The Neutrophil-to-lymphocyte ratio as a diagnostic and prognostic biomarker in pulmonary hypertension: A systematic review
Keywords:
pulmonary hypertension, neutrophil-to-lymphocyte ratio, biomarkers, prognosis, diagnostic techniquesAbstract
Background: The objective of this systematic review is to provide an overview of research that examined the relationship between pulmonary hypertension (PH) and the neutrophil-to-lymphocyte ratio (NLR).
Methods: To identify the studies related to NLR, a search was done on PubMed, Scopus, and Web of Science with an end date of March 30th, 2023. A total of 25 studies were included in the review. These studies included a variety of pathologies that contribute to PH. We employed the Newcastle-Ottawa Scale to assess the quality of studies. For all studies, a significance level of P˂0.05 was used.
Results: In patients with sarcoidosis, chronic obstructive pulmonary disease, systemic sclerosis, chronic kidney disease, and congenital heart disease, NLR appears to be an independent predictor of PH. Also, it was frequently linked to the result, complications, and severity of the disease in PH patients.
Conclusion: NLR may be utilized as a repeatable, inexpensive, and trustworthy proxy for the onset and severity of PH.
References
1. Benza RL, Miller DP, Barst RJ, et al. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest. 2012;142(2):448–56. doi: 10.1378/chest.11-1460
2. Hoeper MM, Kramer T, Pan Z, et al. Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model. Eur Respir J. 2017;50(2):1700740. doi: 10.1183/13993003.00740-2017
3. Humbert M, Sitbon O, Chaouat A, et al. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation. 2010;122(2):156–63. doi: 10.1161/circulationaha.109.911818
4. Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the joint task force of the ESC and ERS. Eur Heart J. 2016;37(1):67–119. doi: 10.1093/eurheartj/ehv317
5. Brewer JM, Allen SA. PH Professional Network: facilitating and improving adherence: the development of a pulmonary arterial hypertension self-care management agreement. Adv Pulm Hypertens. 2019;18(4):157–9. doi: 10.21693/1933-088X-18.4.157
6. Verma AK. Tuberculosis and pulmonary hypertension: commentary. Lung India. 2016;33(2):232. doi: 10.4103/0970-2113.177455
7. Vickers NJ. Animal communication: when I'm calling you, will you answer too? Curr Biol. 2017;27(14):R713–5. doi: 10.1016/j.cub.2017.05.064
8. Scott TE, Qin CX, Drummond GR, et al. Innovative anti-inflammatory and pro-resolving strategies for pulmonary hypertension: High Blood Pressure Research Council of Australia Award 2019. Hypertension. 2021;78(5):1168–84. doi: 10.1161/hypertensionaha.120.1452
9. Rameh V, Kossaify A. Role of biomarkers in the diagnosis, risk assessment, and management of pulmonary hypertension. Biomark Insights. 2016;11:1–9. doi: 10.4137/bmi.s38323
10. Zahorec R. Neutrophil-to-lymphocyte ratio, past, present and future perspectives. Bratisl Lek Listy. 2021;122(7):474–88. doi: 10.4149/bll_2021_078
11. Ataam JA, Amsallem M, Guihaire J, et al. Preoperative C-reactive protein predicts early postoperative outcomes after pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension. J Thorac Cardiovasc Surg. 2021;161(4):1532–42.e5. doi: 10.1016/j.jtcvs.2019.11.133
12. Yıldız A, Kılıç H, Ertaş F, et al. Association between neutrophil to lymphocyte ratio and pulmonary arterial hypertension. Turk Kardiyol Dern Ars. 2013;41(6):485–90. doi: 10.5543/tkda.2013.93385
13. Esheba N, Shahba A. Assessment of neutrophil lymphocyte ratio in systemic sclerosis patients in Tanta University Hospital: a promising marker in predicting disease severity. Egypt J Rheumatol Clin Immunol. 2016;4(1):33–41. doi: 10.21608/ejrci.2015.4475
14. Fallah SA, Ghodsi S, Soleimani H, et al. Incidence and predictors of chronic thromboembolic pulmonary hypertension following first episode of acute pulmonary embolism. Adv Respir Med. 2020;88(6):539–47. doi: 10.5603/arm.a2020.0200
15. Feng X, Liang J, Chen J, et al. A prediction model for intermediate- and high-risk pulmonary hypertension during the acute exacerbation of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2021;16:123–31. doi: 10.21203/rs.3.rs-623670/v1
16. Foris V, Kovacs G, Douschan P, et al. Neutrophil-to-lymphocyte ratio predicts survival in pulmonary arterial hypertension patients. Am J Respir Crit Care Med. 2016;193:A3957
