Circulation, Vol 90, 2236-2240, Copyright © 1994 by American Heart Association
PM Ridker, CH Hennekens, A Cerskus and MJ Stampfer
BACKGROUND--Plasma levels of D-dimer, the primary degradation product of
cross-linked fibrin, are elevated in several acute thrombotic disorders.
However, whether elevated D-dimer levels among healthy individuals are
associated with future coronary thrombosis is unknown. METHODS AND
RESULTS--To evaluate whether levels of D-dimer are associated with the
occurrence of future myocardial infarction (MI) among apparently healthy
men, levels were measured in plasma samples collected at baseline from 296
participants in the Physicians' Health Study who later developed a first MI
and from an equal number of age- and smoking status-matched control
subjects who remained free of vascular disease during a mean follow-up
period of 60.2 months. In univariate analyses, baseline plasma
concentrations of D-dimer in the upper ranges of normal were associated
with elevated risks of MI. Specifically, the relative risk of future MI for
individuals with baseline D-dimer concentration exceeding the 95th
percentile of the control distribution was two times higher than that of
individuals with lower levels (relative risk [RR], 2.02; 95% confidence
interval [CI], 1.04 to 4.02; P = .04). This association persisted in
multivariate analyses controlling for nonlipid cardiovascular risk factors
(RR, 2.12; 95% CI, 1.05 to 4.28; P = .04) and for lipoprotein(a) (RR, 2.02;
95% CI, 1.04 to 3.94; P = .03). In contrast, this association was
attenuated and no longer statistically significant in analyses that
controlled for total and high-density lipoprotein cholesterol (RR, 1.74;
95% CI, 0.78 to 3.91; P = .2) or for endogenous tissue-type plasminogen
activator and its primary inhibitor, plasminogen activator inhibitor type 1
(RR, 1.58; 95% CI, 0.67 to 3.77; P = .3). CONCLUSIONS-- Elevated levels of
D-dimer are associated with increased risks of future MI, although they do
not appear to be an independent predictor when other risk factors are
considered. As the presence of D-dimer in plasma reflects ongoing fibrin
degradation, these data support the hypothesis that activation of the
endogenous fibrinolytic system occurs many years in advance of coronary
arterial occlusion.
ARTICLES
Plasma concentration of cross-linked fibrin degradation product (D- dimer) and the risk of future myocardial infarction among apparently healthy men
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215-1204.
This article has been cited by other articles:
 |
|
 |
|
  Z. Chakhtoura, M. Canonico, A. Gompel, J.-C. Thalabard, P.-Y. Scarabin, and G. Plu-Bureau Progestogen-Only Contraceptives and the Risk of Stroke: A Meta-Analysis Stroke, April 1, 2009; 40(4): 1059 - 1062. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. H. Wirtz, L. S. Redwine, U. Ehlert, and R. von Kanel Independent Association Between Lower Level of Social Support and Higher Coagulation Activity Before and After Acute Psychosocial Stress Psychosom Med, January 1, 2009; 71(1): 30 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. H. Wirtz, L. S. Redwine, C. Baertschi, M. Spillmann, U. Ehlert, and R. von Kanel Coagulation Activity Before and After Acute Psychosocial Stress Increases With Age Psychosom Med, May 1, 2008; 70(4): 476 - 481. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Teede, F. S. Dalais, D. Kotsopoulos, B. P. McGrath, E. Malan, T. E. Gan, and R. E. Peverill Dietary Soy Containing Phytoestrogens Does Not Activate the Hemostatic System in Postmenopausal Women J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 1936 - 1941. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Sosin, G. S. Bhatia, R. C. Davis, and G. Y.H. Lip Heart failure--the importance of ethnicity Eur J Heart Fail, December 1, 2004; 6(7): 831 - 843. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Pradhan, A. Z. LaCroix, R. D. Langer, M. Trevisan, C. E. Lewis, J. A. Hsia, A. Oberman, J. M. Kotchen, and P. M Ridker Tissue Plasminogen Activator Antigen and D-Dimer as Markers for Atherothrombotic Risk Among Healthy Postmenopausal Women Circulation, July 20, 2004; 110(3): 292 - 300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M Ridker, N. J. Brown, D. E. Vaughan, D. G. Harrison, and J. L. Mehta Established and Emerging Plasma Biomarkers in the Prediction of First Atherothrombotic Events Circulation, June 29, 2004; 109(25_suppl_1): IV-6 - IV-19. [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Tracy Thrombin, Inflammation, and Cardiovascular Disease: An Epidemiologic Perspective Chest, September 1, 2003; 124 (2009): 49S - 57S. [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]
