Global comorbidity of ischemic heart disease and liver cancer: an ecological analysis of shared risk factors.

Background: Ischemic heart disease (IHD) and liver cancer (LC), traditionally managed as separate clinical entities, are increasingly linked by the global rise of metabolic syndrome. However, the epidemiological footprint of this comorbidity remains uncharacterized on a global scale. To provide a comprehensive epidemiological assessment of IHD and LC comorbidity, this investigation was designed to map their global co-occurrence patterns, distinguish their underlying shared and unique risk determinants, and evaluate the resultant disease burden. Methods: In this global, cross-sectional ecological analysis, we used 2021 data from the Global Burden of Disease study for 200 countries and territories. We developed a novel classification system to categorize countries into three comorbidity archetypes (IHD-dominant, LC-dominant, or consistent) based on relative age-standardized incidence rates. Machine learning models (Random Forest with Shapley Additive Explanations analysis) were employed to identify and rank the relative importance of environmental, dietary, and metabolic risk factors. The population attributable fraction was calculated to quantify the preventable burden associated with these factors. Results: Our analysis revealed three distinct geographical archetypes: an LC-dominant pattern in high-income nations and China; an IHD-dominant pattern in Russia and South Asia; and a consistent pattern in diverse regions like Egypt and Indonesia. Spatiotemporal analysis from 1990 to 2021 showed a widening inequity, with developing nations facing a persistent and severe dual burden. While high sodium intake was the most strongly associated factor for IHD and low whole grain intake for LC, air pollution emerged as a significant shared correlate. We also identified profound gender disparities: females were disproportionately burdened by air pollution and secondhand smoke, whereas males bore a greater burden from high red meat and sodium intake. Conclusion: The comorbidity of IHD and LC is a defining feature of the modern epidemiological landscape, challenging the traditional single-disease paradigm. The findings compel a shift from siloed interventions toward integrated, gender-sensitive public health strategies that address shared metabolic and environmental roots, thereby profoundly diminishing their global public health impact.