ArticleCardiovascular diabetology2025
Proteomic signature of metabolic dysfunction-associated steatotic liver disease and risk of atherosclerotic cardiovascular disease.
Article in Cardiovascular diabetology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- The cholesterol, high-density lipoprotein, and glucose index and its derived indices predict cardiometabolic multimorbidity development and progression in metabolic dysfunction-associated steatotic liver disease individuals: a prospective cohort study.Cardiovascular diabetology · 2026Article
- MASLD and Cardiovascular Risk: Mechanisms and Implications for Clinical Practice.Current hypertension reports · 2026Review
- Joint association of Insulin resistance and frailty index with incident ASCVD and MACE in individuals with cardiovascular-kidney-metabolic syndrome stages 0-3: a multi-cohort study.Cardiovascular diabetology · 2026Observational
- Associations between the C-reactive protein-triglyceride-glucose index and its derived indices and the incidence and progression of cardiometabolic multimorbidity in participants with metabolic dysfunction-associated steatotic liver disease: a large-scale prospective cohort study.Cardiovascular diabetology · 2026Article
- Comment on "Glucagon like peptide-1 receptor agonist therapy and long-term renal outcomes after radical nephrectomy: a propensity-matched cohort analysis".International urology and nephrology · 2026Article
- The prognostic significance of cholesterol, high-density lipoprotein and glucose (CHG) index in evaluating all-cause mortality risk in metabolic dysfunction-associated steatotic liver disease (MASLD) individuals: evidence from two cohort studies.Cardiovascular diabetology · 2026Article
- Link between Metabolic Dysfunction-Associated Steatotic Liver Disease and Cardiovascular Diseases.Research (Washington, D.C.) · 2026Review
- Orosomucoid 2 (ORM2) in type 2 diabetes and coronary artery disease: a potential link between insulin resistance and vascular inflammation.Frontiers in cardiovascular medicine · 2026Review
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7 authors.
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Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. However, evidence on proteomic mechanisms linking MASLD to ASCVD is limited. This study aims to identify proteomic signatures of MASLD and ASCVD subtypes (ischemic heart disease [IHD], peripheral artery disease [PAD], and stroke), evaluate mediating effects of proteins, and develop a proteomic-based ASCVD risk prediction model in MASLD patients. Among 40,913 UK Biobank participants (median follow-up 13.42 years [interquartile range, 12.52-14.22]), 14,425 (35.26%) had MASLD at baseline, and 6,014 (14.70%) developed ASCVD during follow-up (4,420 IHD, 866 PAD, and 1,767 stroke events; subtypes not mutually exclusive). We constructed a binary variable representing proteomics-inferred MASLD (cProMASLD) from MASLD-associated proteins. Two-step Mendelian randomization was applied to assess the mediating effects of proteins associated with MASLD and ASCVD subtypes. Furthermore, we integrated the all shared proteins associated with both MASLD and ASCVD subtypes into the conventional SCORE2 model to develop a prediction model specifically for ASCVD subtypes in the MASLD population, named Pro-SCORE2. Both MASLD and cProMASLD were significantly associated with an increased risk of ASCVD subtypes, with stronger associations observed for cProMASLD (IHD: HR 1.50 [95% CI 1.41-1.60] vs. 1.58 [1.48-1.68]; PAD: 1.25 [1.09-1.44] vs. 1.43 [1.24-1.64]; stroke: 1.19 [1.08-1.31] vs. 1.21[1.10-1.34]). After adjusting for MASLD, cProMASLD remained positively associated with ASCVD risk. This suggests that cProMASLD may capture MASLD-related physiological heterogeneity beyond clinical MASLD classification. We found 15, 3, and 3 proteins mediating the associations of MASLD with IHD, PAD, and stroke, respectively, including FABP4 (MASLD-IHD, mediation proportion: 15.12%), IL7R (MASLD-PAD, 7.45%), and EDA2R (MASLD-stroke, 9.24%). The Pro-SCORE2 significantly improved ASCVD risk prediction in the MASLD population, with a c-index increase of 7.5-9.6% and a 10-year AUC increase of 5.8-9.2% compared to SCORE2. These findings may offer new insights for risk stratification and potential therapeutic targets for ASCVD in MASLD patients.
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