Neutrophil-to-lymphocyte ratio as a prognostic biomarker in patients with peripheral artery disease: A systematic review and meta-analysis

Background: The neutrophil-to-lymphocyte ratio (NLR) is a simple and routinely obtained parameter reflecting systemic inflammation, including in peripheral artery disease (PAD). Methods: This systematic review aimed to assess the role of NLR as a prognostic biomarker in patients with PAD. A systematic search was conducted across PubMed, ScienceDirect, Web of Science, Scopus, ProQuest, EBSCO, and Cochrane. Random-effects meta-analysis was used to pool risk ratios, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). A bivariate model was used to generate summary receiver operating characteristics with the corresponding area under the curve (AUC). Results: This review included 5243 patients with PAD from nine eligible studies. High NLR corresponded to at least a twofold increased risk of all-cause mortality (ACM), major adverse limb events (MALE), and major adverse cardiovascular events (MACE). NLR's performance was good for predicting 1-year ACM (AUC 0.71 [95% CI: 0.59-0.79], sensitivity 58.2% [95% CI: 45.3-71.0], specificity 72.6% [95% CI: 65.6-79.62], PPV 41.0% [95% CI: 31.2-50.7], NPV 82.7% [95% CI: 74.1-91.3]) and 1-year MALE (AUC 0.78 [95% CI: 0.75-0.80], sensitivity 65.4% [95% CI: 41.6-89.2], specificity 77.7% [95% CI: 71.0-84.3], PPV 53.7% [95% CI: 47.3-60.1], NPV 83.91% [95% CI: 73.2-94.6]). However, these values tended to decrease as the follow-up duration extended, except for the pooled specificities, which exhibited the opposite pattern. Conclusion: NLR emerges as a simple and cost-effective prognostic biomarker with decent performance for poor outcomes in patients with PAD (PROSPERO Registration No.: CRD42023486607).