MASLD Linked to Increased Risk of New-Onset Heart Failure

Jia-Horng Kao, MD, PhD

Credit: National Taiwan University Hospital

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with a heightened risk of heart failure (HF), specifically HF with preserved ejection fraction (HFpEF), according to findings from a recent study.¹

Results showed that compared to patients without MASLD, those with MASLD face a 2.59-fold increased risk of new-onset HF and a 2.30-fold greater risk of HF-related hospitalization. Of note, a dose-dependent relationship was observed between cardiometabolic risk factors and HF.¹

MASLD, formerly known as nonalcoholic fatty liver disease (NAFLD), is the most common chronic liver disease, affecting more than 30% of the global population. Whereas a NAFLD diagnosis required the exclusion of other chronic liver diseases, MASLD is diagnosed based on hepatic steatosis with the presence of cardiometabolic risk factors and does not necessarily exclude other co-existing liver diseases.²

“Metabolic dysfunction-associated steatotic liver disease, defined by steatotic liver disease and cardiometabolic factors, is increasing in prevalence, but its association with heart failure is unclear,” Jia-Horng Kao, MD, PhD, director and distinguished professor at the Graduate Institute of Clinical Medicine at National Taiwan University, and colleagues wrote.¹

To explore the relationship between HF and MASLD, investigators conducted a retrospective hospital-based cohort study at the National Taiwan University Hospital. They consecutively screened patients ≥ 20 years of age with chronic liver disease diagnosed by ICD-9/10 codes from January 2006 to February 2021 through the National Taiwan University Hospital integrated Medical Database.¹

Patients were included in the study if persistent steatotic liver disease (SLD) was documented from serial abdominal ultrasound exams. Those with HF, defined by ≥ 1 inpatient or 2 outpatient diagnosis codes within 6 months of the index date, were excluded.¹

The diagnosis of MASLD was confirmed by the presence of liver steatosis with any of the following cardiometabolic risk factors: body mass index ≥ 23 kg/m2; fasting glucose ≥ 100 mg/dl or glycated hemoglobin≥ 5.7% or type 2 diabetes; hypertension; plasma triglycerides ≥ 150 mg/dl; plasma high-density lipoprotein cholesterol ≤ 40 mg/dl for males and ≤ 50 mg/dl for females; or receiving lipid-lowering agents.¹

Patients with chronic liver diseases were followed at least every 6–12 months in the hospital with abdominal ultrasound until the development of HF, death, or their last clinic visit. The primary outcome was the development of new-onset HF, diagnosed by ≥ 1 inpatient or 2 outpatient diagnosis codes, and further classified by echocardiography based on the latest European Society of Cardiology guidelines.¹

Overall, 26,676 patients with SLD were included, with a median age of 51 years and 57% of whom were male. Among the cohort, 18,977 (71%) patients were classified as having MASLD.¹

During a median follow-up of 6 years, 429 (1.61%) patients developed HF, and 76% were HF with preserved ejection fraction (HFpEF). Investigators noted the cumulative incidence of HF was significantly higher for patients with MASLD than those without MASLD (P <.001). Further analysis adjusting for HF-associated factors and competing mortality revealed the risk of HF was significantly increased in patients with MASLD (subdistribution hazard ratio [SHR], 2.59; 95% CI,1.84–3.64).¹

Investigators additionally called attention to a dose-dependent increase in HF risk, with 12% additional risk observed per 1 additional cardiometabolic risk factor (SHR, 1.12; 95% CI, 1.04–1.22).¹

After adjustment for HF-associated factors and competing mortality, MASLD was significantly associated with a 1.91-fold greater risk of HFpEF (SHR, 1.91; 95% CI, 1.27–2.86; P = .002). Additional sensitivity analysis showed MASLD was associated with a 2.30-fold increased risk of HF-related hospitalization (SHR, 2.30; 95% CI, 1.31–4.04; P = .004).¹

In propensity score-matched cohorts matching baseline characteristics and comorbidities between the MASLD and non-MASLD groups, MASLD was associated with a 2.52-fold greater risk of HF (SHR, 2.52; 95% CI, 1.71–3.73).¹

Investigators outlined multiple limitations to these findings, including the retrospective nature of the study; the inability to confirm causal effects; the use of serial abdominal ultrasound rather than liver biopsy to detect hepatic steatosis; and the potential underdiagnosis of HF without apparent symptoms.¹

“Cardiovascular risk stratification is crucial in patients with SLD. Patients with cardiometabolic risk factors contributing to MASLD show a significant risk of developing HF, especially HFpEF, compared to those without MASLD,” investigators concluded.¹ “Disease awareness and identification for HF are of great importance in patients with MASLD.”

References

1. ^{Chang KC, Su TH, Wu CK, et al. Metabolic dysfunction-associated steatotic liver disease is associated with increased risks of heart failure. European Journal of Heart Failure. https://doi.org/10.1002/ejhf.3567}
2. ^{American Association for the Study of Liver Diseases. New MASLD Nomenclature. Accessed January 8, 2025. https://www.aasld.org/new-masld-nomenclature}