Review

The Relation Between Atherosclerosis and the Neutrophil–Lymphocyte Ratio

Clinical and Applied Thrombosis/Hemostasis 1-7 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/1076029615569568 cat.sagepub.com

Sevket Balta, MD1, Turgay Celik, MD2, Dimitri P. Mikhailidis, MD3, Cengiz Ozturk, MD2, Sait Demirkol, MD2, Mustafa Aparci, MD4, and Atila Iyisoy, MD2

Abstract Inflammation plays an important role in the pathophysiology of vascular disease. In this review, we consider the associations between the neutrophil–lymphocyte ratio (NLR; an indicator of inflammation) and vascular disease and its associated risk factors. The NLR has received attention due to its role as an independent prognostic factor for coronary artery disease. The NLR can also be affected by atherosclerotic risk factors, such as hypercholesterolemia, metabolic syndrome, diabetes, and hypertension. Importantly, it can predict mortality in cardiovascular diseases. There are also reports of a positive correlation between the NLR and commonly used inflammatory markers. Inflammation is important not only in pathophysiology but also clinical outcomes of many diseases. The NLR is a widely available, easily derived, and reproducible marker of inflammation. Unlike many other inflammatory markers, the NLR is inexpensive and readily available and it provides additional risk stratification beyond conventional risk scores. Keywords neutrophil–lymphocyte ratio, atherosclerosis, inflammation

Introduction Elevated levels of systemic inflammatory markers are associated with cardiovascular disease (CVD).1 The white blood cell (WBC) count is a useful inflammatory biomarker in clinical practice. The neutrophil–lymphocyte ratio (NLR) can also be an indicator of systemic inflammation.2 The NLR is calculated by dividing the neutrophil count by the lymphocyte count.3 This ratio is easily accessible inflammatory marker with predictive power for death, myocardial infarction, and high risk of coronary artery disease (CAD).4-6 Furthermore, many epidemiological studies have highlighted that chronic low grade inflammation, as measured by the NLR, has also been linked to risk factors like diabetes mellitus (DM), hypertension, metabolic syndrome (MetS), obesity, hyperlipidemia, lifestyle habits, and endothelial dysfunction (Figure 1).7,8

progression of atherosclerosis. Several processes have been postulated, including plaque disruption caused by neutrophil infiltration and increased neutrophil platelet adhesion. Direct visualization in recent studies conducted in animal models has shown that there is a neutrophil invasion of the atherosclerotic plaque.11 In addition, neutrophils may make plaques more vulnerable through the release of proteolytic enzymes, arachidonic acid derivatives, and superoxide radicals.11 Neutrophils also secrete inflammatory mediators and are associated with an acute inflammatory response to tissue injury.11 A higher NLR, even within the normal WBC count range, has been associated with atherosclerotic events.4 The NLR also has prognostic importance in CVD. The relation between atherosclerosis progression and leukocyte subtype was evaluated.12 The NLR was a more accurate marker of cardiac adverse events rather than the differential leucocyte count.12 A high NLR is a

Cardiovascular Disease and NLR 1

The relationship between the NLR and CVD is not fully defined; systemic factors like inflammation, endothelial dysfunction, and oxidative stress may play a role.9 The interaction between neutrophils and endothelial tissue has been hypothesized to cause increased damage to the endothelium. Severe inflammation is present in cases of ischemic tissue damage, in which leukocytes play a key role.10 Chronic inflammation in the arterial wall plays a crucial role in the initiation and

Department of Cardiology, Eskisehir Military Hospital, Eskis¸ ehir, Turkey Department of Cardiology, Gulhane Medical Academy, Ankara, Turkey 3 Department of Clinical Biochemistry, University College London Medical School London, University College London (UCL), London, England 4 Department of Cardiology, Etimesgut Military Hospital, Ankara, Turkey 2

Corresponding Author: Sevket Balta, Department of Cardiology, Eskis¸ ehir Military Hospital, Eskis¸ ehir, Turkey. Email: [email protected]

Downloaded from cat.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on February 13, 2015

2

Clinical and Applied Thrombosis/Hemostasis

Figure 1. Endothelial dysfunction can be observed in several diseases. Endothelial dysfunction can lead to higher neutrophil–lymphocyte ratio.

