Liver fat content predicts cardiovascular events in 39,953 individuals without ASCVD

https://doi.org/10.1007/s00392-025-02625-4

Martin Reugels (Aachen)1, B. Kurt (Aachen)1, K. M. Schneider (Aachen)2, A. G. Antwerpen (Aachen)1, K. Rex (Aachen)1, K. L. Aygar (Aachen)1, J. Bornemann (Aachen)1, N. Ganesh (Aachen)1, A. Giacin (Aachen)1, K. Kneizeh (Aachen)1, S. Just (Aachen)1, A. Kapoor (Aachen)1, A. M. Mertens (Aachen)1, K. Müser (Aachen)1, M. Neuhaus (Aachen)1, L. B. Quintana Selek (Aachen)1, R. Salagundi (Aachen)1, M. Sausen (Aachen)1, N. Tabaza (Aachen)1, K. Just (Aachen)3, J. Stingl (Aachen)3, A. Gombert (Aachen)4, M. Lehrke (Traunstein)5, N. Marx (Aachen)1, C. V. Schneider (Aachen)2, F. Kahles (Aachen)1

1Uniklinik RWTH Aachen Med. Klinik I - Kardiologie, Angiologie und Internistische Intensivmedizin Aachen, Deutschland; 2Uniklinik RWTH Aachen Med. Klinik III - Gastroenterologie und Stoffwechselkrankheiten Aachen, Deutschland; 3Uniklinik RWTH Aachen Institut für Klinische Pharmakologie Aachen, Deutschland; 4Uniklinik RWTH Aachen Klinik für Gefäßchirurgie Aachen, Deutschland; 5Klinikum Traunstein Kardiologie Traunstein, Deutschland

 

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a major global health issue, with potential implications for cardiovascular risk. While traditional cardiovascular risk factors are well established, the role of liver fat content as an independent risk factor for cardiovascular events remains uncertain. Current evidence suggests a possible causal link between MASLD and cardiovascular disease (CVD). However, more research is needed to determine whether liver fat itself could serve as an independent and clinically useful biomarker for cardiovascular risk stratification. This study aims to investigate the prognostic value of liver fat content, measured as proton density fat fraction (PDFF) in predicting cardiovascular events among individuals without prior atherosclerotic cardiovascular disease (ASCVD).

 

Methods: PDFF as a marker of hepatic steatosis was available in a subset of 39,953 UK Biobank participants with no history of previous ASCVD. The UK Biobank is a population-based cohort study that was conducted in the UK from 2006 to 2010, which recruited 502,505 volunteers aged 37 - 73 years at baseline. The primary composite outcome of the study was the first occurrence of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke (3P-MACE).

 

Results: Mean age of the participants at baseline was 56.6 years and 46% were male, mean body-mass-index (BMI) was 27.4 kg/m2 and 2% had type 2 diabetes (T2D) at baseline. 1063 3P-MACE events occurred during the median follow-up period of 13.4 years. Kaplan-Meier plots showed that increasing baseline PDFF levels were associated with a higher rate of CV events. This association remained significant after multiple adjustment. The addition of PDFF on top of a multivariable model (age, sex, BMI, T2D, smoking status, total cholesterol, high-density lipoprotein cholesterol (HDL-C), systolic blood pressure and estimated glomerular filtratrion rate (eGFR)) or the SCORE2 significantly improved model performance in prediction of 3P-MACE (model without PDFF: Chi2: 576.82; model with PDFF: Chi2: 605.45; delta Chi2: 28.63; p<0.0001; Fraction of new information: 4.73%; SCORE2 without PDFF: Chi2: 349.01; SCORE2 with PDFF: Chi2: 371.29, delta Chi2: 22.28; p<0.0001; Fraction of new information: 6%)

 

Conclusion: Liver fat content (PDFF) is an independent and strong predictor of cardiovascular events in individuals without ASCVD adding incremental value on top of SCORE2. Measuring PDFF might serve as a novel biomarker to improve CV risk stratification in primary prevention.


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