Predictive Value of Neutrophil-to-Lymphocyte Ratio on Drug-Eluting Stent Restenosis in Patients with Type 2 Diabetes Mellitus
In-stent restenosis (ISR) remains a significant complication following percutaneous coronary intervention (PCI), despite advancements in stent technology and antithrombotic therapies. Drug-eluting stents (DES) have reduced ISR rates to 5–10% by mitigating inflammatory responses and neointimal hyperplasia through localized drug delivery. However, ISR continues to pose clinical challenges, particularly in high-risk populations such as patients with type 2 diabetes mellitus (T2DM). These patients exhibit heightened inflammatory states and endothelial dysfunction, which contribute to accelerated atherosclerosis and restenosis. Identifying biomarkers for ISR risk stratification is critical for optimizing post-PCI management. Among emerging biomarkers, the neutrophil-to-lymphocyte ratio (NLR), a cost-effective and readily accessible inflammatory marker, has shown promise in predicting adverse cardiovascular outcomes. This study investigates the predictive utility of pre-procedural NLR values before the first PCI and follow-up coronary angiography (CAG) for DES-ISR in patients with T2DM.
Study Design and Population
A retrospective analysis was conducted on 96 patients with T2DM (mean age: 65.3 ± 8.4 years; 70.8% male) who underwent elective PCI with DES implantation followed by follow-up CAG between January 2016 and January 2019. Inclusion criteria required a diagnosis of stable or unstable angina, age 45–80 years, and follow-up angiography within 6–15 months post-PCI. Exclusion criteria included recent myocardial infarction (<2 months before stenting), systemic inflammatory or infectious conditions, chronic kidney disease, or therapies affecting blood cell parameters. All patients received standard dual antiplatelet therapy (aspirin 100 mg/day and clopidogrel 75 mg/day for ≥12 months) and underwent successful DES implantation per guidelines.
Definition of ISR and NLR Measurement
ISR was defined as stenosis >50% within the stent or 5 mm proximal/distal to the stent on follow-up angiography. NLR was calculated as the ratio of absolute neutrophil count to absolute lymphocyte count from pre-procedural blood samples collected before the initial PCI (NLR1) and follow-up CAG (NLR2).
Key Findings
Patients were stratified into ISR (n=32) and non-ISR (n=64) groups based on follow-up angiography. Baseline demographic, clinical, and angiographic characteristics were comparable between groups, with no significant differences in cardiovascular risk factors, comorbidities, or medications.
NLR as a Predictor of ISR
- Pre-Procedural NLR Values: The ISR group exhibited significantly higher NLR levels compared to the non-ISR group before both the initial PCI (NLR1: 3.08 ± 1.17 vs. 2.31 ± 0.91, P=0.001) and follow-up CAG (NLR2: 3.16 ± 0.92 vs. 2.26 ± 0.66, P<0.001).
- ROC Analysis:
- NLR1 demonstrated moderate predictive accuracy for ISR, with an optimal cutoff of 2.86 (sensitivity: 59%, specificity: 73%; AUC=0.71, 95% CI: 0.59–0.81, P=0.001).
- NLR2 showed superior predictive performance, with a cutoff of 2.51 (sensitivity: 75%, specificity: 70%; AUC=0.80, 95% CI: 0.71–0.89, P<0.001).
- The difference in AUC between NLR1 and NLR2 (0.098, 95% CI: 0.016–0.212) approached but did not reach statistical significance (P=0.090).
Multivariate Analysis
In logistic regression adjusted for confounders, only pre-procedural NLR (both NLR1 and NLR2) independently predicted ISR. Other hematologic parameters, including platelet-to-lymphocyte ratio (PLR), red cell distribution width (RDW), mean platelet volume (MPV), and platelet distribution width (PDW), showed no significant associations.
Mechanistic and Clinical Implications
The study underscores the role of systemic inflammation in DES-ISR pathogenesis, particularly in T2DM. Neutrophils promote oxidative stress and cytokine release, exacerbating vascular injury, while lymphocytes modulate adaptive immune responses. An elevated NLR reflects a pro-inflammatory state favoring neointimal hyperplasia and impaired endothelial repair. The stronger predictive value of NLR2 may indicate persistent inflammation contributing to delayed restenosis, highlighting the utility of serial NLR measurements in risk assessment.
These findings align with prior studies linking NLR to ISR. For instance, Li et al. identified pre-PCI NLR as an independent predictor of ISR in chronic total occlusion lesions, while Gabbasov et al. reported similar associations in T2DM cohorts. However, this study uniquely evaluates dynamic NLR changes across two timepoints, suggesting that follow-up NLR enhances risk stratification.
Limitations and Future Directions
The study’s retrospective design and single-center cohort limit generalizability. Visual assessment of stenosis, rather than quantitative coronary angiography, may underestimate ISR incidence. Additionally, the small sample size (n=96) and lack of data on diabetes duration, lesion complexity, and stent types constrain subgroup analyses. Future prospective studies with larger cohorts, standardized imaging modalities, and extended follow-up are needed to validate NLR’s predictive utility and explore interactions with glycemic control or novel anti-inflammatory therapies.
Conclusion
Pre-procedural NLR, particularly before follow-up angiography, is a robust and independent predictor of DES-ISR in patients with T2DM. With its simplicity and accessibility, NLR may serve as a valuable tool for identifying high-risk patients requiring intensified surveillance or adjunctive therapies. Incorporating serial NLR measurements into clinical practice could enhance personalized management and improve outcomes in this vulnerable population.
doi.org/10.1097/CM9.0000000000001045
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