title: -455G/A polymorphism and preprocedural plasma levels of fibrinogen show no association with the risk of clinical restenosis in patients with coronary stent placement.
abstract: The effect of preprocedural fibrinogen levels on in-stent restenosis is largely unknown. The -455G/A polymorphism of the fibrinogen beta-gene is associated with baseline plasma level or acute phase increase of fibrinogen. Therefore, we hypothesized that there is a relationship between this polymorphism and preprocedural fibrinogen level and clinical restenosis at follow-up among patients with coronary stent placement. The GENetic DEterminants of Restenosis (GENDER) project is a multicenter follow-up study that enrolled 3,146 consecutive patients after successful percutaneous coronary intervention. A coronary stent was placed in 2,309 patients. Of these, 2,257 (97.7%) patients were successfully genotyped for the -455G/A polymorphism. Plasma fibrinogen levels were measured at baseline in a subpopulation of 623 stented patients with the von Clauss method and patients were grouped into tertiles according to fibrinogen levels. Primary endpoint was target vessel revascularization (TVR); secondary combined endpoint was defined as death presumably from cardiac causes, MI not attributable to another coronary artery than the target vessel, and TVR. No association was observed between the -455G/A polymorphism and TVR or combined endpoint (p=0.99, p=0.97, respectively). Multivariate regression analysis revealed that the risk of TVR and combined endpoint was not higher for patients in the highest tertile for fibrinogen versus the lowest tertile (RR=0.60, 95% CI: 0.26-1.37 for TVR, RR=0.64, 95% CI: 0.29-1.44 for combined endpoint). In conclusion, the presence of -455G/A polymorphism in the fibrinogen beta-gene and preprocedural fibrinogen level is not associated with an increased risk of TVR or combined endpoint in a patient population with coronary stent placement. Therefore, these parameters are not worthwhile for stratifying patients at risk for restenosis pre-stenting.
authors.affiliation: Department of Cardiology, Leiden University Medical Center, The Netherlands. J.W.Jukema@lumc.nl
authors.forename: Pascalle S
authors.initials: PS
authors.lastname: Monraats
authors.forename: Jamal S
authors.initials: JS
authors.lastname: Rana
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: Moniek P M
authors.initials: MP
authors.lastname: de Maat
authors.forename: John P
authors.initials: JP
authors.lastname: Kastelein
authors.forename: Willem R P
authors.initials: WR
authors.lastname: Agema
authors.forename: Pieter A F
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: de Winter
authors.forename: René A
authors.initials: RA
authors.lastname: Tio
authors.forename: Johannes
authors.initials: J
authors.lastname: Waltenberger
authors.forename: Rune R
authors.initials: RR
authors.lastname: Frants
authors.forename: Arnoud
authors.initials: A
authors.lastname: van der Laarse
authors.forename: Ernst E
authors.initials: EE
authors.lastname: van der Wall
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
mesh_terms: D000368:Aged; D023903:Coronary Restenosis / Q000209:etiology*; D005260:Female; D005340:Fibrinogen / Q000032:analysis* / Q000235:genetics*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009204:Myocardial Revascularization; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012044:Regression Analysis; D012306:Risk; D015607:Stents / Q000009:adverse effects*
chemical_list: D005340:Fibrinogen