Predicting Cardiovascular Events in Non-Small Cell Lung Cancer Patients: The Role of Cumulative Risk Factors and Inflammation Beyond Surgery

Background Improved survival in non-small cell lung cancer (NSCLC) amplifies cardiovascular morbidity risks, yet predictive models integrating cumulative cardiovascular disease risk factors (CVDRFs) and inflammation remain underdeveloped. This study assessed the joint prognostic value of CVDRFs burden，N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) and neutrophil-to-lymphocyte ratio (NLR) for composite cardiovascular endpoints (CCEs) post-surgery. Methods In 501 stage II-III NSCLC patients undergoing radical surgery (2016–2024), this study quantified cumulative CVDRFs (hypertension, diabetes, hyperlipidemia, obesity, smoking, heart disease history)， NT-proBNP and preoperative NLR. CCEs included cardiovascular death, myocardial infarction, stroke, unstable angina, or heart failure. Fine-Gray competing risk models (accounting for non-cardiovascular mortality) evaluated predictors total time 60-month follow-up. Subgroup analyses stratified CVDRFs burden (low: ≤1, medium: 2, high: ≥3) and NLR thresholds. Results CCEs occurred in 68.1% (n=341). Each additional CVDRFs increased CCEs risk by 29% (sHR=1.29, 95% CI:1.01–1.64; p =0.038), while each NLR unit increment raised risk by 8.9% (sHR=1.089, 95% CI:1.005–1.180; p =0.037). Patients with ≥3 CVDRFs + NLR>2.1 exhibited synergistic risk (60-month CCEs incidence: 86.7%; sHR=4.21, 95% CI:2.58–6.87). NT-proBNP >111.15 pg/mL independently predicted CCEs (sHR=1.80, 95% CI:1.01–3.21; p =0.038). Treatment-stratified analysis revealed: EGFR-TKI therapy reduced CCEs risk (sHR=0.65, 95% CI:0.48–0.88), especially in low-CVDRFs patients (sHR=0.52)；Immune checkpoint inhibitors amplified risk in high-CVDRFs patients (≥3 CVDRFs: sHR=1.78, 95% CI:1.15–2.76). Stage III patients with high CVDRFs/NLR had significantly reduced median CCEs-free survival (24 vs. 49 months in Stage II; p <0.001). Conclusions Cumulative CVDRFs burden and NLR independently predict accelerated CCEs in postoperative NSCLC, with synergistic risk in high-burden patients (≥3 CVDRFs + NLR>2.1). NT-proBNP elevation further stratifies risk. EGFR-TKIs demonstrate cardioprotection, while ICIs exacerbate risk in comorbid patients. Intensified surveillance integrating CVDRFs, NLR, and NT-proBNP is warranted for high-risk subgroups to mitigate inflammation-driven cardiovascular morbidity.