Lei Wang

M.Phil.

Vanderbilt University Medical Center

PhD candidate

PLCO (Learn more about this study)

PLCO-1820

Feb 19, 2025

Validation of blood metabolites related to diet and cardiovascular mortality

Diet plays an important role in human health outcomes, especially in the development and progression of cardiovascular diseases (CVD). Various dietary indexes have been developed to assess overall dietary quality based on recommendations (e.g., Healthy Eating Index [HEI] and Dietary Approaches to Stop Hypertension [DASH]), certain biomarkers (e.g., Empirical Dietary Inflammatory Potential [EDIP] and Empirical Dietary Index for Hyperinsulinemia [EDIH]), or food processing levels (e.g., Ultra-Processed Foods [UPF]). Meta-analyses have shown that higher HEI or DASH scores are associated with 19-23% decreased CVD incidence or mortality, while 35-38% increased CVD risks were observed for higher EDIP and UPF scores. The biological mechanisms through which healthy or unhealthy dietary patterns exert protective or harmful effects on cardiovascular health are complex and not yet well understood. Blood metabolomics, which provides a comprehensive picture of the underlying metabolic responses to dietary intakes, is a powerful tool for mechanistic investigation. Recent reviews suggested ten replicated metabolites related to HEI and five related to DASH, while most other metabolites showed inconsistent associations across studies. The metabolic profiling of EDIP, EDIH, or UPF has not been well elucidated. Additionally, few studies have prospectively evaluated the associations between dietary pattern-related metabolites and CVD outcomes. To fill these research gaps, we identified circulating metabolites related to diet and examined for their associations with incident coronary heart disease (CHD) and CVD mortality among Black/African American and White American participants in the Southern Community Cohort Study (SCCS). We found: 1) 258 metabolites associated with at least one dietary pattern (i.e., HEI, DASH, EDIP, EDIH, or UPF), 48 of which were associated with CHD incidence or CVD mortality; 2) 92 metabolites related to peanut consumption, with 24 significantly associated with CHD risk. All associations had a Benjamini–Hochberg false discovery rate<0.1. We propose to validate the SCCS results in PLCO. Findings from this project may advance our understanding of the biological mechanism underlying diet-CVD association and aid in utilizing metabolites as biomarkers for assessing dietary quality and cardiovascular health.