Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China.
Department of Local Diseases Control and Prevention, Fujian Provincial Center for Disease Control and Prevention, Fuzhou 350001, China.
Metabolism. 2022 Aug;133:155220. doi: 10.1016/j.metabol.2022.155220. Epub 2022 May 23.
Evidence suggests that nonalcoholic fatty liver disease (NAFLD) is associated with cardiovascular diseases (CVDs). However, the results are inconsistent, and the causality remains to be established.
We aimed to investigate the potential causal relationship between NAFLD and CVDs, including arterial stiffness, coronary artery disease, heart failure, stroke, ischemic stroke and its subtypes using two-sample Mendelian randomization (MR).
Genetic instruments were used as proxies for NAFLD. Publicly available summary-level data were obtained from the UK Biobank, the CARDIoGRAMplusC4D Consortium, the MEGASTROKE Consortium, and other consortia. Six complementary MR methods were performed, including inverse variance weighted method (IVW), MR-Egger, weighted median, weighted mode, MR-PRESSO, and MR-RAPS.
NAFLD was significantly associated with arterial stiffness (β = 0.04 [95%CI, 0.02-0.06], P = 5.53E-04). Moreover, the results remained consistent and robust in the sensitivity analysis. As for heart failure, the IVW method suggested that NAFLD was significantly associated with heart failure (OR = 1.08, 95%CI: 1.02-1.14, P = 0.005) in the absence of pleiotropy. However, there were no significant associations of NAFLD with coronary artery disease, stroke, ischemic stroke, or any ischemic stroke subtype.
The MR study supported the causal effect of NAFLD on arterial stiffness. However, the study did not provide enough evidence suggesting the causal associations of NAFLD with heart failure, coronary artery disease, and any stroke subtypes.
有证据表明，非酒精性脂肪性肝病（NAFLD）与心血管疾病（CVDs）有关。然而，结果并不一致，其因果关系仍有待确定。
我们旨在使用两样本 Mendelian 随机化（MR）研究非酒精性脂肪性肝病与 CVDs（包括动脉僵硬、冠心病、心力衰竭、中风、缺血性中风及其亚型）之间的潜在因果关系。
遗传工具被用作 NAFLD 的替代物。从英国生物银行（UK Biobank）、CARDIOGRAMplusC4D 联盟、MEGASTROKE 联盟和其他联盟获得了公开的汇总水平数据。进行了六种互补的 MR 方法，包括逆方差加权法（IVW）、MR-Egger、加权中位数、加权众数、MR-PRESSO 和 MR-RAPS。
NAFLD 与动脉僵硬显著相关（β=0.04[95%CI，0.02-0.06]，P=5.53E-04）。此外，敏感性分析结果也一致且稳健。至于心力衰竭，在不存在多效性的情况下，IVW 方法表明 NAFLD 与心力衰竭显著相关（OR=1.08，95%CI：1.02-1.14，P=0.005）。然而，NAFLD 与冠心病、中风、缺血性中风或任何缺血性中风亚型均无显著关联。
MR 研究支持 NAFLD 对动脉僵硬的因果作用。然而，该研究没有提供足够的证据表明 NAFLD 与心力衰竭、冠心病和任何中风亚型之间存在因果关系。