predictor of progression of atherosclerosis.10 Admission NLR is an independent predictor of in-hospital and 6-month mortality in patients with acute coronary syndromes (ACSs).13 The NLR was also recently shown to be an independent predictor of death/myocardial infarction in patients undergoing coronary angiography. The NLR has been investigated as a predictor of long-term mortality in patients undergoing percutaneous coronary intervention (PCI).12 The NLR was a strong independent predictor of long-term mortality after ST-segment elevation myocardial infarction (STEMI) treated with very early revascularization.14 Also, Soylu et al15 investigated the relationship between the NLR and coronary flow velocity after PCI in patients presenting with STEMI. They concluded that the NLR was an independent indicator for no-reflow development in these patients.15 The NLR may predict contrast-induced nephropathy in patients undergoing PCI.16 Gibson et al investigated leukocyte subtypes such as the NLR in patients undergoing coronary artery bypass graft (CABG).17 The authors concluded that an elevated NLR is associated with a poorer survival after CABG. Moreover, they found that the prognostic utility is independent of other recognized risk factors.17 Among patients with higher NLR, minimally invasive CABG was associated with a significantly improved survival compared with sternotomy CABG.18 The NLR has been associated with poor outcomes in patients with CVD. Hartaigh and coworkers19 found a significant relationship between the NLR and cardiovascular (CV) deaths. In-hospital major adverse cardiac events (MACEs) were significantly higher in patients with no reflow, and there was a significant and positive correlation between high sensitivity C-reactive protein (hsCRP) and the NLR.20 The NLR is also an inflammatory marker of MACEs in both ACSs and stable CAD. Patients with the lowest NLR had fewer MACEs compared with the highest NLR.21

Cardiovascular Disease Risk Factors and NLR The NLR has been proposed as a useful biomarker to predict CV risk.22 Inflammation is present in MetS,23 and there is

evidence that the NLR in MetS may be an early marker of developing CV events.24 The vascular inflammatory process plays a role in the pathophysiology of hypertension,25 and a high NLR may reflect vascular inflammation in these patients.8 Antihypertensive treatment may improve CV outcomes and decrease biomarkers such as the NLR.26 Several studies have suggested that chronic, subclinical inflammation plays a role in the development of insulin resistance, which may then proceed to overt DM.27 Risk factors for DM, such as obesity, smoking, and physical inactivity, are associated with chronic low-grade inflammation.27 Patients with DM have worse long-term outcomes after acute myocardial infarction (AMI) than nondiabetics.28 Increased NLR post-AMI is an independent predictor of MACEs in diabetics.28 In another study, patients with DM had significantly higher NLRs than those of the healthy control group, and also the NLR of the patients with diabetic retinopathy (DR) was higher than those of the patients without DR with DM.29 Furthermore, there was a statistically significant difference between NLR in diabetic patients with and without complications.30 The NLR is a significant independent predictor of MACEs in diabetic patients.21 Furthermore, an increased NLR may be associated with microvascular complications of DM in the elderly patients.30 The NLR was negatively correlated with high-density lipoprotein (HDL), which has anti-inflammatory activity. The NLR is significantly elevated in patients with low HDL-cholesterol when compared with control participants.31 In a landmark clinical study, increased inflammation was found to be common in patients with chronic kidney disease (CKD) and associated with increased adverse CV events.32 The authors demonstrated that the NLR is independently related to endothelial dysfunction and could predict composite CV end points independent of traditional confounding factors in patients with moderate to severe CKD.32 Overall and CVD-free survival rates were compared according to NLR in peritoneal dialysis patients. The NLR was a strong predictor of overall and CV mortality in these patients.33 The NLR might provide significant information regarding inflammation in CKD including predialysis and dialysis patients.34 The WBC count is an independent predictor of CV events and mortality, and the NLR is independently associated with CAD severity and 3-year clinical outcome. The NLR appears additive to conventional risk factors and commonly used biomarkers.35 The NLR also relates to the SYNTAX score (an index of the severity of coronary artery lesions). The NLR was significantly correlated with angiographic severity of ACS assessed by SYNTAX score. In patients with STEMI, an NLR 4.5 independently predicted an occluded infarct-related artery on initial angiography.36 The preoperative NLR identifies patients at increased risk of death within 2 years of major vascular surgery.37 This simple index demonstrates the balance of neutrophils, the active inflammatory component, with lymphocytes the regulatory and ‘‘protective’’ component.37 Therefore, a higher NLR represents