17. Gursoy M, Salihoglu E, Hatemi AC, et al. Inflammation and congenital heart disease associated pulmonary hypertension. Heart Surg Forum. 2015;18(3):E123–7. doi: 10.1532/hsf.1228
18. Harbaum L, Baaske KM, Simon M, et al. Exploratory analysis of the neutrophil to lymphocyte ratio in patients with pulmonary arterial hypertension. BMC Pulm Med. 2017;17(1):1–9. doi: 10.1186/s12890-017-0407-5
19. Herlambang G, Widjaja SL, Hafidh Y, et al. Hubungan rasio netrofil limfosit dengan hipertensi arteri pulmonal pada anak dengan penyakit jantung bawaan asianotik. Sari Pediatri. 2019;21(2):96–101. doi: 10.14238/sp21.2.2019.96-101
20. Kivrak T, Bolayir H, Kanar B, et al. The relationship between vitamin D deficiency and pulmonary artery atherosclerosis in chronic thromboembolic patients. Vitam Miner. 2017;6(159):1–5. doi: 10.4172/2376-1318.1000159
21. Korkmaz C, Demircioglu S. The association of neutrophil/lymphocyte and platelet/lymphocyte ratios and hematological parameters with diagnosis, stages, extrapulmonary involvement, pulmonary hypertension, response to treatment, and prognosis in patients with sarcoidosis. Can Respir J. 2020;2020:1696450. doi: 10.1155/2020/6760456
22. MacKenzie A, Irvine V, Jayasekera G, et al. S120 Metabolic dysfunction in pulmonary arterial hypertension and response to exercise therapy. BMJ Open Respir Res. 2018;5(Suppl 1):A120. doi: 10.1136/thorax-2018-212555.126
23. Mirsaeidi M, Mortaz E, Omar HR, et al. Association of neutrophil to lymphocyte ratio and pulmonary hypertension in sarcoidosis patients. Tanaffos. 2016;15(1):44–9. PMID: 27403178
24. Özpelit E, Akdeniz B, Özpelit ME, et al. Prognostic value of neutrophil-to-lymphocyte ratio in pulmonary arterial hypertension. J Int Med Res. 2015;43(5):661–71. doi: 10.1177/0300060515589394
25. Podder S, Shlobin OA, King CS, et al. Complete blood count parameters as predictor of outcomes in patients with pulmonary arterial hypertension. In: D56. X Marks the Spot: New Biomarkers in PAH; 2019 May. Am Thorac Soc. p. A6817. doi: 10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a6817
26. Sakr BR, Rabea RE, ElHamid SM. Value of hematological parameters as biomarkers of disease manifestations and severity in systemic sclerosis. Egypt Rheumatol. 2021;43(2):159–65. doi: 10.1016/j.ejr.2020.06.008
27. Senturk B, Akdeniz B, Yilmaz MB, et al. Whole blood viscosity in systemic sclerosis: a potential biomarker of pulmonary hypertension? Clin Rheumatol. 2020;39(1):49–56. doi: 10.1007/s10067-019-04603-4
28. Tezcan D, Turan Ç, Yılmaz S, et al. What do simple hematological parameters tell us in patients with systemic sclerosis? Acta Dermatovenerol Alp Pannonica Adriat. 2020;29(3):101–7. PMID: 32975295
29. Yanartas M, Kalkan ME, Arslan A, et al. Neutrophil/lymphocyte ratio can predict postoperative mortality in patients with chronic thromboembolic pulmonary hypertension. Ann Thorac Cardiovasc Surg. 2015;21(5):486–92. doi: 10.5761/atcs.oa.14-00190
30. Yayla ME, İlgen U, Okatan İE, et al. Association of simple hematological parameters with disease manifestations, activity, and severity in patients with systemic sclerosis. Clin Rheumatol. 2020;39(1):77–83. doi: 10.1007/s10067-019-04685-0
31. Yin X, Xin M, Ding S, et al. Predictive role of perioperative neutrophil to lymphocyte ratio in pediatric congenital heart disease associated with pulmonary arterial hypertension. BMC Surg. 2021;21(1):1–7. PMID: 33397333
32. Zhang X, Zhao W, Ma X, et al. Prognostic value of pulmonary hypertension in pre-dialysis chronic kidney disease patients. Int Urol Nephrol. 2020;52(12):2329–36. doi: 10.1007/s11255-020-02589-6
33. Zuo H, Xie X, Peng J, et al. Predictive value of novel inflammation-based biomarkers for pulmonary hypertension in the acute exacerbation of chronic obstructive pulmonary disease. Anal Cell Pathol (Amst). 2019;2019:5189165. doi: 10.1155/2019/5189165
34. Sun Y, Lu SQ, Tu S, et al. Xueye biaozhishi he xinzang caochao jiancha zai manxing zhusai xing fei jibing jixing jiazhong qi xiangguan xing fei dongmai gaoya de pinggu jiazhi. Zhongguo Jiuji Yixue. 2018;39(11):1058–64. doi: 10.3969/j.issn.1002-1949.2019.11.010
35. Shen Y, Liu X, Lu KM, et al. Waizhou xue zhongxing li xibao/lin ba xibao biji zai manxing zhusai xing fei bing xiangguan fei dongmai gaoya huanzhe zhong de yuzhi jiazhi. Linchuang Yu Bingli Zazhi. 2017;36(12):1893–9. doi: 10.3978/j.issn.2095-6959.2016.12.001
