Under Smoke: The Impact of Smoking on Inflammatory Indices in Patients with Saphenous Vein Graft Degeneration: A Retrospective Study

Coronary artery bypass grafting (CABG) surgery, a cornerstone of revascularization therapy, is widely performed for advanced coronary lesions. The saphenous vein graft (SVG), favored over arterial grafts due to ease of access and lower perioperative risk, is commonly used. However, SVGs demonstrate considerable rates of degeneration and occlusion over time, with 3-12% occluding prior to hospital discharge, 8-25% failing within the first year, and only 50-60% remaining patent after a decade (1, 2).

SVG degeneration (SVGD) is a multifactorial process. Three pathophysiological mechanisms lead to SVG failure: thrombosis and technical failure predominate in the early post-CABG period (first week to first month); intimal hyperplasia occurs between one month and one year; and atherosclerosis develops after one year. SVG atherosclerosis progresses more rapidly than native coronary artery disease, often presenting as concentric, diffuse lesions that lack a fibrous cap and are prone to rupture. Endothelial dysfunction and inflammatory responses trigger these changes (1, 3). Smoking exacerbates many of these factors by increasing vascular inflammation, impairing endothelial function, and creating a pro-atherogenic environment (4).

Inflammatory indices derived from hematological parameters, such as neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), atherogenic index of plasma (AIP), and pan-immune inflammation value (P-IV), have recently gained prominence as prognostic markers in clinical practice (5-8). However, their relationship with SVGD has been studied only in limited contexts.

This study hypothesizes that smoking markedly elevates systemic inflammation in patients with SVGD and that this effect can be objectively quantified using widely available inflammatory indices.

Study Design and Population

We included individuals who underwent coronary angiography at our cardiology clinic from January 2017 to December 2023 and were identified as having ≥50% stenosis in at least one SVG. A total of 213 patients were divided into non-smokers (n=82) and smokers (n=131) based on smoking status. University of Health Sciences Türkiye, Hamidiye Faculty of Medicine Ethics Board approved the study (decision no: 10/20, date: 08.05.2025). The study was carried out in compliance with the ethical principles outlined in the Declaration of Helsinki.

Exclusion Criteria

Patients with active infection, malignancy, chronic inflammatory diseases, autoimmune disorders, or hematological diseases were excluded.

Definitions

SVGD was defined as ≥50% stenosis in the graft lumen outside the anastomosis site. Smoking was defined as self-reported consumption of at least one cigarette per day for the past six months.

Data Collection

Demographic data, comorbidities (hypertension, diabetes mellitus, peripheral artery disease, etc.), medical treatment histories, and laboratory results were obtained from hospital records. Hematological and biochemical parameters were derived from blood samples collected within 24 hours of coronary angiography.

Inflammatory Index Calculations:

• NLR: neutrophil count/lymphocyte count

• LMR: lymphocyte count/monocyte count

• SII: (neutrophil × platelet)/lymphocyte

• SIRI: (neutrophil × monocyte)/lymphocyte

• P-IV: (neutrophil × monocyte × platelet)/lymphocyte

• AIP: log (triglycerides/HDL)

• Prognostic nutritional index (PNI): [10 × serum albumin (g/dL)] + [0.005 × total lymphocyte count (mm³)]

Statistical Analysis

Statistical analyses were performed using IBM SPSS Statistics 27. Normality was assessed using the Kolmogorov-Smirnov test. Normally distributed variables were presented as mean ± standard deviation; non-normal variables were presented as median (interquartile range). Group comparisons were performed using t-tests or Mann-Whitney U tests for continuous variables and chi-square tests for categorical variables. To identify factors associated with smoking status, variables with p-values <0.10 in the univariate analysis (age, sex, peripheral artery disease, neutrophil count, monocyte count, and white blood cell count) were entered into a backward stepwise multivariate logistic regression model. Results were reported as odds ratios (OR) with 95% confidence intervals (CI). A two-tailed p-value <0.05 was considered statistically significant.

Of the 213 patients included, 131 (61.5%) were active smokers and 82 (38.5%) were non-smokers. The smoker group was significantly younger (66.3±8.7 vs. 69.0±8.2 years; p=0.029) and had a higher proportion of males (90.1% vs. 79.3%; p=0.027) (Table 1).

Comorbidities and Clinical Characteristics

Peripheral artery disease (PAD) was significantly more prevalent in smokers (22.9% vs. 7.3%, p=0.003). No significant differences were observed between groups with respect to hypertension, diabetes, chronic kidney disease, or cerebrovascular disease (p>0.05) (Table 1).

Laboratory Findings

Smokers had significantly higher neutrophil counts (5.2 vs. 4.2 ×10³/µL, p<0.001), monocyte counts (0.53 vs. 0.47 ×10³/µL, p=0.001), and white blood cell counts (8.0 vs. 7.2 ×10³/µL, p=0.006). No significant differences were found in lymphocyte counts, hemoglobin, platelet counts, cholesterol, or glucose levels. Inflammatory indices NLR (2.55 vs. 2.25, p=0.027), SII (576 vs. 457, p=0.002), SIRI (1.33 vs. 0.99, p<0.001), P-IV (319 vs. 230, p<0.001), and AIP (0.52 vs. 0.45, p=0.048) were significantly elevated in smokers, whereas LMR was significantly lower (3.84 vs. 4.78, p=0.007) (Table 2).

