Inflammation in liver fibrosis and atrial fibrillation: a prospective population-based proteomic study
JHEP Reports, 2024
Boeckmans J., Michel M., Gieswinkel A., Tüscher O., Konstantinides S., König J., Münzel T., Lackner K., Kerahrodi J., Schuster A., Wild P., Galle P., Schattenberg J.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
CVD Hepatology | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
Background & Aims
Elevated liver stiffness relates to prevalent atrial fibrillation (AFib) in the general population. The mechanism underlying this association is unclear.
Methods
Participants were recruited from the general population and prospectively enrolled with follow-up for 5 years. The fibrosis-4 (FIB-4) index was used as a surrogate marker for liver fibrosis. Proteomics analysis using the 92-target Olink inflammation panel was employed. Validation was performed using the NAFLD fibrosis score (NFS), AST to platelet index (APRI), and repeated proteomics.
Results
A sample of 11,509 participants with a mean age of 54.0 +/- 11.1 years, 51.3% women, and a median FIB-4 index of 0.85 (0.65/1.12) was used. The FIB-4 index was predictive for prevalent (FIB-4 index adjusted odds ratio (aOR) per SD: 1.100 with 95% confidence interval (CI) [1.011; 1.196], p = 0.026), but not incident AFib (log(FIB-4 index) adjusted hazard ratio: 1.125 with 95% CI [0.943; 1.342], p = 0.19). Elastic net regularized regression identified CCL20, DNER, and CXCL10 for prevalent AFib, and AXIN1, CXCL10, and Flt3L for the log(FIB-4 index) (per SD) as most important in common regulated proteins. The relationship between the FIB-4 index, the identified proteins, and AFib was relevant and reproduced at 5 years follow-up for CXCL10 after adjusting for confounders (log(FIB-4 index) per SD – CXCL10 (per SD) adjusted β: 0.160 with 95% CI [0.127; 0.194], p < 0.0001; CXCL10 (per SD) - AFib aOR: 1.455 with 95% CI [1.217; 1.741], p < 0.0001), reproduced using the NFS and APRI, and corresponding to increased serum levels.ConclusionsCXCL10 connects liver fibrosis as determined by the FIB-4 index to prevalent AFib.