Why the study?
Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined by hepatic steatosis and at least one of five cardiometabolic risk factors (CMRFs), but whether individual CMRFs carry equivalent prognostic information for cardiovascular outcomes remained unclear.
Does the specific type and combination of cardiometabolic risk factors (specifically diabetes mellitus and low HDL-C) improve prediction of major adverse cardiac and cerebrovascular events compared to risk factor count alone in patients with MASLD?
Cohort (n=2,962)
No
Does the specific type and combination of cardiometabolic risk factors (specifically diabetes mellitus and low HDL-C) improve prediction of major adverse cardiac and cerebrovascular events compared to risk factor count alone in patients with MASLD?
In patients with MASLD, diabetes mellitus and low HDL-C are independently associated with long-term major adverse cardiac and cerebrovascular events, providing better prognostic risk stratification than a simple count of cardiometabolic risk factors.
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).
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Shibata et al. (2026) conducted a cohort in Metabolic dysfunction-associated steatotic liver disease (MASLD) (n=2,962). Coexisting diabetes mellitus and low HDL-C vs. Neither diabetes mellitus nor low HDL-C was evaluated on Major adverse cardiac and cerebrovascular events (MACCE), a composite of cardiac death, nonfatal myocardial infarction, coronary revascularization, neurological death, and stroke (HR 2.12, 95% CI 1.42-3.16, p=<0.001).
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