Do biomarkers matter? Cardiovascular risk stratification in Asian patients with metabolic dysfunction-associated steatotic liver disease in the era of fibrosis-centric assessment

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a multisystem disorder with significant cardiovascular implications, particularly in Asian populations characterized by a high prevalence of lean phenotypes and early metabolic dysregulation. Identifying reliable biomarkers for cardiovascular risk stratification in this group remains a clinical priority. This review critically appraises the current evidence on metabolic, inflammatory, cardiac, and fibrosis-related biomarkers in Asian patients with MASLD. Metabolic indices such as the uric acid-to-high-density lipoprotein ratio and triglyceride-glucose index capture underlying insulin resistance and oxidative stress and show consistent associations with steatotic liver disease. However, direct validation for cardiovascular outcomes remains limited. Inflammatory markers, including high-sensitivity C-reactive protein and homeostasis model assessment of insulin resistance, are mechanistically important but are confounded by their inclusion within MASLD diagnostic criteria, limiting their incremental predictive value. Cardiac biomarkers such as high-sensitivity troponins and natriuretic peptides demonstrate strong associations with adverse outcomes but lack sufficient validation in Asian MASLD cohorts for routine screening. In contrast, fibrosis-based indices, particularly the fibrosis-4 score, consistently associate with cardiovascular events, coronary artery calcification, and mortality across multiple Asian studies. These markers likely reflect cumulative metabolic and inflammatory injury linking hepatic and vascular pathology. An integrated, multivariable approach incorporating fibrosis markers alongside metabolic and cardiac indices may provide the most clinically meaningful framework for cardiovascular risk assessment in Asian patients with MASLD.

Keywords: Cardiovascular diseases; Metabolic dysfunction-associated steatotic liver disease; Obesity; Uric acid; Endothelial dysfunction; High-density lipoprotein cholesterol; Framingham risk score

Core Tip: Cardiovascular risk in Asian patients with metabolic dysfunction-associated steatotic liver disease is multifactorial and not adequately captured by single biomarkers. While metabolic indices reflect upstream metabolic stress, their prognostic value for cardiovascular events remains limited. Inflammatory markers are mechanistically relevant but confounded by their inclusion in disease definitions. In contrast, fibrosis-based scores, consistently associate with cardiovascular outcomes across Asian cohorts, likely reflecting cumulative metabolic injury. An integrated, multivariable approach combining metabolic, inflammatory, and fibrosis markers is more appropriate for cardiovascular risk stratification in this population.