MASLD and metALD: the number of cardiometabolic risk factors and the amount of liver fat in relation to the risk of type 2 diabetes and cardiovascular disease

Gabrielle Alblas#* , Jeroen H.P.M. van der Velde^, Maarten E. Tushuizen*, Wouter J.W. Jukema ~,

Hildo.J. Lamb^$, Frits R. Rosendaal^, Bart van Hoek*, Renée de Mutsert^, Minneke J. Coenraad*

^#Department of Internal Medicine, ^$Department of Radiology, ^Department of Epidemiology, *Department of Gastroenterology and Hepatology, ~Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands

Corresponding author:

Gabrielle Alblas

LUMC: Albinusdreef 2 postbox 2300RC Leiden, The Netherlands

Emailaddress: g.alblas@lumc.nl

Abstract

Background and aims: Metabolic dysfunction associated steatotic liver disease (MASLD) and metabolic alcohol-associated liver disease (MetALD), defined as the presence of liver fat in combination with at least one of five cardiometabolic risk factors and alcohol consumption (max 50 gram/day (women), 60 gram/day (men)), is associated with an increased risk of type 2 diabetes and cardiovascular diseases. It is unclear to what extent the number of cardiometabolic risk factors and increasing amounts of liver fat may result in further risk increases. We aimed to examine the associations between the number of cardiometabolic risk factors and increasing amounts of liver fat with the occurrence of cardiometabolic disease.

Materials and methods: In the Netherlands Epidemiology of Obesity study, a population-based prospective cohort study, liver fat content was assessed at baseline using proton magnetic resonance spectroscopy in middle-aged population with overweight. During up to 10 years follow-up, incident cardiometabolic disease (type 2 diabetes, myocardial infarction, stroke, TIA) were collected via medical records. Cox regression was used to examine associations, adjusted for age, sex, education, ethnicity, alcohol use, physical activity and total body fat.

Results: The overall population (50% women) had a mean age (95% CI) of 55 (55-56) years, BMI of 29.2 (29.0-29.4) kg/m², liver fat content of 8.1 (7.7-8.6)%. After exclusion of preexisting diabetes and cardiovascular disease, 139 new cases of cardiometabolic disease occurred, which resulted in an adjusted hazard ratio (HR, 95% CI) of 2.07 (1.5-3.3) for those with MASLD/metALD, compared with those without MASLD. Having MASLD/metALD with one cardiometabolic criterion resulted in an adjusted HR of 0.98 (0.42-2.24) for the occurrence of cardiometabolic disease, compared with those without MASLD. The adjusted HR with two criteria was 2.18 (1.32-3.58), three 2.58 (1.49-4.46) and four 2.98 (1.68-5.32). Participants with liver fat content between 2.5-5% had an adjusted HR 1.02 (0.54-1.93), between 5-10% 1.86 (1.04-3.31), for 10-15% 1.89 (0.96-3.72), for 15-20% 1.98 (0.96-4.05), for 20-25% 2.27 (1.04-4.98), for 25-30% 2.44 (0.93-6.44)), and for those with liver fat content of 30% or more it was 3.23 (1.57-6.63) for the occurrence of cardiometabolic disease, compared to those with a liver fat content between 0 and 2.5%.

Conclusions: Participants with MASLD/metALD have a 2-fold increased risk of cardiometabolic disease compared with participants without MASLD. Having four cardiometabolic criteria resulted in a 3 fold increased risk for the occurrence of cardiometabolic disease. Liver fat content above 5% resulted in an increased HR of the occurrence of cardiometabolic disease up to 3 fold for >30% liver fat. Showing that the number of cardiometabolic risk factors and the amount of liver fat matter, therefore a multidisciplinary approach to treat the CM risk factors is essential.