Early verification of myocardial ischemia with a novel biomarker of acute tissue damage: C-reactive protein fractional forms
We evaluated the utility of an independent biomarker of early ischemic cellular damage-circulating fractional forms of C-reactive protein (fracCRP), to verify the diagnostic relevance of low Troponin I (TnI) values within the context of a workup for Acute Coronary Syndrome (ACS).
On a semi-preparative scale, the molecular characteristics of fracCRP were established by electron microscopy and Western Blot, using isolates captured from patient serum on phosphorylcholine beads and purified by size exclusion high-pressure liquid chromatography (SE-HPLC). Captured on an analytical scale, the diagnostic utility of fracCRP was evaluated in first-draw plasma specimens (total CRP not exceeding 6 mg/l) recovered from 300 cardiac emergency patients with final discharge diagnoses of ACS ruled out (N=132) or ruled in (N=168).
At a cutoff value chosen for 97.7% test specificity, the test metric (fracCRP×TnI) identified in the first blood draw 39.9% of all emergency patients ultimately diagnosed with ACS, and 17.9% of ultimately diagnosed patients who arrived with TnI values within the normal reference range (0.01-0.04 ng/ml).
These findings suggest that the fracCRP test metric could serve as a rule-in test for ACS in a significant proportion of low to moderate risk emergency patients.
Available from: Valmore Bermudez
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ABSTRACT: Cardiovascular disease is the leading cause of morbidity and mortality in the adult population worldwide, with atherosclerosis being its key pathophysiologic component. Atherosclerosis possesses a fundamental chronic inflammatory aspect, and the involvement of numerous inflammatory molecules has been studied in this scenario, particularly C-reactive protein (CRP). CRP is a plasma protein with strong phylogenetic conservation and high resistance to proteolysis, predominantly synthesized in the liver in response to proinflammatory cytokines, especially IL-6, IL-1íµí»½, and TNF. CRP may intervene in atherosclerosis by directly activating the complement system and inducing apoptosis, vascular cell activation, monocyte recruitment, lipid accumulation, and thrombosis, among other actions. Moreover, CRP can dissociate in peripheral tissue—including atheromatous plaques— from its native pentameric form into a monomeric form, which may also be synthesized de novo in extrahepatic sites. Each form exhibits distinct affinities for ligands and receptors, and exerts different effects in the progression of atherosclerosis. In view of epidemiologic evidence associating high CRP levels with cardiovascular risk—reflecting the biologic impact it bears on atherosclerosis—measurement of serum levels of high-sensitivity CRP has been proposed as a tool for assessment of cardiovascular risk.
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ABSTRACT: Background: Monomeric CRP (mCRP) plays an important role in the process of atherosclerotic plaque rupture. Recently, it has been reported that mCRP was associated with acute myocardial infarction (AMI). Objectives: The aim of this study was to examine whether mCRP is increased in AMI patients and to investigate the possibility of using circulating mCRP as a biomarker for AMI diagnosis and severity assessment of disease. Methods: A mCRP monoclonal antibody was generated and verified for its specificity. Immunofluorescence was used to assess the localization of mCRP in the infarcted myocardium. Furthermore, 101 AMI, 38 unstable angina pectoris (UAP) and 41 stable angina pectoris (SAP) patients were enrolled, and 43 healthy volunteer were recruited as controls in the study. Venous blood samples were collected to measure the circulating mCRP, cardiac Troponin T and hs-CRP levels. Results: Significantly increased mCRP levels were observed in the infarcted myocardium of model mice. In addition, significantly increased plasma mCRP levels were also detected in AMI patients (20.96±1.64ng/ml) compared to those with UAP, SAP or in control patients (all 0ng/ml, p<0.001). ROC analysis revealed that circulating mCRP had considerable diagnostic accuracy for AMI with an AUC of 0.928 (95% confidence interval 0.887-0.969). Furthermore, nine patients (9/101, 8.91%) in AMI group died before the 30-day follow-up, and their plasma mCRP concentration was significantly higher than those in surviving patients (36.70±10.26 vs. 19.41±1.43ng/ml, P=0.002). Conclusions: These results indicate that mCRP is increased in AMI and that circulating mCRP might be a potential biomarker for diagnosis and severity assessment of disease in AMI.
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