<International Circulation>:  Lipid therapies present new possibilities and identify additional uncertainties as they evolve. Comparing LDL particle number to LDL cholesterol as a predictor of risk is of practical significance in the management of coronary artery disease patients. Can you tell us the latest progress in this area of study?

    Dr Brown: There are several studies now that have looked at either the protein component of VLDL and LDL called Apo-B. There is one Apo-B molecule on all LDL and VLDL particles. By measuring Apo-B we can get a measure of particle number. It looks as though that is a stronger predictor of events than the LDL-cholesterol. Another way of measuring particle number is by looking at the magnetic resonance spectral analysis of the plasma lipoproteins. The hydrogen atoms at the ends of these fat molecules in lipoproteins actually resonate when you put them in a very strong magnetic field and the composite signal transmitted back can be used to calculate not only the number of particles but the size of the particles. This type of analysis has been done in patients contained in a dozen large retrospective studies of both interventional trials and community-based studies where large populations have baseline lipoprotein measures and are then monitored over time to see what the incidence of vascular disease would be in various groups. The particle number seems to have a stronger predictive power than the LDL-cholesterol in virtually every study that has been done to date， whether with Apo-B or the magnetic resonance spectral analysis has been compared to the standard cholesterol concentrations in lipoproteins. The time is now right for considering particle number as a guide to treatment by either one of these methods of measurement. In the United States we have a panel discussing this issue right now. We don’t know how they are going to settle on this - whether they are going to say that we should set goals for particle numbers for LDL or VLDL and HDL or whether we should wait a bit longer for further evidence. There are many aspects to guideline setting: the availability of the test; the cost; all these additional measures must come into play. This is up in the air at the moment but the science seems to be strongly in favor of knowing particle number and consequently guiding therapy based on those numbers. I should point out that statins lower particle number and the question is， should we titrate particle number lower because sometimes when you use cholesterol reducing drugs， the chol