Differential Prevalence and Prognostic value of Metabolic Syndrome Components Among MASLD Patients

Highlights•Metabolic syndrome components impact survival and risk of fibrosis incrementally•Hypertension is associated with the highest risk of all-cause mortality•The associations between cardiometabolic disorders and mortality attenuate with increasing age•An increased waist circumference has the strongest association with fibrosisAbstractBackground and AimsMetabolic-dysfunction associated steatotic liver disease (MASLD) is becoming increasingly prevalent in the general population. This study aims to describe the cardiometabolic burden of the MASLD population and to identify those at the highest risk of all-cause mortality and liver fibrosis.MethodsWe analyzed individuals with MASLD enrolled in the National Health and Nutrition Survey (NHANES) III (N=3,628) and NHANES 2017-2020 (N=2,618). MASLD was defined as hepatic steatosis (by ultrasonography or controlled attenuation parameter), together with cardiometabolic dysfunction. Primary endpoints were all-cause mortality and liver fibrosis (liver stiffness measurement ≥8kPa). Regression models were adjusted for age, sex, race, marital status, education, and smoking, and results were stratified by age groups (20-40, 40-60, 60-80).ResultsAmong the total MASLD population (median age = 48 P25-P75: 36–62 years, 44.8% males), 65% had ≥3 cardiometabolic disorders. The most frequent were obesity (89.1%), (pre-)diabetes (66.6%), and low-HDL (54.7%). During a median follow-up of 22.3 P25-P75: 16.9 – 24.2 years, 1,405 deaths occurred. Hypertension (aHR 1.42, 95%CI 1.26-1.61), (pre-)diabetes (aHR 1.28, 95%CI 1.09-1.49), and hypertriglyceridemia (aHR 1.19, 95% CI 1.05-1.34) were the strongest predictors of all-cause mortality. Consistent results were obtained regarding the association between cardiometabolic disorders and fibrosis. Here, increased waist circumference (aOR 3.45, 95% CI 1.44-8.25), (pre-)diabetes (aOR 1.90, 95% CI 1.44-2.25), and hypertension (aHR 1.84, 95% CI 1.40-2.43) showed the strongest associations.ConclusionsMASLD patients vary greatly in their cardiometabolic burden and consequently, in their prognosis. Our results highlight MASLD as a disease spectrum rather than as a single disease entity, necessitating an individualized treatment approach.Graphical abstract