Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jun 6:13:908831.
doi: 10.3389/fimmu.2022.908831. eCollection 2022.

Systemic Lupus Erythematosus and Cardiovascular Disease: A Mendelian Randomization Study

Ning Gao  1 , Minjian Kong  1 , Xuebiao Li  1 , Dongdong Wei  1 , Xian Zhu  1 , Ze Hong  1 , Ming Ni  1 , Yifan Wang  1 , Aiqiang Dong  1
Affiliations

Systemic Lupus Erythematosus and Cardiovascular Disease: A Mendelian Randomization Study

Ning Gao et al. Front Immunol. .

Abstract

Background: Previous 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.

Methods: The 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.

Results: MR 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.

Conclusion: Our 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.

Keywords: Mendelian randomization; cardiovascular disease; genome-wide association study; systemic lupus erythematosus; the causal link.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Study design flowchart of the Mendelian randomization study. The Mendelian randomization method is based on three hypotheses: 1. the instrumental variables is closely related to exposure; 2. instrumental variables is independent of any confounding factor; 3. instrumental variables affects the results only through exposure but not through other ways.
Figure 2
Figure 2
Mendelian randomization estimates of SLE on the risk for CVD. SNPs, Single nucleotide polymorphisms; OR, Odds ratio; CI, Confidence interval; IVW, inverse-variance weighted; IVW (fixed), fixed-effects inverse-variance weighted; MR-RAPS, MR-robust adjusted profile score; MR-PRESSO, MR-pleiotropy residual sum and outlier; *No outlier was detected; AF, atrial fibrillation; CAD, coronary artery disease; HF, heart failure; IS, ischemic stroke; T2DM, type 2 diabetes. VTE, Venous Thromboembolism.
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Tsao CW, Aday AW, Almarzooq ZI, Alonso A, Beaton AZ, Bittencourt MS, et al. . Heart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association. Circulation (2022) 145(8):e153–639. doi: 10.1161/CIR.0000000000001052 - DOI - PubMed
    1. Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. . Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study. J Am Coll Cardiol (2020) 76(25):2982–3021. doi: 10.1016/j.jacc.2020.11.010 - DOI - PMC - PubMed
    1. Flora GD, Nayak MK. A Brief Review of Cardiovascular Diseases, Associated Risk Factors and Current Treatment Regimes. Curr Pharm Des (2019) 25(38):4063–84. doi: 10.2174/1381612825666190925163827 - DOI - PubMed
    1. Zhang Y, Bauersachs J, Langer HF. Immune Mechanisms in Heart Failure. Eur J Heart Fail (2017) 19(11):1379–89. doi: 10.1002/ejhf.942 - DOI - PubMed
    1. Barber MRW, Drenkard C, Falasinnu T, Hoi A, Mak A, Kow NY, et al. . Global Epidemiology of Systemic Lupus Erythematosus. Nat Rev Rheumatol (2021) 17(9):515–32. doi: 10.1038/s41584-021-00668-1 - DOI - PMC - PubMed

Publication types

MeSH terms