Downloaded from cat.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on February 13, 2015

Balta et al

3

a greater level of inflammation. A study determined whether the NLR is related to atherosclerosis as measured by brachial-ankle pulse wave velocity and coronary calcium score (CCS). A higher NLR was independently associated with arterial stiffness and CCS.38 An elevated NLR is associated with a poorer limb survival after embolectomy.39 Moreover, the preoperative NLR is an independent predictor of saphenous vein graft patency in patients after CABG.40 Also, a preoperative NLR >5 may be a significant predictor of 30-day mortality and long-term outcome in elective and urgent open abdominal aortic aneurysm repair. The NLR may have identified patients with subclinical CV disease.41 Chronic inflammation was found to be correlated with coronary (coronary artery calcification) and thoracic periaortic calcification.42 The NLR may also be associated with troponin levels in patients with ACS.43 An increased NLR is significantly associated with patients at high risk of critical limb ischemia and other vascular end points.44 In patients with peripheral arterial disease, after adjustment of several vascular risk factors, an NLR >3 was an independent predictor of long-term CV mortality.45 A meta-analysis showed that the NLR is a predictor of allcause mortality and CV events in patients undergoing angiography or cardiac revascularization.46 Also, the NLR can reclassify upward patients at intermediate-risk category according to the Framingham risk score.47

Other Inflammatory Diseases and the NLR Behc¸et disease (BD) is a chronic, multisystemic, and inflammatory disorder characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions.48 It is a systemic immunoinflammatory vasculitis.49 Several studies have reported indirect evidence of endothelial dysfunction in BD.50 We assessed the relationship between NLR and BD. There were statistically significant differences in NLR between the patients with BD and controls.51 Receiver–operating characteristic curve analysis suggested that the optimum NLR cutoff point for patients with BD was 1.29, with a sensitivity, specificity, negative predictive value, and positive predictive value of 97%, 77%, 96%, and 75%, respectively (P < .001; Figure 2).51 We concluded that the higher NLR may be related to endothelial dysfunction and may reflect disease activity in patients with BD.

Inflammatory Markers and the NLR In a large mortality study,52 involving patients with STEMI who underwent primary PCI, an elevated NLR on admission was strongly correlated with hsCRP levels. In another study, correlation analysis revealed a positive correlation between hsCRP and NLR in patients with BD.51 Some studies investigated the correlation between NLR and another indirect inflammatory marker, the carotid intima–media thickness (cIMT). We reported a positive correlation between the cIMT and NLR in patients with BD.51 We also showed that the NLR was

Figure 2. Receiver–operating characteristic curve of the neutrophil– lymphocyte ratio for predicting Behcet disease. PPV indicates positive predictive value; NPV, negative predictive value; AUC, area under the curve.

positively and moderately correlated with cIMT in slow coronary flow and control participants.53 In addition to the NLR, a full blood count can include measurements such as mean platelet volume (MPV), platelet distribution width (PDW), red cell distribution width (RDW), and platelet–lymphocyte ratio (PLR).54 These indices have also been used as inflammatory markers and are independent predictors of CVD and have been compared with the NLR in various clinical situations.10,54-57 The results have been variable but the NLR has been usually the best marker of disease progression. One key issue is to establish whether combinations of these markers are more effective predictors of the progression of several diseases compared with using a single marker. Platelet activation is a link in the pathophysiology of diseases prone to thrombosis and inflammation. Numerous platelet markers, including MPV and PDW, have been investigated in connection with both thrombosis and inflammation. Ma et al58 have investigated that whether MPV is independently associated with the cIMT in normotensive, euglycemic, and normolipidemic middle-aged and elderly adults. Mean platelet volume is independently associated with carotid atherosclerosis in normotensive, euglycemic, and normolipidemic males. The MPV could be an easily measured marker of atherosclerosis for males. In addition, it is well known that platelet volume indices are associated with adverse outcomes undergoing PCI. Kim et al59 investigated whether the association between platelet size and clinical outcomes is the result of high residual platelet reactivity after antiplatelet therapy in patients with large platelets. They concluded that platelets with a higher volume

Downloaded from cat.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on February 13, 2015

