Associations of plasma fibrinogen assays, C-reactive protein and interleukin-6 with previous myocardial infarction

Abstract

Summary. Background: The association of plasma ®brinogen with myocardial infarction (MI) may (like that of C-reactive protein, CRP) be a marker of subclinical in¯ammation, mediated by cytokines such as interleukin-6 (IL-6). There are well-recognized discrepancies between commonly performed ®brinogen assays. Increased ratio of clottable ®brinogen to intact ®brinogen (measured by a recently developed immunoassay) has been proposed as a measure of hyperfunctional ®brinogen, and is elevated in acute MI. Objective: To compare the associations of intact ®brinogen and four routine ®brinogen assays (two von Clauss assays; one prothrombin-time derived; and one immunonephelometric) in a case±control study of previous MI. Patients/methods: Cases (n 399) were recruited 3±9 months after their event; 413 controls were age-and sexmatched from the case±control study local population. Intact ®brinogen was measured in 50% of subjects. Results: All routine ®brinogen assays showed high intercorrelations (r 0.82±0.93) and signi®cant (P < 0.0001) increased mean levels in cases vs. controls. These four routine assays correlated only moderately with intact ®brinogen (r 0.45±0.62), while intact ®brinogen showed only a small, nonsigni®cant increase in cases vs. controls. Consequently, the ratio of each of the four routine assays to the intact ®brinogen assay was signi®cantly higher (P < 0.0003) in cases vs. controls. Each ®brinogen assay correlated with plasma levels of CRP and IL-6 (which were also elevated in cases vs. controls). Each routine ®brinogen assay remained signi®cantly elevated in cases vs. controls after further adjustment for C-reactive protein and interleukin-6. Conclusions: These data provide evidence for acquired, increased hyperfunctional plasma ®brinogen in MI survivors, which is not associated with markers of in¯ammatory reactions.The causes and signi®cance of these results remain to be established in prospective studies.

Effects of inflammatory cytokines on the release and cleavage of the endothelial cell–derived ultralarge von Willebrand factor multimers under flow

“…Although normal plasma concentrations of these cytokines are very low, they increase up to several hundred to thousand folds during myocardial infarction 32,33 and other conditions with acute inflammation. 34 For example, Ueda et al reported that plasma IL-6 levels increased to 27 ng/mL from less than 10 pg/mL.…”

The association between homocysteine and myocardial infarction is independent of age, sex, blood pressure, cholesterol, smoking and markers of inflammation: the Glasgow Myocardial Infarction Study

“…The aim of the Glasgow Myocardial Infarction Study (GLAMIS) [16] is to establish the associations of plasma haemostatic and inflammatory variables with previous myocardial infarction and conventional risk factors in a case-control study, and with incident CHD events in a subsequent follow-up study. The aim was to recruit all men and women with MI in the North Glasgow MONICA study [17] diagnosed by MONICA criteria [18] from July 1994, between 3 and 9 months after the event, when acute-phase protein reactions in acute MI had settled.…”

“…A forearm venous sample was taken after a full overnight fast. Lipid assays were measured as previously described [16]. For assays of homocysteine, fibrinogen and inflammatory variables, blood was anticoagulated with trisodium citrate (0.11 mol/l, 9:1 v:v).…”

Fibrinogen Assays for Cardiovascular Risk Assessment

“…Ratios of clottable fibrinogen to the "intact" fibrinogen synthesized by the liver are associated with cardiovascular risk, an observation that raises the possibility that the functionality of fibrinogen may be related to the risk of thrombosis (13 ). As reviewed by Lovely et al (1 ), one determinant of the clottability of fibrinogen-and the lysability of fibrin-is the ␥Ј isoform of fibrinogen (14 ).…”

“…Experimental and observational studies of ␥Ј fibrinogen concentrations (as well as their genetic determinants) compared with standard fibrinogen concentrations should help elucidate the functional role of fibrinogen in atherogenesis, thrombogenesis, and ischemia (2,11,13 ). Further large prospective studies of ␥Ј fibrinogen and standard fibrinogen assays should also be performed to establish their potential utility in adding to the currently used risk-prediction scores.…”