|
|
|
|
 |
|
 M. Cushman, A. R. Folsom, L. Wang, N. Aleksic, W. D. Rosamond, R. P. Tracy, and S. R. Heckbert Fibrin fragment D-dimer and the risk of future venous thrombosis Blood, February 15, 2003; 101(4): 1243 - 1248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.L. Komarov, E.P. Panchenko, A.B. Dobrovolsky, Yu.A. Karpov, A.D. Deev, E.V. Titaeva, K.K. Davletov, A.R. Eshkeeva, and L.A. Markova D-dimer and platelet aggregability are related to thrombotic events in patients with peripheral arterial occlusive disease Eur. Heart J., August 2, 2002; 23(16): 1309 - 1316. [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]
|
|
|
|
|
|
P. M. Ridker Inflammatory Biomarkers, Statins, and the Risk of Stroke: Cracking a Clinical Conundrum Circulation, June 4, 2002; 105(22): 2583 - 2585. [Full Text] [PDF]
|
|
|
|
 |
|
 B. Salobir, M. Sabovic, P. Peternel, and M. Stegnar Fibrinolytic Parameters and Lipoprotein(a) in Young Women with Myocardial Infarction Angiology, March 1, 2002; 53(2): 157 - 163. [Abstract] [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. Oldgren, R. Linder, L. Grip, A. Siegbahn, and L. Wallentin Coagulation Activity and Clinical Outcome in Unstable Coronary Artery Disease Arterioscler Thromb Vasc Biol, June 1, 2001; 21(6): 1059 - 1064. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Danesh, P. Whincup, M. Walker, L. Lennon, A. Thomson, P. Appleby, A. Rumley, and G. D.O. Lowe Fibrin D-Dimer and Coronary Heart Disease : Prospective Study and Meta-Analysis Circulation, May 15, 2001; 103(19): 2323 - 2327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. O. Lowe, J. W. G. Yarnell, A. Rumley, D. Bainton, and P. M. Sweetnam C-Reactive Protein, Fibrin D-Dimer, and Incident Ischemic Heart Disease in the Speedwell Study : Are Inflammation and Fibrin Turnover Linked in Pathogenesis? Arterioscler Thromb Vasc Biol, April 1, 2001; 21(4): 603 - 610. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Folsom, N. Aleksic, E. Park, V. Salomaa, H. Juneja, and K. K. Wu Prospective Study of Fibrinolytic Factors and Incident Coronary Heart Disease : The Atherosclerosis Risk in Communities (ARIC) Study Arterioscler Thromb Vasc Biol, April 1, 2001; 21(4): 611 - 617. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Y. H. Lip and A. D. Blann Thrombogenesis and fibrinolysis in acute coronary syndromes: Important facets of a prothrombotic or hypercoagulable state? J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2044 - 2046. [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Sechi, L. Zingaro, C. Catena, D. Casaccio, and S. De Marchi Relationship of Fibrinogen Levels and Hemostatic Abnormalities With Organ Damage in Hypertension Hypertension, December 1, 2000; 36(6): 978 - 985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. F. Pieper, K. M. K. Rao, M. S. Currie, T. B. Harris, and H. J. Cohen Age, Functional Status, and Racial Differences in Plasma D-Dimer Levels in Community-Dwelling Elderly Persons J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2000; 55(11): 649M - 657. [Abstract] [Full Text]
|
|
|
|
|
|
P.J. Grant The Edinburgh Artery Study: is lytic activity bad for the heart? Eur. Heart J., October 1, 2000; 21(19): 1566 - 1567. [PDF]
|
|
|
|
 |
|
 H. P. Kohler and P. J. Grant Plasminogen-Activator Inhibitor Type 1 and Coronary Artery Disease N. Engl. J. Med., June 15, 2000; 342(24): 1792 - 1801. [Full Text] [PDF]
|
|
|
|
 |
|
 M. A Ferguson, B. Gutin, S. Owens, P. Barbeau, R. P Tracy, and M. Litaker Effects of physical training and its cessation on the hemostatic system of obese children Am. J. Clinical Nutrition, June 1, 1999; 69(6): 1130 - 1134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Moss, R. E. Goldstein, V. J. Marder, C. E. Sparks, D. Oakes, H. Greenberg, H. J. Weiss, W. Zareba, M. W. Brown, C.