Impact of systemic lupus erythematosus on cardiovascular morphologic and functional phenotypes: a Mendelian randomization analysis.

Abstract

Background: Previous studies have established a correlation between systemic lupus erythematosus (SLE) and cardiovascular health, but the potential causal effects of SLE on heart function and structure remain poorly understood. Cardiovascular magnetic resonance imaging (CMR), a novel non-invasive technique, provides a unique assessment of cardiovascular structure and function, making it an essential tool for evaluating the risk of heart disease. In this study, we performed a Mendelian randomization analysis to determine the causal relationship between SLE and CMR traits.

Methods: Genetic variants independently linked to SLE were selected from a genome-wide association study (GWAS) containing 5,201 cases and 9,066 controls as instrumental variables. A set of 82 CMR traits was obtained from a recent GWAS, serving as preclinical indicators and providing preliminary insights into the morphology and function of the four cardiac chambers and two aortic segments. Primary analysis employed a two-sample Mendelian randomization study using the inverse-variance weighted method. Heterogeneity testing, sensitivity analyses, and instrumental variable strength assessments confirmed the robustness of the findings.

Results: SLE exhibited a correlation with increased stroke volume (β_LVSV = 0.007, P = 0.045), regional peak circumferential strain (β_{Ecc_AHA_9} = 0.013, P = 0.002; β_{Ecc_AHA_12} = 0.009, P = 0.043; β_{Ecc_AHA_14} = 0.013, P = 0.006), and global peak circumferential strain of the LV (β_{Ecc_global} = 0.010, P = 0.022), as well as decreased regional radial strain (β_{Err_AHA_11} = -0.010, P = 0.017).

Conclusions: This research presents evidence of a potential causal association between traits of SLE and alterations in cardiac function, guiding cardiac examinations and disease prevention in lupus patients.