Reduced procedural risk for coronary catheter interventions in carriers of the coagulation factor VII-Gln353 gene.
OBJECTIVE
We have focused on the role of coagulation factor VII (FVII) Arg353Gln polymorphism as a risk predictor of complications following percutaneous transluminal coronary angioplasty (PTCA), directional coronary atherectomy (DCA), and stenting.


BACKGROUND
The FVII Arg353Gln mutation decreases FVII activity, and presence of the Gln353 allele could be protective against thrombus formation during catheter interventions.


METHODS
A total of 666 consecutive patients with coronary artery disease who had undergone PTCA (n = 280), DCA (n = 104), or stenting (n = 282) were followed up for a 30-day composite end point, which included need for target vessel revascularization, myocardial infarction, and death. The Arg353Gln polymorphism of FVII was determined by PCR/RFLP assay.


RESULTS
Carriers of the Gln353 allele had significantly lower levels of total FVII activity (FVIIc, -20.7%, p < 0.001) and of activated circulating FVII (FVIIa, -32.7%, p = 0.03) compared with Arg353/Arg353. The composite end point occurred in 43 patients: 4 were heterozygous Arg353/Gln353, and 39 were homozygous Arg353/Arg353. The incidence of the composite end point was 2.5% in carriers of the Gln353 allele and 7.7% in Arg353/Arg353 homozygotes (p = 0.013). This corresponds to a 72% risk reduction in carriers of the Gln353 allele (relative risk: 0.28; 95% confidence interval: 0.09-0.81; p = 0.02).


CONCLUSIONS
The Gln353 allele of FVII is associated with substantial risk reduction in adverse events that complicate coronary catheter interventions. With the perspective of active site-blocked activated FVII (FVIIai) as conjunctive medication, the results suggest that the FVII genotype should be taken into due consideration in assessment of FVIIai medication and of its dosage.
Mrozikiewicz
P M
PM
Institute of Clinical Pharmacology, Charité University Medical Center, Humboldt University of Berlin, Germany.
Cascorbi
I
I
Ziemer
S
S
Laule
M
M
Meisel
C
C
Stangl
V
V
Rutsch
W
W
Wernecke
K
K
Baumann
G
G
Roots
I
I
Stangl
K
K
D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D001120:Arginine / Q000235:genetics; D017225:Atherectomy, Coronary / Q000009:adverse effects*; D006328:Cardiac Catheterization / Q000009:adverse effects*; D003327:Coronary Disease / Q000097:blood / Q000235:genetics* / Q000628:therapy*; D005167:Factor VII / Q000235:genetics*; D005260:Female; D005973:Glutamine / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012307:Risk Factors; D015607:Stents / Q000009:adverse effects*; D013997:Time Factors
D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D005973:Glutamine; D005167:Factor VII; D001120:Arginine