<International Circulation>: Combination therapy may be an important concept in developing more effective strategies to treat and prevent atherosclerosis and coronary heart disease. Combination therapy with statins， PPARS (peroxisome proliferators-activated receptor agonists)， and RAAS (renin-angiotensin-aldosterone system) blockers demonstrate additive beneficial effects. What is the current thinking on the relationship between PPARs and RAAS as presented at this meeting?

    Prof. Eckel: The important place to start is that the PPARs are a different class of compounds. It is just not simply PPARs but there are agents that have PPAR-alpha agonistic properties， those with –gamma agonistic properties and a newer class， the PPAR-delta agonists. These all modify metabolism in a somewhat different way. The interesting thing about the PPARs is that all have anti-inflammatory effects. That is where the idea of cross-talk with the RAAS compounds makes some sense. The question arises， because we have no clinical trials where the intent of the study was to examine these two classes of drugs head-to-head， whether the anti-inflammatory effects of the PPARs are additive or redundant with those of the RAAS inhibitors? Renin inhibitors， ACE inhibitors， and the ARB blockers， all modify inflammation in a favorable way， perhaps better characterized for the ACE inhibitors and the ARBs than the renin inhibitors. Never-the-less， the types of molecules that the renin-angiotensin-aldosterone system modifies are the same types of molecules that the PPARs do. They could be additive or even synergistic， but alternatively together they could add no additional value.

    The PPAR-alpha agonists are mostly lipid-modifying agents， whereas the PPAR-gamma agents are important in glucose metabolism and the treatment of diabetes. There is a small amount of overlap between the –alpha and –gamma functionally but not much. The PPAR-delta group seem to be more involved in energy balance and maybe also important in modifying body weight favorably. These various types of agonists in the PPAR system need to be distinguished one from the other in terms of their indications their interaction with the RAAS.