# Association between antiphospholipid antibodies, rheumatic-immune inflammation, and coronary in-stent restenosis

## TL;DR

This study found that antiphospholipid antibodies and higher IL-6 levels are linked to a higher risk of coronary in-stent restenosis and revascularization in patients with drug-eluting stents.

## Contribution

The study is the first to show that immune markers like aPL and IL-6 improve risk prediction for in-stent restenosis beyond traditional clinical factors.

## Key findings

- aPL positivity and IL-6 were independently associated with in-stent restenosis (ISR) in adjusted analyses.
- Adding aPL and IL-6 to clinical models improved discrimination, calibration, and reclassification for predicting ISR.
- Higher aPL and IL-6 levels were also linked to increased risk of clinically driven target-lesion revascularization (TLR).

## Abstract

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.

In this prospective cohort, we enrolled 2,503 consecutive adults who received at least one new-generation DES between May 2022 and January 2024. Preprocedural 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 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 vs. 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.

Of the 2,503 enrolled participants, 2,388 completed 12-month imaging, with ISR occurring 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, integrated discrimination improvement (IDI) 0.04). Optimism-corrected AUC was 0.78. The 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.

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.