4

Clinical and Applied Thrombosis/Hemostasis

are associated with high residual platelet reactivity after conventional dual antiplatelet therapy. Mean platelet volume was independently and significantly associated with adverse CV outcome in patients with asymptomatic carotid atherosclerosis.60 Mean platelet volume is also a predictor of cardiac death after PCI.61 Mean platelet volume is positively associated with the GRACE risk score, and it may complement the scoring system in predicting CVD events in patients with ACS.62 Platelet distribution width measures the variability in platelet size and is a marker of platelet activation. Platelet distribution width may be used as a novel inflammatory marker. Admission PDW and MPV are independent correlates of no reflow and inhospital MACEs among patients with STEMI undergoing primary PCI.63 The PDW is a readily available platelet index that can predict coronary total occlusion.64 Recent studies have reported increased RDW has been associated with adverse outcomes in CAD.65 In a previous study, we have investigated RDW level in patients with cardiac syndrome X (CSX) and compare patients having CAD and normal subjects. Patients with CSX and CAD had significantly higher RDW measurements compared with controls. The relationship between CSX and higher RDW level suggests that endothelial dysfunction may also contribute to the etiopathogenesis of the CSX as it does with CAD.66 Also, RDW is closely related to the poor prognosis and adverse events of CVD. Kurtul et al67 have investigated the association of serum RDW levels and in-stent restenosis (ISR) after coronary stenting with bare-metal stent in patients with stable CAD. They concluded that increased serum RDW levels were independently associated with bare-metal ISR in patients with stable CAD. The RDW has been shown to predict not only CV mortality but also all-cause mortality.68 The RDW has been described to be a stronger biomarker for CHD death than widely used inflammatory markers like hsCRP.69 Furthermore, in addition to the NLR, some ratios like the PLR have been shown to be an inflammatory marker. A recent study70 investigated the relationship between the PLR and inhospital mortality in patients with ST-elevated AMI. They showed that the PLR is an independent predictor of CV mortality in patients with ST-elevated AMI. Yildiz et al71 evaluated the utility of the preprocedural PLR and NLR for predicting no reflow in patients undergoing PCI for the treatment of STEMI. They concluded that high preprocedural PLR and NLR are significant and independent predictors of no reflow in patients undergoing primary PCI.71 In addition to this study, Cic¸ek et al72 have investigated the effect of combination of NLR and PLR in predicting in-hospital and long-term mortality in patients undergoing primary PCI. The combination of PLR and NLR can be useful for the prediction of in-hospital and long-term mortality in patients undergoing primary PCI.

Major Confounding Factors The NLR may be related to nonvascular conditions associated with inflammation. For example, several types of cancer and their progression have been linked to the NLR.73-75 Cancer is

a common condition that may coexist with CVD. Cancer itself may be associated with an increased risk of thrombosis. In addition, some medications may affect the NLR. The NLR significantly decreased after statin therapy.76 Antihypertensive therapy like nebivolol significantly lowered the NLR.26 In this context, medication should be considered, when the NLR is assessed.

Conclusions The NLR can be easily calculated from the differential WBC count, which is widely available and routinely performed. Unlike many other inflammatory markers, the NLR is inexpensive and readily available and provides additional risk stratification beyond conventional risk scores (eg, to predict in-hospital and long-term mortality). Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

References 1. Balta I, Balta S, Demirkol S, et al. Aortic arterial stiffness is a moderate predictor of cardiovascular disease in patients with psoriasis vulgaris. Angiology. 2014;65(1):74-78. 2. Balta S, Demirkol S, Unlu M, Arslan Z, Celik T. Neutrophil to lymphocyte ratio may be predict of mortality in all conditions. Br J Cancer. 2013;109(12):3125-3126. 3. Arbel Y, Finkelstein A, Halkin A, et al. Neutrophil/lymphocyte ratio is related to the severity of coronary artery disease and clinical outcome in patients undergoing angiography. Atherosclerosis. 2012;225(2):456-460. 4. Horne BD, Anderson JL, John JM, et al. Which white blood cell subtypes predict increased cardiovascular risk? J Am Coll Cardiol. 2005;45(10):1638-1643. 5. Papa A, Emdin M, Passino C, Michelassi C, Battaglia D, Cocci F. Predictive value of elevated neutrophil–lymphocyte ratio on cardiac mortality in patients with stable coronary artery disease. Clin Chim Acta. 2008;395(1-2):27-31. 6. Sabatine MS, Morrow DA, Cannon CP, et al. Relationship between baseline white blood cell count and degree of coronary artery disease and mortality in patients with acute coronary syndromes: a TACTICS-TIMI 18 (Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction 18 trial) substudy. J Am Coll Cardiol. 2002;40(10):1761-1768. 7. Balta S, Kurtoglu E, Kucuk U, Demirkol S, Ozturk C. Neutrophil– lymphocyte ratio as an important assessment tool. Expert Rev Cardiovasc Ther. 2014;12(5):537-538. 8. Karaman M, Balta S, Ay SA, et al. The comparative effects of valsartan and amlodipine on vWf Levels and N/L ratio in patients

