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...

Establishment and characterization of a novel murine model of pancreatic cancer cachexia

“…Our data demonstrate a robust and sexually dimorphic up‐regulation of pentraxin 2/APCS, the functional murine equivalent of C‐reactive protein in human. C‐reactive protein and APCS are induced in response to a variety of inflammatory stimuli primarily via IL‐6, serving a key role in acute‐phase responses 27, 28. We also found that KPC increases hepatic expression of Orm1 , another key acute‐phase reactant in both mouse and human known to serve numerous important roles in energy balance, immunity, and capillary barrier modulation.…”

“…We specifically examined the acute‐phase proteins pentraxin 2/APCS, which in mice serves an analogous role to C‐reactive protein in humans, and Orm1, which has recently been shown to have anorexigenic properties 18, 27, 28. In males, KPC induced a 34.42 ± 6.89‐fold increase in Apcs ( P  < 0.001, n  = 4–5 per group) and a 6.61 ± 0.32‐fold increase in Orm1 relative to controls ( P  < 0.001, n  = 4–5 per group) ( Figure 7A).…”

Serum high-sensitivity C-reactive protein, amyloid-associated protein and N-terminal proBNP levels do not predict reversible myocardial ischaemia

“…hs-CRP circulates freely in the plasma because there are no specific transporters for it 1,2. It has been shown that hs-CRP is a powerful predictor of cardiovascular adverse events and mortality in unstable coronary heart disease 3-5.…”

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“…CRP is a blood plasma protein that is indicative of inflammation and infection and a risk predictor of cardiovascular disease. It is considered an indicator of bacterial infection, pneumonia, and tissue damage (Pepys & Hirschfield, 2003; Pearson et al, 2003; Simon, Gauvin, Amre, Saint‐Louis, & Lacroix, 2004; Tillett & Francis, 1930). The median of CRP in our sample is 1.7 mg/L, but its distribution is highly skewed.…”

“…The value rises within few hours of disease onset. Inflammation and bacterial infection can produce a rise in CRP values up to 1,000‐fold (Gruys, Toussaint, Niewold, & Koopmans, 2005; Pepys & Hirschfield, 2003). Fibrinogen is a coagulation protein produced by the liver that helps the body in the formation of blood clots.…”