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

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...

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Autores principales:	Youjin Kim, Sophia Lu, Jennifer E. Ho, Shih‐Jen Hwang, Chen Yao, Tianxiao Huan, Daniel Levy, Jiantao Ma
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	cardiovascular disease diet quality mediator mortality proteomics Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/f48271ec610548e494d20c8d60b51690
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spelling	oai:doaj.org-article:f48271ec610548e494d20c8d60b516902021-11-23T11:36:35ZProteins as Mediators of the Association Between Diet Quality and Incident Cardiovascular Disease and All‐Cause Mortality: The Framingham Heart Study10.1161/JAHA.121.0212452047-9980https://doaj.org/article/f48271ec610548e494d20c8d60b516902021-09-01T00:00:00Zhttps://www.ahajournals.org/doi/10.1161/JAHA.121.021245https://doaj.org/toc/2047-9980Background 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.Youjin KimSophia LuJennifer E. HoShih‐Jen HwangChen YaoTianxiao HuanDaniel LevyJiantao MaWileyarticlecardiovascular diseasediet qualitymediatormortalityproteomicsDiseases of the circulatory (Cardiovascular) systemRC666-701ENJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 10, Iss 18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cardiovascular disease diet quality mediator mortality proteomics Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	cardiovascular disease diet quality mediator mortality proteomics Diseases of the circulatory (Cardiovascular) system RC666-701 Youjin Kim Sophia Lu Jennifer E. Ho Shih‐Jen Hwang Chen Yao Tianxiao Huan Daniel Levy Jiantao Ma Proteins as Mediators of the Association Between Diet Quality and Incident Cardiovascular Disease and All‐Cause Mortality: The Framingham Heart Study
description	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.
format	article
author	Youjin Kim Sophia Lu Jennifer E. Ho Shih‐Jen Hwang Chen Yao Tianxiao Huan Daniel Levy Jiantao Ma
author_facet	Youjin Kim Sophia Lu Jennifer E. Ho Shih‐Jen Hwang Chen Yao Tianxiao Huan Daniel Levy Jiantao Ma
author_sort	Youjin Kim
title	Proteins as Mediators of the Association Between Diet Quality and Incident Cardiovascular Disease and All‐Cause Mortality: The Framingham Heart Study
title_short	Proteins as Mediators of the Association Between Diet Quality and Incident Cardiovascular Disease and All‐Cause Mortality: The Framingham Heart Study
title_full	Proteins as Mediators of the Association Between Diet Quality and Incident Cardiovascular Disease and All‐Cause Mortality: The Framingham Heart Study
title_fullStr	Proteins as Mediators of the Association Between Diet Quality and Incident Cardiovascular Disease and All‐Cause Mortality: The Framingham Heart Study
title_full_unstemmed	Proteins as Mediators of the Association Between Diet Quality and Incident Cardiovascular Disease and All‐Cause Mortality: The Framingham Heart Study
title_sort	proteins as mediators of the association between diet quality and incident cardiovascular disease and all‐cause mortality: the framingham heart study
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/f48271ec610548e494d20c8d60b51690
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Proteins as Mediators of the Association Between Diet Quality and Incident Cardiovascular Disease and All‐Cause Mortality: The Framingham Heart Study

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