biostudies-literaturePan LShanghai Municipal Science and Technology Major ProjectShanghai Municipal Natural Science Foundationthe Three-Year Public Health Action Plan of ShanghaiNational Natural Science Foundation of China20https://www.ebi.ac.uk/biostudies/studies/S-EPMC12822008biostudies-literatureUnknown25(1)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 variabCardiovascular diabetologyProteomic signature of metabolic dysfunction-associated steatotic liver disease and risk of atherosclerotic cardiovascular disease.PMC1282200822ZR1414900GWVI-11.2-XD1082473724ZD2021CY00182273730Shen MLiu YHuang CLin RQin GPan LYu YfalseProteomic signature of metabolic dysfunction-associated steatotic liver disease and risk of atherosclerotic cardiovascular disease.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 variab2025-01-01T00:00:00Z2025 Dec2026-06-06T18:09:19.784Z2026-06-04T03:10:46.326ZS-EPMC128220084139228010.1186/s12933-025-03034-7