Long-term glucocorticoid exposure ups risk of incident CVD

Long-term glucocorticoid levels, particularly cortisone measured in scalp hair, are associated with a higher risk of incident cardiovascular disease (CVD) among younger adults, suggests a study. 

“Our results ... highlight the potential role of glucocorticoid action in the development of CVD and reveal hair glucocorticoid levels as promising biomarkers that may be used to identify individuals with increased cardiovascular risk,” the researchers said. 

A total of 6,341 hair samples of participants from the Lifelines cohort study were examined for cortisol and cortisone levels. The researchers explored the association of glucocorticoid levels with incident CVD during 5 to 7 years of follow-up. 

The odds ratio (OR) of long-term glucocorticoid levels in scalp hair (HairGCs) for incident CVD was estimated using logistic regression, with adjustments for classical cardiovascular risk factors.  

The researchers conducted a sensitivity analysis in subcohorts of participants aged <60 years and ≥60 years. Finally, they assessed the correlation of HairGC levels with  immune parameters (ie, total leukocytes and subtypes). 

Overall, 4,701 individuals had available data on hair cortisone levels, which independently correlated with incident CVD (p<0.001), particularly in those aged <60 years (adjusted OR, 4.21, 95 percent confidence interval [CI], 1.91–9.07 per point increase in 10-log cortisone concentration [pg/mg]; p<0.001). [J Clin Endoc Metab 2024;109:2520-2529] 

Except for oesinophils, all immune parameters were found to have an association with hair cortisone (all multivariable-adjusted p<0.05). 

“In this large, prospective cohort study, we found that long-term cortisone levels ... represent a relevant and significant predictor for future CVD in younger [adults],” the researchers said.  

“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,” they added. 

Cardiometabolic health 

Previous studies have established the association of higher hair glucocorticoid levels, which indicate chronic systemic exposure, with cardiometabolic parameters, including BMI, waist circumference, metabolic syndrome, and CVD. [Obes Rev 2022;23:e13376; J Clin Endocrinol Metab 2013;98:2078‐2083; J Clin Endocrinol Metab 2013;98:2573‐2580] 

However, the above findings seem to be unclear due to the lack of longitudinal studies, and the current work fills this gap by providing evidence on the relevant clinical outcome of incident CVD. [Curr Obes Rep 2018;7:193‐203; Curr Cardiol Rep 2019;21:116] 

Notably, the current study also supports previous findings on metabolic syndrome and waist circumference, indicating that the most pronounced association with cardiometabolic health among HairGCs are for biologically inactive cortisone rather than cortisol. [Curr Obes Rep 2018;7:193‐203; Curr Cardiol Rep 2019;21:116] 

“It has been hypothesized that hair cortisone levels reflect the ‘reservoir’ of circulating glucocorticoids, that can be activated by the enzyme 11-beta-hydroxysteroid dehydrogenase type 1 to biologically active cortisol,” the researchers said.  

“However, it should be noted that we did not meet the anticipated statistical power that was required to detect a significant difference for cortisol. Thus, our cortisol results should be interpreted with high caution, and the high number of cortisol measurements that had to be excluded for technical reasons is a limitation of the current study,” they added.