ZJU指数在NAFLD与ASCVD关联中的统计学中介作用——基于NHANES数据的横断面研究

Statistical Mediating Effect of the ZJU Index on the Association between NAFLD and ASCVD—A Cross-Sectional Study Based on NHANES Data

摘要: 背景：非酒精性脂肪性肝病(Non-Alcoholic Fatty Liver Disease, NAFLD)是一种与代谢综合征密切相关的疾病，其全球患病率超过25%，而在我国，这一比例更是高达29.2%，成为目前西方国家和我国肝脏疾病的最主要类型。NAFLD的危害不仅仅局限于肝脏本身，它与代谢性疾病如肥胖、2型糖尿病和心血管疾病等有着复杂的关联。流行病学证据表明，NAFLD患者心血管疾病(Cardiovascular Disease, CVD)风险显著升高，其中动脉粥样硬化性心血管疾病(Atherosclerotic Cardiovascular Disease, ASCVD)作为CVD的主要临床表型，构成全球CVD相关死亡与致残的核心负担，并已成为NAFLD患者的首要死因之一。有鉴于此，特别需要对NAFLD患者进行早期心血管风险评估，制定优化的管理策略。ZJU指数由浙江大学Wang等提出，该指数整合了体重指数(Body Mass Index, BMI)、空腹血糖(Fasting Blood Glucose, FPG)、甘油三酯(Triglyceride, TG)及丙氨酸转氨酶(Alanine Aminotransferase, ALT)与天门冬氨酸转氨酶比值(Aspartate Aminotransferase, AST)，为评估个体代谢健康状况提供了一个综合性的量化工具。现有研究表明，ZJU指数在NAFLD的诊断和风险评估中显示出了较高的预测效能，并被广泛运用于相关的研究领域。本研究旨在基于大样本人群数据，明确NAFLD与ASCVD之间的独立关联，评估ZJU指数在这一关联中的解释路径，为NAFLD患者心血管风险分层及临床管理提供实证依据。方法：本研究基于美国国家健康与营养调查(National Health And Nutrition Examination Survey, NHANES)数据库从1999到2020年间的数据，总共纳入21,463名研究对象。采用逻辑回归与线性回归模型分析NAFLD与ASCVD及ZJU指数的关联，并分析探讨代谢异常在NAFLD-ASCVD关联中的潜在统计学中介作用。结果：研究结果显示，NAFLD与ASCVD风险存在显著关联，在充分校正混杂因素后，NAFLD仍是ASCVD的独立危险因素(OR = 1.39, 95% CI: 1.16~1.67, P < 0.001)。同时，ZJU指数与NAFLD呈显著正相关(校正后β = 1.32，95% CI：1.16~1.48)。统计学中介作用分析表明，ZJU指数可解释NAFLD-ASCVD关联中15.28%的效应量。结论：基于NHANES数据库的分析结果显示，ZJU指数在一定程度上介导了NAFLD与ASCVD的关联，提示其有望成为NAFLD相关心血管风险评估的辅助工具，在临床心血管风险筛查中具有潜在应用价值。

Abstract: Background: Non-alcoholic fatty liver disease (NAFLD) is a disease closely related to metabolic syndrome, with a global prevalence of more than 25%. In China, the proportion is as high as 29.2%, which has become the most important type of liver disease in Western countries and China. The harm of NAFLD is not limited to the liver itself. It has a complex association with metabolic diseases such as obesity, type 2 diabetes and cardiovascular diseases. Epidemiological evidence shows that the risk of cardiovascular disease (CVD) in patients with NAFLD is significantly increased. Atherosclerotic cardiovascular disease (ASCVD), as the main clinical phenotype of CVD, constitutes the core burden of global CVD-related death and disability, and has become one of the leading causes of death in patients with NAFLD. In view of this, it is particularly necessary to carry out early cardiovascular risk assessment for NAFLD patients and formulate optimized management strategies. ZJU index was proposed by Wang et al. from Zhejiang University. This index integrates body mass index (BMI), fasting blood glucose (FPG), triglyceride (TG) and the ratio of alanine aminotransferase (ALT) to aspartate aminotransferase (AST), which provides a comprehensive quantitative tool for assessing individual metabolic health status. Existing studies have shown that the ZJU index shows high predictive efficacy in the diagnosis and risk assessment of NAFLD and is widely used in related research fields. The purpose of this study is to clarify the independent association between NAFLD and ASCVD based on large sample population data, and to evaluate the interpretation path of ZJU index in this association, so as to provide empirical evidence for cardiovascular risk stratification and clinical management of NAFLD patients. Methods: This study was based on data from the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2020, and a total of 21,463 subjects were included. Logistic regression and linear regression models were used to analyze the association between NAFLD and ASCVD and ZJU index, and to explore the potential statistical mediating role of metabolic abnormalities in the association between NAFLD and ASCVD. Results: The results showed that NAFLD was significantly associated with the risk of ASCVD. After fully adjusting for confounding factors, NAFLD was still an independent risk factor for ASCVD (OR = 1.39, 95% CI: 1.16~1.67, P < 0.001). At the same time, ZJU index was significantly positively correlated with NAFLD (corrected β = 1.32, 95% CI: 1.16~1.48). Mediation analysis showed that ZJU index could explain 15.28% of the effect size in NAFLD-ASCVD association. Conclusions: The ZJU index mediates the association between NAFLD and ASCVD to a certain extent, suggesting that it is expected to become an auxiliary tool for NAFLD-related cardiovascular risk assessment and has potential application value in clinical cardiovascular risk screening.