【作者】 杨帆；

【导师】 赵星；

【作者基本信息】 四川大学 ， 流行病与卫生统计学， 2021， 硕士

【摘要】 背景随着人口老龄化和城市化进程的加快,心脑血管疾病(Cardio-cerebrovascular Diseases,CVD)已成为中国成年人死亡的主要原因,2016年,中国40%以上的死亡由CVD导致,超过2亿人患有心脑血管疾病。膳食作为CVD可控主要危险因素之一,其与CVD之间的关联已经得到了广泛的研究,但是此关联机制尚不明确。代谢风险因素如高血脂、高血压、糖尿病、超重等被认为是其中重要的中间因素,膳食因素可通过升高血压、血脂等从而导致CVD,因此通过对代谢风险因素进行干预可以达到间接控制膳食危险效应的目的。但大多数研究仅研究单个代谢风险因素的中介效应。关于多个代谢风险因素的效应估计研究十分缺乏。方法研究对象来自西南区域自然人群队列(the China Multi-Ethnic Cohort Study,CMEC)。通过面对面问卷调查、体格检查和生化检测等方法于2018年5月至2019年9月间收集了99 556位调查对象的暴露及结局信息。在排除暴露或结局数据缺失及能量或BMI异常的人群后,本研究共纳入91452名30-79岁的四川、云南、西藏、重庆、贵州常住人群。暴露信息来自问卷调查中的食物频率表及饮酒、饮茶部分等,中介信息来自身体测量及血样检测数据,结局信息来自问卷调查中个人及家庭健康状况部分。为了对混杂进行筛选和控制,本研究对相关领域文献进行大量综述以建立暴露-中介-结局-混杂关系网络假设,并通过后门准则识别最小充分混杂控制集。使用因子分析主成分法提取膳食模式后,本研究通过二元多因素logistic回归探究膳食模式与CVD之间的关系。对发现有危险/保护作用的膳食模式,本研究使用基于回归的中介分析方法分别估计单个代谢风险因素在膳食模式与CVD之间的关联中起到的中介效应,随后本研究使用边际结构模型(marginal structural models)进一步估计多种代谢风险因素的中介效应。结果1.本研究共纳入91452位调查对象,女性55277人,占60.4%。女性参与人数略多于男性。调查对象平均年龄为51.7(标准差:11.5)岁。47922名调查对象为少数民族,占比为52.4%。共有2889名调查对象患有CVD,患病率为3.16%。四川盆地和青藏高原的CVD患病率均较高,分别为3.97%和3.74%,而云贵高原地区CVD患病率最低,为2.11%。2.本研究使用因子分析中的主成分法提取出了三种膳食模式,并根据其特征将其命名为四川盆地膳食模式(鱼/海鲜、家禽、蛋、乳制品、新鲜水果、新鲜蔬菜和植物油高摄入)、云贵高原膳食模式(动物油、大米、盐、腌菜、酒类和豆制品高摄入)和青藏高原膳食模式(粗粮、小麦、薯类和茶叶高摄入)。3.多因素logistic回归模型显示,四川盆地膳食模式对CVD患病具有保护作用(OR:0.76;95%CI:0.65,0.89),而青藏高原膳食模式增大了CVD的患病风险(OR:1.42;95%CI:1.22,1.65)。云贵高原膳食模式虽然也表示出了一定的保护作用,但结果无统计学意义(OR:0.87;95%CI:0.74,1.01)。4.本研究对高血压、高血脂、超重、高尿酸血症、糖尿病在四川盆地膳食模式与青藏高原膳食模式与CVD关联的中介效应进行探究。在考虑单个代谢风险因素时,本研究发现所有代谢风险因素在现代均衡模式中均体现出了较强的中介作用。超重、高尿酸血症、糖尿病、高血脂、高血压介导的效应分别为0.73(95%CI:0.72,0.74),0.76(95%CI:0.75,0.77),0.84(95%CI:0.84,0.85),0.78(95%CI:0.78,0.78),0.73(95%CI:0.72,0.74),占总效应的49.8%,41.8%,32.2%,39.4,46.6%。而在青藏高原膳食模式中,本研究发现代谢风险因素介导的中介效应与直接效应呈相反的关系。通过超重、高尿酸血症、糖尿病、高血脂、高血压的自然直接作用分别为0.73(95%CI:0.72,0.74)、0.76(95%CI:0.76,0.77)、0.86(95%CI:0.86,0.87)、0.76(95%CI:0.76,0.76)、0.76(95%CI:0.76,0.77)。从单中介分析中,本研究发现代谢风险因素均在现代均衡模式及青藏高原膳食模式中起到了中介作用。5.当综合考虑多个代谢风险因素及其相互关系时,本研究发现,将人群的体重控制在推荐水平将增大四川盆地膳食模式的保护效应(OR:0.65;95%CI:0.48,0.88)。而控制其他代谢风险因素如高尿酸血症、糖尿病、高血脂、高血压没有明显的效应。对于青藏高原膳食模式,控制血脂、血压、血尿酸均有利于减轻其有害效应,效应值分别为1.30(95%CI:1.08,1.57),1.36(95%CI:1.10,1.69),1.35(95%CI:1.13,1.61)。而控制糖尿病、超重对改善青藏高原膳食模式的危险性几乎无作用。结论在坚持不同膳食模式的人群之间,坚持四川盆地膳食模式的调查对象CVD患病风险更低,且在该人群中控制体重至合理水平能使其膳食模式的保护效应达到最大,而坚持青藏高原膳食模式的调查对象CVD患病风险更高,且在该人群中控制血脂、血压、血尿酸至合理水平能减轻其膳食模式的危险效应。更多还原

