Evaluation of the atherogenic risk of isotretinoin-induced and etretinate-induced alterations of lipoprotein cholesterol metabolism.
Inverse alterations in plasma levels of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol are recognized side effects of systemic treatment with the synthetic retinoids isotretinoin and etretinate. The mass quotients of total plasma cholesterol and high-density lipoprotein cholesterol as well as low-density lipoprotein cholesterol and high-density lipoprotein cholesterol are well-established predictive risk factors of cardiovascular disease. We evaluated and compared these lipoprotein cholesterol ratios of 80 patients treated systemically with isotretinoin (13-cis-retinoic acid) and 81 patients treated with etretinate (aromatic retinoid). Lipoprotein cholesterol data were derived from 5 lipid studies on isotretinoin, including our own results, and 4 published lipid studies on etretinate. For all isotretinoin and etretinate lipid studies, significant increases in the mean plasma levels of total cholesterol and low-density lipoprotein cholesterol and significant decreases in the mean concentration of high-density lipoprotein cholesterol were demonstrated. In comparison with etretinate, oral isotretinoin gave rise to a nearly twofold percent increase of both lipoprotein cholesterol ratios from pretreatment levels. Furthermore, for isotretinoin, an approximately linear dose-related increase of the ratio of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol could be observed. If sustained over long periods, the mean differential rise of the ratio of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol of 0.92 +/- 0.51 for isotretinoin and 0.56 +/- 0.10 for etretinate indicates an increased risk of cardiovascular disease for both retinoids. Etretinate could be identified as the less harmful retinoid for prolonged oral therapy.
Melnik
B C
BC
Bros
U
U
Plewig
G
G
D001161:Arteriosclerosis / Q000139:chemically induced*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005050:Etretinate / Q000494:pharmacology*; D006801:Humans; D015474:Isotretinoin; D012176:Retinoids / Q000627:therapeutic use; D012306:Risk; D014212:Tretinoin / Q000494:pharmacology*
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D012176:Retinoids; D014212:Tretinoin; D005050:Etretinate; D002784:Cholesterol; D015474:Isotretinoin