Abstract 620: Circulating Sex-specific Markers of Plaque Instability in Women and Men with Severe Carotid Atherosclerosis

Introduction: Strokes are mainly caused by cerebral ischemia due to rupture of unstable carotid atherosclerotic plaques. Although men have higher stroke incidence rates than women, women have greater mortality rates post-stroke. A lack of sex-specific guidelines has led to suboptimal prevention/treatment of strokes. Thus, we aimed to identify sex-specific markers of plaque instability in patients with severe carotid atherosclerosis. Methods: Pre-operative blood samples and plaque specimens were collected from consecutive men and women who underwent a carotid endarterectomy. Plaque stability was determined by vascular pathologists. Adiponectin (AdipoR1/AdipoR2), estrogen (ER-α, ER-ß, GPER), and androgen receptor gene expression on peripheral blood monocytes was assessed via qRT-PCR. Total and HMW adiponectin plasma levels were measured by ELISA. A highly specific and sensitive method was developed to measure circulating sex hormones (testosterone, androstenedione, DHEA, and estradiol) using liquid chromatography mass spectrometry. Results: Sex was a strong and independent determinant of plaque instability (OR [95% CI]: 2.67 [1.71-4.17]), where men (n=277) had more unstable plaques than women (n=116). A greater proportion of monocyte to white blood cell counts was observed in men vs. women with unstable plaques (P=0.008). Men with stable plaques had significantly lower AdipoR1 (1.58-fold) and ER-α (1.57-fold) expression on blood monocytes vs. women with stable plaques. However, in cases of unstable plaques, no significant difference in AdipoR1 expression was observed between men and women, while ER-α was 1.88-fold higher in men vs. women (P<0.05). AdipoR2 and GPER followed a similar pattern of expression as AdipoR1 and ER-α, respectively. ER-ß and androgen receptor were not expressed on monocytes. Decreased circulating HMW:total adiponectin ratio was significantly associated with greater plaque instability in women. Sex hormone sera levels are currently being measured. Conclusion: HMW:total adiponectin ratio may be a potential marker of plaque instability in women. A sexual pattern was observed in the distribution of adiponectin/sex hormone receptors on blood monocytes of women and men with stable vs. unstable carotid plaques.