Abstract
BACKGROUND: In-stent neoatherosclerosis (ISNA) is a key mechanism underlying drug-eluting stent in-stent restenosis (DES-ISR), with inflammation playing a critical role. This study aimed to assess the association between the systemic immune-response index (SIRI) and ISNA in DES-ISR patients. METHODS: A retrospective analysis included 212 patients with DES-ISR who underwent coronary angiography and optical coherence tomography (OCT) at least 12 months after stent implantation. SIRI was calculated as (neutrophil count × monocyte count)/lymphocyte count and divided into tertiles. Multivariate logistic regression, smooth curve fitting, threshold effect, and subgroup analyses were performed to evaluate the relationship between SIRI and ISNA risk. RESULTS: Higher SIRI tertiles were associated with ISNA and thin-cap fibroatheroma (all P < 0.05). Multivariate analysis identified SIRI as an independent risk factor for ISNA (OR per unit increase 1.23, 95% CI 1.04-1.47, P = 0.018). Smooth curve fitting identified a non-linear association, highlighting a distinct threshold at a SIRI level of 3.95, below which the risk of ISNA rose sharply. Subgroup analysis revealed that the association between SIRI and ISNA risk was largely consistent across most subgroups, with a significant interaction observed only among patients younger than 60 years (OR 1.94, 95% CI 1.23-3.05, P for interaction = 0.010). CONCLUSION: SIRI is independently and non-linearly associated with the risk of ISNA in DES-ISR patients, with a distinct inflection point observed at a SIRI value of 3.95, below which elevated SIRI levels were significantly correlated with increased ISNA risk. Prospective studies are needed for further validation.