Atherosclerotic plaque vulnerability in the statin era

Life style changes and improved medical therapy have decreased cardiovascular mortality in many countries over the last decades. This has been accompanied by changes in disease characteristics including more non-ST segment elevation myocardial infraction and less vulnerable plaques as assessed by histological analysis of surgical specimens. However, many patients with established disease still suffer from recurrent cardiovascular events in spite of treatment with state-of-the-art-therapy including statins. It is likely that this reflects a state of the disease in which statins control the pro-inflammatory effects of lipids allowing other statin-unresponsive disease mechanisms to become increasingly important. If this assumption is correct it means that patients with established disease with time will get insuffient protection by current therapies alone. Against this background it is critical to reach a better understanding of alternative mechanisms for plaque vulnerability. Examples of such mechanisms include altered patterns of blood flow caused by plaque stenosis resulting in down-regulation of the anti-inflammatory and anti-thrombotic signals in the endothelium, impaired vascular repair associated with diabetes and plaque inflammation driven by cholesterol crystals, infectious pathogens as well as autoimmune responses against modified plaque components. Novel biomarkers and other diagnostics are needed to establish the clinical importance of these mechanisms as well as to determine how they are affected by current treatments. Consequently, there will also be a need for development of new treatments targeting these mechanisms and that can act in concert with current therapies.