Neutrophil–Lymphocyte Ratio: A Simple Marker Reflecting the Complex Biology of Myocardial Infarction

Abstract

The association of inflammation and atherosclerosis has, for many years, now been recognized as one of the cornerstones in the pathophysiology of cardiovascular disease. In addition to cholesterol and thrombosis, the process of atherogenesis is now understood as a chronic inflammatory process encompassing both innate and adaptive immune pathways. In this context, the study by Mostafa et al., from Sharourah General Hospital, KSA, appearing in this issue of the Pakistan Heart Journal, comes at an opportune time to underscore the clinical utility of the neutrophil-to-lymphocyte ratio (NLR) in patients presenting with acute myocardial infarction (AMI) [1]. The rupture of an atherosclerotic plaque and subsequent thrombosis mark the culmination of years of subclinical inflammation. The acute event itself triggers a second inflammatory cascade—characterized by a surge of circulating neutrophils and depletion of lymphocytes—which influences infarct size, myocardial remodeling, and prognosis. Unlike sophisticated biomarkers such as interleukin-6 or high-sensitivity CRP, NLR can be derived easily from a standard blood count, offering an attractive, inexpensive, and rapid surrogate for inflammatory activity [2]. Mostafa et al. retrospectively analyzed 125 consecutive patients admitted with acute coronary syndromes between the years 2021 and 2023. Almost 38% presented with STEMI and 62% with NSTEMI. The investigators demonstrated that NLR values were significantly higher in STEMI compared with NSTEMI (median 4.2 vs 2.2, p = 0.006). Receiver-operating characteristic analysis yielded an optimal cutoff of > 4.17 for predicting STEMI with a sensitivity of 53% and specificity of 83%. Importantly, NLR correlated positively with white-cell and platelet counts in both groups, underscoring its inflammatory basis. Although these findings reinforce previously reported trends, they are particularly pertinent to resource-poor settings in which advanced inflammatory or imaging tests are not typically available. The observation by the authors that increasing NLR parallels the severity of myocardial injury lends support to the hypothesis that the systemic inflammatory response reflects plaque instability and thrombosis. This simplicity of the NLR belies its biological richness: neutrophils, as first responders to plaque rupture, release proteolytic enzymes, reactive oxygen species, and NETs, all of which propagate endothelial injury and thrombus formation. Lymphopenia reflects cortisol-mediated stress and impaired adaptive immunity. The ratio of these two components integrates both pro- and anti-inflammatory influences into a single quantifiable measure. Several studies have demonstrated that a high admission NLR predicts not only poor short-term but also long-term outcomes related to ACS, such as heart failure, arrhythmia, and mortality [3]. Moreover, NLR was found to be related to impaired coronary flow following primary PCI, reflecting microvascular obstruction. The cut-off value by Mostafa et al. (> 4.17) agrees quite well with international data, though with some inter-study variability due to population differences and timing of sampling. This study deserves praise for representing one of the few research works emanating from Saudi Arabia on the NLR in AMI, adding regional data to a growing global evidence base. The fact that the two subtypes, STEMI and NSTEMI, were both included provides an opportunity for direct comparison of the inflammatory responses across the ACS spectrum. However, the retrospective design inherently limits causal inference. The absence of outcome data, such as mortality or heart failure rates, precludes any assessment of the prognostic power of NLR beyond diagnosis. Furthermore, potential confounders such as infection, smoking, and medications that are well known to alter leukocyte dynamics were not fully controlled. Future, prospective, multicenter studies with serial NLR measurements and correlations with outcomes would provide stronger evidence. Notwithstanding these caveats, the findings have important clinical implications: Risk Stratification: NLR can complement the existing markers, like troponin and CK-MB, in stratifying patients into high-risk groups who will benefit from aggressive therapy or closer monitoring. Resource-Limited Utility: In peripheral or non-tertiary hospitals, NLR represents a free adjunct to ECG and enzymes for early triage. Integration into Prognostic Models: Combining NLR with the GRACE or TIMI score could help further delineate risk. Therapeutic Targeting: Baseline NLR may serve to guide emerging anti-inflammatory treatments, such as colchicine or IL-1β inhibitors, toward personalized therapy. The association between high NLR and STEMI is not merely statistical. Activated neutrophils express tissue factor and engage in a cross-talk with platelets to enhance thrombosis. Neutrophil-derived NETs serve as scaffolds for fibrin and mediate microvascular plugging, thus worsening the reperfusion outcome. Concurrent lymphocyte apoptosis impairs anti-inflammatory cytokine secretion, which further shifts the immune balance toward thrombosis. Thus, NLR serves as a mirror of this immunothrombotic interplay-its rise signals the dominance of inflammation over repair. A recent meta-analysis including more than 20,000 ACS patients confirmed that a high NLR independently predicted in-hospital mortality and major adverse cardiac events [4]. Moreover, dynamic changes in the NLR-from admission to 48 hours-carry prognostic significance and indicate that serial monitoring could be even more informative than a single baseline value. Studies in COVID-19 and metabolic syndrome have also extended NLR's utility as a systemic inflammatory marker, reinforcing its biological coherence across conditions. In summary, this study convincingly shows that NLR is significantly higher in STEMI as compared to NSTEMI and reflects enhanced inflammatory activation. Though NLR cannot replace established diagnostic criteria for the diagnosis of STEMI, it may act as an important aid in risk stratification, especially in resource-poor settings. As inflammation-modulating therapies gain center stage in cardiovascular medicine, simple indices like NLR may help in identifying the subset of patients who stand to benefit most. This paper enriches regional cardiovascular literature and invites larger, prospective validation. The message is clear: the next frontier in myocardial infarction management may not only lie in reopening the artery-but also in tempering the inflammation that closes it. AUTHORS' CONTRIBUTION KAH, AA, and AH: Concept and design, data acquisition, interpretation, drafting, final approval, and agree to be accountable for all aspects of the work. Acknowledgment: None. Funding: No specific grant for this research from any public, commercial, or not-for-profit funding agency References Mostafa MM, Alburaiki TA, Al-Siari SS, Al-Siari MA, Safhi WM. Neutrophil-Lymphocyte Ratio in Patients with Acute Myocardial Infarction: A Retrospective Study. Pak Heart J. 2025;58(04):403-410. DOI: 10.47144/phj.v58i4.2895 Henein MY, Vancheri S, Longo G, Vancheri F. The Role of Inflammation in Cardiovascular Disease. Int J Mol Sci. 2022; 23(21):12906. DOI: 10.3390/ijms232112906 Gul U, Kayani AM, Munir R, Hussain S. Neutrophil-Lymphocyte Ratio: A Prognostic Marker in Acute ST-Elevation Myocardial Infarction. J Coll Physicians Surg Pak. 2017; 27(1):4-7. PMID: 28292359 Kazem N, Hofer F, Koller L, Hammer A, Hofbauer TM, Hengstenberg C, et al. Age-Specific Prognostic Impact of Platelet-to-Lymphocyte Ratio on Long-Term Outcome After Acute Coronary Syndrome. Eur Heart J Open. 2021; 2(1):oeab031. DOI: 10.1093/ehjopen/oeab031