Abstract 1925: The Effects of Intensive Statin Therapy on Markers of Cholesterol Synthesis and Absorption
There is great inter-individual response to statins in terms of lipid lowering. To gain more insight into this process, we investigated the impact of intensive statin therapy on surrogate markers of cholesterol synthesis and absorption. We also investigated whether baseline levels of these markers predicted treatment response. Measurements were performed in a subset of the STELLAR trial participants at baseline (n=135) and after 6 weeks of either rosuvastatin (n=66) or atorvastatin (n=69) therapy. Lathosterol (a marker of synthesis) and campesterol, sitosterol and cholestanol (all markers of absorption) were measured using gas-liquid chromatography and were expressed in absolute terms, as well as corrected for plasma total cholesterol levels (C). After therapy, both statins reduced total cholesterol levels by 40%. Rosuvastatin and atorvastatin significantly (P<0.001 for all changes) reduced lathosterol:C (−61% and −68%) and increased campesterol:C (48% and 70%), sitosterol:C (62% and 91%) and cholestanol:C (45% and 55%). The increase of campesterol:C and sitosterol:C was significantly different between the two treatment groups (both P=0.001). When the study subjects were classified as high or low synthesizers and absorbers, based on changes in absolute lathosterol and campesterol concentrations during treatment, the greatest reduction of total cholesterol was observed in low absorbers/high synthesizers, while the lowest reductions of total cholesterol was seen in high absorbers/low synthesizers (−132 ± 32 mg/dL (−46%) versus −96 ± 40 mg/dL (−34%), P difference = 0.001). Similar effects were observed for non-HDL-cholesterol and LDL-cholesterol changes. In addition to the known effects on cholesterol synthesis, both statins significantly increased markers of cholesterol absorption. Based on these markers, the most effective lipid lowering was observed in patients who were high synthesizers and low absorbers, with the converse also being the case.