Identification of Protein Biomarkers of the Dietary Approaches to Stop Hypertension Diet in Randomized Feeding Studies and Validation in an Observational Study

Abstract

Background The Dietary Approaches to Stop Hypertension (DASH) diet is recommended for cardiovascular disease prevention. We aimed to identify protein biomarkers of the DASH diet using data from 2 randomized feeding studies and validate them in an observational study, the ARIC (Atherosclerosis Risk in Communities) study. Methods and Results Large‐scale proteomic profiling was conducted in serum specimens (SomaLogic) collected at the end of 8‐week and 4‐week DASH diet interventions in multicenter, randomized controlled feeding studies of the DASH trial (N=215) and the DASH‐Sodium trial (N=396), respectively. Multivariable linear regression models were used to compare the relative abundance of 7241 proteins between the DASH and control diet interventions. Estimates from the 2 trials were meta‐analyzed using fixed‐effects models. We validated significant proteins in the ARIC study (N=10 490) using the DASH diet score. At a false discovery rate <0.05, there were 71 proteins that were different between the DASH diet and control diet in the DASH and DASH‐Sodium trials. Nineteen proteins were validated in the ARIC study. The 19 proteins collectively improved the prediction of the DASH diet intervention in the feeding studies (range of difference in C statistics, 0.267–0.313; P <0.001 for both tests) and the DASH diet score in the ARIC study (difference in C statistics, 0.017; P <0.001) beyond participant characteristics. Conclusions We identified 19 proteins robustly associated with the DASH diet in 3 studies, which may serve as biomarkers of the DASH diet. These results suggest potential pathways that are impacted by consumption of the DASH diet. Registration URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT03403166, NCT00000608.