title: Cholesterol synthesis and absorption in coronary patients with lipid triad and isolated high LDL cholesterol in a 4S subgroup.
abstract: We assumed that assaying serum cholesterol precursors (synthesis markers) and plant sterols and cholestanol (absorption markers of cholesterol) reveals differences in cholesterol synthesis and absorption in the Finnish 4S subgroup divided in high triglyceride-low HDL cholesterol (lipid triad=HTG) and isolated high LDL cholesterol (ILDL) groups. Serum squalene and non-cholesterol sterol ratios to cholesterol were measured with gas-liquid chromatography at baseline, 6 weeks, 1 year, and 5 years on simvastatin. Patients with HTG (n=135) exhibited features of metabolic syndrome and, in spite of similar serum total and LDL cholesterol levels, ratios of synthesis markers were higher and those of absorption markers lower than in ILDL (n=133). The latter patients accumulated to a subgroup shown earlier to be clinical non-responders to simvastatin in 4S. Serum cholesterol reduction by simvastatin only tended to be higher in HTG than ILDL. The synthesis marker ratios were markedly reduced, and more effectively in HTG than ILDL, while the absorption marker ratios were increased, and for plant sterols more in ILDL than HTG. In conclusion, HTG is associated with high synthesis and low absorption of cholesterol, these events being opposite in ILDL. Synthesis is more effectively reduced by simvastatin in HTG than ILDL in spite of similar reduction in serum cholesterol. Patients defined by highest baseline absorption marker ratios in ILDL group are poor coronary event-reducers on regular simvastatin treatment.
authors.affiliation: Department of Medicine, Division of Internal Medicine, University of Helsinki, Biomedicum Helsinki, C 4 22, Haartmaninkatu 8, PL 700 00029 HUS Helsinki, Finland. tatu.a.miettinen@helsinki.fi
authors.forename: Tatu A
authors.initials: TA
authors.lastname: Miettinen
authors.forename: Helena
authors.initials: H
authors.lastname: Gylling
mesh_terms: D000042:Absorption / Q000187:drug effects; D015992:Body Mass Index; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D019821:Simvastatin / Q000627:therapeutic use*; D013185:Squalene / Q000097:blood; D013261:Sterols / Q000097:blood; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D008055:Lipids; D013261:Sterols; D014280:Triglycerides; D013185:Squalene; D002784:Cholesterol; D019821:Simvastatin