Systemic Lupus Erythematosus and Cardiovascular Disease: A Mendelian Randomization Study

Abstract

BackgroundPrevious studies have shown that patients with systemic lupus erythematosus (SLE) tend to have a higher risk of cardiovascular disease (CVD), but the potential causal relationship between genetic susceptibility to SLE and CVD risk is not clear. This study systematically investigated the potential association between genetically determined SLE and the risk of CVD.MethodsThe genetic tools were obtained from genome-wide association studies of SLE and CVD, with no overlap between their participating populations. Mendelian randomization (MR) analysis was performed using inverse variance weighting as the primary method. Simultaneously, a series of repeated analyses, sensitivity analyses, and instrumental variable strength evaluations were performed to verify the reliability of our results.ResultsMR analysis showed that genetic susceptibility to SLE was associated with a higher risk of heart failure (OR=1.025, 95% CI [1.009-1.041], P=0.002), ischemic stroke (OR=1.020, 95% CI [1.005-1.034], P=0.009), and venous thromboembolism (OR=1.001, 95% CI [1.000-1.002], P=0.014). However, genetic susceptibility to SLE was negatively correlated with the risk of type 2 diabetes (OR=0.968, 95% CI [0.947-0.990], P=0.004). Sensitivity analysis found no evidence of horizontal pleiotropy or heterogeneity.ConclusionOur MR study explored the causal role of SLE in the etiology of CVD, which would help improve our understanding of the basic disease mechanisms of SLE and provide comprehensive CVD assessment and treatment for SLE patients.

Immune-mediated inflammatory diseases and risk of venous thromboembolism: A Mendelian randomization study

“…Specifically, during a median follow-up of 8.5 years, the incidence of VTE was 6.03% (95%CI: 5.17%-6.98%) in SLE patients and 1.68% (95%CI: 1.44%-1.95%) in controls (42). However, results from an MR study of SLE and cardiovascular disease conducted by Gao et al demonstrated no causal associations exist between SLE and VTE risk (OR=1.001, 95% CI [1.000-1.002]), which is consistent with our findings (20).…”

“…The availability of large-scale genome-wide association studies (GWAS) on IMIDs and cardiovascular disease made it possible to implement MR analysis to investigate the relationship between various diseases. For example, Gao et al (20) established a causal relationship between SLE and cardiovascular disease, while Li et al suggested that varicose veins may have a causal role in DVT (21). However, to date, no MR studies focused on the effect caused by IMIDs on VTE risk.…”

The potential causal association of systemic lupus erythematosus with congestive heart failure in the East Asian population: A two-sample Mendelian randomization study

“…In the US retrospective studies, SLE was associated with a 2.7–3.17-fold increase in the risk of CHF (3, 4). Recently, European-dominant MR studies also revealed that SLE potentially increases the risk of CHF, coronary artery disease, ischemic stroke, and venous thromboembolism (5, 6). A Korean nationwide study found that patients with SLE had a 4.6-fold higher risk of CHF (13).…”

“…Cardiovascular manifestation and complications of SLE include pericarditis, coronary artery disease, arrhythmias, valvular heart disease, and heart failure (2). Several retrospective cohort analyses and Mendelian randomization (MR) studies demonstrated that SLE increases the risk of coronary artery disease and heart failure, and worsens cardiovascular outcomes (3)(4)(5)(6). However, most studies have been conducted in the European-dominant population, and the underlying mechanisms remain unclear.…”

Commentary: Systemic lupus erythematosus and cardiovascular disease: A Mendelian randomization study

“…Mendelian randomization (MR) is a causal inference method that measures and correlates the effect sizes of exposure-associated genetic variants in large-scale genetic association studies on traits of interest. We therefore read with great interest the recent report by Gao and colleagues ( 3 ) which used MR methods to explore the potential genetic link between lupus and a number of cardiovascular diseases.…”