Serum homocysteine concentrations, gemfibrozil treatment, and progression of coronary atherosclerosis.
The present study aimed to assess the effect of gemfibrozil on serum total homocysteine (tHcy) concentration and to evaluate the influence of tHcy on the angiographically determined progression of coronary atherosclerosis in a randomised, placebo-controlled trial of 395 post-coronary bypass men with low HDL cholesterol levels. The baseline levels of tHcy and those after 16 months of randomised therapy were measured by high-pressure liquid chromatography. Patients were genotyped for the thermolabile variant of N5,N10-methylenetetrahydrofolate reductase (MTHFR) (677C > T substitution). Gemfibrozil therapy was associated with a median 18% increase in tHcy levels (P < 0.01). In the gemfibrozil group increases in tHcy and HDL cholesterol were related (r = 0.217, P = 0.004), but changes in tHcy and triglycerides were not. Levels of tHCy were not associated with baseline extent or progression of coronary-artery disease. Subjects homozygous for the rare MTHFR T allele had 34% higher median tHcy concentrations than CC homozygotes or CT heterozygotes, but responses to gemfibrozil did not differ significantly among genotypes. The MTHFR genotype was not associated with extent or progression of coronary atherosclerosis. We conclude that gemfibrozil causes a significant elevation in tHcy levels, but the clinical relevance of this is unknown at present.
Syvänne
Mikko
M
Department of Medicine, Division of Cardiology, Helsinki University Central Hospital, P.O. Box 340, Haartmaninkatu 4, Helsinki, 00029 HUS, Finland. mikko.syvanne@hus.fi
Whittall
Roslyn A
RA
Turpeinen
Ursula
U
Nieminen
Markku S
MS
Frick
M Heikki
MH
Kesäniemi
Y Antero
YA
Pasternack
Amos
A
Humphries
Steve E
SE
Taskinen
Marja-Riitta
MR
D008076:Cholesterol, HDL / Q000097:blood; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics; D018450:Disease Progression; D004311:Double-Blind Method; D015248:Gemfibrozil / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents; D014280:Triglycerides; D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D015248:Gemfibrozil