Review article
C-reactive protein: history and revival

https://doi.org/10.1016/S0953-6205(02)00132-2Get rights and content

Abstract

C-reactive protein (CRP) is the prototype acute-phase protein, which can increase up to 1000-fold after the onset of a stimulus. Aside from its disputed role as a marker of infection and/or inflammation in daily clinical practice, the protein has a wide variety of biological properties and functions. Due to its opsonizing abilities and its capability to activate human complement, CRP plays an important role in the innate host defense against different microorganisms, such as bacteria and fungi. The same opsonophagocyting properties can lead to clearance of host cell material, including nuclear constituents. Inflammation is one of the cornerstones in the etiology and pathogenesis of atherosclerosis, which led to worldwide attention being focused on CRP and its role in the process of atherosclerosis. This role may have a dual character. First, CRP levels reflect the ‘burden’ of inflammation within atherosclerotic lesions, thus reflecting the grade of vulnerability and instability of the plaques. For this reason, an increased level of the protein may be a prelude to rupture of the plaque and, thus, to occlusive arterial disease. Secondly, CRP may play an active role in the atherosclerotic process. CRP plays a role in the expression of different adhesion molecules on endothelial cells and the protein is able to activate human complement within the plaque. Furthermore, the recent discovery of local production of CRP and complement proteins within the plaque suggests an active role for the protein in the inflammatory cascade. Whatever the role for CRP in the atherosclerotic process, it has been proven that an elevated CRP level, with a cut-off point of approximately 3 mg/l, is associated with an increased risk of occlusive arterial disease, especially acute coronary syndromes.

Introduction

C-reactive protein (CRP) is an acute-phase constituent with a record of service for more than seven decades. In the last decade, the protein experienced a revival in attention due to the inflammatory pathogenesis of atherosclerosis. In particular, the role of CRP in the vulnerability and instability of atherosclerotic plaques, leading to rupture, thrombosis and thus to occlusive arterial disease, has been studied.

This review is divided into two sections. The first part covers the first six decades, starting with the discovery of CRP and reviewing the fundamental aspects of the protein. In the second part, the role of CRP in atherosclerotic disease is discussed.

Section snippets

Historical perspectives

C-reactive protein (CRP) is an acute-phase protein that was discovered in 1930 by William S. Tillet and Thomas Francis at the Rockefeller Institute for Medical Research [1]. Studying the immune response of patients with pneumococcal pneumonia, they found that sera of these patients precipitated with a soluble extract of the Pneumococcus pneumoniae. This soluble extract was called fraction C, later identified as a polysaccharide of the cell wall. After resolution of the pneumonia, no

Atherosclerosis and plaque formation

Atherosclerosis is a slowly progressive disease that begins in early childhood and smolders until it becomes manifest at middle age or later by a cardiac event, stroke, or peripheral vascular disease [35]. The first macroscopic stadium of atherosclerosis is the fatty streak, a slightly elevated yellow lesion within the intima, microscopically filled with foam cells (macrophages loaded with cholesterol esters and free cholesterol), smooth muscle cells, and a few T lymphocytes. In a later stage,

Conclusions

Measuring hsCRP in patients who are at risk for arterial occlusive disease may become a new risk assessment tool for the physician, whatever the role of CRP in the atherosclerotic process. The value of measuring CRP in asymptomatic, low-risk subjects, however, is unclear.

CRP levels may also be a useful marker for monitoring drug therapy. Of particular interest are the effects of statin therapy and anti-inflammatory drugs in high-risk patients (i.e. those with diabetes mellitus, obesity,

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