Research Square · Oct 22, 2026
Individual Cardiometabolic Risk Factors and Long-Term Cardiovascular Outcomes in Metabolic Dysfunction-Associated Steatotic Liver Disease
By Shibata N, Morita Y, Ito T et al.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined by hepatic steatosis and at least one of five cardiometabolic risk factors (CMRFs); however, whether individual CMRFs carry equivalent prognostic information for cardiovascular outcomes remains unclear. Methods: We retrospectively analyzed 2,962 patients with MASLD who underwent abdominal ultrasonography between 2006 and 2015. Patients were randomly assigned to derivation (n = 2,073) and validation (n = 889) cohorts. Associations of five MASLD-qualifying CMRFs with major adverse cardiac and cerebrovascular events (MACCE) were evaluated using multivariable Cox regression. Patients were subsequently classified according to CMRFs independently associated with MACCE. Results: During follow-up of up to 10 years, 183 MACCE occurred in the derivation cohort. After adjustment for age, sex, and all five CMRFs, diabetes mellitus (DM) (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.06–1.90) and low high-density lipoprotein cholesterol (HDL-C) (HR, 1.43; 95% CI, 1.05–1.95) were independently associated with MACCE, whereas body mass index ≥ 23 kg/m², hypertension, and hypertriglyceridemia were not. Patients were classified as having neither factor, DM alone, low HDL-C alone, or both factors. MACCE risk differed significantly among the four groups in both the derivation and validation cohorts (log-rank P < 0.001 and P = 0.019, respectively). In the validation cohort, the 5-year time-dependent area under the curve was 0.757 for age and sex, 0.763 after incorporating CMRF count, and 0.777 after incorporating the DM/low HDL-C classification. Conclusions: Among patients with MASLD, individual CMRFs were not equally associated with cardiovascular and cerebrovascular outcomes. The type and combination of CMRFs, particularly DM and low HDL-C, may provide useful prognostic information beyond CMRF count alone. Retrospectively registered: The study was approved by the ethics committee of Ogaki Municipal Hospital (approval number: 20230928-11).