The effect of methodological differences in the measurement of Lp(a) on the interpretation of clinical data

Abstract

In the majority of clinical studies, Lp(a) levels have been determined by methods affected by apo(a) size heterogeneity. Despite the importance of this topic, no studies have been performed to evaluate the impact of method inaccuracy on the interpretation of clinical data. We have evaluated to what extent method inaccuracy affects the correct classification of subjects for being at risk or not for CAD based on their Lp(a) values. Lp(a) levels were measured in samples from the Framingham study participants by our reference ELISA, by a turbidimetric method and by a commercial ELISA using an Lp(a) value of 75 nmol/l as the clinical decision point. The number of false positive and false negative values obtained by the turbidimetric methods was almost entirely explained by the apo(a) size dependency of this assay. However, the large number of false positive values obtained by the commercial ELISA method was not. To evaluate method differences in the interpretation of clinical data, a study was performed to compare the ability of our ELISA method and a nephelometric method to predict future angina pectoris in men participating in the Physicians' Health Study. Lp(a) values determined by ELISA were associated with increased relative risk for angina while those obtained by the nephelometric method were not. The results of these two studies clearly indicate the importance of using suitable and standardized methods for risk assessment and for the interpretation of clinical outcomes.