Abstract
BACKGROUND: Plant-based diets are associated with a lower risk of cardiovascular disease (CVD). Proteomics may improve our understanding of the biological pathways underlying these associations. OBJECTIVES: Using large-scale proteomics, we aimed to examine if plant-based diet-related proteins, which have been previously identified, are associated with incident CVD and subtypes of CVD in the Atherosclerosis Risk in Communities (ARIC) Study and Framingham Heart Study (FHS) Offspring cohort. METHODS: Discovery analyses were based on 9078 participants free of CVD at ARIC visit 3 (1993-1995). Cox proportional hazards regression was used to evaluate the associations between plant-based diet-related proteins and incident CVD, coronary artery disease, heart failure, and stroke. Replication analyses were based on 1279 participants without CVD in the FHS Offspring cohort. RESULTS: In the ARIC study, over a median follow-up of 21 y, there were 3167 CVD events. At a false discovery rate <0.05, 26 of 73 plant-based diet-related proteins were significantly associated with incident CVD, after adjusting for important confounders. Eighteen, 1, and 0 proteins were associated with heart failure, stroke, and coronary artery disease, respectively. Three and 2 additional proteins were associated with CVD and heart failure risk in the FHS Offspring cohort at the nominal threshold (P < 0.05). In the ARIC Study and FHS Offspring cohort, soluble advanced glycosylation end product-specific receptor was inversely associated with incident CVD whereas thrombospondin-2 (THBS2) and N-terminal pro-BNP was positively associated with incident CVD. THBS2 was positively associated with incident heart failure, whereas neuronal growth factor regulator 1 and insulin-like growth factor-binding protein 1 was inversely associated. CONCLUSIONS: These proteins highlight several pathways that could explain plant-based diets-CVD associations.