C-reactive protein: a critical update

Abstract

IntroductionIn the mid 1990s, immunoassays for C-reactive protein (CRP), with greater sensitivity than those previously in routine use, revealed that increased CRP values, even within the range previously considered normal, strongly predict future coronary events. These findings triggered widespread interest, especially, remarkably, in the US, where the clinical use of CRP measurement had been largely ignored for about 30 years. CRP production is part of the nonspecific acute-phase response to most forms of inflammation, infection, and tissue damage and was therefore considered not to provide clinically useful information. Indeed, CRP values can never be diagnostic on their own and can only be interpreted at the bedside, in full knowledge of all other clinical and pathological results. However, they can then contribute powerfully to management, just as universal recording of the patient's temperature, an equally nonspecific parameter, is of great clinical utility.The present torrent of studies of CRP in cardiovascular disease and associated conditions is facilitated by the ready commercial availability of automated CRP assays and of CRP itself as a research reagent. However, unlike the earlier rejection in the US of CRP as an empirical test because of its perceived lack of specificity, the current enthusiasm over CRP in cardiovascular disease is widely characterized by failure to recognize appropriately the nonspecific nature of the acutephase response, and by lack of critical biological judgment. Quality control of the source, purity, and structural and functional integrity of the CRP, and the relevance of experimental design before ascribing pathophysiological functions, are also often ignored.This article provides information about CRP as a protein and an acute-phase reactant, and a knowledge-based framework for interpretation and analysis of clinical observations of CRP in relation to cardiovascular and other diseases. We also review the properties of CRP, its possible role in pathogenesis of disease, and our own observations that identify it as a possible therapeutic target.The acute-phase response CRP, named for its capacity to precipitate the somatic C-polysaccharide of Streptococcus pneumoniae, was the first acute-phase protein to be described and is an exquisitely sensitive systemic marker of inflammation and tissue damage (1). The acute-phase response comprises the nonspecific physiological and biochemical responses of endothermic animals to most forms of tissue damage, infection, inflammation, and malignant neoplasia. In particular, the synthesis of a number of proteins is rapidly upregulated, principally in hepatocytes, under the control of cytokines originating at the site of pathology. Other acute-phase proteins include proteinase inhibitors and coagulation, complement, and transport proteins, but the only molecule that displays sensitivity, response speed, and dynamic range comparable to those of CRP is serum amyloid A protein (SAA) (Table 1) (1). Circulating CRP concentrationIn healthy young adul...

Plasma levels of pentraxin-3, an inflammatory protein involved in fertility, are reduced in women with polycystic ovary syndrome

“…Moreover, PTX3 production is stimulated by several proinflammatory cytokines, such as IL1b, TNFa and IL10, and by TLR-agonists and oxidised LDL, but not by IL6 (26). Conversely, the latter is the most potent activator of CRP secretion (4). In addition, in several studies carried out in different conditions, the correlation between PTX3 and CRP levels was weak or even absent (9,27,28).…”

“…It belongs to the pentraxin superfamily and is one of the best characterised biomarkers of low-grade chronic inflammation, a key process in the pathogenesis of atherosclerosis (4). Several epidemiological studies, both in subjects with increased cardiovascular risk and in the general population, have shown that serum CRP independently predicts cardiovascular events (5).…”

Integrating Biomarkers into Research with Latino Immigrants in the United States

“…CRP is a nonspecific acute phase reactant that rapidly increases in plasma concentration in response to inflammation, infection, and injury (Pepys & Hirschfeld, 2003 linked minor CRP elevations, previously considered clinically normal, with increased cardiovascular risk (Ridker et al, 1998). Elevated levels of CRP are linked to factors such as obesity (Rexrode et al, 2003), and with several dimensions of psychosocial stress, including lack of social integration (Ford et al, 2006) and low SES (Nazmi & Victora, 2007).…”

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“…The prognostic impact of CRP has also been demonstrated in a range of other malignancies [23,24,25,26,27,28,29,30]. CRP is an acute-phase reactant and a sensitive, albeit non-specific, marker of tissue damage and inflammation which have established roles in carcinogenesis [31,32,33]. Pro-inflammatory cytokines released from the tumor microenvironment induce CRP synthesis by the liver [34].…”