Sex and Age Differences in the Association Between Metabolic Dysfunction-Associated Fatty Liver Disease and Heart Failure: A Prospective Cohort Study

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a risk factor for heart failure (HF) occurrence, but it remains unclear whether the association between MAFLD and HF differs in different sexes and ages. METHODS: A total of 96 576 participants of Kailuan Study were included. MAFLD was defined as presence of hepatic steatosis and metabolic dysfunction and classified as mild and significant by ultrasound. Hazard ratios (HRs) were calculated by Cox regression models. RESULTS: After a median follow-up of 14.0 years, 2939 participants developed HF. Adjusting for confounding factors, mild-MAFLD (HR, 1.27 [95% CI, 1.16–1.39]) and significant-MAFLD (HR, 1.45 [95% CI, 1.31–1.63]) were associated with a higher risk of HF in all participants, and the risk differed by sex ( P interaction <0.05) and age ( P interaction <0.001). Compared with non-MAFLD participants, in women, significant-MAFLD was associated with an 84% (HR, 1.84 [95% CI, 1.43–2.37]) increased risk of HF; however, in men, the risk was 36% (HR, 1.36 [95% CI, 1.20–1.53]). In participants under 45 years, mild-MAFLD and significant-MAFLD had a 55% (HR, 1.55 [95% CI, 1.07–2.25]) and 172% (HR, 2.72 [95% CI, 1.87–3.97]) increased risk of HF; however, in participants over 65 years, even significant-MAFLD did not associate with a higher risk of HF (HR, 1.11 [95% CI, 0.92–1.34]). Afterwards, we stratified all participants by both sex and age and found that the risk of MAFLD-associated HF decreased with age in men ( P interaction <0.05) and women ( P interaction <0.05), but the sex difference in this risk was only present in participants younger than 45 years ( P interaction <0.05). CONCLUSIONS: MAFLD greatly increased the risk of HF in women, especially young women. With increasing age, MAFLD-related risk of HF decreased and the difference between men and women disappeared.