Original article Coronary Artery Atherosclerosis in Hypertensive Patients: The Role of Fibrinogen Genetic Variability Nikolaos Papageorgiou, a,b Alexandros Briasoulis, a,d Georgios Hatzis, a Emmanuel Androulakis, a,e Maria Kozanitou, a Antigoni Miliou, a Marietta Charakida, c Effimia Zacharia, a Spyridon Papaioannou, a Ioannis Paroutoglou, a Gerasimos Siasos, a Zoi Pallantza, a and Dimitris Tousoulis a, * a 1st Cardiology Department, Athens University Medical School, Hippokration Hospital, Athens, Greece b Barts Heart Centre, St. Bartholomew’s Hospital, London, United Kingdom c Department of Cardiovascular Imaging, King’s College, London, United Kingdom d Cardiovascular Institute, Wayne State University, Detroit, United States e Department of Cardiology, John Radcliffe, Oxford University Hospital, Oxford, United Kingdom Rev Esp Cardiol. 2017;70(1):34–41 Article history: Received 18 December 2015 Accepted 17 May 2016 Available online 21 August 2016 Keywords: Coronary artery disease Fibrinogen Hypertension Polymorphisms A B S T R A C T 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) (b = 0.257  18.6; P < .001), but not hypertension status (b = 0.05  11.9; P = .29) was an independent predictor of fibrinogen levels. In hypertensive patients, higher fibrinogen levels > 443 mg/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 (b = 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.  C 2016 Sociedad Espan ˜ola de Cardiologı ´a. Published by Elsevier Espan ˜a, S.L.U. All rights reserved. Ateroesclerosis coronaria en pacientes hipertensos: el papel de la variabilidad gene ´ tica del fibrino ´ geno Palabras clave: Enfermedad coronaria Fibrino ´ geno Hipertensio ´n Polimorfismos R E S U M E N Introduccio ´n y objetivos: Se examina si los polimorfismos rs180070 y rs2070011 del gen del fibrino ´ geno podrı ´an afectar al riesgo de enfermedad coronaria de los pacientes hipertensos al modificar el proceso inflamatorio y la coagulacio ´ n. Me ´todos: Se practico ´ una angiografı ´a coronaria a causa de sı ´ntomas de angina estable a 744 partici- pantes, de los que 332 tenı ´an hipertensio ´ n. Resultados: La presencia del alelo A (rs180070) se asocio ´a cifras de fibrino ´ geno significativamente elevadas en los pacientes hipertensos (p = 0,05). En el ana ´ lisis multivariable, la homocigosis para A (rs180070) (b = 0,257  18,6; p < 0,001), pero no la presencia de hipertensio ´n (b = 0,05  11,9; p = 0,29), fue un factor independiente predictivo de la concentracio ´n de fibrino ´ geno. En los pacientes hipertensos, la concentracio ´n de fibrino ´ geno > 443 mg/dl (odds ratio = 3,50; intervalo de confianza del 95%, 1,14-10,90; p = 0,029), pero no la homocigosis para A (odds ratio = 3,00; intervalo de confianza del 95%, 0,78- 11,90; p = 0,110), fueron un factor independiente predictivo de enfermedad coronaria. Adema ´ s, los valores de interleucina 6 fueron ma ´s altos en los individuos homocigotos para el polimorfismo rs180070 que en todos los dema ´s genotipos (p = 0,046). De hecho, este genotipo fue el u ´ nico factor independiente * Corresponding author: Athens University Medical School, Hippokration Hospital, Vasilisis Sofias 114, 115 28 Athens, Greece. E-mail address: drtousoulis@hotmail.com (D. Tousoulis). http://dx.doi.org/10.1016/j.rec.2016.05.024 1885-5857/  C 2016 Sociedad Espan ˜ola de Cardiologı ´a. Published by Elsevier Espan ˜a, S.L.U. All rights reserved.