Activated thrombin activatable fibrinolysis inhibitor levels are associated with the risk of cardiovascular death in patients with coronary artery disease: the AtheroGene study

TY - JOUR

T1 - Activated thrombin activatable fibrinolysis inhibitor levels are associated with the risk of cardiovascular death in patients with coronary artery disease: the AtheroGene study

AU - Tregouet, D A

AU - Schnabel, R

AU - Alessi, M C

AU - Godefroy, T

AU - Declerck, P J

AU - Nicaud, V

AU - Munzel, T

AU - Bickel, C

AU - Rupprecht, H J

AU - Lubos, E

AU - Zeller, T

AU - Juhan-Vague, I

AU - Blankenberg, S

AU - Tiret, L

AU - Morange, P E

AU - AtheroGene Investigators

PY - 2009/1

Y1 - 2009/1

N2 - BACKGROUND: Thrombin activatable fibrinolysis inhibitor (TAFI) attenuates fibrinolysis. Results on the association between TAFI levels and the risk of coronary artery disease (CAD) are inconsistent.OBJECTIVES: We investigated the association between TAFI levels and the risk of cardiovascular events in CAD.PATIENTS/METHODS: 1668 individuals with angiographically proven CAD at baseline were followed for a median of 2.3 years, as part of the prospective AtheroGene cohort. Fifty-six deaths from cardiovascular (CV) causes and 35 non-fatal CV events were observed.RESULTS: At baseline, three TAFI measurements were available: one evaluating the total amount of TAFI (t-TAFI), one measuring the TAFIa/TAFIai amount, and the last the released activated peptide (TAFI-AP). TAFIa/TAFIai levels were associated with increased risk of CV death [hazard ratio (HR) for one tertile increase, 2.38 (1.56-3.63); P < 10(-4)]. This association remained significant after adjustment for conventional risk factors, CRP levels, white blood count and markers of thrombin generation and fibrinolysis [HR = 1.69 (1.07-2.67); P = 0.01]. In addition, CPB2 gene polymorphisms explained 12%, 6%, and 3% of t-TAFI, TAFIa/TAFIai and TAFI-AP levels, respectively, but none was associated with CV events.CONCLUSIONS: The amount of activated TAFI, measured by TAFIa/TAFIai ELISA, but not of the t-TAFI is independently associated with the risk of CV death.

AB - BACKGROUND: Thrombin activatable fibrinolysis inhibitor (TAFI) attenuates fibrinolysis. Results on the association between TAFI levels and the risk of coronary artery disease (CAD) are inconsistent.OBJECTIVES: We investigated the association between TAFI levels and the risk of cardiovascular events in CAD.PATIENTS/METHODS: 1668 individuals with angiographically proven CAD at baseline were followed for a median of 2.3 years, as part of the prospective AtheroGene cohort. Fifty-six deaths from cardiovascular (CV) causes and 35 non-fatal CV events were observed.RESULTS: At baseline, three TAFI measurements were available: one evaluating the total amount of TAFI (t-TAFI), one measuring the TAFIa/TAFIai amount, and the last the released activated peptide (TAFI-AP). TAFIa/TAFIai levels were associated with increased risk of CV death [hazard ratio (HR) for one tertile increase, 2.38 (1.56-3.63); P < 10(-4)]. This association remained significant after adjustment for conventional risk factors, CRP levels, white blood count and markers of thrombin generation and fibrinolysis [HR = 1.69 (1.07-2.67); P = 0.01]. In addition, CPB2 gene polymorphisms explained 12%, 6%, and 3% of t-TAFI, TAFIa/TAFIai and TAFI-AP levels, respectively, but none was associated with CV events.CONCLUSIONS: The amount of activated TAFI, measured by TAFIa/TAFIai ELISA, but not of the t-TAFI is independently associated with the risk of CV death.

KW - Aged

KW - Carboxypeptidase B/genetics

KW - Carboxypeptidase B2/blood

KW - Coronary Artery Disease/blood

KW - Death, Sudden, Cardiac

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Proportional Hazards Models

KW - Risk

KW - Risk Factors

U2 - 10.1111/j.1538-7836.2008.03221.x

DO - 10.1111/j.1538-7836.2008.03221.x

M3 - SCORING: Journal article

C2 - 19017260

VL - 7

SP - 49

EP - 57

JO - J THROMB HAEMOST

JF - J THROMB HAEMOST

SN - 1538-7933

IS - 1

ER -