The Intertwined Fate of Liver and Heart: Unravelling the Complex Relationship between Metabolic Dysfunction-associated Steatotic Liver Disease and Coronary Artery Disease

INTRODUCTION Metabolic dysfunction-associated steatotic liver disease (MASLD), also known as metabolic dysfunction-associated fatty liver disease or non-alcoholic fatty liver disease, has become a global health concern, affecting an estimated one-fourth to one-third of adults worldwide. This alarming prevalence parallels the rise of obesity and type 2 diabetes, which are the key drivers of MASLD. Beyond its impact on liver health, MASLD is increasingly recognised for its strong association with cardiovascular disease (CVD), particularly coronary artery disease (CAD). This journal scan delves into the intricate relationship between MASLD and CAD, drawing insights from recent research to highlight the need for an integrated approach to their co-management. SHARED RISK FACTORS AND BEYOND MASLD has been identified as an independent risk factor for CVD.[1] This association extends beyond shared risk factors such as obesity, type 2 diabetes and metabolic syndrome. A recent review emphasise that these metabolic conditions share a complex interplay between many modifiable and non-modifiable risk factors, with potential causal links.[2] This interconnectedness is highlighted by the striking statistic that CVD, specifically CAD, is the primary cause of mortality in patients with MASLD, surpassing complications directly related to liver dysfunction.[3] MECHANISMS LINKING METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE AND CORONARY ARTERY DISEASE[2] Several mechanisms contribute to the intertwined pathophysiology of MASLD and CAD. The key three mechanisms are discussed here. Chronic inflammation: MASLD is characterised by chronic low-grade inflammation in the hepatocytes, which can spill over systemically and contribute to atherosclerosis, which is the underlying process in CAD. Key inflammatory mediators, such as interleukin-6 and tumour necrosis factor-alpha, are implicated in both conditions Insulin resistance and lipotoxicity: Insulin resistance, a hallmark of metabolic syndrome, plays a central role in both MASLD and CAD. It promotes hepatic steatosis and dyslipidaemia, contributing to both liver damage and atherosclerotic plaque formation Altered lipid metabolism: MASLD is associated with an atherogenic lipid profile, characterised by elevated triglycerides, low high-density lipoprotein cholesterol and increased small, dense low-density lipoprotein particles. These lipid abnormalities accelerate atherosclerosis and increase CAD risk. LIVER FIBROSIS: A CRITICAL LINK The severity of MASLD, particularly the presence of liver fibrosis, significantly influences CAD risk. Studies have demonstrated a strong correlation between advanced fibrosis and increased cardiovascular events. This highlights the importance of assessing and staging liver disease in individuals with MASLD to stratify their cardiovascular risk.[4,5] CLINICAL IMPLICATIONS AND MANAGEMENT STRATEGIES[2] The close relationship between MASLD and CAD necessitates an interdisciplinary approach to their management. The review advocates for collaboration between hepatologists, cardiologists, endocrinologists and other specialists to provide comprehensive care. The public health specialists and those focused on preventive hepatology can also play a critical role in addressing these interconnected conditions and delivering comprehensive preventive liver care.[6,7] Early detection: Early identification of MASLD, even in the absence of overt liver disease, is crucial for mitigating CAD risk. This involves screening individuals with metabolic risk factors and utilising non-invasive tests to assess liver health Lifestyle interventions: Lifestyle modifications, including weight loss, healthy diet and regular exercise, are fundamental for managing both MASLD and CAD. These interventions improve insulin sensitivity, reduce inflammation and promote a favourable lipid profile Pharmacotherapy: Lifestyle interventions remain the foundation of management for MASLD, but specific pharmacological therapies can offer dual benefits for both liver and cardiovascular health. The role of aspirin, a cornerstone in the prevention and management of CAD, is gaining attention in MASLD, with preliminary evidence suggesting potential benefits. Statins, widely used for cholesterol reduction, also exhibit anti-inflammatory properties and may contribute to improved liver enzyme profiles. Furthermore, anti-diabetic medications, including glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter 2 inhibitors, have demonstrated significant promise in reducing cardiovascular events and enhancing liver outcomes in individuals with MASLD and type 2 diabetes.[8,9] EMERGING THERAPIES AND FUTURE DIRECTIONS Ongoing research is exploring novel therapies specifically targeting the MASLD-CAD axis. These include agents that address liver fibrosis, reduce inflammation and improve metabolic function. Further studies are needed to evaluate their efficacy and safety in this patient population.[10,11] CONCLUSION The intricate relationship between MASLD and CAD demands a paradigm shift in clinical practice. An integrated approach, involving early detection, comprehensive lifestyle interventions and judicious use of pharmacotherapy, is essential for optimising outcomes in individuals with these intertwined conditions. By recognising the shared pathophysiological pathways and implementing collaborative care strategies, including the merging of expertise from preventive cardiology and preventive hepatology, healthcare providers can effectively address the growing burden of MASLD and CAD, ultimately improving patient well-being and reducing cardiovascular morbidity and mortality. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.