Homocysteine and lipid lowering agents. A comparison between atorvastatin and fenofibrate in patients with mixed hyperlipidemia

Background: Hyperhomocysteinemia is a risk factor for cardiovascular diseas e. Elevation in homocysteine levels has recently been demonstrated during l ipid lowering treatment with fibrates. We compared the effect of a statin a nd a fibrate (atorvastatin acid fenofibrate) on plasma levels of homocystei ne and other thiol compounds in hyperlipidemic patients. Method and results : The study was of open randomized. parallel design with a preliminary scre ening phase. and a 6 week placebo period. After the placebo period. patient s were allocated randomly to atorvastatin or fenofibrate for a 6 month peri od. Plasma thiols were assayed by high pressure liquid chromatography with fluorescence detection. There were 29 patients in the fenofibrate group and 24 in the atorvastatin group. Fenofibrate induced a significant increase i n both homocysteine and cysteine plasma levels (+ 35.8 and + 18%, respectiv ely. P < 0.0001); by contrast, cysteinylglycine remained stable. There were no significant changes in any thiol compounds in the atorvastatin group. B oth treatments induced a significant decrease in uric acid, although fenofi brate was noticeably more effective than atorvastatin ( - 22.8 and - 6.4%, respectively). Fenofibrate induced a non-significant increase in creatinine (12%) while atorvastatin reduced it (4.7%,, NS). Conclusion: Our study con firms that the induction of elevations in plasma homocysteine and cysteine levels are a distinct feature of the pleiotropic effects of librates. Furth er studies are needed not only to investigate the potential deleterious eff ects of this modification, but also to define the specific mechanism which underlies such fibrate-mediated action. (C) 2001 Elsevier Science Ireland L td. All rights reserved.