Kim Hyunju, Chen Jingsha, Prescott Brenton, Walker Maura E, Grams Morgan E, Yu Bing, Vasan Ramachandran S, Floyd James, Sotoodehnia Nona, Smith Nicholas L, Arking Dan E, Coresh Josef, Rebholz Casey M
Department of Epidemiology, University of Washington, Seattle, WA, United States; Cardiovascular Health Research Unit, Department of Medicine, University of Washington School of Public Health, Seattle, WA, United States.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
J Nutr. 2025 Jun;155(6):1741-1750. doi: 10.1016/j.tjnut.2025.04.011. Epub 2025 Apr 12.
Plant-based diets are associated with a lower risk of cardiovascular disease (CVD). Proteomics may improve our understanding of the biological pathways underlying these associations.
Using large-scale proteomics, we aimed to examine if plant-based diet-related proteins, which have been previously identified, are associated with incident CVD and subtypes of CVD in the Atherosclerosis Risk in Communities (ARIC) Study and Framingham Heart Study (FHS) Offspring cohort.
Discovery analyses were based on 9078 participants free of CVD at ARIC visit 3 (1993-1995). Cox proportional hazards regression was used to evaluate the associations between plant-based diet-related proteins and incident CVD, coronary artery disease, heart failure, and stroke. Replication analyses were based on 1279 participants without CVD in the FHS Offspring cohort.
In the ARIC study, over a median follow-up of 21 y, there were 3167 CVD events. At a false discovery rate <0.05, 26 of 73 plant-based diet-related proteins were significantly associated with incident CVD, after adjusting for important confounders. Eighteen, 1, and 0 proteins were associated with heart failure, stroke, and coronary artery disease, respectively. Three and 2 additional proteins were associated with CVD and heart failure risk in the FHS Offspring cohort at the nominal threshold (P < 0.05). In the ARIC Study and FHS Offspring cohort, soluble advanced glycosylation end product-specific receptor was inversely associated with incident CVD whereas thrombospondin-2 (THBS2) and N-terminal pro-BNP was positively associated with incident CVD. THBS2 was positively associated with incident heart failure, whereas neuronal growth factor regulator 1 and insulin-like growth factor-binding protein 1 was inversely associated.
These proteins highlight several pathways that could explain plant-based diets-CVD associations.
以植物为基础的饮食与较低的心血管疾病(CVD)风险相关。蛋白质组学可能会增进我们对这些关联背后生物学途径的理解。
利用大规模蛋白质组学,我们旨在研究先前已鉴定出的与以植物为基础的饮食相关的蛋白质是否与社区动脉粥样硬化风险(ARIC)研究和弗雷明汉心脏研究(FHS)子代队列中的新发CVD及其亚型相关。
发现性分析基于ARIC第3次随访(1993 - 1995年)时9078名无CVD的参与者。采用Cox比例风险回归来评估与以植物为基础的饮食相关的蛋白质与新发CVD、冠状动脉疾病、心力衰竭和中风之间的关联。重复性分析基于FHS子代队列中1279名无CVD的参与者。
在ARIC研究中,中位随访21年期间,有3167例CVD事件。在错误发现率<0.05的情况下,在调整重要混杂因素后,73种与以植物为基础的饮食相关的蛋白质中有26种与新发CVD显著相关。分别有18种、1种和0种蛋白质与心力衰竭、中风和冠状动脉疾病相关。在FHS子代队列中,另外有3种和2种蛋白质在名义阈值(P < 0.05)下与CVD和心力衰竭风险相关。在ARIC研究和FHS子代队列中,可溶性晚期糖基化终产物特异性受体与新发CVD呈负相关,而血小板反应蛋白-2(THBS2)和N末端脑钠肽前体与新发CVD呈正相关。THBS2与新发心力衰竭呈正相关,而神经生长因子调节因子1和胰岛素样生长因子结合蛋白1与新发心力衰竭呈负相关。
这些蛋白质突出了几条可以解释以植物为基础的饮食与CVD关联的途径。