膳食、血浆及红细胞脂肪酸与中老年人动脉粥样硬化关系的6年前瞻性研究

Total fat intake and different types of fatty acids (FAs) have been proposed to play an important role in the development and progress of atherosclerosis (AS). Many large-scale studies have evaluated the effects of traditional saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), n-3 or n-6 polyunsaturated fatty acid (PUFA), and their ratios (i.e., SFA:MUFA:PUFA) on progression of AS in European countries, however, scare studies were conducted in Chinese. In addition, few studies have focused on FA patterns and FAs in de novo lipogenesis pathway. Up to date, the dietary recommandance intakes (DRIs) of fat and fatty acids for Chinese residents were made mainly based on data from foreign countries which have different diet habits, and no large prospective studies have assessed the effects of different (or types or subtypes of) FAs, or FA patterns on the risk of AS in Chinese. To address these issues, we proposed this study based on a community-based cohort of 3216 Guangzhou residents (40-75y) established during 2008-2010, subjects completed baseline survey and first follow-up during 2011-2013 (2564 subjects) and will complete the second follow-up during 2014-2016 (~2100 subjects). Nutritional and dietary factors would and will be collected using food frequency questionnaire and blood or 24-h urinary analyses. Dietary consumption and blood (plasma and erythrocytes) composition of 27 types of FAs were/will be assessed at baseline and the followups. Inflammatory cytokines, oxidative/anti-oxidative factors, blood lipids and body fat composition at each visit will be determined. The intima-media thicknesses (IMTs) of common carotid artery (CCA) and bifurcation (BIF) and endothelial function (FMD) were determined via B-mode ultrasound with a high-resolution, 7.0-12.0 MHz linear-array transducer system (Aplio TOSHIBA, Japan). Univariate and multivariate analyses were used to determine the associations of various FAs, FA patterns, blood inflammatory cytokines and oxidative/anti-oxidative factors with the IMT changes in 6-y and risk of AS , and these results will provide the scientific evidence for making the reasonable DRIs of different types of FAs for the AS prevention in Chinese. To address the potential mechanism of AS, path analysis will be used to determine the role of endothelial function, inflammatory cytokines, oxidative stress, blood lipids and body fat composition in the causal chain between FAs and IMT changes or risk of AS.

脂肪摄入总量及脂肪酸（FA）类型是影响动脉粥样硬化（AS）性心脑血管病（CVD）的重要因素。国外对传统的饱和、单不饱和及多不饱和FA(尤其是n3系列）及其比例对AS或CVD的影响研究较多，但对FA适宜比例或模式及内生FA的研究较少。迄今，修订我国居民脂肪DRI主要依据国外资料，国内尚无大型前瞻性研究来验证不同FA对AS的作用，也未能确立不同FA的适宜比或总体模式。为此，本研究拟利用2008-10年建立的3千余名40-75岁广州社区居民队列，于第0、3和6年三次调查，通过6年的前瞻性研究，验证及比较膳食、血浆和红细胞膜不同种类、比例及模式的FA对颈动脉内中膜厚度6年变化及AS发生风险的作用，确立该人群FA各大类及亚型的适宜摄入量和适宜比例及总体模式，为修订我国居民DRIs提供科学依据；通过路径分析，检验血管内皮功能、炎性反应、氧化应激、血脂和体脂在FA影响AS途径中的作用以阐明其作用机制。

背景：脂肪摄入总量及脂肪酸（FA）类型是影响动脉粥样硬化（AS）性心脑血管病（CVD）的重要因素。国外对传统的饱和、单不饱和及多不饱和FA(尤其是n3系列）及其比例对AS或CVD的影响研究较多，但国内尚无大型前瞻性研究来验证不同FA对AS的作用。..目的：（1）检验血液不同类别脂肪酸及部分其他营养因素对颈动脉AS及其相关的CVD危险因素（糖尿病、代谢综合征、肥胖、脂肪肝）的影响。..研究内容：本项目基于前期建立的约4048人40-80岁的社区居民队列平台进行研究。该队列于基线（2008-2010年）招募和访问了3216人，第2次（2010-2013年）访问随访了2580人和新招募了870人，第3次（2014-2017年）访问随访了2892人。每次访问调查了研究的一般情况、详细的膳食资料、运动情况和健康相关行为及体格指标等因素。于第1次、第2次和第3次分别采用超声仪检测了双侧颈总和分叉处颈动脉内中膜厚度（IMT）、有无增厚及斑块；检测了3500人的血液21种脂肪酸、炎性因子[超敏C反应蛋白（hsCRP）和视黄醇结合蛋白4(RBP4)]，采用DXA检测了全身和各部位脂肪含量，亦利用既往检测的类胡萝卜素。..结果：（1）单不饱和脂肪酸越高，IMT增加值越少；（2）长链饱和脂肪酸越高、多不饱和脂肪酸越低发生颈动脉斑块的风险越高；（3）在女性中SFA/PUFA模式越高，LCUFA模式越低，低VLCSFA模式越高，颈动脉新发斑块风险越高；（4）红细胞膜C18:0和C20:0含量越高，2型糖尿病发病风险越高，而红细胞膜EPA和DPA含量越高，2型糖尿病发病风险越低，高多不饱和脂肪酸和低饱和脂肪酸模式有助于降低2型糖尿病发病风险；（5）总n-3脂肪酸、EPA、DPA和DHA含量越高，代谢综合征（MS）患病风险越低；n-3 PUFAs 和n-6 PUFAs较高，MS发生风险越低；（6）从头合成脂肪酸越高，n-3脂肪酸越低，机体体脂肪含量越高；（7）n-3脂肪酸也是非酒精性脂肪肝患病和进展存在保护性关联。..意义：结果提示增加血液中多不饱和脂肪酸，尤其是n-3PUFA的含量，提高MUFA，降低长链饱和脂肪酸的含量，有助于降低颈动脉粥样硬化的风险，以及其他代谢性疾病（如2型糖尿病、代谢综合和脂肪肝）的风险。研究结果为制导我国人群脂肪摄入提供了科学依据。