Evidence suggests association of red blood cell distribution width (RDW) with cardiovascular diseases (CVDs). On the contrary, we underline that the sole RDW values cannot represent a valid CVD biomarker. High RDW values are expression of biological effects of a lot of both endogenous and exogenous factors (i.e., age, sex, genetic background, inflammation, hormones, drugs, diet, exercise, hematological analyzers, and ranges of values), modulating the biology and physiology of erythrocytes. Thus, the singular monitoring of RDW cannot be used to predict cardiovascular disorders. Accordingly, we have reviewed the evidence for potential relationship of RDW values with alterations in the cardiovascular system (i.e., regenerative capacity, endothelial turnover, and senescence of cardiovascular cells), associated with vascular aging and disease. In addition, we highlight the inevitable impact of biases in clinical application of RDW related to CVDs. Based on our thorough review of literature, we suggest a combined evaluation of RDW with other emerging biomarkers related to vascular aging and the diagnosis and prognosis of CVDs, including telomere length of leukocytes, circulating nucleated red blood cells (nRBCs) and endothelial progenitor cells (EPCs) in future large scale studies.
