In Reply: Drs Jones and Blumenthal comment that our study did not adequately address limitations of the lipoprotein(a) assays used for plasma levels. In particular, they state that the lipoprotein(a) assay used in 2001 through 2003 in the CGPS, an immunoturbidimetric assay from DiaSys (DiaSys Diagnostic Systems, Holzheim, Germany) measuring total mass of lipoprotein(a), is biased compared with current isoform-independent molar assays.
However, the risk estimates for myocardial infarction in our study were based on the Copenhagen City Heart Study (CCHS), in which lipoprotein(a) total mass was measured in 1991 through 1994 using a well-validated in-house turbidimetric assay using rabbit antihuman lipoprotein(a) polyclonal antibodies.1 The polyclonal antibodies were purified by immunoadsorption against apolipoprotein B and plasminogen, ensuring no cross-reactivity with either of these components, confirmed by immunoelectrophoresis. In addition, the polyclonal antibodies were tested by Western blot targeting 12 different isoforms of lipoprotein(a), with adequate detection of all isoforms and no tendency for the larger isoforms to have increased signal intensity. Therefore, any tendency to overestimate concentrations of large isoforms (bias) in our assay is probably modest.
Kamstrup PR, Nordestgaard BG. Lipoprotein(a) Measurement and Determining Risk of Myocardial Infarction—Reply. JAMA. 2009;302(15):1645-1646. doi:10.1001/jama.2009.1484