C-reactive protein: linking inflammation to cardiovascular complications.

In the present issue, Chew and colleagues 1 show that elevated baseline C-reactive protein (CRP) levels before percutaneous coronary intervention (PCI) are associated with a progressive increase in the risk of death or myocardial infarction at 30 days. The independent association of risk attributable to the marker CRP remained, even after adjusting for a number of baseline variables that are known to influence early events after PCI. This finding is not a surprise to those who have followed the trail of CRP in the last few years. However, to those who have not followed the CRP story, some explanation is in order. See p 992 Our understanding of atherosclerosis has evolved immensely over the years. When William Osler wrote his textbook of medicine more than a century ago, atherosclerosis was viewed as being caused by the hardening of blood vessels as a consequence of the aging process. More recently, the perils of hypercholesterolemia and its causative association with atherosclerosis at all ages were uncovered through many large epidemiological studies. 2 However, cholesterol deposits in the arterial wall do not fully explain all the features of the proliferation of smooth muscle cells that attempt to form scars to wall off these lipid deposits. With the discovery of growth factors and their role in tissue repair, the “response to injury” hypothesis has become a dominant paradigm. In the last decade, however, a new perspective on atherosclerosis has been developed based on accumulating evidence that the entry of inflammatory cells such as monocytes into the arterial wall plays a pivotal role in this disease. 3,4 This new paradigm might be collectively called the inflammation hypothesis. Any inflammatory stimulus, such as oxidized LDL or infection, alters the endothelial lining of the artery to make it “sticky” through the expression of adhesion molecules (such as vascular cell adhesion molecule-1 and intercellular adhesion molecule-1) and the secretion of chemokines (such as monocyte chemoattractant protein-1) on the luminal surface. The sticky endothelium attracts or captures circulating monocytes or other inflammatory cells onto the arterial surface. Once monocytes are arrested on the surface of the endothelium, they travel across the junction between 2 endothelial cells and become tissue macrophages, which can ingest lipid deposits to form foam cells. With the continuous entry of monocytes into the arterial wall, the lesion develops from the initial fatty streak to the more advanced fibrous plaque. If one can prevent the entry of monocytes into the arterial wall, then one can ameliorate the development of atherosclerosis. This prediction has been tested and proved in many animal models.5 As inflammation began to be recognized as a major contributor to the pathogenesis of atherosclerosis, cardiologists started to ask whether markers of inflammation could be used to predict the