Background

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.

Methods

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.

Findings

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; I²=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; I²=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.

Interpretation

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.

Funding

None.

中文翻译：

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非酒精性脂肪肝和致命和非致命心血管事件的风险：更新的系统评价和荟萃分析

背景

研究报告了非酒精性脂肪肝 (NAFLD) 与心血管疾病 (CVD) 发病率增加之间的显着关联。然而，风险的大小以及这种风险是否随着 NAFLD 的严重程度而变化仍然不确定。我们对观察性研究进行了荟萃分析，以量化 NAFLD 与 CVD 事件风险之间的关联程度。

方法

我们系统地检索了从数据库创建到 2021 年 7 月 1 日的 PubMed、Scopus 和 Web of Science，以确定符合条件的观察性研究，这些研究检查了患有和不患有 NAFLD 的成年（≥18 岁）个体发生 CVD 事件的风险，其中 NAFLD 是通过影像学、国际疾病分类代码或肝活检诊断。主要结局是 CVD 死亡、非致命性 CVD 事件，或两者兼而有之。提取选定研究的数据，并使用随机效应模型进行荟萃分析，以获得具有 95% CI 的汇总风险比 (HR)。证据质量使用 Cochrane 偏倚风险工具进行评估。这项研究在开放科学框架上注册，编号为 osf.io/5z7gf。

发现

我们确定了 36 项纵向研究，其汇总数据涉及 5 802 226 名中年人（平均年龄 53 岁 [SD 7]）和 99 668 例致命和非致命 CVD 事件，中位随访时间为 6·5 年（IQR 5·0–10·2）。NAFLD 与致命或非致命 CVD 事件风险中度增加相关（合并随机效应 HR 1·45，95% CI 1·31–1·61；I ² =86·18%）。这种风险在 NAFLD 的严重程度期间显着增加，尤其是纤维化阶段（合并随机效应 HR 2·50，95% CI 1·68–3·72；I ² =73·84%）。所有风险均与年龄、性别、肥胖指标、糖尿病和其他常见的心脏代谢风险因素无关。敏感性分析没有修改这些结果。

解释

NAFLD 与致命或非致命 CVD 事件的长期风险增加有关。随着肝脏疾病的进展，尤其是纤维化阶段较高，CVD 风险会进一步增加。这些结果提供证据表明 NAFLD 可能是 CVD 发病率和死亡率的独立危险因素。

资金

没有任何。