36. Wells GA, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Oxford: University of Oxford; 2000.
37. Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the joint task force of the ESC and ERS. Eur Heart J. 2015;37(1):67–119. doi: 10.1093/eurheartj/ehv317
38. Grymuza M, Małaczyńska-Rajpold K, Jankiewicz S, et al. Right heart catheterization procedures in patients with suspicion of pulmonary hypertension: experiences of a tertiary center. Adv Interv Cardiol. 2017;13(4):295–9. PMID: 29362571
39. Vachiéry JL, Tedford RJ, Rosenkranz S, et al. Pulmonary hypertension due to left heart disease. Eur Respir J. 2019;53(1):1801897. doi: 10.1183/13993003.01897-2018
40. Hegazy Y, Aryan M, Panchani N, et al. The correlation in echocardiogram to right heart catheterization in identifying pulmonary hypertension as a barrier to liver transplantation. Am J Med Sci. 2023;365(6):496–501. doi: 10.1016/j.amjms.2023.03.012
41. Paliogiannis P, Fois AG, Sotgia S, et al. Neutrophil to lymphocyte ratio and clinical outcomes in COPD: recent evidence and future perspectives. Eur Respir Rev. 2018;27(147):170113. doi: 10.1183/16000617.0113-2017
42. Wang Q, Li J, Wang X. The neutrophil-lymphocyte ratio is associated with postoperative mortality of cardiac surgery. J Thorac Dis. 2020;13(1):67–75. PMID: 33569186
43. Radic M, Marion TN. Neutrophil extracellular chromatin traps connect innate immune response to autoimmunity. Semin Immunopathol. 2013;35(4):465–80. doi: 10.1007/s00281-013-0376-6
44. Howard R, Kanetsky PA, Egan KM. Exploring the prognostic value of the neutrophil-to-lymphocyte ratio in cancer. Sci Rep. 2019;9(1):19673. PMID: 31873162
45. Tan TP, Arekapudi A, Metha J, et al. Neutrophil–lymphocyte ratio as predictor of mortality and morbidity in cardiovascular surgery: a systematic review. ANZ J Surg. 2015;85(6):414–9. doi: 10.1111/ans.13036
46. Fest J, Ruiter TR, Groot Koerkamp B, et al. The neutrophil-to-lymphocyte ratio is associated with mortality in the general population: the Rotterdam Study. Eur J Epidemiol. 2019;34(5):463–70. doi: 10.1007/s10654-018-0472-y
47. Azab B, Camacho-Rivera M, Taioli E. Average values and racial differences of neutrophil lymphocyte ratio among a nationally representative sample of United States subjects. PLoS One. 2014;9(11):e112361. doi: 10.1371/journal.pone.0112361
48. Forget P, Khalifa C, Defour JP, et al. What is the normal value of the neutrophil-to-lymphocyte ratio? BMC Res Notes. 2017;10(1):12–5. doi: 10.1186/s13104-016-2335-5
49. Huitema MP, Grutters JC, Rensing BJWM, et al. Pulmonary hypertension complicating pulmonary sarcoidosis. Neth Heart J. 2016;24(6):390–9. doi: 10.1007/s12471-016-0847-1
50. Arslan D, Cimen D, Guvenc O, et al. Platelet distribution width and mean platelet volume in children with pulmonary arterial hypertension secondary to congenital heart disease with left-to-right shunt: new indices of severity? Pediatr Cardiol. 2013;34(4):1013–6. doi: 10.1007/s00246-012-0600-5
51. Sonaglioni A, Cassandro R, Luisi F, et al. Correlation between Doppler echocardiography and right heart catheterisation-derived systolic and mean pulmonary artery pressures: determinants of discrepancies between the two methods. Heart Lung Circ. 2021;30(5):656–64. doi: 10.1016/j.hlc.2020.10.009
52. Seyyedi SR, Mozafari M, Sharif-Kashani B, et al. Correlation of echocardiographic and right heart catheterization estimations of pulmonary artery systolic pressure. Tanaffos. 2022;21(1):78–84. PMID: 36258907
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Shokoufeh Khanzadeh, Sarina Aminizadeh, Shima Nourigheimasi, Brandon Lucke-Wold, Farid Rashidi, Cihangir Kaymaz, Pavel Janda, Abilio Reis, Michael Goutnik, Monireh Khanzadeh, Hamed Bazrafshan Drissi, Fatemeh Chichagi

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers.
Authors retain the copyright for their published work. No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.