ORIGINAL RESEARCH article
Front. Cardiovasc. Med.
Sec. Coronary Artery Disease
This article is part of the Research TopicImmune-Cardiac Axis: exploring immune response interactions with cardiovascular function in health and diseaseView all articles
Association Between Antiphospholipid Antibodies, Rheumatic-Immune Inflammation, and Coronary In-Stent Restenosis
Provisionally accepted
- Nanjing First Hospital, Nanjing, China
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Abstract Background: Antiphospholipid antibodies (aPL) and systemic rheumatic-immune inflammation (RII) may be associated with angiographic in-stent restenosis (ISR) after drug-eluting stent (DES) implantation. We prospectively evaluated these associations in a large Chinese cohort of DES recipients. Methods: In this prospective cohort, we enrolled 2,503 consecutive adults who received at least one new-generation DES between May 2022 and January 2024. Pre-procedural blood samples were assessed for antiphospholipid antibodies (anticardiolipin IgG/IgM, anti-β2-glycoprotein I IgG/IgM, and lupus anticoagulant) and inflammatory biomarkers (RII; high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), erythrocyte sedimentation rate (ESR), complement C3/C4, rheumatoid factor, and anti-cyclic citrullinated peptide (anti-CCP) antibodies. At 12 months, invasive coronary angiography or coronary CT angiography (CCTA) was used to assess in-stent restenosis (ISR). All ISR analyses were restricted to participants who completed 12‑month imaging (the imaging‑complete cohort). Multivariable logistic regression adjusted for prespecified clinical/lesion/stent covariates and imaging modality. Model performance was compared for a Clinical model versus an Immune‑enhanced model (Clinical + aPL + IL‑6) with internal bootstrap validation. ICA‑only analyses were prespecified. Clinically driven target‑lesion revascularization (TLR) was evaluated with Cox models in all enrolled patients. Results: Of 2,503 enrolled, 2,388 completed 12‑month imaging with ISR occurred in 193 participants (8.1%; 95% CI 6.9–9.1). In adjusted analyses, any aPL positivity (OR 1.92, 95% CI 1.34–2.74) and IL‑6 (per doubling) (OR 1.25, 95% CI 1.10–1.42) were independently associated with ISR. Adding aPL and IL‑6 improved discrimination (AUC 0.79 vs 0.72, Δ = 0.07, p = 0.008), calibration, and reclassification (categorical NRI 0.18, IDI 0.04). Optimism‑corrected AUC was 0.78. Findings were consistent in the ICA‑only cohort (aPL OR 1.95; IL‑6 OR 1.27). Over 12 months, TLR occurred in 100/2,503 (4.0%). aPL positivity (HR 2.08, 95% CI 1.36–3.18) and IL‑6 (per doubling; HR 1.29, 95% CI 1.11–1.50) were associated with higher TLR risk. Conclusion: Baseline aPL seropositivity and higher IL‑6 were associated with 12‑month ISR and clinically driven TLR. Incorporating these immune markers improves risk discrimination beyond clinical and angiographic factors. External validation and interventional studies are warranted.
Keywords: Antiphospholipid antibodies, Interleukin-6, Immune-inflammatory profiling, In-stent Restenosis, Drug-Eluting Stents
Received: 29 Jun 2025; Accepted: 03 Nov 2025.
Copyright: © 2025 Mao, Wu, Wei, Wang, Xiong, Chang and Ye. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Fei Ye, yefei8800@163.com
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