Plasma proteome of the EAT-Lancet diet and long-term risks of cardiovascular disease and mortality.

Background: The EAT-Lancet diet, designed for planetary and human health, has been associated with lower risk of cardiovascular disease (CVD) and mortality. Identifying plasma proteins associated with the EAT-Lancet diet may help elucidate biological pathways underlying dietary associations with health outcomes. Methods: In 9623 Atherosclerosis Risk in Communities study participants with proteomic data at visit 3 (1993-1995, baseline) measured using the SomaScan™ v4.0 platform, multivariable linear regression was used to identify proteins associated with Planetary Health Diet Index (PHDI) score in a randomly selected subset of 2/3 of the study population (discovery, n = 6415) and the remaining 1/3 subset (internal replication, n = 3208). Cox models were used to evaluate associations of PHDI score-related proteins with incident CVD and all-cause mortality from baseline through December 31, 2022. Results: Among 4955 proteins examined, 154 were significantly associated with PHDI score at a false discovery rate <0.05 and 74 replicated. During a median follow-up of 21 years, 3401 incident CVD events occurred; during a median follow-up of 24 years, 5899 deaths occurred. Of the 74 PHDI score-related proteins, 9 were significantly associated with both incident CVD and all-cause mortality and an additional 8 were associated with all-cause mortality only in discovery and replication. For example, higher ASGR1 levels were associated with higher risk of incident CVD and all-cause mortality. Conclusions: PHDI-related proteins were prospectively associated with long-term CVD and mortality risk and may support future risk stratification and dietary prevention strategies.