Neutrophil-Lympocyte Ratio and Cardiovascular Diseases: An Update.

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The neutrophil–lymphocyte ratio (NLR) has gained significant interest for the prediction of outcomes in patients with vascular disease. The NLR is easily obtained from a full blood count. The NLR is a reflection of the following 2 different yet complementary systems: neutrophils are part the inflammatory response and lymphocytes part of the adaptive immune response. An increased neutrophil count is associated with adverse angiographic outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and peripheral vascular dysfunction in individuals at low cardiovascular risk. Lower lymphocyte counts are associated with adverse outcomes in patients with chronic coronary artery disease (CAD) and heart failure. Horne et al were the first to report the relevance of the NLR in stable CAD. In an average follow-up of 3.5 years, the total white blood cell count was an independent predictor of death/myocardial infarction, but the NLR provided better risk prediction. Recently, Pan et al reported that the NLR was independently correlated with coronary blood flow and was an independent risk factor for in-hospital mortality in patients with STEMI undergoing percutaneous coronary intervention (PCI). In this prospective study, patients were stratified on admission into NLR tertiles. During the 12-month follow-up, a significant increase in long-term mortality was observed in tertiles I to III. Others also reported that the NLR was independently associated with the severity of CAD in patients with STEMI. In another prospective multicenter study, the NLR was an independent predictor of both in-hospital and long-term outcomes among patients with STEMI undergoing primary PCI (pPCI). Similarly, Sen et al found that in patients with STEMI who underwent pPCI, elevated NLRs on admission correlated with both no-reflow phenomenon and long-term prognosis. Cicek et al suggested that the combined use of NLR and platelet–lymphocyte ratio may be useful for the prediction of inhospital and long-term mortality in patients undergoing pPCI. There are some conflicting results on the association between baseline leukocyte profile and prognosis in patients with STEMI. Smit et al showed that the leukocyte profile at baseline was not associated with 1-year mortality. Park et al measured total and differential leukocyte counts once at admission and 24 hours thereafter in patients with STEMI treated with pPCI; they found that the leukocyte profile 24 hours after admission, but not the admission leukocyte profile, was associated with clinical outcomes (all-cause death). Indeed, Chia et al showed that total leukocyte and neutrophil counts at 24 hours after pPCI, but not the baseline hematologic indices, were an independent predictor of adverse cardiac events in patients with STEMI. In contrast, Sulaiman et al reported that admission leukocyte count was an independent risk factor for in-hospital cardiogenic shock and mortality in patients with acute coronary syndrome. In another study, in patients with STEMI, preprocedural high NLR was significantly associated with both stent thrombosis and higher mortality rates. There are no established cutoff values for the NLR. Azab et al reported that patients with non-STEMIs with an average NLR >4.7 had increased mortality. Horne et al proposed an NLR >4.71 as a cutoff value for patients with stable CAD. In the study of Park et al, the cutoff value was 5.44. Those studies have mainly used the highest quartile of NLR as the cutoff value. In contrast, in the Pan et al and Ayca et al studies, the NLR cutoff value for predicting in-hospital mortality was derived from receiver–operating characteristic curve analysis with threshold values of 5.9 and 4.9, respectively. On the other hand, a few studies have reported a higher prevalence of previous PCI in the lowest admission NLR tertile and suggested that anti-inflammatory actions of some medications after PCI, such as clopidogrel and statins, lower the NLR. The NLR has been also associated with contrastinduced nephropathy, which is an emerging important issue in patients receiving contrast media. The NLR, measured at admission, 24 hours after PCI, immediately before PCI and 1, 2, 3, 5, and 30 + 2 days later or calculated as an average or maximum value has been found to be an independent predictor of mortality and adverse outcomes. A study of 692 Chinese patients with STEMI found that the NLR measured at admission, 24, and 72 hours after admission, before discharge, and both maximum and average NLR during hospitalization all predicted mortality. In STEMI, the peripheral leukocyte count usually increases within 2 hours after the onset of chest pain and peaks 2 to 4 days after infarction returning to normal in 1 week. The shorter life span (around 7 hours) with a rapid turnover of