Immune-mediated inflammatory diseases and the risk of valvular heart disease: a Mendelian randomization study

Observational studies have suggested that immune-mediated inflammatory diseases (IMIDs) are associated with a higher risk of valvular heart disease (VHD). But the potential causal association is not clear. Therefore, we used Mendelian randomization (MR) analysis to assess the causal association of IMIDs with VHD risk.

A two-sample MR analysis was performed to confirm the causal association of several common IMIDs (systemic lupus erythematosus, SLE; rheumatoid arthritis, RA; multiple sclerosis, MS; ankylosing spondylitis, AS; psoriasis, PSO; inflammatory bowel disease, IBD) with the risk of VHD. The exposure data is derived from published genome-wide association studies (GWASs) and outcome data come from the FinnGen database (47,003 cases and 182,971 controls). Inverse-variance weighted (IVW), MR-Egger, and weighted median methods were performed to assess the causal association. The study design applied univariable MR and multivariable MR.

The MR analysis indicated that several genetically predicted IMIDs increased the risk of VHD, including SLE (odds ratio (OR) = 1.014; 95% confidence interval (CI) =  < 1.001,1.028 > ; p = 0.036), RA (OR = 1.017; 95% CI =  < 1.002,1.031 > ; p = 0.025), and IBD (OR = 1.018; 95% CI =  < 1.002,1.033 > ; p = 0.023). Multivariable MR indicated that the adverse effect of these IMIDs on VHD was dampened to varying degrees after adjusting for smoking, obesity, coronary artery disease, and hypertension.

Our findings support the first genetic evidence of the causality of genetically predicted IMIDs with the risk of developing into VHD. Our results deliver a viewpoint that further active intervention needs to be explored to mitigate VHD risk in patients with SLE, RA, and IBD. Key Points • Genetically predicted systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD) are causally associated with valvular heart disease (VHD). • To reduce the risk of VHD in patients with SLE, RA, and IBD, active interventions should be further explored.