Published online 18 April 2009
Haematologica, Vol 94, Issue 6, 811-818 doi:10.3324/haematol.2008.002386
Copyright © 2009 by Ferrata Storti Foundation
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Original Article

Low thrombin activatable fibrinolysis inhibitor activity levels are associated with an increased risk of a first myocardial infarction in men

Mirjam E. Meltzer2, Carine J.M. Doggen2, Philip G. de Groot1, Joost C.M. Meijers3, Frits R. Rosendaal2,4,5, Ton Lisman1,6

1 Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht
2 Department of Clinical Epidemiology, Leiden University Medical Center, Leiden
3 Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam
4 Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden
5 Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden
6 Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Correspondence: Frits R. Rosendaal, Department of Clinical Epidemiology, C9-P Leiden University Medical Center P.O. Box 9600 The Netherlands. E-mail:f.r.rosendaal{at}lumc.nl

Background: Studies on the relation between thrombin activatable fibrinolysis inhibitor (TAFI) and arterial thrombosis have produced conflicting results.TAFI regulates fibrinolysis, but other roles of this inhibitor, including anti-inflammatory properties, have also been demonstrated.

Design and Methods: We investigated the association between TAFI activity and the risk of myocardial infarction. Additionally, we studied the association of common single nucleotide polymorphisms in the TAFI gene with levels of the TAFI protein and risk of myocardial infarction.We included 554 men under 70 years old with a first myocardial infarction and 643 controls participating in the Study of Myocardial Infarctions Leiden (SMILE), a case-control study.

Results: We found odds ratios (95% confidence intervals) of a first myocardial infarction of 2.4 (1.6–3.6), 3.2 (2.1–4.7) and 3.4 (2.3–5.1) for subjects whose TAFI levels were in the third, second and first quartiles (lowest TAFI levels), respectively, compared with the fourth quartile, after adjusting for arterial disease risk factors. The rare -438A and 1040T alleles were associated with lower, and the rare 505G allele with higher TAFI levels than the common alleles. Carriers of the -438A allele had an increased risk of myocardial infarction (odds ratio 1.6 (1.0–2.5) for AA; odds ratio 1.2 (0.9–1.5) for AG compared with GG). The other single nucleotide polymorphisms were not associated with myocardial infarction.

Conclusions: Low TAFI activity levels are associated with increased risk of a first myocardial infarction in men. The results on the association between TAFI single nucleotide polymorphisms and myocardial infarction were inconsistent.

Key words: TAFI, myocardial infarction, genetics, epidemiology.