Long-Term Glucocorticoid Exposure and Incident Cardiovascular Diseases-The Lifelines Cohort

Context: Long-term glucocorticoid levels in scalp hair (HairGCs), including cortisol and the inactive form cortisone, represent the cumulative systemic exposure to glucocorticoids over months. HairGCs have repeatedly shown associations with cardiometabolic and immune parameters, but longitudinal data are lacking. Design: We investigated 6341 hair samples of participants from the Lifelines cohort study for cortisol and cortisone levels and associated these to incident cardiovascular diseases (CVD) during 5 to 7 years of follow-up. We computed the odds ratio (OR) of HairGC levels for incident CVD via logistic regression, adjusting for classical cardiovascular risk factors, and performed a sensitivity analysis in subcohorts of participants < 60 years and >= 60 years of age. We also associated HairGC levels to immune parameters (total leukocytes and subtypes). Results: Hair cortisone levels (available in n = 4701) were independently associated with incident CVD (P < .001), particularly in younger individuals (multivariate-adjusted OR 4.21, 95% CI 1.91-9.07 per point increase in 10-log cortisone concentration [pg/mg], P < .001). All immune parameters except eosinophils were associated with hair cortisone (all multivariate-adjusted P < .05). Conclusion: In this large, prospective cohort study, we found that long-term cortisone levels, measured in scalp hair, represent a relevant and significant predictor for future CVD in younger individuals. These results highlight glucocorticoid action as possible treatment target for CVD prevention, where hair glucocorticoid measurements could help identify individuals that may benefit from such treatments.