Issues Concerning the Monitoring of Statin Therapy in Hypercholesterolemic Subjects with High Plasma Lipoprotein(a) Levels

Most studies on the topic have shown that statin therapy decreases plasma LDL levels but not those of lipoprotein(a) [Lp(a)]. This specificity of action, although previously noted, has not been systematically investigated. In the current study we approached this problem by monitoring LDL- and Lp(a) cholesterol in 80 hypercholesterolemic subjects with high Lp(a) levels, at entry and 8 mon after initiation of statin therapy. We found that commonly used direct and indirect LDL cholesterol assays gave an LDL cholesterol value that comprised both true LDL- and Lp(a) cholesterol. We estimated these two analytes from the values of Lp(a) protein determined by ELISA and from knowledge of the Lp(a) chemical composition, complemented by data from immunochemical and ultracentrifugal analyses. Statin therapy, while not affecting plasma Lp(a) protein levels (21.7+/-10.4, before, and 22.0+/-10.1 mg/dL, after), caused a decrease in the estimated or true LDL cholesterol (P < 0.0001) to values in some cases as low as 10 mg/dL. This drop in true LDL was validated by the decrease in the LDL band in the ultracentrifugation profiles, and its magnitude was proportional to the degree of total cholesterol lowering and to the pretreatment true LDL/Lp(a) cholesterol weight ratio. We conclude that true LDL but not Lp(a) cholesterol is affected by statin therapy and that this specific response cannot be monitored by current LDL cholesterol assays and must, rather, rely on estimates of these two analytes.