背景:人造甜味剂作为糖或高热量甜味剂的替代品在世界范围内广泛流行,但关于它们与心血管疾病(CVD)的关联,仍有一些重要的未知和争议.我们旨在广泛评估英国生物库队列中人造甜味剂与CVD和CVD死亡率之间的关联和亚组差异。并进一步探讨2型糖尿病(T2DM)遗传易感性的改变效应和中介作用。
方法:这项研究包括了英国生物银行的133,285名参与者,他们在招募时没有心血管疾病和糖尿病。从重复的24小时饮食回忆中获得人工甜味剂的摄入量。Cox比例风险模型用于估计HR。使用多基因风险评分(PRS)估计遗传易感性。此外,进行了时间依赖性调解。
结果:在我们的研究中,人工甜味剂的摄入量(每增加一茶匙)与整体心血管事件的风险增加显着相关(HR1.012,95CI:1.008,1.017),冠状动脉疾病(CAD)(HR:1.018,95CI:1.001,1.035),外周动脉疾病(PAD)(HR:1.035,95CI:1.010,1.061),与心力衰竭(HF)风险略有显著相关(HR:1.018,95CI:0.999,1.038)。在分层分析中,非白人患者发生人工甜味剂引起的整体CVD的风险更大.没有肥胖的人(BMI<30kg/m2)也倾向于更容易发生人造甜味剂引起的CVD。虽然肥胖的相互作用并不显著。同时,与人造甜味剂相关的CVD风险与遗传易感性无关,遗传易感性和人工甜味剂之间在累加或倍增效应方面没有显著的相互作用。此外,我们的研究表明,人工甜味剂摄入量与总体CVD之间的关系是显着介导的,在很大程度上,既往T2DM(间接效应比例:70.0%)。在特定的CVD亚型(CAD,PAD,和HF),间接效应的比例为68.2%至79.9%。
结论:我们的研究结果表明,人造甜味剂与CVD及其亚型之间存在显着或微不足道的关联(CAD,PAD,和HF)。这种关联与遗传易感性无关,主要由T2DM介导。因此,人工甜味剂的大规模应用应谨慎,应更好地表征具有不同特征的个体对人造甜味剂的反应,以指导消费者的人造甜味剂消费行为。
BACKGROUND: Artificial sweeteners are widely popular worldwide as substitutes for sugar or caloric sweeteners, but there are still several important unknowns and controversies regarding their associations with cardiovascular disease (CVD). We aimed to extensively assess the association and subgroup variability between artificial sweeteners and CVD and CVD mortality in the UK Biobank cohort, and further investigate the modification effects of genetic susceptibility and the mediation role of type 2 diabetes mellitus (T2DM).
METHODS: This study included 133,285 participants in the UK Biobank who were free of CVD and diabetes at recruitment. Artificial sweetener intake was obtained from repeated 24-hour diet recalls. Cox proportional hazard models were used to estimate HRs. Genetic predisposition was estimated using the polygenic risk score (PRS). Furthermore, time-dependent mediation was performed.
RESULTS: In our study, artificial sweetener intake (each teaspoon increase) was significantly associated with an increased risk of incident overall CVD (HR1.012, 95%CI: 1.008,1.017), coronary artery disease (CAD) (HR: 1.018, 95%CI: 1.001,1.035), peripheral arterial disease (PAD) (HR: 1.035, 95%CI: 1.010,1.061), and marginally significantly associated with heart failure (HF) risk (HR: 1.018, 95%CI: 0.999,1.038). In stratified analyses, non-whites were at greater risk of incident overall CVD from artificial sweetener. People with no obesity (BMI < 30 kg/m2) also tended to be at greater risk of incident CVD from artificial sweetener, although the obesity interaction is not significant. Meanwhile, the CVD risk associated with artificial sweeteners is independent of genetic susceptibility, and no significant interaction exists between genetic susceptibility and artificial sweeteners in terms of either additive or multiplicative effects. Furthermore, our study revealed that the relationship between artificial sweetener intake and overall CVD is significantly mediated, in large part, by prior T2DM (proportion of indirect effect: 70.0%). In specific CVD subtypes (CAD, PAD, and HF), the proportion of indirect effects ranges from 68.2 to 79.9%.
CONCLUSIONS: Our findings suggest significant or marginally significant associations between artificial sweeteners and CVD and its subtypes (CAD, PAD, and HF). The associations are independent of genetic predisposition and are mediated primarily by T2DM. Therefore, the large-scale application of artificial sweeteners should be prudent, and the responses of individuals with different characteristics to artificial sweeteners should be better characterized to guide consumers\' artificial sweeteners consumption behavior.