Proteomic signature of healthy dietary patterns and risk of cardiovascular disease in the framingham heart study.
BACKGROUND & AIMS Healthy dietary patterns are associated with a lower risk of cardiovascular disease (CVD). Proteomic correlates of healthy dietary patterns are understudied and may provide mechanistic insight and suggest putative markers between diet and CVD risk. We investigated the prospective association of a dietary proteomic score with cardiometabolic risk factors and CVD in a multi-generational cohort of middle-aged adults. METHODS We examined participants from the Framingham Heart Study Generation 2 (n = 1611, mean age 55 ± 10, 55.4% women) and Generation 3 (n = 862, mean age 46 ± 8, 56.6% women) who had complete dietary, proteomic, and covariate data, and were free from prevalent CVD. We analyzed plasma proteins using DNA aptamer-based technology, and three dietary pattern indices were derived from a semiquantitative food frequency questionnaire. With elastic net regression, we identified 11 diet-related proteins and created a weighted DPS, which had the strongest correlation with the DASH diet score (r = 00.30, p < 0.0001). RESULTS Over a median of 25 and 13 years we observed 533 CVD events. A 1-standard deviation (SD) increase in dietary proteomic score was associated with a 54% lower prevalence of Metabolic Syndrome (P ≤ 0.001) in multivariable-adjusted logistic regression models. Using multivariable Cox regression models adjusted for adjusting for lifestyle factors and the Dietary Approaches to Stop Hypertension (DASH) diet score, a 1-SD increase in the dietary proteomic score was associated with a 20% lower risk of CVD (HR [95% CI], 0.80 [0.73, 0.88]) and those in the highest tertile of the dietary proteomic score, compared to the lowest, had a 38% reduced risk of CVD (0.62 [0.49, 0.78]). However, these associations were attenuated after further adjustment for known cardiometabolic risk factors (1-SD: HR 0.94, [0.85, 1.04]; T3 vs T1: 0.81 [0.63, 1.03]). CONCLUSION A dietary proteomic score of three healthy dietary pattern indices was strongly associated with prevalent metabolic health cross-sectionally and incident CVD prospectively. These findings provide insight into the mechanisms linking diet quality and cardiometabolic health, and suggest future dietary proteomic studies in independent populations, as well as incorporating proteomics into dietary intervention trials.