Downloaded from cat.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on February 13, 2015

Balta et al

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

5

with newly diagnosed hypertension. Clin Exp Hypertens. 2013; 35(7):516-522. Demirkol S, Balta S, Unlu M, et al. Neutrophils/lymphocytes ratio in patients with cardiac syndrome X and its association with carotid intima-media thickness. Clin Appl Thromb Hemost. 2014; 20(3):250-255. Kalay N, Dogdu O, Koc F, et al. Hematologic parameters and angiographic progression of coronary atherosclerosis. Angiology. 2012;63(3):213-217. Eriksson EE, Xie X, Werr J, Thoren P, Lindbom L. Direct viewing of atherosclerosis in vivo: plaque invasion by leukocytes is initiated by the endothelial selectins. FASEB J. 2001;15(7): 1149-1157. Duffy BK, Gurm HS, Rajagopal V, Gupta R, Ellis SG, Bhatt DL. Usefulness of an elevated neutrophil to lymphocyte ratio in predicting long-term mortality after percutaneous coronary intervention. Am J Cardiol. 2006;97(7):993-996. Tamhane UU, Aneja S, Montgomery D, Rogers E-K, Eagle KA, Gurm HS. Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome. Am J Cardiol. 2008;102(6):653-657. Shen X-H, Chen Q, Shi Y, Li H-W. Association of neutrophil/ lymphocyte ratio with long-term mortality after ST elevation myocardial infarction treated with primary percutaneous coronary intervention. Chin Med J (Engl). 2010;123(23): 3438-3443. Soylu K, Yuksel S, Gulel O, et al. The relationship of coronary flow to neutrophil/lymphocyte ratio in patients undergoing primary percutaneous coronary intervention. J Thorac Dis. 2013; 5(3):258-264. Demirkol S, Balta S, Kucuk U, Karaman M, Kucuk HO, Kurt O. Neutrophil-to-lymphocyte ratio may predict contrast-induced nephropathy. Angiology. 2014;65(1):57-58. Gibson PH, Croal BL, Cuthbertson BH, et al. Preoperative neutrophil–lymphocyte ratio and outcome from coronary artery bypass grafting. Am Heart J. 2007;154(5):995-1002. Azab B, Shariff MA, Bachir R, Nabagiez JP, McGinn JT. Elevated preoperative neutrophil/lymphocyte ratio as a predictor of increased long-term survival in minimal invasive coronary artery bypass surgery compared to sternotomy. J Cardiothorac Surg. 2013;8(1):193. Hartaigh B, Bosch JA, Thomas GN, et al. Which leukocyte subsets predict cardiovascular mortality? From the LUdwigshafen RIsk and Cardiovascular Health (LURIC) Study. Atherosclerosis. 2012;224(1):161-169. Akpek M, Kaya MG, Lam YY, et al. Relation of neutrophil/ lymphocyte ratio to coronary flow to in-hospital major adverse cardiac events in patients with ST-elevated myocardial infarction undergoing primary coronary intervention. Am J Cardiol. 2012;110(5):621-627. Azab B, Chainani V, Shah N, McGinn JT. Neutrophil–lymphocyte ratio as a predictor of major adverse cardiac events among diabetic population: a 4-year follow-up study. Angiology. 2013; 64(6):456-465. Gillum RF, Mussolino ME, Madans JH. Counts of neutrophils, lymphocytes, and monocytes, cause-specific mortality and

23.

24.

25.

26.

27.

28.

29.

30.

31.

32.

33.

34.

35.

36.

