Atherosclerosis and diabetes are largely recognized as inflammatory disorders underlying cardiovascular disease. C-reactive protein, interleukin-6 and fibrinogen constitute the most established inflammatory biomarkers in clinical practice for the characterization of individuals affected by atherosclerosis, diabetes and heart failure. In addition to their traditional role as inflammatory markers, emerging evidence suggests their role as active mediators in cardiovascular pathogenesis. The interplay between these circulating inflammatory biomarkers and established cardiovascular risk factors, such as dyslipidemia, hyperglycemia, insulin resistance and elevated NTproBNP needs to be investigated. In this review, we aim to determine whether these biomarkers are merely hallmarks of inflammation or active factors in the pathogenesis of cardiovascular diseases by analyzing their links with HDL/LDL, glycemia, insulin resistance and NT-pro-BNP, respectively. C-reactive protein directly promotes atherosclerosis by increasing LDL transcytosis across endothelial cells and enhancing LOX-1 expression. It provides complementary information to NT-pro-BNP for high risk of major adverse cardiac events in post-MI patients and predicts mortality in type 2 diabetic subjects. Interleukin- 6 activates hepatic LDL receptor transcription and correlates with endothelial dysfunction and carotid intima-media thickness. It is related to higher NT-pro-BNP levels and insulin resistance. Fibrinogen is independently associated with a more atherogenic lipoprotein subfraction profile in diabetic patients and insulin resistance. In these patients the fibrinogen glycation level is higher and forms fibrin clots with enhanced resistance to fibrinolysis. Finally, the fibrinogen-to-albumin ratio in heart failure is positively correlated with NT-pro-BNP. In conclusion, C-reactive protein, interleukin-6 and fibrinogen may emerge as active drivers and promising therapeutic targets in cardiovascular diseases.
Papa et al. (2025) studied this question.