【Abstract】 BackgroundWith the aging of the population and the acceleration of urbanization,cardiocerebrovascular diseases(CVD)have become the leading cause of death in Chinese adults.In 2016,more than 40% of deaths were caused by CVD,and more than 200 million people suffered from CVD.As one of its main controllable risk factors,diet has been extensively studied for its association with CVD,but its association mechanism is still unclear.Metabolic risk factors such as hyperlipidemia,hypertension,diabetes,and overweight are considered as important intermediate factors.Dietary factors can cause CVD by raising blood pressure,blood lipids,etc.Metabolic risk factors can be intervened to control of dietary risk effects indirectly.However,most studies only study the mediating effects of a single metabolic risk factor.The research on the role of multiple metabolic risk factors in the association between dietary pattern and CVD is scanty.MethodThe research subjects came from the China Multi-Ethnic Cohort Study(CMEC).Through face-to-face questionnaire surveys,physical examinations and biochemical tests,99 556 survey subjects’ exposure and outcome information were collected during May 2018 to September 2019.After excluding people with missing exposure data,outcome data,and abnormal energy and BMI,this study included 91,452 permanent residents of Sichuan,Yunnan,Tibet,Chongqing,and Guizhou who were 30-79 years old.The exposure information came from the food frequency questionnaire and the drinking and tea part of the questionnaire,the mediator information came from the body measurement and blood sample test data,and the outcome information came from the personal and family health status part of the questionnaire.In order to screen and control confounding,we conducted a large number of literature reviews in related fields to establish the hypothesis of the exposure-mediation-outcome-confounding relationship network,and identified the minimum sufficient confounding control set through the backdoor criterion.After extracting dietary patterns using factor analysis,we explored the relationship between dietary patterns and CVD through binary multivariate logistic regression.For dietary patterns found to be dangerous/protective,we used regressionbased mediation analysis methods to estimate the mediating effects of individual metabolic risk factors in the association between dietary patterns and CVD,and then we used marginal structural models to further estimate the mediating effects of multiple metabolic risk factors.Result1.A total of 91452 subjects were included in this study,55,277 women,accounting for 60.4%.The number of women participating was slightly more than that of men.The average age of the survey subjects was 51.7(standard deviation: 11.5)years old.47,922 respondents were ethnic minorities,accounting for 52.4%.A total of 2889 survey subjects had CVD,with a prevalence rate of 3.16%.The prevalence of CVD in the Sichuan Basin and the Qinghai-Tibet Plateau were both high,at 3.97% and 3.74%,respectively,while the Yunnan-Guizhou Plateau had the lowest CVD prevalence at2.11%.2.We used factor analysis to extract three dietary patterns,and named them modern balanced dietary patterns based on their characteristics(high intake of fish/seafood,poultry,eggs,dairy products,fresh fruits,fresh vegetables,and vegetable oils),the traditional agricultural diet(high intake of animal oil,rice,salt,pickles,alcohol and soy products)and the Tibetan diet(high intake of coarse grains,wheat,potatoes and tea).3.The multivariate logistic regression model showed that the modern balanced diet pattern had a protective effect on CVD(OR: 0.76;95% CI: 0.65,0.89),while the Tibetan diet pattern increased the risk of CVD(OR: 1.42;95% CI: 1.22,1.65).Although traditional agricultural dietary pattern also showed a certain protective effect,the result was not statistically significant(OR: 0.87;95% CI: 0.74,1.01).4.We explored the mediating effects of hypertension,hyperlipidemia,overweight,hyperuricemia,and diabetes in the relationship between modern balanced diet pattern and Tibetan diet pattern and CVD.When considering individual metabolic risk factors alone,we found that all metabolic risk factors have a strong mediating effect in the modern balanced diet pattern.The effects mediated by overweight,hyperuricemia,diabetes,hyperlipidemia,and hypertension were 0.73(95% CI: 0.72,0.74),0.76(95%CI: 0.75,0.77),0.84(95% CI: 0.84,0.85),0.78(95% CI: 0.78,0.78),0.73(95% CI:0.72,0.74),accounting for 49.8%,41.8%,32.2%,39.4%,46.6% of the total effect.In the Tibetan diet,we found that the mediating effect mediated by mediating factors were opposite to the direct effect.The natural direct effects of overweight,hyperuricemia,diabetes,hyperlipidemia,and hypertension were 0.73(95% CI: 0.72,0.74),0.76(95%CI: 0.76,0.77),0.86(95% CI: 0.86,0.87),0.76(95% CI: 0.76,0.76),0.76(95% CI:0.76,0.77),respectively.From the analysis of single mediators,we found that metabolic risk factors all played a mediating role in modern balanced patterns and Tibetan dietary patterns.5.When considering multiple metabolic risk factors and their mediated effects,we found that controlling the population’s weight at the recommended level would increase the protective effect of the modern balanced diet pattern(OR: 0.65;95% CI: 0.48,0.88).However,controlling other metabolic risk factors such as hyperuricemia,diabetes,hyperlipidemia,and hypertension did not seem to have a significant effect.For the Tibetan dietary pattern,controlling blood lipids,blood pressure,and blood uric acid were all beneficial to alleviate its harmful effects.The effect values were 1.30(95% CI:1.08,1.57),1.36(95% CI: 1.10,1.69),and 1.35(95% CI: 1.13,1.61).However,controlling diabetes and overweight had little effect on reducing the risk of Tibetan dietary patterns.ConclusionAmong the people who adhered to different dietary patterns,the subjects who adhered to the modern balanced dietary pattern had a lower risk of CVD,and control of weight in this population to a reasonable level can maximize the protective effect of the dietary pattern.However,the subjects who adhered to the Tibetan dietary pattern were at higher risk of CVD,and controlling blood lipids,blood pressure,and blood uric acid to reasonable levels in this population can reduce the harmful effects of their dietary patterns.更多还原