<International Circulation>:  I would like to thank Professor Eckel and Professor Hu for participating in our dialogue at WCC with International Circulation.  Today we are here to talk about residual risk， defining it as narrowly as we can， and specifically talking about the risks associated with HDL， LDL， triglycerides， and athrogenic dyslipidemia.  In what populations are increases triglyceride levels and low HDL levels of particular concern?

　　Prof. Eckel:  Triglycerides remains a complex issue.  The reason is complex because a suitable clinical trial has yet to be conducted.  The trials that have been done so far using fibrates in patients that have been treated with statins have included many patients with normal levels of triglycerides.  Ultimately， the trial that needs to be done is a trial where the fibrates are used in a population of patients who have hyperglyceridemia， mostly in patients with diabetes and would have to be done in patients with diabetes only.  The Veterans Administration in the United States is planning such a trial and， hopefully some time in the next five years， we will have a hard outcomes study that examines the fibrates in addition to a statin in patients with high risk of cardiovascular disease because of known CVD or because of some other risk.  This will be the triglyceride alone trial that will really be informative but at this time we really don’t have solid evidence that lowering triglycerides with fibrates is beneficial.

　　Prof. Hu:There is some evidence that there is some benefit for small vessels， especially for diabetes.

　　Prof. Eckel:  That is true.  This is somewhat the case for retinopathy but certainly for nephropathy.  There may be an actual benefit in these situations due to fibrates because there may be an association with lower triglycerides.

　　Prof. Hu:There may also be some evidence for improved outcomes for heart attack and stroke.  Like Professor Eckel mentioned， the results of preliminary studies are not ideal and further investigations are needed.

　　Prof. Eckel:  That is a mistake actually in designing previous trials， to use a drug in a group of patients that we would not normally treat.

　　Prof. Hu:We may be able to see that if we continue developing this kind of investigation addressing residual risk， we may be able to see more than just the typical risk factors like smoking， hypertension， or dyslipidemia.  In some developing countries this is an area that greatly needs improvement.  Even in patients that have a history of adverse events like heart attack or coronary artery disease there is still an alarmingly low 18.6% of patients who continue to take aspirin.  Less that 5% of this type of patient in China continue taking statins.

　　Prof. Eckel:  I don’t think the data in the West are much better.  If we talk about antithrombotic therapy like aspirin， or perhaps a second agent in cases where stents are placed， statins， ACE inhibitors， or an ARB， I am not sure that western countries are doing that much better than what you see here in China， that is， getting people on all of these agents to modify existing risk.  Another issue that arises is HDL cholesterol as a target for therapy.  As we all know HDL cholesterol has not been determined to be a suitable target for therapy.  Speaking of that， what are you thoughts about the AIM HIGH study?

　　Prof. Hu:Regarding AIM HIGH， I think there is still some problem with the design.  The sample size and the heart and placebo controls also had problems.

　　Prof. Eckel:  As you know in both groups the LDL cholesterol was quite low.  The way that most clinicians practice medicine， at least in The United States， is that they add niacin under existing statin therapy; they simply don’t tolerate the high LDL levels before they add niacin.  The practice of lipid related medicine hasn’t really been met by the AIM HIGH trial.  The AIM HIGH trial does have a message; unless the LDL is quite low increasing HDL doesn’t seem to have much additional benefit.  We have a whole new class of drugs though becoming available in the next 5-10 years.  CETP for instance， which Professor Hu， you are involved in one of the trials.

　　Prof. Hu:After AIM HIGH there is the HPS II THRIVE in China is very important.  In China it is possible to have some useful data in the next 2-3 years that could give us a final answer about what is happening.

　　Prof. Eckel:  That is an important trial because it is more about the standard of care with regard to adding niacin to existing therapy.  What are your thoughts about the CETP inhibitors and how they may or may not benefit patients?

　　Prof. Hu:The trial is ongoing and as of now there has been no increase in adverse events or outcomes.  It is too early to know if there is a significant benefit.

　　Prof. Eckel: This trial is a nice one because only HDL will be modified since a lot of the other CETP inhibitors modify other things than just HDL.  This should be a very informative study and help to answer the question if trying a different drug besides niacin will lead to better outcomes.