Association between systemic lupus erythematosus and pulmonary hypertension: Evidence from Meta-Analysis and Mendelian Randomization

Abstract

Background Pulmonary hypertension (PH) is one of the most severe pulmonary complications of systemic lupus erythematosus (SLE). Nevertheless, studies of the prevalence of PH in SLE diversify tremendously, and the prevalence has not been updated for a long time. With the aim of estimating a more accurate prevalence of PH in SLE patients, we commenced a meta-analysis. Further analysis using the mendelian randomization (MR) approach was conducted to investigate whether SLE has a causal association with PH. Methods Pubmed, Embase, Web of Science and Cochrane Library were searched until October 2022 to identify eligible studies. We performed a heterogeneity and evaluated publication bias. Regional subgroup analyses were also performed. To further investigate the causal relationship between genetically predisposed SLE and PH, a two example mendelian randomization was performed. With 86 single nucleotide polymorphisms (SNPs) of mixed ancestors from the latest GWAS of SLE and 39 SNPs from another cohort as the replication group, we applied the inverse variance weighted (IVW) method to further estimate the causality, and conducted sensitivity analysis to measure the robustness of our results. Results Random effect model analysis showed a combined prevalence of 3.2% (95%CI 2.3-4.0%). However, the funnel plot showed a certain publication bias (p = 0.009). Subgroup analyses carried out on the basis of different regions demonstrated a salient difference in PH prevalence in SLE patients. Correspondingly, the mendelian randomization results showed that systemic lupus erythematosus was causally related to a higher risk of pulmonary hypertension among mixed ancestors (OR 1.33; 95%CI 1.04–1.69; P = 0.023), while no significant result was observed among European patients (OR 1.06; 95%CI 0.95–1.19; P = 0.297). Moreover, the results of MR sensitive analysis confirm the robustness of our causal estimates. Conclusion Our study suggested that a relatively low prevalence of PH in SLE when using right heart catheterization (RHC) to diagnose, but it was significantly different between regions. MR analysis also suggested that SLE might contribute to the progression of PH. The underlying mechanism regarding the causality between the two diseases requires further investigations.