37.

coronary heart disease: the NHANES-I epidemiologic follow-up study. Ann Epidemiol. 2005;15(4):266-271. Athyros VG, Elisaf M, Mikhailidis DP. Inflammatory markers and the metabolic syndrome. Atherosclerosis. 2005;183(1): 187-188. Balta S, Cakar M, Demirkol S, Arslan Z, Akhan M. Higher neutrophil to lymhocyte ratio in patients with metabolic syndrome. Clin Appl Thromb Hemost. 2013;19(5):579. Unlu M, Karaman M, Ay SA, et al. The comparative effects of valsartan and amlodipine on vascular microinflammation in newly diagnosed hypertensive patients. Clin Exp Hypertens. 2013;35(6):418-423. Fici F, Celik T, Balta S, et al. Comparative effects of nebivolol and metoprolol on red cell distribution width and neutrophil/lymphocyte ratio in patients with newly diagnosed essential hypertension. J Cardiovasc Pharmacol. 2013;62(4):388-393. Pitsavos C, Tampourlou M, Panagiotakos DB, et al. Association between low-grade systemic inflammation and type 2 diabetes mellitus among men and women from the ATTICA Study. Rev Diabet Stud. 2007;4(2):98-104. Lee G-K, Lee L-C, Chong E, et al. The long-term predictive value of the neutrophil-to-lymphocyte ratio in type 2 diabetic patients presenting with acute myocardial infarction. QJM. 2012; 105(11):1075-1082. Ulu SM, Dogan M, Ahsen A, et al. Neutrophil-to-lymphocyte ratio as a quick and reliable predictive marker in the diagnose and the severity of diabetic retinopathy. Diabetes Technol Ther. 2013; 15(11):942-947. Oztu¨rk ZA, Kuyumcu ME, Yesil Y, et al. Is there a link between neutrophil–lymphocyte ratio and microvascular complications in geriatric diabetic patients? J Endocrinol Invest. 2013;36(8): 593-599. Varol E, Bas HA, Aksoy F, Ari H, Ozaydin M. Relationship between neutrophil–lymphocyte ratio and isolated low highdensity lipoprotein cholesterol. Angiology. 2013;65(7):630-633. Solak Y, Yilmaz MI, Sonmez A, et al. Neutrophil to lymphocyte ratio independently predicts cardiovascular events in patients with chronic kidney disease. Clin Exp Nephrol. 2013;17(4):532-540. An X, Mao H-P, Wei X, et al. Elevated neutrophil to lymphocyte ratio predicts overall and cardiovascular mortality in maintenance peritoneal dialysis patients. Int Urol Nephrol. 2012;44(5): 1521-1528. Okyay GU, Inal S, Onec¸ K, et al. Neutrophil to lymphocyte ratio in evaluation of inflammation in patients with chronic kidney disease. Ren Fail. 2013;35(1):29-36. Arbel Y, Finkelstein A, Halkin A, et al. Neutrophil/lymphocyte ratio is related to the severity of coronary artery disease and clinical outcome in patients undergoing angiography. Atherosclerosis. 2012;225(2):456-460. Altun B, Turkon H, Tasolar H, et al. The relationship between high-sensitive troponin T, neutrophil lymphocyte ratio and SYNTAX Score. Scand J Clin Lab Invest. 2014;74(2):108-115. Bhutta H, Agha R, Wong J, Tang TY, Wilson YG, Walsh SR. Neutrophil–lymphocyte ratio predicts medium-term survival following elective major vascular surgery: a cross-sectional study. Vasc Endovascular Surg. 2011;45(3):227-231.

Downloaded from cat.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on February 13, 2015

