Glucocorticoids impair HDL-mediated cholesterol efflux besides increased HDL cholesterol concentration - a proof of concept.

Objective Glucocorticoids (GC) are associated with increased cardiovascular morbidity despite increased HDL-C concentration. HDL-mediated cholesterol efflux, a major anti-atherogenic property of HDL particles, is negatively associated with CVD risk. We aimed to determine whether HDL-mediated cholesterol efflux was influenced by GC. Design Prospective, observational study. Methods Lipid parameters, HDL composition, HDL-mediated cholesterol efflux, Cholesteryl Ester Transfer Protein, Phospholipid Transfer Protein and Lecithin Cholesterol Acyl-Transferase (LCAT) activities were determined in 10 patients with giant cell arteritis before and 3 months after GC introduction and in 7 control subjects. HDL concentration and composition, HDL-mediated cholesterol efflux and LCAT activity were determined in GC-treated mice. Results In patients, HDL-C concentration was higher after than before treatment GC-treatment (p=0.002) while HDL-mediated cholesterol efflux was decreased (p=0.008) and negatively associated with the proportion of cholesteryl ester in HDL (p=0.04), independently of CRP. As well, in mice, HDL-C level was increased after GC exposure (p=0.04) and HDL-mediated cholesterol efflux decreased (p=0.04). GC-treated patients had higher cholesteryl ester content in HDL, higher HDL2-to-HDL3 ratio and higher LCAT activity than before treatment (p=0.008, p=0.02 and p=0.004, respectively). Conclusions We report, for the first time, that in patients with giant cell arteritis and mice treated with GC, HDL-mediated cholesterol efflux was impaired by GC besides an increased HDL-C level. This impaired HDL functionality, possibly related to HDL enrichment in cholesteryl ester, could contribute to the increased CVD risk observed in GC-treated patients. Further studies are needed in larger populations, to further decipher the effect of GC on HDL.