Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Wuhan Children's Hospital (Wuhan Maternal and Child Health Care Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430019, China.
Environ Int. 2022 Jun;164:107261. doi: 10.1016/j.envint.2022.107261. Epub 2022 Apr 25.
Acrylamide (ACR) exposure and consequent health hazards are alarming public health issues that attract worldwide concern. The World Health Organization urges more researches into health hazards from ACR exposure. However, whether and how ACR exposure increases cardiovascular risk remain unclear, and we sought to address these issues in this prospective cohort study conducted on 3024 general adults with 3-year follow-up (N = 871 at follow-up). Individual urinary ACR metabolites (N-Acetyl-S-(2-carbamoylethyl)-L-cysteine [AAMA] and N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine [GAMA]) as credible biomarkers of ACR exposure were detected to assess their cross-sectional and longitudinal relationships with 10-year cardiovascular disease (CVD) risk, a well measure of overall cardiovascular risk. Besides, biomarkers of oxidative stress (urinary 8-hydroxy-deoxyguanosine [8-OHdG] and 8-iso-prostaglandin-F2α [8-iso-PGF2α]) and inflammation (circulating mean platelet volume [MPV] and plasma C-reactive protein [CRP]) as well as plasma transforming growth factor-β1 (TGF-β1) were measured to assess their mediating/mechanistic roles in the relationships of ACR metabolites with 10-year CVD risk. We found AAMA, GAMA, and ΣUAAM (AAMA + GAMA) were cross-sectionally and longitudinally related to increased 10-year CVD risk with odds ratios (95% confidence intervals [CIs]) of 1.32 (1.04, 1.70), 1.81 (1.36, 2.40), and 1.40 (1.07, 1.82), respectively, and risk ratios (95% CIs) of 1.99 (1.10, 3.60), 2.48 (1.27, 4.86), and 2.13 (1.15, 3.94), respectively. Furthermore, 8-OHdG, 8-iso-PGF2α, MPV, CRP, and TGF-β1 were found to significantly mediate 8.06-48.92% of the ACR metabolites-associated 10-year CVD risk increment. In summary, daily ACR exposure of general adults was cross-sectionally and longitudinally associated with increased cardiovascular risk, which was partly mediated by oxidative stress, inflammation, and TGF-β1, suggesting for the first time that ACR exposure may well increase cardiovascular risk of general adult population partly by mechanisms of inducing oxidative stress, inflammation, and TGF-β1. Our findings have important public health implications that provide potent epidemiological evidence and vital mechanistic insight into cardiovascular risk increment from ACR exposure.
丙烯酰胺（ACR）暴露及其导致的健康危害是令人震惊的公共卫生问题，引起了全球关注。世界卫生组织敦促开展更多关于 ACR 暴露对健康危害的研究。然而，ACR 暴露是否以及如何增加心血管风险仍不清楚，我们试图在这项对 3024 名普通成年人进行的为期 3 年的前瞻性队列研究（随访时 871 人）中解决这些问题。个体尿 ACR 代谢物（N-乙酰-S-（2-氨甲酰基乙基）-L-半胱氨酸[AAMA]和 N-乙酰-S-（2-氨甲酰基-2-羟乙基）-L-半胱氨酸[GAMA]）作为 ACR 暴露的可靠生物标志物，用于评估它们与 10 年心血管疾病（CVD）风险的横断面和纵向关系，这是衡量整体心血管风险的一个很好的指标。此外，还测量了氧化应激（尿 8-羟基脱氧鸟苷[8-OHdG]和 8-异前列腺素 F2α[8-iso-PGF2α]）和炎症（循环平均血小板体积[MPV]和血浆 C 反应蛋白[CRP]）以及血浆转化生长因子-β1（TGF-β1）的生物标志物，以评估它们在 ACR 代谢物与 10 年 CVD 风险之间的关系中的中介/机制作用。我们发现 AAMA、GAMA 和 ΣUAAM（AAMA+GAMA）与增加的 10 年 CVD 风险呈横断面和纵向相关，比值比（95%置信区间[CI]）分别为 1.32（1.04，1.70）、1.81（1.36，2.40）和 1.40（1.07，1.82），风险比（95%CI）分别为 1.99（1.10，3.60）、2.48（1.27，4.86）和 2.13（1.15，3.94）。此外，发现 8-OHdG、8-iso-PGF2α、MPV、CRP 和 TGF-β1 显著介导了 ACR 代谢物相关的 10 年 CVD 风险增加的 8.06%-48.92%。总之，普通成年人的日常 ACR 暴露与心血管风险增加呈横断面和纵向相关，这部分是由氧化应激、炎症和 TGF-β1 介导的，这首次表明 ACR 暴露可能通过诱导氧化应激、炎症和 TGF-β1 的机制，在一定程度上增加普通成年人群的心血管风险。我们的研究结果具有重要的公共卫生意义，为 ACR 暴露导致心血管风险增加提供了有力的流行病学证据和重要的机制见解。
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