6

Clinical and Applied Thrombosis/Hemostasis

38. Park B-J, Shim J-Y, Lee H-R, et al. Relationship of neutrophil– lymphocyte ratio with arterial stiffness and coronary calcium score. Clin Chim Acta. 2011;412(11-12):925-929. 39. Tas¸ og˘lu I, C ¸ ic¸ek OF, Lafci G, et al. Usefulness of neutrophil/ lymphocyte ratio as a predictor of amputation after embolectomy for acute limb ischemia. Ann Vasc Surg. 2014;28(3): 606-613. 40. Tasoglu I, Turak O, Nazli Y, et al. Preoperative neutrophil– lymphocyte ratio and saphenous vein graft patency after coronary artery bypass grafting. Clin Appl Thromb Hemost. 2014;20(8): 819-824. 41. Appleton ND, Bailey DM, Morris-Stiff G, Lewis MH. Neutrophil to lymphocyte ratio predicts perioperative mortality following open elective repair of abdominal aortic aneurysms. Vasc Endovascular Surg. 2014;48(4):311-316. 42. Turkmen K, Ozcicek F, Ozcicek A, Akbas EM, Erdur FM, Tonbul HZ. The relationship between neutrophil-to-lymphocyte ratio and vascular calcification in end-stage renal disease patients. Hemodial Int. 2014;18(1):47-53. 43. Korkmaz A, Yildiz A, Gunes H, Duyuler S, Tuncez A. Utility of neutrophil–lymphocyte ratio in predicting troponin elevation in the emergency department setting [published online January 14, 2014]. Clin Appl Thromb Hemost. 2014. 44. Gary T, Pichler M, Belaj K, et al. Neutrophil-to-lymphocyte ratio and its association with critical limb ischemia in PAOD patients. PLoS One. 2013;8(2):e56745. 45. Erturk M, Cakmak HA, Surgit O, et al. The predictive value of elevated neutrophil to lymphocyte ratio for long-term cardiovascular mortality in peripheral arterial occlusive disease. J Cardiol. 2014;64(5):371-376. 46. Wang X, Zhang G, Jiang X, Zhu H, Lu Z, Xu L. Neutrophil to lymphocyte ratio in relation to risk of all-cause mortality and cardiovascular events among patients undergoing angiography or cardiac revascularization: a meta-analysis of observational studies. Atherosclerosis. 2014;234(1):206-213. 47. Shah N, Parikh V, Patel N, et al. Neutrophil lymphocyte ratio significantly improves the Framingham risk score in prediction of coronary heart disease mortality: insights from the National Health and Nutrition Examination Survey-III. Int J Cardiol. 2014;171(3):390-397. 48. Balta I, Akbay G, Kalkan G, Eksioglu M. Demographic and clinical features of 521 Turkish patients with Behc¸et’s disease. Int J Dermatol. 2014;53(5):564-569. 49. Ekiz O, Balta I, Sen BB, et al. Mean platelet volume in recurrent aphthous stomatitis and Behc¸et disease. Angiology. 2014;65(2): 161-165. 50. Balta I, Balta S, Koryurek OM, et al. Serum endocan levels as a marker of disease activity in patients with Behc¸et disease. J Am Acad Dermatol. 2014;70(2):291-296. 51. Ozturk C, Balta S, Balta I, et al. Neutrophil–lymphocyte ratio and carotid-intima media thickness in patients with Behcet disease without cardiovascular involvement [published online March 25, 2014]. Angiology. 2014. 52. Sen N, Afsar B, Ozcan F, et al. The neutrophil to lymphocyte ratio was associated with impaired myocardial perfusion and long term adverse outcome in patients with ST-elevated myocardial

53.

54.

55.

56.

57.

58.

59.

60.

61.

62.

63.

64.

65.

66.

67.

