All these data raise intriguing biological issues concerning mechanisms linking inflammation in general and CRP in particular to atherothrombosis. As indicated earlier, it is no longer thought that this association is simply due to confounding by cigarette consumption, nor is it believed that this is simply due to an acute phase response or an innocent bystander effect, because many studies demonstrate predictive value 5, 10, and even 15 years in advance of the first vascular event. On the other hand, cytokine function is a very important part of this process. Several studies by investigators around the world have now demonstrated that cytokine mediators such as IL-6, TNF-", and IL-1 also are elevated among individuals at risk, and these are important since these are the primary hepatic drivers of CRP production. In addition, there are many direct effects of CRP on the vascular system. CRP is a pentraxin and is part of the native immune response. It is involved in complement activation, and very intriguing data have been presented suggesting that CRP itself may increase the expression of several cell adhesion molecules that are associated with the attachment and transmigration of white cells at the vascular endothelium. It has also been suggested that infection by Chlamydia, Helicobacter pylori, or cytomegalovirus may be associated with chronic inflammation. On the right side of this slide is a look towards the future. Many of us think that the inflammatory markers may have a role in the detection of subclinical atherosclerosis, and it is now clear that insulin resistance and obesity are involved in this process as well. Because of the interrelation of endothelial dysfunction and the dysmetabolic syndrome with the inflammatory processes, CRP response in general may provide us with a marker for plaque vulnerability.