Age-related amplification of inflammatory risk after percutaneous coronary Intervention: a 10-year large-sample prospective cohort study

Background Accumulating evidence indicates that systemic inflammatory burden increases with advancing age and represents a hallmark of biological aging. However, whether aging amplifies the prognostic impact of inflammatory biomarkers on long-term cardiovascular outcomes after percutaneous coronary intervention (PCI) remains unclear. Purpose To investigate age-related effect modification in the associations between inflammatory biomarkers and long-term cardiovascular risk among patients with coronary artery disease (CAD) undergoing PCI. Methods This prospective cohort study enrolled 10,724 consecutive CAD patients undergoing PCI between January and December 2013, with follow-up of up to 10 years. Patients were divided into three groups according to age (<60, 60–74, and ≥75 years). Inflammatory burden was assessed using 12 biomarkers, including white blood cell count and subtypes, derived inflammatory indices, and high-sensitivity C-reactive protein (hsCRP). All biomarkers were analyzed as continuous variables and by quartiles. Multivariable Cox proportional hazards models, ranging from unadjusted (Model 1) to fully adjusted models (Model 6), were performed. The primary outcome was major adverse cardiovascular and cerebrovascular events (MACE, including death, myocardial infarction, and revascularization) and the secondary outcomes were each component of MACE and cardiac death. Results Among 9,570 patients included in the final analysis (mean age 58.6 ± 10.3 years; 22.8% women), 3,551 (37.1%) experienced MACE during 10-year follow-up. Significant age-related effect modification was observed for the associations between multiple inflammatory biomarkers and MACE. Restricted cubic spline analyses showed clear age-related modification of the dose–response relationships between inflammatory biomarkers and MACE, with predominantly non-linear patterns in patients <60 years but more linear risk increases in older patients (Figure 1). In fully adjusted models, higher quartiles of inflammatory biomarkers were associated with increased risks of MACE and mortality, with substantially stronger associations in older patients, particularly for systemic and composite inflammatory markers such as hsCRP, NLR, SII, SIRI, AISI, and PLR (Figure 2). Conclusions In this large-scale real-world cohort with 10-year follow-up, advancing age significantly amplified inflammation-related cardiovascular risk after PCI, with older patients exhibiting stronger associations between inflammatory biomarkers and long-term adverse outcomes, highlighting the importance of age-informed risk stratification and targeted anti-inflammatory strategies in elderly patients.