Long-term Prognosis after Treatment of Total Occluded Coronary Artery is well Predicted by Neutrophil to High-Density Lipoprotein Ratio: a Comparison Study

Aim    Mortality prediction is very important for more effective treatment of patients with acute coronary syndrome. Hematological and lipid parameters have been used for this purpose, as this approach is non-invasive and cost effective. In this study, our aim was to evaluate which parameter predicts mortality most accurately.
Material and Methods    Data of 554 patients with at least one total coronary artery occlusion were collected retrospectively. Receiver operating characteristic curves were used to determine the optimal cut-off points of Neu / HDL, Neu / Lym, Mono / HDL, Trig / HDL, HDL / LDL, Plt / Lym and Lym / HDL according to long-term cardiovascular survival. Median follow-up time was 520 days, and 30 patients died.
Results    The mean age was 60.96±0.50 yrs. The area under the curve (AUC) for Neu / HDL was 0.830 (p<0.001, 95 % confidence interval [CI]: 0.753 to 0.908). The cut-off point was 0.269, with a sensitivity of 74.2 % and a specificity of 74.2 %. The AUC for Neu / Lym was 0.688 (p<0.001, 95 % CI: 0.586 to 0.790). The cut-off point was 5.322, with a sensitivity of 67.7 % and a specificity of 67.1 %. The Neu / HDL (hazard ratio, HR [confidence interval, CI]: 0.202 [0.075–0.545], p=0.002) and Neu / Lym (0.306 [0.120–0.777], p=0.013) were associated with increased risk of death according to multivariate Cox regression analysis.
Conclusions    Neu / HDL offers a better long-term mortality prediction than Neu / Lym, Mono / HDL, Trig / HDL, HDL / LDL, Plt / Lym, or Lym / HDL after treatment of total coronary artery occlusion.

1. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. The Lancet. 2006;367(9524):1747–57. DOI: 10.1016/S0140-6736(06)68770-9

2. Body R, Carley S, McDowell G, Jaffe AS, France M, Cruickshank K et al. Rapid Exclusion of Acute Myocardial Infarction in Patients With Undetectable Troponin Using a High-Sensitivity Assay. Journal of the American College of Cardiology. 2011;58(13):1332–9. DOI: 10.1016/j.jacc.2011.06.026

3. Winter M-P, Wiesbauer F, Blessberger H, Pavo N, Sulzgruber P, Huber K et al. Lipid profile and long-term outcome in premature myocardial infarction. European Journal of Clinical Investigation. 2018;48(10):e13008. DOI: 10.1111/eci.13008

4. Stoner L, Lucero AA, Palmer BR, Jones LM, Young JM, Faulkner J. Inflammatory biomarkers for predicting cardiovascular disease. Clinical Biochemistry. 2013;46(15):1353–71. DOI: 10.1016/j.clinbiochem.2013.05.070

5. Lewingston S, Whitlock G, Clarke R, Sherliker P, Emberson J, Hasley J et al. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths. The Lancet. 2007;370(9602):1829–39. DOI: 10.1016/S0140-6736(07)61778-4

6. Hansson GK. Inflammation, Atherosclerosis, and Coronary Artery Disease. New England Journal of Medicine. 2005;352(16):1685–95. DOI: 10.1056/NEJMra043430

7. Guo T, Cheng B, Ke L, Guan S, Qi B, Li W et al. Prognostic Value of Neutrophil to Lymphocyte Ratio for In-hospital Mortality in Elderly Patients with Acute Myocardial Infarction. Current Medical Science. 2018;38(2):354–9. DOI: 10.1007/s11596-018-1887-0

8. Wang HH, Garruti G, Liu M, Portincasa P, Wang DQ-H. Cholesterol and Lipoprotein Metabolism and Atherosclerosis: Recent Advances in Reverse Cholesterol Transport. Annals of Hepatology. 2017;16(Suppl 1):S27–42. DOI: 10.5604/01.3001.0010.5495

9. Soehnlein O. An elegant defense: how neutrophils shape the immune response. Trends in Immunology. 2009;30(11):511–2. DOI: 10.1016/j.it.2009.07.002

10. Cogny A, Atger V, Paul J-L, Soni T, Moatti N. High-density lipoprotein 3 physicochemical modifications induced by interaction with human polymorphonuclear leucocytes affect their ability to remove cholesterol from cells. Biochemical Journal. 1996;314(1):285–92. DOI: 10.1042/bj3140285

11. Curcic S, Holzer M, Frei R, Pasterk L, Schicho R, Heinemann A et al. Neutrophil effector responses are suppressed by secretory phospholipase A2 modified HDL. Biochimica et Biophysica Acta. 2015;1851(2):184–93. DOI: 10.1016/j.bbalip.2014.11.010

12. Aukrust P, Halvorsen B, Yndestad A, Ueland T, Øie E, Otterdal K et al. Chemokines and Cardiovascular Risk. Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28(11):1909–19. DOI: 10.1161/ATVBAHA.107.161240

13. Huang J-B, Chen Y-S, Ji H-Y, Xie W-M, Jiang J, Ran L-S et al. Neutrophil to high-density lipoprotein ratio has a superior prognostic value in elderly patients with acute myocardial infarction: a comparison study. Lipids in Health and Disease. 2020;19(1):59. DOI: 10.1186/s12944-020-01238-2

