Coronary Artery Atherosclerosis in Hypertensive Patients: The Role of Fibrinogen Genetic Variability.

INTRODUCTION AND OBJECTIVES: We examined whether the rs180070 and rs2070011 polymorphisms of the fibrinogen gene could affect the risk of coronary artery disease in hypertensive patients by modifying the inflammatory process and coagulation. METHODS: A total of 744 participants underwent coronary angiography due to symptoms of stable angina, while hypertension was present in 332 patients. RESULTS: The presence of the A allele (rs180070) was associated with significantly high levels of fibrinogen in hypertensive patients (P=.05). On multivariate analysis, A homozygosity (rs180070) (ß = 0.257 ± 18.6; P<.001), but not hypertension status (ß = 0.05 ± 11.9; P=.29) was an independent predictor of fibrinogen levels. In hypertensive patients, higher fibrinogen levels>443mg/dL (odds ratio = 3.50; 95% confidence interval, 1.14-10.90; P=.029), but not A homozygosity (odds ratio = 3.00; 95% confidence interval, 0.78-11.90; P = .110) were independent predictors of the presence of coronary artery disease. Moreover, interleukin-6 levels were higher in A homozygotes for the rs180070 polymorphism compared with all other genotypes (P=.046). Indeed, this genotype was the only adjusted independent predictor of interleukin-6 levels (ß = 0.151 ± 0.642; P=.032). It was also associated with higher D-dimer levels in hypertension compared with G allele carriers (P=.048). CONCLUSIONS: The presence of A homozygosity (rs180070) is associated with increased levels of inflammatory mediators and a higher incidence of angiographic coronary artery disease. Importantly, fibrinogen is an independent predictor of the angiographic presence of coronary artery disease in hypertensive patients.

Recent therapeutic approaches to platelet activation in coronary artery disease.

We have examined the role of platelets and platelet activation, and related emerging therapeutic approaches, in acute coronary syndromes (ACS). The role of platelets in atherothrombosis and ACS is critical, since platelet activation is a key step in the manifestation of these syndromes. Adhesion of sub-endothelial collagen and von Willebrand Factor (vWF) to the glycoprotein (GP) platelet receptors (GPIaIIa and GPIb/IX/V respectively) stimulates platelet activation. During activation, platelets present pseudopodia, which ensures a tighter adhesion to the sub-endothelial matrix and, via GPIIbIIIa receptors, facilitates platelet aggregation and platelet binding to fibrinogen and vWF. Although all laboratory methods estimating platelet activation and antiplatelet therapy have specific limitations, the use of antiplatelet agents such as aspirin, clopidogrel, and GPIIbIIIa inhibitors remains essential in ACS prevention and treatment. Platelet-related genetic polymorphisms can modulate the response to these agents. Presently, antiplatelet intervention remains an important therapeutic modality, with novel antiplatelet therapies, such as prasugrel and ticagrelor under clinical investigation.