infarction undergoing primary coronary intervention. Atherosclerosis. 2013;228(1):203-210. Cingoz F, Iyisoy A, Demirkol S, et al. Carotid intima–media thickness in patients with slow coronary flow and its association with neutrophil-to-lymphocyte ratio: a preliminary report. Clin Appl Thromb Hemost. 2014;20(4):393-399. Balta S, Demirkol S, Celik T, et al. Association between coronary artery ectasia and neutrophil–lymphocyte ratio. Angiology. 2013; 64(8):627-632. Yao M, Liu Y, Jin H, et al. Prognostic value of preoperative inflammatory markers in Chinese patients with breast cancer. Onco Targets Ther. 2014;7:1743-1752. Ayhan S, Ozturk S, Erdem A, et al. Hematological parameters and coronary collateral circulation in patients with stable coronary artery disease. Exp Clin Cardiol. 2013;18(1):e12-e15. Kilincalp S, Coban S, Akinci H, et al. Neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and mean platelet volume as potential biomarkers for early detection and monitoring of colorectal adenocarcinoma [published online October 9, 2014]. Eur J Cancer Prev. 2014. Ma H, Lin H, Hu Y, et al. Mean platelet volume in relation to carotid atherosclerosis in normotensive, euglycemic, and normolipidemic chinese middle-aged and elderly adults. Angiology. 2014; 65(6):512-518. Kim YG, Suh J-W, Yoon C-H, et al. Platelet volume indices are associated with high residual platelet reactivity after antiplatelet therapy in patients undergoing percutaneous coronary intervention. J Atheroscler Thromb. 2014;21(5):445-453. Mayer FJ, Hoke M, Schillinger M, et al. Mean platelet volume predicts outcome in patients with asymptomatic carotid artery disease. Eur J Clin Invest. 2014;44(1):22-28. Ki Y-J, Park S, Ha S-I, Choi D-H, Song H. Usefulness of mean platelet volume as a biomarker for long-term clinical outcomes after percutaneous coronary intervention in Korean cohort: a comparable and additive predictive value to high-sensitivity cardiac troponin T and N-terminal pro-B type natriu. Platelets. 2014; 25(6):427-432. Wan Z-F, Zhou D, Xue J-H, et al. Combination of mean platelet volume and the GRACE risk score better predicts future cardiovascular events in patients with acute coronary syndrome. Platelets. 2014;25(6):447-451. Celik T, Kaya MG, Akpek M, et al. Predictive value of admission platelet volume indices for in-hospital major adverse cardiovascular events in acute ST-segment elevation myocardial infarction. Angiology. 2015;66(2):155-162. Vatankulu MA, Sonmez O, Ertas G, et al. A new parameter predicting chronic total occlusion of coronary arteries: platelet distribution width. Angiology. 2014;65(1):60-64. Demirkol S, Balta S, Cakar M, Unlu M, Arslan Z, Kucuk U. Red cell distribution width: a novel inflammatory marker in clinical practice. Cardiol J. 2013;20(2):209. Demirkol S, Balta S, Celik T, et al. Assessment of the relationship between red cell distribution width and cardiac syndrome X. Kardiol Pol. 2013;71(5):480-484. Kurtul A, Murat SN, Yarlioglues M, et al. The association of red cell distribution width with in-stent restenosis in patients with

Downloaded from cat.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on February 13, 2015

Balta et al

68.

69.

70.

71.

7

stable coronary artery disease [published online May 15, 2014]. Platelets. 2014;1-5. Arbel Y, Weitzman D, Raz R, et al. Red blood cell distribution width and the risk of cardiovascular morbidity and all-cause mortality. A population-based study. Thromb Haemost. 2014;111(2): 300-307. Veeranna V, Zalawadiya SK, Panaich S, Patel K V, Afonso L. Comparative analysis of red cell distribution width and high sensitivity C-reactive protein for coronary heart disease mortality prediction in multi-ethnic population: findings from the 19992004 NHANES. Int J Cardiol. 2013;168(6):5156-5161. ¨ , et al. Platelet/lymphocyte ratio and Temiz A, Gazi E, Gu¨ngo¨r O risk of in-hospital mortality in patients with ST-elevated myocardial infarction. Med Sci Monit. 2014;20:660-665. Yildiz A, Yuksel M, Oylumlu M, et al. The utility of the platelet-lymphocyte ratio for predicting no reflow in patients with ST-segment elevation myocardial infarction [published online January 14, 2014]. Clin Appl Thromb Hemost. 2014.

72. Cic¸ek G, Ac¸ıkgoz SK, Bozbay M, et al. Neutrophil–lymphocyte ratio and platelet-lymphocyte ratio combination can predict prognosis in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention [published online May 16, 2014]. Angiology. 2014. 73. Xue T-C, Zhang L, Xie X-Y, et al. Prognostic significance of the neutrophil-to-lymphocyte ratio in primary liver cancer: a metaanalysis. PLoS One. 2014;9(5):e96072. 74. Li M-X, Liu X-M, Zhang X-F, et al. Prognostic role of neutrophilto-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer. 2014;134(10):2403-2413. 75. Templeton AJ, McNamara MG, Sˇeruga B, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106(6): dju124. 76. Akin F, Ayc¸a B, Ko¨se N, et al. Effect of atorvastatin on hematologic parameters in patients with hypercholesterolemia. Angiology. 2013; 64(8):621-625.

Downloaded from cat.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on February 13, 2015

The Relation Between Atherosclerosis and the Neutrophil-Lymphocyte Ratio.

Inflammation plays an important role in the pathophysiology of vascular disease. In this review, we consider the associations between the neutrophil-l...
322KB Sizes 0 Downloads 7 Views