Alexander Garev, Nikolay Runev, Yulia Petrova, Emil Manov, Ralitsa Pancheva, Ventsislava Pencheva 


Department of Cardiology and Pulmonology 2, Clinic of Propaedeutics of Internal Diseases, Medical University, UMHAT "Alexandrovska", Sofia; Neurology Clinic 1, Medical University, UMHAT "Alexandrovksa", Sofia, Bulgaria


Background: Major adverse cardiovascular events (MACE, including stroke and cardiovascular mortality) in patients with carotid arterial disease (CAD) are still a significant global issue. 

Aims: Our goal was to analyze the prognostic role of risk factors (RF), comorbidities and levels of specific biomarkers: asymmetric dimethylarginine (ADMA), homocysteine (HCY) and vitamin B12 (VB12) for MACE in Bulgarian patients with significant CAD.

Materials and methods: We studied 98 patients with significant CAD, mean age 67.46 years, hospitalized in Cardiology Clinic of UMHAT “Alexandrovska” during the period between 2014 and 2020 years. They were divided into two groups, depending on whether they underwent carotid arterial stenting (CAS) (84 in total) or not (14 in total). The differences in RF, comorbidities and ADMA, HCY and VB12 between the two studied groups were assessed, as well as their prognostic value for MACE appearance, using parametric  methods (Chi-square test) and ROC analysis. 

Results: Patients with stroke had a significantly higher incidence of arterial hypertension (AH) (87.1 %, p < 0.009), diabetes mellitus (DM) type 2 (29,0  %  p < 0.028) and smoking (38.7  %, p < 0.028) compared to those without stroke. The rates of dyslipidemia and obesity did not show statistically significant differences between the two studied groups. Regression analysis showed that AH was the most significant RF for the occurrence of stroke (OR 3.99, p <0.04). Moreover, the incidence of AH was significantly higher in patients with previous myocardial infarction (p <0.031). No statistical significance was found for dyslipidemia, DM type 2, obesity and smoking in both groups (with/without MI). In the studied patients with CAD, potential factors for MACE were: previous stroke (p < 0.017) and MI ( p < 0.047), and the presence of stroke increased almost 4 times the risk of death /OR=3.765/. Importantly in all patients with known significant CAD, whether or not they underwent stenting, ADMA and HCY values were significantly elevated (p <0.001), compared to the control group (healthy volunteers without known carotid pathology were assessed as a control group), and cut-off values related to an increased risk for MACE were > 0.91 for ADMA and > 12.25 for HCY, respectively.

Conclusion: Based on these data we could recommend: patients with known carotid artery disease with or without interventional treatment, aged over 69.5 years, with the presence of AH, DM type 2 and smoking, and ADMA / HCY values above 0.91/12.25 Mmol/l respectively, are associated with elevated risk of MACE. The risk is significantly increased if these patients have previous stroke and/or myocardial infarction. 


carotid artery disease, ADMA, risk factors.