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Observational Study
. 2024 Jul 23;10(3):e004546.
doi: 10.1136/rmdopen-2024-004546.

Biological use influences the impact of inflammation on risk of major adverse cardiovascular events in rheumatoid arthritis

George Athanasios Karpouzas  1   2 , Sarah R Ormseth  3 , Piet Leonardus Cornelis Maria van Riel  4   5 , Miguel A Gonzalez-Gay  6   7 , Alfonso Corrales  8 , Solbritt Rantapää-Dahlqvist  9 , Petros P Sfikakis  10 , Patrick Dessein  11 , Linda Tsang  12 , Carol Hitchon  13 , Hani El-Gabalawy  14 , Virginia Pascual-Ramos  15 , Irazú Contreras-Yáñez  16 , Iris J Colunga-Pedraza  17 , Dionicio Angel Galarza-Delgado  18 , Jose Ramon Azpiri-Lopez  19 , Anne Grete Semb  20 , Durga Prasanna Misra  21 , Ellen-Margrethe Hauge  22   23 , George Kitas  24
Affiliations
Observational Study

Biological use influences the impact of inflammation on risk of major adverse cardiovascular events in rheumatoid arthritis

George Athanasios Karpouzas et al. RMD Open. .

Abstract

Objectives: Chronic inflammation promotes cardiovascular risk in rheumatoid arthritis (RA). Biological disease-modifying antirheumatic drugs (bDMARDs) improve disease activity and cardiovascular disease outcomes. We explored whether bDMARDs influence the impact of disease activity and inflammatory markers on long-term cardiovascular risk in RA.

Methods: We studied 4370 participants without cardiovascular disease in a 10-country observational cohort of patients with RA. Endpoints were (1) major adverse cardiovascular events (MACE) encompassing myocardial infarction, stroke and cardiovascular death; and (2) any ischaemic cardiovascular events (iCVE) including MACE plus revascularisation, angina, transient ischaemic attack and peripheral arterial disease.

Results: Over 26 534 patient-years, 239 MACE and 362 iCVE occurred. The interaction between 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and bDMARD use was significant for MACE (p=0.017), suggesting the effect of DAS28-CRP on MACE risk differed among bDMARD users (n=515) and non-users (n=3855). DAS28-CRP (per unit increase) is associated with MACE risk in bDMARD non-users (HR 1.21 (95% CI 1.07 to 1.37)) but not users (HR 0.69 (95% CI 0.40 to 1.20)). The interaction between CRP (per log unit increase) and bDMARD use was also significant for MACE (p=0.011). CRP associated with MACE risk in bDMARD non-users (HR 1.16 (95% CI 1.04 to 1.30)), but not users (HR 0.65 (95% CI 0.36 to 1.17)). No interaction was observed between bDMARD use and DAS28-CRP (p=0.167) or CRP (p=0.237) for iCVE risk.

Conclusions: RA activity and inflammatory markers associated with risk of MACE in bDMARD non-users but not users suggesting the possibility of biological-specific benefits locally on arterial wall independently of effects on systemic inflammation.

Keywords: Arthritis, Rheumatoid; Biological Therapy; Cardiovascular Diseases; Inflammation.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1. Cumulative hazard plots of (A) MACE and (B) any ischaemic CVE in bDMARD users and non-users at low DAS28-CRP (1 SD below the mean, coinciding with DAS28-CRP=2.4) and high DAS28-CRP (1 SD above the mean, coinciding with DAS28-CRP=5.1). bDMARD, biological disease-modifying antirheumatic drug; CVE, cardiovascular event; DAS28-CRP, 28-joint Disease Activity Score with C-reactive protein; MACE, major adverse cardiovascular event.
Figure 2
Figure 2. Effect of inflammation on cardiovascular event risk overall and stratified by bDMARD use. Models adjust for age, gender, hypertension, diabetes, smoking, total cholesterol/high-density lipoprotein cholesterol ratio and disease duration. bDMARD, biological disease-modifying antirheumatic drug; CVE, cardiovascular event; DAS28-CRP, 28-joint Disease Activity Score with C-reactive protein; MACE, major adverse cardiovascular event.
See this image and copyright information in PMC

References

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