Plasma metabolites, blood-borne microvesicles, and history of preeclampsia as predictors of coronary artery calcification in postmenopausal women

Compared with men, women with similar coronary artery calcification (CAC) scores face higher cardiovascular disease (CVD) mortality. We posited that circulatory factors, such as blood-borne extracellular vesicles (EVs) and metabolites, may be associated with the development of CAC and subsequent CVD in postmenopausal women. In addition, we hypothesized that a history of preeclampsia (PE), a sex-specific risk factor, might be a contributing factor. Clinical data were obtained from medical records for postmenopausal women (median age 60 yr) free of cardiovascular events with (n = 29) and without (n = 29) CAC. EVs per microliter 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 the Agatston score. Patients with, versus those without, CAC demonstrated 1) less favorable cardiovascular and metabolic profiles; 2) elevation in six EV populations, including those positive for tissue factor, CD3 (T-cells), SM22α (smooth muscle cells), Pref-1 (adipocytes), fatty acid-binding protein 4 (adipocytes/macrophages), and p16 (senescent cells); 3) significantly higher levels of proline, allothreonine (amino acid metabolism), and ribitol (carbohydrate metabolism), and lower levels of lactic acid (carbohydrate metabolism); and 4) significantly increased risk of developing CVD and chronic kidney disease (CKD) (P < 0.05 for all). In the CAC-positive group, women with PE versus those with normotensive pregnancy histories demonstrated a four times higher risk of developing cardiovascular events or CKD later in life (P = 0.028). Selected plasma metabolites, EVs, and PE history could serve as biomarkers and potential therapeutic targets for CAC and CVD in postmenopausal women.NEW & NOTEWORTHY Circulating extracellular vesicles, proinflammatory/pro-oxidant metabolites, and history of preeclampsia may be used as biomarkers for diagnosis of early CAC in postmenopausal women.