Inflammatory and metabolic markers mediate the association of hepatic steatosis and fibrosis with 10-year ASCVD risk
Zihao Gui, Xingying Chen, Dongmei Wang, Zhi Chen, Si‐Yang Maggie Liu, Genfeng Yu, Yuqi Jiang, Hualin Duan, Dao-Yan Pan, Xü Lin, Lan Liu, Heng Wan, Jie Shen
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.