Proteins as Mediators of the Association Between Diet Quality and Incident Cardiovascular Disease and All‐Cause Mortality: The Framingham Heart Study

Abstract

Background Biological mechanisms underlying the association of a healthy diet with chronic diseases remain unclear. Targeted proteomics may facilitate the understanding of mechanisms linking diet to chronic diseases. Methods and Results We examined 6360 participants (mean age 50 years; 54% women) in the Framingham Heart Study. The associations between diet and 71 cardiovascular disease (CVD)‐related proteins were examined using 3 diet quality scores: the Alternate Healthy Eating Index, the modified Mediterranean‐style Diet Score, and the modified Dietary Approaches to Stop Hypertension diet score. A mediation analysis was conducted to examine which proteins mediated the associations of diet with incident CVD and all‐cause mortality. Thirty of the 71 proteins were associated with at least 1 diet quality score ( P <0.0007) after adjustment for multiple covariates in all study participants and confirmed by an internal validation analysis. Gene ontology analysis identified inflammation‐related pathways such as regulation of cell killing and neuroinflammatory response (Bonferroni corrected P <0.05). During a median follow‐up of 13 years, we documented 512 deaths and 488 incident CVD events. Higher diet quality scores were associated with lower risk of CVD ( P ≤0.03) and mortality ( P ≤0.004). After adjusting for multiple potential confounders, 4 proteins (B2M [beta‐2‐microglobulin], GDF15 [growth differentiation factor 15], sICAM1 [soluble intercellular adhesion molecule 1], and UCMGP [uncarboxylated matrix Gla‐protein]) mediated the association between at least 1 diet quality score and all‐cause mortality (median proportion of mediation ranged from 8.6% to 25.9%). We also observed that GDF15 mediated the association of the Alternate Healthy Eating Index with CVD (median proportion of mediation: 8.6%). Conclusions Diet quality is associated with new‐onset CVD and mortality and with circulating CVD‐related proteins. Several proteins appear to mediate the association of diet with these outcomes.

Identifying and Analyzing Topic Clusters in a Nutri-, Food-, and Diet-Proteomic Corpus Using Machine Reading

“…A separate study examined the AHEI and modified versions of the Mediterranean-style Diet Score (mMDS) and mDASH in 6360 participants (mean age 50 years; 54% women) in the same Framingham Heart Study [ 22 ]. The proteomic analysis used a modified sandwich ELISA method multiplexed on a Luminex xMAP (Sigma-Aldrich, St. Louis, MO, USA).…”

DIA-PRM Proteomic Analysis of Phlegm-Dampness Constitution with Glucolipid Metabolic Disorders by the Intervention of Hua Tan Qu Shi Recipe

“…Moreover, higher B2MG was correlated with a higher occurrence of major adverse cardiac events [36]. And B2MG as a mediator had been linked to the diet and incident cardiovascular disease, also including all-cause mortality [37]. Lately, it was reported that circulating B2MG with higher levels could be a predictor for the progression of diabetic nephropathy in T2D patients [38].…”

Association between inflammatory biomarkers and cognitive aging

“…CD14 serves as a positive control as previous work demonstrates an association between sCD14 and dementia in FHS [4]. Details on protein biomarker measurement have been described in previous publications [27,28]. In brief, the proteins were measured by the Systems Approach to Biomarker Research (SABRe) that was established by the National Heart, Lung, and Blood Institute [27].…”