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DOI: 10.1160/TH11-11-0760
Impaired fibrinolytic capacity and increased fibrin formation associate with myocardial infarction
Publication History
Received:
02 November 2011
Accepted after major revision:
12 March 2012
Publication Date:
29 November 2017 (online)
Summary
We assessed whether abnormality of haemostasis measured by a newly developed global method is associated with risk of a first myocardial infarction (MI). The global markers Coagulation activation profile (Cp), Fibrinolysis activation profile (Fp) and sum of fibrin optical density over time (Fibrin OD- sum) were determined in plasma from 800 MI cases and 1,123 controls included in the Stockholm Heart Epidemiology Program. Clot lysis time (CLT) was also determined based on raw data of fibrin OD from the global assay. Odds ratios (OR) of MI with 95% confidence intervals (CI) were calculated using logistic regression. A Fp value <10th percentile value in controls was significantly associated with increased MI risk; OR after multivariate adjustments for conventional cardiovascular risk factors 1.66 (95% CI 1.22–2.27). For an abnormally long CLT (>90th percentile value in controls) the adjusted OR of MI was 2.62 (95% CI 1.87–3.66) and for a high Fibrin OD-sum value (>90th percentile in controls) it was 1.86 (95% CI 1.37–2.53). A high Cp value was not significantly associated with MI. In conclusion, we found that abnormal haemostasis in platelet-poor plasma, reflected either as an attenuated fibrinolytic capacity or the resulting increase of fibrin formation, was associated with increased MI risk.
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References
- 1 Meade TW, North WR, Chakrabarti R. et al. Haemostatic function and cardiovascular death: early results of a prospective study. Lancet 1980; 1: 1050-1054.
- 2 Wilhelmsen L, Svardsudd K, Korsan-Bengtsen K. et al. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984; 311: 501-505.
- 3 Folsom AR, Wu KK, Rosamond WD. et al. Prospective study of hemostatic factors and incidence of coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation 1997; 96: 1102-1108.
- 4 Wannamethee SG, Whincup PH, Shaper AG. et al. Circulating inflammatory and hemostatic biomarkers are associated with risk of myocardial infarction and coronary death, but not angina pectoris, in older men. J Thromb Haemost 2009; 7: 1605-1611.
- 5 He S, Antovic A, Blomback M. A simple and rapid laboratory method for determination of haemostasis potential in plasma. II. Modifications for use in routine laboratories and research work. Thromb Res 2001; 103: 355-361.
- 6 He S, Zhu K, Skeppholm M. et al. A global assay of haemostasis which uses recombinant tissue factor and tissue-type plasminogen activator to measure the rate of fibrin formation and fibrin degradation in plasma. Thromb Haemost 2007; 98: 871-882.
- 7 von dem Borne PA, Meijers JC, Bouma BN. Feedback activation of factor XI by thrombin in plasma results in additional formation of thrombin that protects fibrin clots from fibrinolysis. Blood 1995; 86: 3035-3042.
- 8 Reuterwall C, Hallqvist J, Ahlbom A. et al. Higher relative, but lower absolute risks of myocardial infarction in women than in men analysis of some major rsk factors in the SHEEP study. The SHEEP Study Group. J Intern Med 1999; 246: 161-174.
- 9 Leander K, Hallqvist J, Reuterwall C, Ahlbom A, de Faire U. Family history of coronary heart disease, a strong risk factor for myocardial infarction interacting with other cardiovascular risk factors: results from the Stockholm Heart Epidemiology Program (SHEEP). Epidemiology 2001; 12: 215-221.
- 10 Wiman B, Andersson T, Hallqvist J. et al. Plasma levels of tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor are significant risk markers for recurrent myocardial infarction in the Stockholm Heart Epidemiology Program (SHEEP) study. Arterioscler Thromb Vasc Biol 2000; 20: 2019-2023.
- 11 Leander K, Wiman B, Hallqvist J. et al. PAI-1 level and the PAI-1 4G/5G polymorphism in relation to risk of non-fatal myocardial infarction: results from the Stockholm Heart Epidemiology Program (SHEEP. Thromb Haemost 2003; 89: 1064-1071.
- 12 Guimaraes AH, de Bruijne EL, Lisman T. et al. Hypofibrinolysis is a risk factor for arterial thrombosis at young age. Br J Haematol 2009; 145: 115-120.
- 13 Smith A, Patterson C, Yarnell J, Rumley A, Ben-Shlomo Y, Lowe G. Which hemostatic markers add to the predictive value of conventional risk factors for coronary heart disease and ischemic stroke? The Caerphilly Study. Circulation 2005; 112: 3080-3087.
- 14 Thogersen AM, Jansson JH, Boman K. et al. High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor. Circulation 1998; 98: 2241-2247.
- 15 Meltzer ME, Doggen CJ, de Groot PG. et al. The impact of the fibrinolytic system on the risk of venous and arterial thrombosis. Semin Thromb Hemost 2009; 35: 468-477.
- 16 Meltzer ME, Doggen CJ, de Groot PG. et al. Reduced plasma fibrinolytic capacity as a potential risk factor for a first myocardial infarction in young men. Br J Haematol 2009; 145: 121-127.
- 17 Saraf S, Christopoulos C, Salha IB. et al. Impaired endogenous thrombolysis in acute coronary syndrome patients predicts cardiovascular death and nonfatal myocardial infarction. J Am Coll Cardiol 2010; 55: 2107-2115.
- 18 Gorog DA. Prognostic value of plasma fibrinolysis activation markers in cardiovascular disease. J Am Coll Cardiol 2010; 55: 2701-2709.
- 19 Faber CG, Lodder J, Kessels F. et al. Thrombin generation in plateletrich plasma as a tool for the detection of hypercoagulability in young stroke patients. Patho-physiol Haemost Thromb 2003; 33: 52-58.
- 20 Mosesson MW. Update on antithrombin I (fibrin). Thromb Haemost 2007; 98: 105-108.
- 21 Antovic A, Perneby C, Ekman G J. et al. Marked increase of fibrin gel permeability with very low dose ASA treatment. Thromb Res 2005; 116: 509-517.
- 22 Bjornsson TD, Schneider DE, Berger Jr. H. Aspirin acetylates fibrinogen and enhances fibrinolysis. Fibrinolytic effect is independent of changes in plasminogen activator levels. J Pharmacol Exp Ther 1989; 250: 154-161.