Abstract 12603: Fibrinogen and its Genetic Polymorphisms Modify the Risk for Coronary Artery Disease by Altering the Coagulation Process in Subjects Admitted for Stable Angina Symptoms
Background: Coronary artery disease (CAD) is characterized by altered coagulation, while increased fibrinogen levels are associated with the risk of CAD. In the present study we examined the effects of the rs180070 and rs2070011 polymorphisms on coagulation and the risk for CAD in subjects suspected for CAD.
Methods: Subjects (744) were admitted for coronary angiography. The two polymorphisms were determined by PCR-RFLP technique. Circulating levels of fibrinogen, CD40L, D-dimer were measured with appropriate methods. Patients were also divided in 3 sub-categories according to fibrinogen levels (≤347; 347[[Unable to Display Character: –]]443; >443 mg/dl).
Results: CAD was present in 448 subjects, whereas no CAD in 296 subjects. Multivariate logistic regression analysis after adjustment for age, gender, smoking, hypercholesterolemia, hypertension and diabetes mellitus as independent predictors revealed that fibrinogen levels >443 mg/dl were associated with higher risk for CAD [OR: 3.9, 95% CI (1.7-9.4), p=0.002)] compared to levels ≤347 mg/dl. The intermediate fibrinogen levels subcategory had no significant effect on the risk of CAD [(adjusted OR: 1.02, 95% CI (0.46-2.24) p=0.97)]. The presence of AA (rs1800700) was also significantly associated with increased risk of CAD [OR: 3.2, 95% CI (1.01-10.1, p=0.049)]. Importantly, the AA homozygotes had significantly higher fibrinogen levels compared to the G allele carriers (503.4±18.8 vs 402.6±5.14, p≤0.001). In our general cohort, AA homozygotes of the rs180070 presented with significantly higher levels (compared to the GG+GA) of CD40L (2.55±0.35 vs 2.13±0.19, p=0.019) and D-dimer (555.3±43 vs 469.1±19.6, p=0.033). In our cohort, the presence of the A allele (rs180070 and rs2070011) was neither associated with angiographic severity [(OR: 1.36, 95%CI (0.63[[Unable to Display Character: –]]2.95) p=0.434 and OR:0.99, 95%CI (0.56-1.78,) p=0.995 respectively) nor with the occurrence of acute myocardial infarction [OR:1.87, 95%CI (0.37[[Unable to Display Character: –]]8.9), p=0.46] and [OR: 0.75, 95%CI (0.39-1.43), p=0.378] respectively.
Conclusions: Fibrinogen represents an independent risk factor for CAD and this risk increases due with the presence of the AA homozygosity of the rs180070 via its modulating effects on the coagulation.
- © 2013 by American Heart Association, Inc.