Autoimmune diseases and cardiovascular risk: Mendelian randomization analysis for the impact of 19 autoimmune diseases on 14 cardiovascular conditions.

BACKGROUD: Autoimmune diseases (AIDs) have been associated with various cardiovascular diseases (CVDs) in observational data. However, the causality of these associations remains uncertain. Therefore, a systematic assessment of the impact of AIDS on cardiovascular risk is required.

RESULTS

We assessed the impact of 19 common AIDs on 14 CVDs using bidirectional Mendelian randomization (MR). Celiac disease (odds ratio [OR] = 2.949, 95 % confidence interval [CI]: 1.111-7.827, P = 0.030) and type 1 diabetes mellitus (T1DM) (OR = 1.044, 95 % CI: 1.021-1.068, P = 1.82e-4) were associated with an increased risk of peripheral arterial disease (PAD). Additionally, celiac disease was linked to an increased risk of arrhythmia (OR = 1.008, 95 % CI: 1.002-1.013, P = 0.004), multiple sclerosis to venous thromboembolism (OR = 1.001, 95 % CI: 1.000-1.001, P = 0.010), and psoriasis to heart failure (OR = 1.048, 95 % CI: 1.021-1.077, P = 0.001). Sensitivity analyses were conducted to enhance the robustness of these findings. Predominantly, immune response and inflammation-related pathways were enriched in the aforementioned associations. Mediation analysis identified human leukocyte antigen-DR positive myeloid dendritic cells as partially mediating the effect of T1DM on PAD, with a mediated proportion of 16.61 % (P = 0.028). Potential therapeutic agents, such as tumor necrosis factor-alpha inhibitors and interferon, may have efficacy in treating AID-related CVDs.

CONCLUSIONS

This study presents genetic evidence of certain AIDs impacting specific CVDs and identifies potential mediators and drugs.