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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:955.)
© 2007 American Heart Association, Inc.

Thrombosis

Thrombin Activatable Fibrinolysis Inhibitor Activation Peptide Shows Association With All Major Subtypes of Ischemic Stroke and With TAFI Gene Variation

Claes Ladenvall; Ann Gils; Katarina Jood; Christian Blomstrand; Paul J. Declerck; Christina Jern

From the Institute of Neuroscience and Physiology (C.L., K.J., C.B., C.J.), the Sahlgrenska Academy at Göteborg University, Sweden; Department of Clinical Genetics (C.L., C.J.), Sahlgrenska University Hospital/Östra, Göteborg, Sweden; and Laboratory for Pharmaceutical Biology (A.G., P.J.D.), Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, Belgium.

Correspondence to Claes Ladenvall, Institute of Neuroscience and Physiology, Department of Neuroscience and Rehabilitation, the Sahlgrenska Academy at Göteborg University, Guldhedsgatan 19, S-413 45 Göteborg, Sweden. E-mail claes.ladenvall{at}neuro.gu.se

Objective— Thrombin activatable fibrinolysis inhibitor (TAFI) attenuates fibrinolysis. The aim of the present study was to investigate the possible association between TAFI and overall ischemic stroke and ischemic stroke subtypes.

Methods and Results— The Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) comprises 600 cases (18 to 69 years) and 600 matched population controls. Stroke subtype was defined by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. TAFI was investigated at the protein level, by analyzing plasma levels of intact TAFI and released activation peptide [AP], and at the genetic level, by genotyping a selection of eleven single nucleotide polymorphisms. After adjustment for traditional risk factors, both TAFI measurements showed association with overall ischemic stroke (AP: odds ratio, 2.22; 95% confidence interval, 1.89 to 2.61; intact TAFI: odds ratio, 1.21; 95% confidence interval, 1.06 to 1.38; for 1-SD increase in AP and intact TAFI, respectively). AP showed associations with all 4 major subtypes of ischemic stroke and intact TAFI to large vessel disease and cryptogenic stroke. TAFI genotypes and haplotypes showed significant associations with both TAFI measurements. In contrast, no association was observed between genetic variants and overall ischemic stroke.

Conclusion— TAFI levels show independent association with overall ischemic stroke. This association is stronger for released AP than for intact TAFI, and for released AP, it is present in all ischemic stroke subtypes.

We report that TAFI plasma levels are increased in overall ischemic stroke compared with controls. The association was stronger for released activation peptide than for intact TAFI. Genetic variation at the TAFI locus showed associations to TAFI levels. However, no association was observed between genetic variants and overall ischemic stroke.

Key Words: thrombin activatable fibrinolysis inhibitor • polymorphism • genetics • ischemic stroke subtype

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