Plasma Metabolites, Blood-borne Microvesicles and History of Preeclampsia as predictors of Coronary Artery Calcification in Postmenopausal Women

Background: Compared to men, women with similar coronary artery calcification (CAC) scores face higher cardiovascular disease (CVD) mortality. Objectives: We posited that circulatory factors, like blood-borne extracellular vesicles (EVs) and metabolites, may be associated with the development of CAC and subsequent CVD in postmenopausal women. Additionally, we hypothesized that a history of preeclampsia (PE), a sex-specific risk factor, might be a contributing factor. Methods: Clinical data were obtained from medical records for postmenopausal women (median age 60 years) free of cardiovascular events with (n=29) and without (n=29) CAC. EVs per µL plasma were quantified by digital flow cytometry, and plasma metabolites were measured using gas chromatography-mass spectrometry. CACs were measured by computer tomography and reported as Agatston score. Results: Patients with, versus those without, CAC demonstrated i) less favorable cardiovascular and metabolic profiles; ii) elevation in six EVs populations, including those positive for TF (tissue factor), CD3 (T-cells), SM22α (smooth muscle cells), Pref-1 (adipocytes), FABP4 (adipocytes/macrophages) and p16 (senescent cells); iii) significantly higher levels of proline, allothreonine (amino acid metabolism) and ribitol (carbohydrate metabolism), and lower levels of lactic acid (carbohydrate metabolism); and iv) significantly increased risk of developing CVD and chronic kidney disease (CKD) (PConclusions: Selected plasma metabolites, EVs and PE history could serve as biomarkers of and potential therapeutic targets for CAC and CVD in postmenopausal women.