Method-dependent Changes in “HDL-Cholesterol” with Recombinant Apolipoprotein A-IMilano Infusion in Healthy Volunteers

Abstract

Warnick et al. (1) recently reviewed the status of the measurement of HDL-cholesterol (HDL-C) and cautioned against the use of the new homogeneous methods, when atypical specimens may be present, without additional validation of the accuracy of the methods. We recently had the opportunity to analyze specimens from a clinical trial, which will serve as an excellent example of the warning given by these authors. In a phase I clinical trial, 32 healthy volunteers were infused with a synthetic HDL comprising recombinant apolipoprotein (Apo) A-IMilano and phospholipid [1-palmitoyl-2-oleoyl-sn-3-glycerophosphocholine (POPC)]. This cholesterol-free, HDL-like complex is referred to as ETC-216. The intent of the trial was to determine safety/tolerability before initiating a phase II study in patients with acute coronary syndromes. It has been suggested that ApoA-IMilano/phospholipid infusions may rapidly stabilize atherosclerotic lesions by mobilizing vessel wall cholesterol (2). Initial measurements of HDL-C concentrations before and 30 min after the start of the infusion gave divergent results when we compared results obtained …