Causal relationship between systemic lupus erythematosus and coronary artery disease: Insights from a meta-analysis...

Observational research has produced varied results concerning the association between systemic lupus erythematosus (SLE) and coronary artery disease (CAD). This study employed a meta-analysis of cohort studies alongside a 2-sample Mendelian randomization (MR) method to investigate the causal influence of SLE on CAD risk. A comprehensive literature search was executed across PubMed, Web of Science, Embase, and the Cochrane Library, covering all pertinent cohort studies from their inception to August 14, 2024. The data regarding the causal association between SLE and CAD were synthesized using relative risk (RR), with results presented within a 95% confidence interval (CI). For MR analysis, data were derived from genome-wide association studies (GWAS) focusing on SLE and CAD in European and East Asian populations, respectively. The primary MR analysis employed the inverse-variance weighted (IVW) method, with the weighted median method and MR-Egger regression serving as complementary approaches. This meta-analysis included 13 cohort studies with a total of 2517,781 participants. The combined findings indicated that compared to the general or healthy population, individuals with SLE had a higher risk of developing CAD in the total population (RR [95% CI] = 2.355 [1.924-2.883], 95% prediction interval [PI]: 1.199-4.628). This association was also observed among European (RR [95% CI] = 2.028 [1.310-3.138], 95% PI: 0.539-7.631), East Asian (RR [95% CI] = 2.628 [1.698-4.067], 95% PI: 0.014-487.335), and North American (RR [95% CI] = 2.711 [2.379-3.089], 95% PI: 2.193-3.352) groups. However, MR analysis utilizing the IVW method did not identify a genetically predicted causal relationship between SLE and CAD in either European or East Asian populations (all P > .05). Sensitivity analyses indicated an absence of heterogeneity or horizontal pleiotropy in the MR analysis. Findings from our meta-analysis indicated that SLE is associated with an elevated risk of CAD. Despite the lack of genetic evidence for a direct causal relationship between SLE and CAD, clinicians should remain vigilant and take proactive measures in monitoring CAD among SLE patients, considering the possible indirect effects of SLE on CAD risk.