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
. 2021 Jul 19:8:681327.
doi: 10.3389/fcvm.2021.681327. eCollection 2021.

Patterns of Anti-Inflammatory and Immunomodulating Drug Usage and Microvascular Endothelial Function in Rheumatoid Arthritis

Arduino A Mangoni  1 , Richard J Woodman  2 , Matteo Piga  3   4 , Alberto Cauli  3   4 , Anna Laura Fedele  5 , Elisa Gremese  5 , Gian Luca Erre  6   7 ; EDRA Study Group
Collaborators, Affiliations

Patterns of Anti-Inflammatory and Immunomodulating Drug Usage and Microvascular Endothelial Function in Rheumatoid Arthritis

Arduino A Mangoni et al. Front Cardiovasc Med. .

Abstract

Objectives: Specific anti-inflammatory and/or immunomodulating drugs (AIDs) can influence endothelial function which is often impaired in patients with rheumatoid arthritis (RA). We sought to determine whether overall patterns of AID usage are similarly associated with endothelial function. Methods: The reactive hyperaemia index (RHI), a marker of microvascular endothelial function, was measured in 868 RA patients reporting their intake of seven AIDs known to affect endothelial function. Latent class analysis (LCA) was performed to characterise patterns of AID usage. Models for 2-6 classes were compared using the AIC and BIC statistics and Lo-Mendell-Rubin likelihood ratio tests. Associations between the classes and RHI were adjusted for age, gender, body mass index, diabetes, HDL-cholesterol, LDL-cholesterol, family history of ischaemic heart disease, smoking status, RA duration, DAS28 score, steroid dose, existing hypertension, and C-reactive protein. Results: LCA identified five distinct AID usage classes: Class 1, generally low medication usage; Class 2, using either sulfasalazine or non-tumour necrosis factor (TNF) inhibitors; Class 3, methotrexate users; Class 4, TNF-inhibitor users; and Class 5, hydroxychloroquine users. The geometric mean for the RHI for subjects in classes 1 to 5 was 1.92, 1.81, 1.94, 2.10, and 2.07, respectively, with subjects in classes 4 and 5 having better endothelial function than subjects in class 2 (p = 0.003 for each). The glucocorticoid dosage did not influence the classes formed or the association between the classes and the RHI in sensitivity analyses. Conclusion: There were five broad patterns (classes) of AID usage in RA patients. The RHI was relatively lower in users of either sulfasalazine or non-TNF inhibitors. TNF inhibitors or hydroxychloroquine may counteract the negative effects of RA on endothelial function.

Keywords: TNF-inhibitors; anti-inflammatory drugs; endothelial dysfunction; hydroxychloroquine; immunomodulating drugs; latent class analysis; rheumatoid arthritis.

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
Average medication usage of anti-inflammatory and immunomodulating drugs known to affect endothelial function for each latent class.
See this image and copyright information in PMC

References

    1. Bordy R, Totoson P, Prati C, Marie C, Wendling D, Demougeot C. Microvascular endothelial dysfunction in rheumatoid arthritis. Nat Rev Rheumatol. (2018) 14:404–20. 10.1038/s41584-018-0022-8 - DOI - PubMed
    1. Totoson P, Maguin-Gate K, Prati C, Wendling D, Demougeot C. Mechanisms of endothelial dysfunction in rheumatoid arthritis: lessons from animal studies. Arthritis Res Ther. (2014) 16:202. 10.1186/ar4450 - DOI - PMC - PubMed
    1. Erre GL, Piga M, Fedele AL, Mura S, Piras A, Cadoni ML, et al. . Prevalence and determinants of peripheral microvascular endothelial dysfunction in rheumatoid arthritis patients: a multicenter cross-sectional study. Mediators Inflamm. (2018) 2018:6548715. 10.1155/2018/6548715 - DOI - PMC - PubMed
    1. Gonzalez-Gay MA, Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Martin J, Llorca J. Endothelial dysfunction, carotid intima-media thickness, and accelerated atherosclerosis in rheumatoid arthritis. Semin Arthritis Rheum. (2008) 38:67–70. 10.1016/j.semarthrit.2008.02.001 - DOI - PubMed
    1. Erre GL, Buscetta G, Paliogiannis P, Mangoni AA, Carru C, Passiu G, et al. . Coronary flow reserve in systemic rheumatic diseases: a systematic review and meta-analysis. Rheumatol Int. (2018) 38:1179–90. 10.1007/s00296-018-4039-8 - DOI - PubMed