14. Afari ME, Bhat T. Neutrophil to lymphocyte ratio (NLR) and cardiovascular diseases: an update. Expert Review of Cardiovascular Therapy. 2016;14(5):573–7. DOI: 10.1586/14779072.2016.1154788

15. Ganjali S, Gotto AM, Ruscica M, Atkin SL, Butler AE, Banach M et al. Monocyte‐to‐HDL‐cholesterol ratio as a prognostic marker in cardiovascular diseases. Journal of Cellular Physiology. 2018;233(12):9237–46. DOI: 10.1002/jcp.27028

16. Islam MZ, Islam MN, Bhowmik TK, Saha B, Hossain MS, Ahmed H et al. Relationship between Triglyceride and HDL-C ratio with Acute Coronary Syndrome. Mymensingh medical journal. 2018;27(2):289–93. PMID: 29769492

17. Kurtul A, Ornek E. Platelet to Lymphocyte Ratio in Cardiovascular Diseases: A Systematic Review. Angiology. 2019;70(9):802–18. DOI: 10.1177/0003319719845186

18. Chen H, Xiong C, Shao X, Ning J, Gao P, Xiao H et al. Lymphocyte to High-Density Lipoprotein Ratio As A New Indicator Of Inflammation And Metabolic Syndrome. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2019; 12:2117–23.DOI: 10.2147/DMSO.S219363

19. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). European Heart Journal. 2018;39(2):119–77. DOI: 10.1093/eurheartj/ehx393

20. Collet J-P, Thiele H, Barbato E, Barthélémy O, Bauersachs J, Bhatt DL et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent STsegment elevation. European Heart Journal. 2020;32(23):2999–3054. DOI: 10.1093/eurheartj/ehaa575

21. BARI Investigators. Protocol for the Bypass Angioplasty Revascularization Investigation. Circulation. 1991; 84 (Suppl V): V1–27

22. Goksuluk D, Korkmaz S, Zararsiz G, Karaagaoglu A Ergun. easyROC: An Interactive Web-tool for ROC Curve Analysis Using R Language Environment. The R Journal. 2016;8(2):213. DOI: 10.32614/RJ-2016-042

23. Zazula AD, Précoma-Neto D, Gomes AM, Kruklis H, Barbieri GF, Forte RY et al. Avaliação da relação neutrófilos/linfócitos em pacientes com suspeita de síndrome coronariana aguda. Arquivos Brasileiros de Cardiologia. 2008;90(1):31–6. DOI: 10.1590/S0066-782X2008000100006

24. Wilson PWF. Evidence of Systemic Inflammation and Estimation of Coronary Artery Disease Risk: A Population Perspective. The American Journal of Medicine. 2008;121(10 Suppl 1): S15–20. DOI: 10.1016/j.amjmed.2008.06.012

25. Kehl DW, Iqbal N, Fard A, Kipper BA, De La Parra Landa A, Maisel AS. Biomarkers in acute myocardial injury. Translational Research. 2012;159(4):252–64. DOI: 10.1016/j.trsl.2011.11.002

26. Guasti L, Dentali F, Castiglioni L, Maroni L, Marino F, Squizzato A et al. Neutrophils and clinical outcomes in patients with acute coronary syndromes and/or cardiac revascularisation: A systematic review on more than 34,000 subjects. Thrombosis and Haemostasis. 2011;106(10):591–9. DOI: 10.1160/TH11-02-0096

27. Cetin MS, Ozcan Cetin EH, Kalender E, Aydin S, Topaloglu S, Kisacik HL et al. Monocyte to HDL Cholesterol Ratio Predicts Coronary Artery Disease Severity and Future Major Cardiovascular Adverse Events in Acute Coronary Syndrome. Heart, Lung and Circulation. 2016;25(11):1077–86. DOI: 10.1016/j.hlc.2016.02.023

28. Kunutsor SK, Zaccardi F, Karppi J, Kurl S, Laukkanen JA. Is High Serum LDL/HDL Cholesterol Ratio an Emerging Risk Factor for Sudden Cardiac Death? Findings from the KIHD Study. Journal of Atherosclerosis and Thrombosis. 2017;24(6):600–8. DOI: 10.5551/jat.37184

29. Azab B, Shah N, Akerman M, McGinn JT. Value of platelet/lymphocyte ratio as a predictor of all-cause mortality after non-ST-elevation myocardial infarction. Journal of Thrombosis and Thrombolysis. 2012;34(3):326–34. DOI: 10.1007/s11239-012-0718-6

30. Taghizadeh E, Taheri F, Gheibi Hayat SM, Montecucco F, Carbone F, Rostami D et al. The atherogenic role of immune cells in familial hypercholesterolemia. IUBMB Life. 2020;72(4):782–9. DOI: 10.1002/iub.2179

31. Murphy AJ, Woollard KJ, Suhartoyo A, Stirzaker RA, Shaw J, Sviridov D et al. Neutrophil Activation Is Attenuated by High-Density Lipoprotein and Apolipoprotein A-I in In Vitro and In Vivo Models of Inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology. 2011;31(6):1333–41. DOI: 10.1161/ATVBAHA.111.226258

32. Chen C, Cong BL, Wang M, Abdullah M, Wang XL, Zhang YH et al. Neutrophil to lymphocyte ratio as a predictor of myocardial damage and cardiac dysfunction in acute coronary syndrome patients. Integrative Medicine Research. 2018;7(2):192–9. DOI: 10.1016/j.imr.2018.02.006