W.W. XU1, V.D. de Jong1,2, M. Alings2,3, J.C. Tardif4, A.M. Lincoff5, G.G. Schwartz6, D.E. Grobbee1,2, M. Castro Cabezas2,7,8
- Julius Center, University Medical Center Utrecht, Utrecht, The Netherlands
- Julius Clinical, Zeist, The Netherlands
- Amphia Hospital, Breda, The Netherlands
- Montreal Heart Institute Coordinating Center, Université de Montréal, Montreal, Canada
- Cleveland Clinic Coordinating Center for Clinical Research (C5Research), Cleveland, OH, United States of America
- Rocky Mountain Regional VA Medical Center and University of Colorado School of Medicine, Aurora, CO, United States of America
- Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
- Erasmus MC, Rotterdam, The Netherlands
Background
Metabolic dysfunction-Associated Steatosis Liver Disease (MASLD), is highly prevalent among T2DM patients. Non-invasive tests (NITs) predicting the risk of hepatic fibrosis, the advanced stage of MASLD, are not widely implemented as they have not invariably been linked to clinical outcomes in T2DM.
Previous registry reports suggest that some NITs may be associated with cardiovascular (CV) complications. We studied this association in the AleCardio trial.
Methods
AleCardio was a double-blind, placebo-controlled, randomized CV outcome trial, which was terminated early for lack of efficacy. 7226 T2DM patients were enrolled. We utilized 6 NITs for fibrosis (FIB-4, BARD, FNI, HFS, NFS, and SAFE) to dichotomously estimate the liver fibrosis status at baseline. Results are presented as relative risk (RR;95%CI).
Four out of the six NITs for fibrosis showed an association with both CV death and MACE (FIB-4, BARD, NFS, and SAFE). Compared to those without advanced fibrosis, the RR of CV death in patients with advanced fibrosis as indicated by FIB-4, BARD, NFS, and SAFE was 1.56 (95%CI: 1.17-2.09), 1.84 (1.68-2.91), 1.98 (1.43-2.74) and 1.73 (1.31-2.29), respectively (each p<0.05). Similarly, the relative risk of MACE in patients with advanced fibrosis as indicated by FIB-4, BARD, NFS, and SAFE was 1.20 (1.03-1.40), 1.35 (1.09-1.67), 1.66 (1.39-1.98) and 1.43 (1.23-1.66), respectively (each p<0.05). While the patients with advanced fibrosis were slightly older, the CV risk profile based on HbA1c and lipid levels in patients with advanced fibrosis was slightly better than in patients without advanced fibrosis, suggesting that advanced fibrosis may independently be related to higher CV risk.
NITs for hepatic fibrosis help to identify the subjects with T2DM at the highest CV risk. These data may help in the current discussion on defining targets for therapy in specific subgroups of patients in whom high-intensity CV risk management is necessary.