Current Biomarkers for Carotid Artery Stenosis: A Comprehensive Review of the Literature

Abstract

Carotid artery stenosis (CAS), an atherosclerotic disease of the carotid artery, is one of the leading causes of transient ischemic attacks (TIA) and cerebrovascular attacks (CVA). The atherogenic process of CAS affects a wide range of physiological processes, such as inflammation, endothelial cell function, smooth muscle cell migration and many more. The current gold-standard test for CAS is Doppler ultrasound; however, there is yet to be determined a strong, clinically validated biomarker in the blood that can diagnose patients with CAS and/or predict adverse outcomes in such patients. In this comprehensive literature review, we evaluated all of the current research on plasma and serum proteins that are current contenders for biomarkers for CAS. In this literature review, 36 proteins found as potential biomarkers for CAS were categorized in to the following nine categories based on protein function: (1) Inflammation and Immunity, (2) Lipid Metabolism, (3) Haemostasis, (4) Cardiovascular Markers, (5) Markers of Kidney Function, (6) Bone Health, (7) Cellular Structure, (8) Growth Factors, and (9) Hormones. This literature review is the most up-to-date and current comprehensive review of research on biomarkers of CAS, and the only review that demonstrated the several pathways that contribute to the initiation and progression of the disease. With this review, future studies can determine if any new markers, or a panel of the proteins explored in this study, may be contenders as diagnostic or prognostic markers for CAS.

Inflammatory Biomarkers to Predict Major Adverse Cardiovascular Events in Patients with Carotid Artery Stenosis

“…The mechanisms by which IL-6 and CD163 may increase the risk of major adverse cardiovascular events in patients with carotid artery stenosis include the facilitation of pro-inflammatory and pro-atherogenic pathways that may contribute to plaque progression and instability leading to adverse cardiovascular outcomes [ 10 , 11 , 12 , 13 ]. Over 20 inflammatory cardiovascular disease biomarkers have been investigated [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. We selected 29 specific inflammatory biomarkers for analysis because they have been thoroughly studied and show robust associations with cardiovascular diseases with potential applications to CAS [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ].…”

“…Over 20 inflammatory cardiovascular disease biomarkers have been investigated [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. We selected 29 specific inflammatory biomarkers for analysis because they have been thoroughly studied and show robust associations with cardiovascular diseases with potential applications to CAS [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Although existing papers have shown correlations between these proteins and cardiovascular diseases, few have assessed their implications for prognosis in CAS by assessing their ability to predict adverse events independently of other clinical characteristics [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ].…”

“…We selected 29 specific inflammatory biomarkers for analysis because they have been thoroughly studied and show robust associations with cardiovascular diseases with potential applications to CAS [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Although existing papers have shown correlations between these proteins and cardiovascular diseases, few have assessed their implications for prognosis in CAS by assessing their ability to predict adverse events independently of other clinical characteristics [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. The reason this study focused specifically on CD136 and IL-6 is that these proteins are involved in various metabolic pathways that promote inflammation and atherogenesis, which are fundamental contributors to CAS development and progression [ 8 , 9 ].…”

“…Therefore, CD136 and IL-6 may have strong prognostic value for CAS-related adverse events [ 8 , 9 ]. The novelty of this study stems from the fact that we identified CAS-specific prognostic biomarkers from a large panel of circulating proteins and assessed their ability to independently predict CAS-related outcomes using statistical tests that adjusted for baseline characteristics, which has not been performed by previous studies [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. This study primarily focuses on identifying CAS-specific prognostic biomarkers from a large pool of inflammatory proteins and characterizing the ability of these biomarkers to predict long-term adverse cardiovascular events in individuals with CAS.…”

Estrés oxidativo en la aterosclerosis carotídea y biomarcadores pronósticos relacionados en el desarrollo de ictus

“…Multitud de grupos de investigación han intentado establecer la relación entre diversas proteínas relacionadas con la inflamación y la inmunidad, el metabolismo lipídico, la hemostasia, el sistema cardiovascular, la función renal, el metabolismo óseo, la estructura celular, los factores de crecimiento y el sistema endocrino para su empleo como biomarcadores séricos, histológicos o en líquido cefalorraquídeo de utilidad en la enfermedad estenótica carotídea (Figura 63). Sin embargo, ninguno de estos potenciales biomarcadores ha sido aceptado como clínicamente relevante por falta de sensibilidad y especificidad (252). Es posible que la combinación de algunos de ellos con los FR cardiovascular en algoritmos y modelos computacionales de aprendizaje automáticos pueda ser de utilidad, pero son necesarios más estudios al respecto.…”