부산대학교 도서관

Introduction:There may be unique pathways that contribute to heart disease in women. We used proteomics to evaluate the association between a panel of biomarkers and risk of incident MI in post-menopausal women and thus to inform risk prediction and potential disease biology.Methods:We analyzed 184 candidate biomarkers (Olink CVD II/III) in LOFT, a randomized trial of an osteoporosis drug in post-menopausal women. Cases and controls without prevalent CV disease were matched by age and follow-up time (123 MI cases, 123 controls). A Benjamini-Hochberg correction was applied for false discovery (adj P value <0.05). Conditional logistic regression was adjusted for the ACC/AHA pooled cohort equations (PCE).Results:16 biomarkers assessed at baseline were associated with incident MI at the FDR threshold (Fig). After multivariable adjustment, 8 markers remained significantly associated with incident MI, including BNP (adj OR per SD 2.52, 95% CI 1.49-4.28), NT-proBNP (adj OR 2.41, 95% CI 1.43-4.08) and metalloproteinases including MMP-2 (adj OR 1.86, 95% CI 1.08-3.22) and MMP-12 (adj OR 1.55, 95% CI 1.02-2.37; Fig). Network analyses suggested these markers were overall strongly concentrated in pathways of inflammation, cellular movement and immune cell trafficking.Conclusions:A targeted proteomic approach identified markers of inflammation and immune cell trafficking as predictors of MI in post-menopausal women independent of traditional risk markers. Metalloproteinases, markers of plaque rupture and erosion, may provide insights into plaque biology and atherogenesis in women and warrant further investigation.