Bhatt Nehal K, Agarwal Yashasvi, Neelakantan Ramaswamy Sanathanan, Bendagiri Matam Manvitha, Harikrishnan Samyuktha, Chand Shalvin, Bhatt Hetavi, Malasevskaia Iana
Internal Medicine, Pramukhswami Medical College, Karamsad, IND.
Internal Medicine, Sir H.N. Reliance Foundation Hospital and Research Centre, Mumbai, IND.
Cureus. 2025 Aug 4;17(8):e89355. doi: 10.7759/cureus.89355. eCollection 2025 Aug.
Non-alcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction-associated steatotic liver disease (MASLD), is increasingly implicated as a key risk factor for cardiovascular disease (CVD). However, its independent contribution remains debated due to confounding metabolic factors and methodological heterogeneity. This review aims to synthesize evidence on the association between NAFLD/MASLD and cardiovascular outcomes, focusing on the influence of liver fibrosis and metabolic dysfunction. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we searched PubMed/MEDLINE, ScienceDirect, Europe PMC, and Cochrane Library (through May 2025) for observational studies and trials assessing NAFLD/MASLD and CVD outcomes in adults. NAFLD required imaging/biopsy or validated scores (fatty liver index (FLI) ≥30, Fibrosis-4 Index (FIB-4)); comparators were non-NAFLD controls. Outcomes included myocardial infarction, stroke, CVD mortality, and atherosclerosis. Two reviewers independently screened records, extracted data, and assessed risk of bias (Newcastle-Ottawa Scale (NOS)/Cochrane RoB 2). The systematic search identified 21 eligible studies (18 cohort, two cross-sectional, and one RCT). Sample sizes ranged widely, from a few hundred in clinical cohorts to over 9.5 million in a national database study. Observational studies demonstrated good methodological quality (mean NOS score ≥7/9). NAFLD/MASLD showed a consistent dose-dependent association with cardiovascular risk, with effect sizes ranging from modest (adjusted HR=1.2) to substantial (HR=8.0). Risk stratification revealed (i) advanced fibrosis (FIB-4 >2.67) quadrupled CVD risk (HR >4.5) and (ii) metabolic burden significantly amplified outcomes (HR=8.04 for ≥4 risk factors). While the association remained significant in most studies, rigorous adjustment for metabolic covariates attenuated effects in some analyses, suggesting that MASLD represents both an independent pathogenic factor and a metabolic dysfunction marker. NAFLD/MASLD is a significant risk factor for adverse cardiovascular outcomes, with the degree of risk strongly graded by the severity of liver fibrosis and metabolic comorbidity. While evidence is predominantly observational, these findings support integrating non-invasive fibrosis assessment into CVD risk stratification. Future research requires randomized trial testing whether MASLD-targeted therapies can reduce cardiovascular events.
非酒精性脂肪性肝病（NAFLD），现称为代谢功能障碍相关脂肪性肝病（MASLD），越来越多地被认为是心血管疾病（CVD）的关键危险因素。然而，由于混杂的代谢因素和方法学的异质性，其独立作用仍存在争议。本综述旨在综合关于NAFLD/MASLD与心血管结局之间关联的证据，重点关注肝纤维化和代谢功能障碍的影响。按照系统评价和Meta分析的首选报告项目（PRISMA）2020指南，我们在PubMed/MEDLINE、ScienceDirect、欧洲生物医学中心和考克兰图书馆（截至2025年5月）中检索了评估成人NAFLD/MASLD和CVD结局的观察性研究和试验。NAFLD需要影像学检查/活检或经过验证的评分（脂肪肝指数（FLI）≥30，纤维化-4指数（FIB-4））；对照为非NAFLD对照组。结局包括心肌梗死、中风、CVD死亡率和动脉粥样硬化。两名评价员独立筛选记录、提取数据并评估偏倚风险（纽卡斯尔-渥太华量表（NOS）/考克兰偏倚风险评估工具2）。系统检索确定了21项符合条件的研究（18项队列研究、2项横断面研究和1项随机对照试验）。样本量差异很大，从临床队列中的几百例到国家数据库研究中的950多万例。观察性研究显示方法学质量良好（平均NOS评分≥7/9）。NAFLD/MASLD与心血管风险呈一致的剂量依赖性关联，效应大小从中等（调整后HR=1.2）到显著（HR=8.0）不等。风险分层显示：（i）严重纤维化（FIB-4>2.67）使CVD风险增加四倍（HR>4.5）；（ii）代谢负担显著增加结局风险（≥4个危险因素时HR=8.04）。虽然在大多数研究中这种关联仍然显著，但在一些分析中对代谢协变量进行严格调整后效应减弱，这表明MASLD既是一个独立的致病因素，也是一个代谢功能障碍标志物。NAFLD/MASLD是不良心血管结局的重要危险因素，风险程度由肝纤维化的严重程度和代谢合并症强烈分级。虽然证据主要是观察性的，但这些发现支持将非侵入性纤维化评估纳入CVD风险分层。未来的研究需要进行随机试验，以测试针对MASLD的治疗是否能减少心血管事件。
