© 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
This article has been cited by other articles:
 |
|
 |
|
  J. S. Berger, M. J. Krantz, J. M. Kittelson, and W. R. Hiatt Aspirin for the Prevention of Cardiovascular Events in Patients With Peripheral Artery Disease: A Meta-analysis of Randomized Trials JAMA, May 13, 2009; 301(18): 1909 - 1919. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.-W. Kang, S.-H. Yoo, S. Chun, K.-Y. Kwon, S. U. Kwon, J.-Y. Koh, and J. S. Kim Inflammatory and Hemostatic Biomarkers Associated With Early Recurrent Ischemic Lesions in Acute Ischemic Stroke Stroke, May 1, 2009; 40(5): 1653 - 1658. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Hingorani, T. Shah, J. P. Casas, S. E. Humphries, and P. J. Talmud C-Reactive Protein and Coronary Heart Disease: Predictive Test or Therapeutic Target? Clin. Chem., February 1, 2009; 55(2): 239 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Tousoulis, C. Antoniades, and C. Stefanadis Assessing inflammatory status in cardiovascular disease Heart, August 1, 2007; 93(8): 1001 - 1007. [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Yanbaeva, M. A. Dentener, E. C. Creutzberg, G. Wesseling, and E. F. M. Wouters Systemic Effects of Smoking Chest, May 1, 2007; 131(5): 1557 - 1566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. von Kanel, J. E. Dimsdale, P. J. Mills, S. Ancoli-Israel, T. L. Patterson, B. T. Mausbach, and I. Grant Effect of Alzheimer caregiving stress and age on frailty markers interleukin-6, C-reactive protein, and d-dimer. J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2006; 61(9): 963 - 969. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Aschbacher, T. L. Patterson, R. von Kanel, J. E. Dimsdale, P. J. Mills, K. A. Adler, S. Ancoli-Israel, and I. Grant Coping Processes and Hemostatic Reactivity to Acute Stress in Dementia Caregivers Psychosom Med, November 1, 2005; 67(6): 964 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. G. Wannamethee, G. D.O. Lowe, A. G. Shaper, A. Rumley, L. Lennon, and P. H. Whincup Associations between cigarette smoking, pipe/cigar smoking, and smoking cessation, and haemostatic and inflammatory markers for cardiovascular disease Eur. Heart J., September 1, 2005; 26(17): 1765 - 1773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. G. Best, Y. Zhang, E. T. Lee, J.-L. Yeh, L. Cowan, V. Palmieri, M. Roman, R. B. Devereux, R. R. Fabsitz, R. P. Tracy, et al. C-Reactive Protein as a Predictor of Cardiovascular Risk in a Population With a High Prevalence of Diabetes: The Strong Heart Study Circulation, August 30, 2005; 112(9): 1289 - 1295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. K. MacCallum Markers of Hemostasis and Systemic Inflammation in Heart Disease and Atherosclerosis in Smokers Proceedings of the ATS, April 1, 2005; 2(1): 34 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Wang, X. Zhu, Q. Xu, X. Ding, Y. E. Chen, and Q. Song Effect of C-reactive protein on gene expression in vascular endothelial cells Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1539 - H1545. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Stuveling, S. J. L. Bakker, H. L. Hillege, P. E. de Jong, R. O. B. Gans, and D. de Zeeuw Biochemical risk markers: a novel area for better prediction of renal risk? Nephrol. Dial. Transplant., March 1, 2005; 20(3): 497 - 508. [Full Text] [PDF]
|
|
|
|
|
|
J. Yarnell, E. McCrum, A. Rumley, C. Patterson, V. Salomaa, G. Lowe, A. Evans, and on behalf of the MONICA Optional Haemostasis Study Association of European population levels of thrombotic and inflammatory factors with risk of coronary heart disease: the MONICA Optional Haemostasis Study{dagger} Eur. Heart J., February 2, 2005; 26(4): 332 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Fortmann, E. Ford, M. H. Criqui, A. R. Folsom, T. B. Harris, Y. Hong, T. A. Pearson, D. Siscovick, F. Vinicor, and P. F. Wilson CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: Report From the Population Science Discussion Group Circulation, December 21, 2004; 110(25): e554 - e559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.D.O. Lowe, P.M. Sweetnam, J.W.G. Yarnell, A. Rumley, C. Rumley, D. Bainton, and Y. Ben-Shlomo C-Reactive Protein, Fibrin D-Dimer, and Risk of Ischemic Heart Disease: The Caerphilly and Speedwell Studies Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1957 - 1962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D.O. Lowe, A. Rumley, A. D. McMahon, I. Ford, D. St. J. O'Reilly, C. J. Packard, and for the West of Scotland Coronary Prevention Study Interleukin-6, Fibrin D-Dimer, and Coagulation Factors VII and XIIa in Prediction of Coronary Heart Disease Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1529 - 