Assessing the Accuracy of Estimated Lipoprotein(a) Cholesterol and Lipoprotein(a)-Free Low-Density Lipoprotein Cholesterol

Background Accurate measurement of the cholesterol within lipoprotein(a) (Lp[a]-C) and its contribution to low-density lipoprotein cholesterol (LDL-C) has important implications for risk assessment, diagnosis, and treatment of atherosclerotic cardiovascular disease, as well as in familial hypercholesterolemia. A method for estimating Lp(a)-C from particle number using fixed conversion factors has been proposed (Lp[a]-C from particle number divided by 2.4 for Lp(a) mass, multiplied by 30% for Lp[a]-C). The accuracy of this method, which theoretically can isolate "Lp(a)-free LDL-C," has not been validated. Methods and Results In 177 875 patients from the VLDbL (Very Large Database of Lipids), we compared estimated Lp(a)-C and Lp(a)-free LDL-C with measured values and quantified absolute and percent error. We compared findings with an analogous data set from the Mayo Clinic Laboratory. Error in estimated Lp(a)-C and Lp(a)-free LDL-C increased with higher Lp(a)-C values. Median error for estimated Lp(a)-C <10 mg/dL was -1.9 mg/dL (interquartile range, -4.0 to 0.2); this error increased linearly, overestimating by +30.8 mg/dL (interquartile range, 26.1-36.5) for estimated Lp(a)-C >= 50 mg/dL. This error relationship persisted after stratification by overall high-density lipoprotein cholesterol and high-density lipoprotein cholesterol subtypes. Similar findings were observed in the Mayo cohort. Absolute error for Lp(a)-free LDL-C was +2.4 (interquartile range, -0.6 to 5.3) for Lp(a)-C<10 mg/dL and -31.8 (interquartile range, -37.8 to -26.5) mg/dL for Lp(a)-C >= 50 mg/dL. Conclusions Lp(a)-C estimations using fixed conversion factors overestimated Lp(a)-C and subsequently underestimated Lp(a)-free LDL-C, especially at clinically relevant Lp(a) values. Application of inaccurate Lp(a)-C estimations to correct LDL-C may lead to undertreatment of high-risk patients.