Clinical Report: MASLD's Role in Cardiovascular-Kidney-Metabolic Health Framework

Overview

The editorial discusses the integration of metabolic dysfunction–associated steatotic liver disease (MASLD) within the cardiovascular–kidney–metabolic (CKM) health framework. A large Korean cohort study found that hepatic steatosis, measured by fatty liver index (FLI), is associated with increased cardiovascular disease (CVD) risk across CKM stages, especially in early stages.

Background

The CKM health framework, introduced by the American Heart Association in 2023, conceptualizes cardiovascular, kidney, and metabolic diseases as interconnected multisystem disorders driven by metabolic dysfunction. MASLD, recently renamed from NAFLD, requires metabolic dysfunction alongside hepatic steatosis and is linked to higher CVD risk. Both MASLD and CKM share insulin resistance and metabolic dysfunction as common pathophysiological roots, suggesting potential integration for improved risk stratification and management.

Data Highlights

Key Findings

• The presence of MASLD, defined by hepatic steatosis with metabolic dysfunction, is associated with increased risk of clinical cardiovascular events.
• In a cohort of nearly 1.5 million Korean adults, FLI ≥ 60 correlated with a 32% higher hazard of CVD events over 12.6 years.
• Relative cardiovascular risk associated with higher FLI was greatest in early CKM stages (0/1), decreasing in later stages but with higher absolute risk.
• FLI, a biochemical score including BMI, waist circumference, triglycerides, and γ-glutamyl transferase, may overlap with metabolic abnormalities defining CKM stages.
• Integration of MASLD metrics into CKM staging could improve early risk stratification but requires further validation regarding clinical utility and incremental predictive value.
• Therapeutic advances for MASLD, including FDA-approved resmetirom and GLP-1 receptor agonists, align with CKM framework treatments, suggesting potential for integrated management.

Clinical Implications

Clinicians should recognize MASLD as a marker of increased cardiovascular risk within the CKM framework, particularly in early disease stages. However, reliance on FLI alone for hepatic steatosis detection in individual patients is limited, and the additive value of MASLD beyond existing CKM staging and CVD risk equations remains uncertain. Integration of MASLD assessment may guide earlier preventive strategies and therapeutic interventions targeting metabolic dysfunction.

Conclusion

MASLD represents an important component of the multisystem metabolic dysfunction driving cardiovascular and kidney disease. While promising data support its role in risk stratification within the CKM framework, further research is needed to clarify its clinical utility and impact on treatment decisions.

References

1. Kim et al. 2023 -- Hepatic steatosis in cardiovascular–kidney–metabolic syndrome: fatty liver index as a predictor of cardiovascular outcomes
2. American Heart Association 2023 -- Cardiovascular–Kidney–Metabolic Health Framework