Network Analysis of Sex Differences in Cardiovascular Disease Comorbidities

Objectives: Cardiovascular disease (CVD) co-occurs with multiple chronic conditions, but their structural relationships remain underexplored. This study aimed to explore the comorbidity patterns and disease network structures of CVD patients using nationwide claims data, with attention to differences by sex.Methods: Using National Health Insurance Service claims data from 2002 to 2019, adults diagnosed with CVD (KCD: I20-25) were identified, and comorbidities recorded before the first CVD diagnosis were extracted. Sex-specific odds ratios with 95% confidence intervals were calculated, and disease networks were constructed for the CVD, myocardial infarction (MI), and ischemic heart disease (IHD) groups, with each disease as the central node and the top 10 comorbidities as surrounding nodes.Results: Essential hypertension and type 2 diabetes showed positive associations with CVD and were prominently represented in the disease networks in both sexes. Both associations were stronger in women, with odds ratios for hypertension of 1.379 in men and 1.887 in women, and for diabetes of 1.885 and 2.454, respectively. Similar patterns were observed in the MI and IHD groups, with hypertension and type 2 diabetes showing consistently positive associations in both sexes. Sex-specific differences were also evident: knee osteoarthritis and dyslipidemia were more prominent in women, with odds ratios of 1.796 and 1.296, whereas benign prostatic hyperplasia showed the highest association in men, with an odds ratio of 2.271.Conclusions: Comorbidity structures in CVD patients differed by sex. These findings suggest the importance of early detection and continuous management of hypertension and diabetes, and support sex-specific approaches to chronic disease management in CVD patients.