impact of different cardiometabolic risk factors in MASLD: rethinking overweight/obesity criteria

Abstract Background/introduction Metabolic dysfunction-associated steatotic liver disease (MASLD) is a newly proposed nomenclature that requires any one of five cardiometabolic risk factors (CMRF) including hypertension, hyperglycemia, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C) and overweight/obesity as a prerequisite for diagnosis. However, the specific impact of these CMRFs on all-cause and cardiovascular mortality in the MASLD population is not well understood. Purpose To assess the prognostic impact of CMRFs in MASLD using data from the third National Health and Nutrition Examination Surveys 1988-1994 (NHANES □). Methods A total of 11,397 nonpregnant adults (20-74 years) with complete ultrasound measures, key covariates, data for MASLD definition and mortality status from NHANES □ were included in our analysis. The definition of MASLD and CMRFs definitions aligned with the Delphi consensus statement. The mortality status of the participants was obtained through the linkage to the National Death Index until December 31, 2019. Results Of 2,644 categorized MASLD participants, the prevalence of hypertension, hyperglycemia, hypertriglyceridemia and low HDL-C was similar (45.1%-57.4%), The prevalence of overweight/obesity was higher at 88.6%. During a median follow-up period of 26.1 years, hypertension, hyperglycemia and hypertriglyceridemia were all significantly associated with the increased risk of all-cause mortality and cardiovascular mortality after multivariable adjustment. Low HDL-C was significantly associated with risk of all-cause mortality and borderline significantly associated with risk of cardiovascular mortality. Conversely, overweight or obesity was not associated with mortality risk (all-cause HR: 1.01, 95%CI: 0.77-1.32; cardiovascular HR: 1.04, 95%CI: 0.63-1.72). When overweight/obesity was stratified into WC-based or BMI-based types, Neither WC-based nor BMI based overweight/obesity were associated with mortality risk. Compared to non-MASLD individuals without any CMRFs, MASLD patients with only overweight or obesity was not associated with mortality risk (all-cause HR: 0.84, 95%CI: 0.51-1.39; cardiovascular HR: 0.78, 95%CI: 0.28-2.18). However, patients with the other four components had higher mortality risk, regardless of obesity status. Conclusions hypertension, hyperglycemia, hypertriglyceridemia and low HDL-C are positively associated with higher mortality risk. The criteria for defining overweight and obese in MASLD should be reconsidered in the context of CMRFs. Figure 1