Association between age-related cardiovascular disease and systemic lupus erythematosus: a Mendelian randomization analysis

JOURNAL/agad/04.03/02274129-202512000-00002/figure1/v/2025-10-03T110810Z/r/image-tiff Current research has demonstrated that individuals with systemic lupus erythematosus face a markedly greater risk of cardiovascular disease. However, the exact mechanism linking specific types of heart disease to the incidence of systemic lupus erythematosus remains unclear, and the evidence is insufficient. This study explored and clarified the intrinsic connection between genetic factors of heart disease and susceptibility to systemic lupus erythematosus by investigating the potential causal link between the two. Utilizing aggregated genome-wide association study data, we applied a standardized quality control protocol to select single nucleotide polymorphisms as genetic instrumental variables. Five Mendelian randomization approaches were used to evaluate causal effects, including inverse variance weighting, Mendelian randomization-Egger method, weighting median method, simple mode method, and weighting mode method. Inverse variance weighting was used as the core analysis method, and Mendelian randomization-Egger was used to assess heterogeneity and perform multi-effect testing; Finally, the leave-one-out method was used for sensitivity analysis to ensure the robustness of the results. The Mendelian randomization analysis identified significant associations between valvular heart disease (odds ratio (OR) = 1.866, 95% confidence interval (CI): 1.230–2.830, P = 0.003), hypertensive heart disease (OR = 1.148, 95% CI: 1.041–1.264, P = 0.005), and endocarditis (OR = 1.141, 95% CI: 1.031–1.126, P = 0.011) with increased susceptibility to systemic lupus erythematosus. Additionally, five significant single nucleotide polymorphisms were shared between heart diseases and systemic lupus erythematosus. These findings suggest that patients with valvular heart disease, hypertensive heart disease, or endocarditis should undergo regular screening and risk assessment for systemic lupus erythematosus to facilitate early detection and intervention.