Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Lancet Gastroenterol Hepatol. 2021 Nov;6(11):903-913. doi: 10.1016/S2468-1253(21)00308-3. Epub 2021 Sep 21.
Studies have reported a significant association between non-alcoholic fatty liver disease (NAFLD) and increased incidence of cardiovascular disease (CVD). However, the magnitude of the risk and whether this risk changes with the severity of NAFLD remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between NAFLD and risk of incident CVD events.
We systematically searched PubMed, Scopus, and Web of Science from database inception to July 1, 2021, to identify eligible observational studies examining the risk of incident CVD events amongst adult (age ≥18 years) individuals with and without NAFLD and in which NAFLD was diagnosed by imaging, International Classification of Diseases codes, or liver biopsy. The primary outcomes were CVD death, non-fatal CVD events, or both. Data from selected studies were extracted, and meta-analysis was performed using random-effects models to obtain summary hazard ratios (HRs) with 95% CIs. The quality of the evidence was assessed with the Cochrane risk of bias tool. This study is registered on Open Science Framework, number osf.io/5z7gf.
We identified 36 longitudinal studies with aggregate data on 5 802 226 middle-aged individuals (mean age 53 years [SD 7]) and 99 668 incident cases of fatal and non-fatal CVD events over a median follow-up of 6·5 years (IQR 5·0-10·2). NAFLD was associated with a moderately increased risk of fatal or non-fatal CVD events (pooled random-effects HR 1·45, 95% CI 1·31-1·61; I=86·18%). This risk markedly increased across the severity of NAFLD, especially the stage of fibrosis (pooled random-effects HR 2·50, 95% CI 1·68-3·72; I=73·84%). All risks were independent of age, sex, adiposity measures, diabetes, and other common cardiometabolic risk factors. Sensitivity analyses did not modify these results.
NAFLD is associated with an increased long-term risk of fatal or non-fatal CVD events. CVD risk is further increased with more advanced liver disease, especially with higher fibrosis stage. These results provide evidence that NAFLD might be an independent risk factor for CVD morbidity and mortality.
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研究报告称，非酒精性脂肪性肝病（NAFLD）与心血管疾病（CVD）发病率的增加有显著关联。然而，风险的程度以及这种风险是否会随着 NAFLD 的严重程度而变化仍不确定。我们对观察性研究进行了荟萃分析，以量化 NAFLD 与新发 CVD 事件风险之间的关联程度。
我们系统地检索了 PubMed、Scopus 和 Web of Science 数据库，检索时间从数据库建立到 2021 年 7 月 1 日，以确定符合条件的观察性研究，这些研究检查了成年（年龄≥18 岁）个体中有无 NAFLD 以及通过影像学、国际疾病分类代码或肝活检诊断为 NAFLD 时新发 CVD 事件的风险。主要结局为 CVD 死亡、非致命性 CVD 事件或两者兼有。从选定的研究中提取数据，并使用随机效应模型进行荟萃分析，以获得具有 95%置信区间的汇总风险比（HR）。使用 Cochrane 偏倚风险工具评估证据质量。本研究在 Open Science Framework 上注册，注册号为 osf.io/5z7gf。
我们确定了 36 项具有汇总数据的纵向研究，这些数据涉及 580226 名中年个体（平均年龄 53 岁[标准差 7]）和 99668 例致命和非致命 CVD 事件的发生率，中位随访时间为 6.5 年（IQR 5.0-10.2）。NAFLD 与致命或非致命 CVD 事件的风险中度增加相关（汇总随机效应 HR 1.45，95%CI 1.31-1.61；I=86.18%）。这种风险随着 NAFLD 的严重程度显著增加，尤其是纤维化阶段（汇总随机效应 HR 2.50，95%CI 1.68-3.72；I=73.84%）。所有风险均独立于年龄、性别、肥胖指标、糖尿病和其他常见的心血管代谢危险因素。敏感性分析并未改变这些结果。
NAFLD 与致命或非致命 CVD 事件的长期风险增加有关。随着肝病的进一步发展，尤其是纤维化程度的增加，CVD 风险会进一步增加。这些结果提供了证据表明，NAFLD 可能是 CVD 发病率和死亡率的一个独立危险因素。
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