Regression Analyses

Multivariate logistic regression identified male sex (OR: 0.2963; 95% CI: 0.1031-0.8518; p=0.024), younger age (OR: 0.9454; 95% CI: 0.9007-0.9923; p=0.023), PAD (OR: 3.61; 95% CI: 1.08-12.02; p=0.036), and neutrophil count (OR: 1.23; 95% CI: 1.00-1.52; p=0.045) as independent factors associated with smoking (Table 3).

This study evaluated the effects of smoking on systemic inflammatory indices in patients with SVGD. Our research findings indicate that individuals who smoke have significantly elevated levels of inflammatory markers, including NLR, SII, SIRI, P-IV, and AIP. Additionally, male sex, younger age, PAD, and neutrophil levels were independently associated with smoking.

The impact of smoking on systemic inflammation has been extensively documented. Smoking triggers endothelial dysfunction, leukocyte activation, oxidative stress, and pro-inflammatory cytokine release, accelerating atherosclerotic processes in the vascular wall (4, 8). SII, by integrating platelet, neutrophil, and lymphocyte counts, reflects both inflammatory and thrombotic activity. Its significant elevation in smokers with SVGD highlights the prothrombotic milieu induced by smoking, which may accelerate graft atherosclerosis and plaque instability through enhanced platelet-neutrophil interactions (9).

The marked elevations in SIRI and, especially, P-IV in the smoking group are also clinically relevant. Recent studies have demonstrated the strong prognostic value of these composite indices in various acute and chronic cardiovascular conditions, including prediction of in-hospital mortality in infective endocarditis and in acute pulmonary embolism (10, 11). Smokers exhibited a significantly lower lymphocyte-to-monocyte ratio (LMR) than non-smokers. The reduction in LMR reflects smoking-induced monocyte predominance and relative lymphopenia, consistent with enhanced monocyte-driven chronic inflammation and impaired adaptive immune responses. This finding further supports the pivotal role of the monocyte-macrophage pathway in smoking-related acceleration of intimal hyperplasia and atherosclerosis within SVGs.

These findings reinforce the notion that the heightened immune–inflammatory activation observed in our smoking cohort represents a systemic prothrombotic and proatherogenic state that extends beyond the graft and likely accelerates SVGD.

Although PNI did not differ significantly between smokers and non-smokers in our cohort, this index has repeatedly been shown to predict long-term mortality and adverse cardiovascular outcomes in patients with heart failure with reduced ejection fraction, even in those with implantable cardioverter-defibrillators (12). In the present study, the absence of a smoking-related difference in PNI may indicate that the malnutrition-inflammation complex is not primarily driven by smoking in the SVGD setting; nevertheless, routine nutritional assessment remains important for long-term graft patency and survival in all post-CABG patients.

AIP, indicative of a dyslipidemic profile, was significantly higher in smokers, reflecting smoking’s atherogenic impact on lipid metabolism (13). AIP is a strong predictor of future cardiovascular events in CAD patients (14).

The younger age and higher proportion of males among smokers likely reflect earlier smoking initiation, higher smoking rates among men, and earlier exposure to cardiovascular risk factors (15, 16). These demographic factors may influence inflammatory responses and graft degeneration.

Another notable finding was the significantly higher prevalence of PAD among smokers, suggesting systemic atherosclerosis affecting multiple vascular beds and indicating that SVGD may mirror deterioration of systemic vascular health (17).

From a clinical perspective, these low-cost, routinely available inflammatory indices (NLR, SII, SIRI, P-IV, and AIP) provide a simple, objective tool for risk stratification after CABG. Their incorporation into routine follow-up may enable early identification of smokers at highest risk of rapid graft degeneration, thereby guiding intensified smoking-cessation interventions, closer angiographic surveillance, and tailored anti-inflammatory or antiplatelet therapies. Such inflammation-based risk stratification has the potential to improve long-term graft survival and overall prognosis in this high-risk population.

Previous studies have highlighted NLR and SII as valuable markers not only in acute syndromes but also in chronic vascular diseases. Zhang et al. (18) demonstrated NLR’s diagnostic and prognostic utility, and Oksuz et al. (19) reported associations between SII and graft patency post-CABG. Our results corroborate these findings. Strengths of this study include verification of smoking status through medical records and follow-up rather than sole reliance on patient self-report, and a comprehensive evaluation of inflammatory indices.

Study Limitations

Limitations include the retrospective design, potential selection bias, lack of quantitative smoking exposure assessment (pack-years), and SVGD diagnosis based solely on coronary angiography without advanced imaging modalities such as IVUS or OCT. The single-center setting may limit generalizability.

In conclusion, smoking significantly elevates inflammatory markers in patients with SVGD, indicating that SVGD reflects not only localized graft disease but also a systemic inflammatory response. Smoking cessation is critical not only to prevent new lesions but also to preserve existing graft patency.

This study provides clinicians with important insights, emphasizing the need for close monitoring of inflammatory biomarkers in smokers with SVGD. Incorporating these indices into routine clinical practice may guide prediction of graft prognosis and personalization of treatment strategies.

Ultimately, the detrimental effects of smoking on graft survival are quantitatively demonstrated via inflammatory indices, underscoring that smoking cessation is not merely a lifestyle choice but a therapeutic necessity to maintain graft patency.