follow-up. We did not find consistent associations of hair glucocorticoid levels with HDL levels or blood glucose levels over time.

Conclusion: Over time, individuals with higher chronic biological stress levels have persistent poorer cardiometabolic outcomes including higher waist circumference, triglyceride levels and blood pressure, all of which may increase risk for cardiovascular disease. Adults with high long-term biological stress could benefit from monitoring and early interventions targeting metabolism.