炎症和代谢标志物介导肝脂肪变性和肝纤维化与10年动脉粥样硬化性心血管疾病（ASCVD）风险之间的关联。

Inflammatory and metabolic markers mediate the association of hepatic steatosis and fibrosis with 10-year ASCVD risk.

作者信息

Gui Zihao, Chen Xingying, Wang Dongmei, Chen Zhi, Liu Siyang, Yu Genfeng, Jiang Yuqi, Duan Hualin, Pan Daoyan, Lin Xu, Liu Lan, Wan Heng, Shen Jie

机构信息

Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan, Guangdong, China.

Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People's Republic of China.

出版信息

Ann Med. 2025 Dec;57(1):2486594. doi: 10.1080/07853890.2025.2486594. Epub 2025 Apr 6.

DOI:10.1080/07853890.2025.2486594

PMID:40189927

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11980196/

Abstract

BACKGROUND AND AIMS

Liver steatosis and fibrosis increase the predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risk, though the roles of chronic inflammation and metabolic dysregulation remain unclear. This cross-sectional study quantitatively assesses this association and evaluates the mediating effects of metabolic dysregulation and chronic inflammation.

METHODS

In this study, we enrolled 6110 adults from ten communities in Canton, China. Hepatic steatosis and fibrosis were assessed using vibration-controlled transient elastography (VCTE) through controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), while predicted 10-year ASCVD risk was calculated using the China-PAR project model. Associations between CAP/LSM values and predicted 10-year ASCVD risk were analyzed. Mediation analysis quantified the effects of high-sensitivity C-reactive protein (hs-CRP), homeostasis model assessment of insulin resistance (HOMA-IR), remnant cholesterol (RC), and non-high-density lipoprotein cholesterol (non-HDL-C). The main statistical methods used included logistic regression, restricted cubic splines (RCS) analysis, interaction calculations, and mediation analysis to examine the relationships and mediators.

RESULTS

The study population had a mean age of 50.1 years (SD = 9.7), with 3927 females (64.3%) and 2183 males (35.7%). Additionally, 808 participants (13.2%) had type 2 diabetes, and 1911 participants (31.3%) had hypertension. Compared to the first CAP quartile (Q1), higher CAP quartiles showed increased odds ratios (OR) for predicted moderate to high 10-year ASCVD risk: 1.14 (0.89, 1.45), 1.37 (1.08, 1.73), and 2.44 (1.93, 3.10). Mediation analysis showed hs-CRP and HOMA-IR mediated CAP's link to ASCVD risk, with mediation proportions of 15.40% and 27.37%. RC and non-HDL-C mediated this association at 7.12% and 6.26%. Among patients with hepatic steatosis (CAP ≥ 248 dB/m), LSM Q4 participants had a significantly higher predicted 10-year ASCVD risk than those in LSM Q1 (OR 2.22, [1.52, 3.25]), with hs-CRP and HOMA-IR mediating 2.62% and 13.75%, respectively.

CONCLUSION

Liver steatosis and fibrosis were associated with the increased predicted ASCVD risk, with mediation effects from hs-CRP, HOMA-IR, RC, and non-HDL-C.

摘要

背景与目的

肝脂肪变性和肝纤维化会增加预测的10年动脉粥样硬化性心血管疾病（ASCVD）风险，不过慢性炎症和代谢失调的作用仍不明确。这项横断面研究定量评估了这种关联，并评估了代谢失调和慢性炎症的中介作用。

方法

在本研究中，我们纳入了来自中国广州十个社区的6110名成年人。使用振动控制瞬时弹性成像（VCTE）通过受控衰减参数（CAP）和肝脏硬度测量（LSM）评估肝脂肪变性和肝纤维化，同时使用中国-PAR项目模型计算预测的10年ASCVD风险。分析CAP/LSM值与预测的10年ASCVD风险之间的关联。中介分析量化了高敏C反应蛋白（hs-CRP）、胰岛素抵抗稳态模型评估（HOMA-IR）、残余胆固醇（RC）和非高密度脂蛋白胆固醇（非HDL-C）的作用。主要使用的统计方法包括逻辑回归、受限立方样条（RCS）分析、交互计算和中介分析，以检验关系和中介因素。

结果

研究人群的平均年龄为50.1岁（标准差 = 9.7），其中女性3927名（64.3%），男性2183名（35.7%）。此外，808名参与者（13.2%）患有2型糖尿病，1911名参与者（31.3%）患有高血压。与第一个CAP四分位数（Q1）相比，较高的CAP四分位数显示预测的10年中度至高度ASCVD风险的优势比（OR）增加：1.14（0.89，1.45）、1.37（1.08，1.73）和2.44（1.93，3.10）。中介分析显示hs-CRP和HOMA-IR介导了CAP与ASCVD风险的联系，中介比例分别为15.40%和27.37%。RC和非HDL-C介导这种关联的比例分别为7.12%和6.26%。在肝脂肪变性（CAP≥248 dB/m）患者中，LSM Q4参与者预测的10年ASCVD风险显著高于LSM Q1参与者（OR 2.22，[1.52，3.25]），hs-CRP和HOMA-IR的中介作用分别为2.62%和13.75%。