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


OBJECTIVE
We investigated the association between TAFI levels and the risk of cardiovascular events in CAD.


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.
Tregouet
D A
DA
INSERM, UMR_S 525, F-75013, Paris, France.
Schnabel
R
R
Alessi
M C
MC
Godefroy
T
T
Declerck
P J
PJ
Nicaud
V
V
Munzel
T
T
Bickel
C
C
Rupprecht
H J
HJ
Lubos
E
E
Zeller
T
T
Juhan-Vague
I
I
Blankenberg
S
S
Tiret
L
L
Morange
P E
PE
D000368:Aged; D043424:Carboxypeptidase B / Q000235:genetics; D025901:Carboxypeptidase B2 / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000401:mortality*; D016757:Death, Sudden, Cardiac; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012306:Risk; D012307:Risk Factors
D043424:Carboxypeptidase B; D025901:Carboxypeptidase B2