Changes in Proteome Profiles Linked to Hormonal Contraceptive Use Among African American Women with untreated high blood pressure

Abstract

ABSTRACTBackgroundThe use of oral contraceptives among women with pre-existing cardiometabolic risk factors has been associated with increased risk of cardiovascular events but the underlying mechanisms are not well understood. Analyzing the proteome enables the identification and quantification of proteins involved in various cellular processes, including those affected by oral contraceptives.ObjectiveThe objective of this study was to investigate if current oral contraceptive use was associated with alterations in the plasma proteome among pre-menopausal African American women with hypertension in the Genomics, Environmental Factors, and the Social Determinants of Cardiovascular Disease in African Americans Study (GENE-FORECAST).Study DesignWe evaluated 2,941 serum proteins measured on the Olink platform to assess the associations between oral contraception use and protein levels among 51 pre-menopausal women with untreated Stage 2 hypertension (13 oral contraception users and 38 non-users). A generalized linear model was fitted for each protein, adjusting for age, body mass index, alcohol consumption, level of education, and physical activity. Pathway enrichment analysis was carried out to identify common pathways among the proteins associated with oral contraceptive use. Gene Ontology enrichment analysis was conducted to gain insight into the functional characteristics of the proteins and the underlying biology.ResultsWe identified 44 proteins significantly associated with oral contraceptive use. Among those, 31 showed decreased levels among oral contraceptive users, while 13 exhibited an increase in users. Fourteen proteins were enriched in potentially relevant pathways for the pathogenesis of cardiovascular disease including complement and coagulation cascades, cholesterol metabolism and Notch signaling. There were 25 enriched Gene Ontology terms encompassing 39 of the 44 proteins linked to oral contraceptive use; several of these are involved in peptidase inhibitor activity.ConclusionsThis study provides novel insights into the proteomic landscape associated with oral contraceptive use among African American women with uncontrolled hypertension.