-S. Liang, et al. Thrombogenic Factors and Recurrent Coronary Events Circulation, May 18, 1999; 99(19): 2517 - 2522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Ridker, R. B. Kundsin, M. J. Stampfer, S. Poulin, and C. H. Hennekens Prospective Study of Chlamydia pneumoniae IgG Seropositivity and Risks of Future Myocardial Infarction Circulation, March 9, 1999; 99(9): 1161 - 1164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cushman, R. N. Lemaitre, L. H. Kuller, B. M. Psaty, E. M. Macy, A. R. Sharrett, and R. P. Tracy Fibrinolytic Activation Markers Predict Myocardial Infarction in the Elderly : The Cardiovascular Health Study Arterioscler Thromb Vasc Biol, March 1, 1999; 19(3): 493 - 498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Sakkinen, M. Cushman, B. M. Psaty, B. Rodriguez, R. Boineau, L. H. Kuller, and R. P. Tracy Relationship of Plasmin Generation to Cardiovascular Disease Risk Factors in Elderly Men and Women Arterioscler Thromb Vasc Biol, March 1, 1999; 19(3): 499 - 504. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pahor, M. B. Elam, R. J. Garrison, S. B. Kritchevsky, and W. B. Applegate Emerging Noninvasive Biochemical Measures to Predict Cardiovascular Risk Arch Intern Med, February 8, 1999; 159(3): 237 - 245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Geppert, S. Graf, R. Beckmann, S. Hornykewycz, E. Schuster, B. R. Binder, and K. Huber Concentration of Endogenous tPA Antigen in Coronary Artery Disease : Relation to Thrombotic Events, Aspirin Treatment, Hyperlipidemia, and Multivessel Disease Arterioscler Thromb Vasc Biol, October 1, 1998; 18(10): 1634 - 1642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. DeSouza, P. P. Jones, and D. R. Seals Physical Activity Status and Adverse Age-Related Differences in Coagulation and Fibrinolytic Factors in Women Arterioscler Thromb Vasc Biol, March 1, 1998; 18(3): 362 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. B. Smith, A. J. Lee, F. G. R. Fowkes, J. F. Price, A. Rumley, and G. D. O. Lowe Hemostatic Factors as Predictors of Ischemic Heart Disease and Stroke in the Edinburgh Artery Study Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 3321 - 3325. [Abstract] [Full Text]
|
|
|
|
|
|
C. Giansante, N. Fiotti, S. Calabrese, R. La Verde, C. Pandullo, S. Scardi, and G. Guarnieri D-Dimer and Anticoagulation in Patients With Mechanical Prosthetic Heart Valves : A 2-Year Follow-up Arterioscler Thromb Vasc Biol, July 1, 1997; 17(7): 1320 - 1324. [Abstract] [Full Text]
|
|
|
|
|
|
G. Y. H. Lip Exacerbation of Atherosclerosis by Hypertension: Potential Mechanisms and Clinical Implications Arch Intern Med, June 9, 1997; 157(11): 1265 - 1266. [Abstract] [PDF]
|
|
|
|
|
|
A. P. Burke, A. Farb, G. T. Malcom, Y.-h. Liang, J. Smialek, and R. Virmani Coronary Risk Factors and Plaque Morphology in Men with Coronary Disease Who Died Suddenly N. Engl. J. Med., May 1, 1997; 336(18): 1276 - 1282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Ridker, M. Cushman, M. J. Stampfer, R. P. Tracy, and C. H. Hennekens Inflammation, Aspirin, and the Risk of Cardiovascular Disease in Apparently Healthy Men N. Engl. J. Med., April 3, 1997; 336(14): 973 - 979. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. V. Lee, G. A. Ewald, C. R. McKenzie, and P. R. Eisenberg The Relationship of Soluble Fibrin and Cross-linked Fibrin Degradation Products to the Clinical Course of Myocardial Infarction Arterioscler Thromb Vasc Biol, April 1, 1997; 17(4): 628 - 633. [Abstract] [Full Text]
|
|
|
|
|
|
G. Y.H. Lip, P. L. Lip, J. Zarifis, R. D.S. Watson, D. Bareford, G. D.O. Lowe, and D. G. Beevers Fibrin D-Dimer and ß-Thromboglobulin as Markers of Thrombogenesis and Platelet Activation in Atrial Fibrillation: Effects of Introducing Ultra–Low-Dose Warfarin and Aspirin Circulation, August 1, 1996; 94(3): 425 - 431. [Abstract] [Full Text]
|
|
|
|
|
|
A. J. Lee, F. G. R. Fowkes, G. D. O. Lowe, and A. Rumley Determinants of Fibrin D-Dimer in the Edinburgh Artery Study Arterioscler Thromb Vasc Biol, August 1, 1995; 15(8): 1094 - 1097. [Abstract] [Full Text]
|
|
|
|
|
|
E. Falk, P. K. Shah, and V. Fuster Coronary Plaque Disruption Circulation, August 1, 1995; 92(3): 657 - 671. [Full Text]
|
|
|
|
|
|
P. M. Ridker, C. H. Hennekens, K. Lindpaintner, M. J. Stampfer, P. R. Eisenberg, and J. P. Miletich Mutation in the Gene Coding for Coagulation Factor V and the Risk of Myocardial Infarction, Stroke, and Venous Thrombosis in Apparently Healthy Men N. Engl. J. Med., April 6, 1995; 332(14): 912 - 917. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Balagopal, S. Sweeten, and N. Mauras Increased synthesis rate of fibrinogen as a basis for its elevated plasma levels in obese female adolescents Am J Physiol Endocrinol Metab, April 1, 2002; 282(4): E899 - E904. [Abstract] [Full Text] [PDF]
|
|