Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:603-610
© 2001 American Heart Association, Inc.
Thrombosis |
C-Reactive Protein, Fibrin D-Dimer, and Incident Ischemic Heart Disease in the Speedwell Study
Are Inflammation and Fibrin Turnover Linked in Pathogenesis?
From the University Department of Medicine (G.D.O.L., A.R.), Royal Infirmary, Glasgow; the Department of Epidemiology and Public Health (J.W.G.Y.), The Queen’s University of Belfast, Belfast; Gwent Health Commission (D.B.), Mamhilad, Pontypool, Gwent; and the MRC Epidemiology Unit (P.M.S.), Llandough Hospital, Penarth, South Glamorgan, UK.
Correspondence to Professor G.D.O. Lowe, University Department of Medicine, Third Floor, Queen Elizabeth Building, Royal Infirmary, Glasgow, G31 2ER Scotland. E-mail gdl1J{at}clinmed.gla.ac.uk
Abstract—Plasma levels of C-reactive protein (CRP, a marker of the reactant plasma protein component of the inflammatory response) and of fibrin D-dimer (a marker of cross-linked fibrin turnover) have each been associated in recent studies with the risk of future ischemic heart disease (IHD). Previous experimental studies have shown that fibrin degradation products, including D-dimer, have effects on inflammatory processes and acute-phase protein responses. In the Speedwell Prospective Study, we therefore measured CRP and D-dimer levels in stored plasma samples from 1690 men aged 49 to 67 years who were followed-up for incident IHD for an average of 75±4 months (mean±SD) and studied their associations with each other, with baseline and incident IHD, and with IHD risk factors. CRP and D-dimer levels were each associated with age, plasma fibrinogen, smoking habit, and baseline evidence of IHD. CRP was associated with D-dimer (r=0.21, P<0.00001). On univariate analyses, both CRP and D-dimer were associated with incident IHD. The incidence of IHD increased with CRP independently of the level of D-dimer (P=0.0002) and also increased with D-dimer independently of the level of CRP (P=0.048). In multivariate analyses, inclusion of D-dimer and conventional risk factors reduced the strength of the association between CRP and incident IHD; likewise, inclusion of CRP and conventional risk factors reduced the strength of the association between D-dimer and incident IHD. We conclude that although these respective markers of inflammation and fibrin turnover show modest association with each other in middle-aged men, they may have additive associations with risk of incident IHD. Further larger studies are required to test this hypothesis.
Key Words: C-reactive protein • fibrin D-dimer • ischemic heart disease
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