1534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.W.G Yarnell, C.C Patterson, P.M Sweetnam, and G.D.O Lowe Haemostatic/inflammatory markers predict 10-year risk of IHD at least as well as lipids: the Caerphilly collaborative studies Eur. Heart J., June 2, 2004; 25(12): 1049 - 1056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Danesh, J. G. Wheeler, G. M. Hirschfield, S. Eda, G. Eiriksdottir, A. Rumley, G. D.O. Lowe, M. B. Pepys, and V. Gudnason C-Reactive Protein and Other Circulating Markers of Inflammation in the Prediction of Coronary Heart Disease N. Engl. J. Med., April 1, 2004; 350(14): 1387 - 1397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. von Kanel and J. E. Dimsdale Hemostatic Alterations in Patients With Obstructive Sleep Apnea and the Implications for Cardiovascular Disease Chest, November 1, 2003; 124(5): 1956 - 1967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. B. Ledue and N. Rifai Preanalytic and Analytic Sources of Variations in C-reactive Protein Measurement: Implications for Cardiovascular Disease Risk Assessment Clin. Chem., August 1, 2003; 49(8): 1258 - 1271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Roldan, F. Marin, A. D Blann, A. Garcia, P. Marco, F. Sogorb, and G. Y.H Lip Interleukin-6, endothelial activation and thrombogenesis in chronic atrial fibrillation Eur. Heart J., July 2, 2003; 24(14): 1373 - 1380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Wakai, A Gleeson, and D Winter Role of fibrin D-dimer testing in emergency medicine Emerg. Med. J., July 1, 2003; 20(4): 319 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Imhof, M. Frohlich, H. Loewel, N. Helbecque, M. Woodward, P. Amouyel, G. D.O. Lowe, and W. Koenig Distributions of C-reactive Protein Measured by High-Sensitivity Assays in Apparently Healthy Men and Women from Different Populations in Europe Clin. Chem., April 1, 2003; 49(4): 669 - 672. [Full Text] [PDF]
|
|
|
|
|
|
T. H. Schindler, B. Hornig, P. T. Buser, M. Olschewski, N. Magosaki, M. Pfisterer, E. U. Nitzsche, U. Solzbach, and H. Just Prognostic Value of Abnormal Vasoreactivity of Epicardial Coronary Arteries to Sympathetic Stimulation in Patients With Normal Coronary Angiograms Arterioscler. Thromb. Vasc. Biol., March 1, 2003; 23(3): 495 - 501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Blake and P. M. Ridker C-reactive protein and other inflammatory risk markers in acute coronary syndromes J. Am. Coll. Cardiol., February 19, 2003; 41(4_Suppl_S): 37S - 42S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Zimmerman, C. H. Selzman, C. Cothren, A. C. Sorensen, C. D. Raeburn, and A. H. Harken Diagnostic Implications of C-Reactive Protein Arch Surg, February 1, 2003; 138(2): 220 - 224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Blake and P. M. Ridker C-Reactive Protein, Subclinical Atherosclerosis, and Risk of Cardiovascular Events Arterioscler. Thromb. Vasc. Biol., October 1, 2002; 22(10): 1512 - 1513. [Full Text] [PDF]
|
|
|
|
|
|
J.D. Mills, M.W. Mansfield, and P.J. Grant Elevated fibrinogen in the healthy male relatives of patients with severe, premature coronary artery disease Eur. Heart J., August 2, 2002; 23(16): 1276 - 1281. [Abstract] [PDF]
|
|
|
|
|
|
M. Di Napoli and F. Papa Inflammation, Hemostatic Markers, and Antithrombotic Agents in Relation to Long-Term Risk of New Cardiovascular Events in First-Ever Ischemic Stroke Patients Stroke, July 1, 2002; 33(7): 1763 - 1771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Wannamethee, G. D.O. Lowe, P. H. Whincup, A. Rumley, M. Walker, and L. Lennon Physical Activity and Hemostatic and Inflammatory Variables in Elderly Men Circulation, April 16, 2002; 105(15): 1785 - 1790. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Mills, M. W. Mansfield, and P. J. Grant Tissue Plasminogen Activator, Fibrin D-Dimer, and Insulin Resistance in the Relatives of Patients With Premature Coronary Artery Disease Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 704 - 709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Blake and P. M. Ridker Novel Clinical Markers of Vascular Wall Inflammation Circ. Res., October 26, 2001; 89(9): 763 - 771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Koenig, D. Rothenbacher, A. Hoffmeister, M. Griesshammer, and H. Brenner Plasma Fibrin D-Dimer Levels and Risk of Stable Coronary Artery Disease: Results of a Large Case-Control Study Arterioscler. Thromb. Vasc. Biol., October 1, 2001; 21(10): 1701 - 1705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Mills, M. W. Mansfield, and P. J. Grant Tissue Plasminogen Activator, Fibrin D-Dimer, and Insulin Resistance in the Relatives of Patients With Premature Coronary Artery Disease Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 704 - 709. [Abstract] [Full Text] [PDF]
|
|