Phenotypic Disease Network Analysis to Identify Comorbidity Patterns in Hospitalized Patients with Ischemic Heart Disease Using Large-Scale Administrative Data

Ischemic heart disease (IHD) exhibits elevated comorbidity. However, few studies have systematically analyzed the comorbid status of IHD patients with respect to the entire spectrum of chronic diseases. This study applied network analysis to provide a complete picture of physical and mental comorbidities in hospitalized patients with IHD using large-scale administrative data. Hospital discharge records from a provincial healthcare database of IHD inpatients (n = 1,035,338) and one-to-one matched controls were included in this retrospective analysis. We constructed the phenotypic disease networks in IHD and control patients and further assessed differences in comorbidity patterns. The community detection method was applied to cluster diagnoses within the comorbidity network. Age- and sex-specific patterns of IHD comorbidities were also analyzed. IHD inpatients showed 50% larger comorbid burden when compared to controls. The IHD comorbidity network consisted of 1941 significant associations between 71 chronic conditions. Notably, the more densely connected comorbidities in IHD patients were not within the highly prevalent ones but the rarely prevalent ones. Two highly interlinked communities were detected in the IHD comorbidity network, where one included hypertension with heart and multi-organ failures, and another included cerebrovascular diseases, cerebrovascular risk factors and anxiety. Males exhibited higher comorbid burden than females, and thus more complex comorbidity relationships were found in males. Sex-specific disease pairs were detected, e.g., 106 and 30 disease pairs separately dominated in males and females. Aging accounts for the majority of comorbid burden, and the complexity of the comorbidity network increased with age. The network-based approach improves our understanding of IHD-related comorbidities and enhances the integrated management of patients with IHD.