In the present pilot study (56 patients), some red blood cell parameters in samples from patients with metabolic syndrome and subclinical atherosclerosis, but without any sign of coronary artery disease, have been analyzed. The main goal of this work was to determine, in this preclinical state, new peripheral gender-associated bioindicators of possible diagnostic or prognostic value. In particular, three different “indicators” of red blood cell injury and aging have been evaluated: glycophorin A, CD47, and phosphatidylserine externalization. Interestingly, all these determinants appeared significantly modified and displayed gender differences. These findings could provide novel and useful hints in the research for gender-based real-time bioindicators in the progression of metabolic syndrome towards coronary artery disease. Further, more extensive studies are, however, necessary in order to validate these findings. 1. Introduction Metabolic syndrome (MetS) is a cluster of risk factors for atherosclerosis, including insulin resistance, hypertension, glucose intolerance, hypertriglyceridemia, and low high-density lipoprotein-cholesterol (HDL-C) levels [1]. Affected patients have a significantly increased risk of developing atherosclerotic disease, diabetes, and cardiovascular disease (CVD). This is probably due to a blood hypercoagulability as well as to endothelial cell activation. It has been hypothesized that the hypercoagulability state could predispose patients to venous thromboembolism [2]. Several epidemiological studies, the Framingham, in particular [3], have investigated into the evolution of cardiovascular disease hypothesizing the presence of a gender difference in the pathogenetic and progression determinants detectable in men and women. For instance, women were found to outlive men and to experience fewer atherosclerotic cardiovascular events, with an incidence lagging behind that in men by 10 to 20 years [4]. This gap in incidence closes with advancing age, when CVD becomes the leading cause of death in women as well as in men [5, 6]. In consideration of the high incidence of morbidity and mortality, due to CVD, and of the paucity of well-established gender-associated markers, further studies focused at identifying novel bioindicators should be considered as mandatory. On these bases, a pilot study has been conducted in a low number of patients with MetS of both sexes and subclinical atherosclerosis with the aim to identify innovative peripheral blood biomarker in this preclinical phase [7]. We focused our attention on the red blood cell
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