Prognostic Value of Novel Hematologic Biomarkers in Patients with Pulmonary Arterial Hypertension

Main Article Content

Barış Şensoy
Nur Özer Şensoy
Muhammed Süleymanoğlu
Omaç Tüfekçioğlu

Abstract

Objective: Pulmonary vascular remodeling and inflammation play a major role in pulmonary arterial hypertension (PAH). Novel hematologic biomarkers have recently been recognized as a risk predictor for cardiovascular, oncologic, and inflammatory diseases. We aimed to investigate the association of hematologic biomarkers with mortality in PAH patients.


Materials and Methods: Fourty-five patients diagnosed with PAH and 45 healthy volunteers were evaluated retrospectively. Concurrent data included clinical, echocardiographic, hemodynamic and hematologic variables. The study population was divided into subgroups based on admission neutrophil to lymphocyte ratio (NLR), neutrophil to monocyte ratio (NMR), platelet to lymphocyte ratio (PLR) values.


Results: The median NMR and NLR levels were lower in healthy subjects than in PAH patients (7.7 (7-8.8) vs 9.2 (6.5-11.6); p= 0.03 and 1.9 (1.4-2.9) vs 2.6 (1.9-3.3); p= 0.04) respectively). The estimated mean survival duration was longer in patients with low NMR levels (93 (95% CI, 86-100) vs. 67 (95% CI, 45-88) months (p=0.006) respectively). NMR independently predicted poor outcome and improved the power of the other prognostic markers (OR 1.4 (95% CI, 1-1.8) p= 0.04); (AUC= 0.91; p< 0.0001).


Conclusions: NMR levels alone or combined with other prognostic factors may predict mortality in patients with PAH.

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How to Cite
Şensoy, B., Şensoy, N. Özer, Süleymanoğlu, M. ., & Tüfekçioğlu, O. . (2022). Prognostic Value of Novel Hematologic Biomarkers in Patients with Pulmonary Arterial Hypertension. Medical Science and Discovery, 9(9), 512–522. https://doi.org/10.36472/msd.v9i9.797
Section
Research Article
Received 2022-08-18
Accepted 2022-09-17
Published 2022-09-18

References

Rabinovitch M, Guignabert C, Humbert M, Nicolls MR. Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension. Circulation research. 2014 Jun 20;115(1):165-75. PubMed PMID: 24951765. Pubmed Central PMCID: 4097142. DOI: https://doi.org/10.1161/CIRCRESAHA.113.301141

Zheng YG, Yang T, Xiong CM, He JG, Liu ZH, Gu Q, et al. Platelet Distribution Width and Mean Platelet Volume In Idiopathic Pulmonary Arterial Hypertension. Heart, lung & circulation. 2014 Dec 9. PubMed PMID: 25573235.

Tasoglu I, Sert D, Colak N, Uzun A, Songur M, Ecevit A. Neutrophil-Lymphocyte Ratio and the Platelet-Lymphocyte Ratio Predict the Limb Survival in Critical Limb Ischemia. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2013 Feb 6;20(6):645-50. PubMed PMID: 23393289. DOI: https://doi.org/10.1177/1076029613475474

Gondo T, Nakashima J, Ohno Y, Choichiro O, Horiguchi Y, Namiki K, et al. Prognostic value of neutrophil-to-lymphocyte ratio and establishment of novel preoperative risk stratification model in bladder cancer patients treated with radical cystectomy. Urology. 2012 May;79(5):1085-91. PubMed PMID: 22446338. DOI: https://doi.org/10.1016/j.urology.2011.11.070

Sitbon O, Galie N. Treat-to-target strategies in pulmonary arterial hypertension: the importance of using multiple goals. European respiratory review : an official journal of the European Respiratory Society. 2010 Dec;19(118):272-8. PubMed PMID: 21119185. DOI: https://doi.org/10.1183/09059180.00008210

Galie N, Rubin L, Simonneau G. Developing a heart score: next steps. The American journal of cardiology. 2012 Sep 15;110(6 Suppl):49S-51S. PubMed PMID: 22921032. DOI: https://doi.org/10.1016/j.amjcard.2012.06.016

Baldi F, Fuso L, Arrighi E, Valente S. Optimal management of pulmonary arterial hypertension: prognostic indicators to determine treatment course. Therapeutics and clinical risk management. 2014;10:825-39. PubMed PMID: 25328398. Pubmed Central PMCID: 4199557. DOI: https://doi.org/10.2147/TCRM.S48920

Barst RJ, Rubin LJ, Long WA, McGoon MD, Rich S, Badesch DB, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. The New England journal of medicine. 1996 Feb 1;334(5):296-301. PubMed PMID: 8532025. DOI: https://doi.org/10.1056/NEJM199602013340504

Task Force for D, Treatment of Pulmonary Hypertension of European Society of C, European Respiratory S, International Society of H, Lung T, Galie N, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. The European respiratory journal. 2009 Dec;34(6):1219-63. PubMed PMID: 19749199. DOI: https://doi.org/10.1183/09031936.00139009

Guyatt GH, Pugsley SO, Sullivan MJ, Thompson PJ, Berman L, Jones NL, et al. Effect of encouragement on walking test performance. Thorax. 1984 Nov;39(11):818-22. PubMed PMID: 6505988. Pubmed Central PMCID: 459930. DOI: https://doi.org/10.1136/thx.39.11.818

Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography. 2005 Dec;18(12):1440-63. PubMed PMID: 16376782. DOI: https://doi.org/10.1016/j.echo.2005.10.005

Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982 Apr;143(1):29-36. PubMed PMID: 7063747. DOI: https://doi.org/10.1148/radiology.143.1.7063747

Cook NR. Use and misuse of the receiver operating characteristic curve in risk prediction. Circulation. 2007 Feb 20;115(7):928-35. PubMed PMID: 17309939. DOI: https://doi.org/10.1161/CIRCULATIONAHA.106.672402

Kawut SM, Horn EM, Berekashvili KK, Garofano RP, Goldsmith RL, Widlitz AC, et al. New predictors of outcome in idiopathic pulmonary arterial hypertension. The American journal of cardiology. 2005 Jan 15;95(2):199-203. PubMed PMID: 15642552. DOI: https://doi.org/10.1016/j.amjcard.2004.09.006

Kim YM, Haghighat L, Spiekerkoetter E, Sawada H, Alvira CM, Wang L, et al. Neutrophil elastase is produced by pulmonary artery smooth muscle cells and is linked to neointimal lesions. The American journal of pathology. 2011 Sep;179(3):1560-72. PubMed PMID: 21763677. Pubmed Central PMCID: 3157285. DOI: https://doi.org/10.1016/j.ajpath.2011.05.051

Cowan KN, Heilbut A, Humpl T, Lam C, Ito S, Rabinovitch M. Complete reversal of fatal pulmonary hypertension in rats by a serine elastase inhibitor. Nature medicine. 2000 Jun;6(6):698-702. PubMed PMID: 10835689. DOI: https://doi.org/10.1038/76282

Yeager ME, Reddy MB, Nguyen CM, Colvin KL, Ivy DD, Stenmark KR. Activation of the unfolded protein response is associated with pulmonary hypertension. Pulmonary circulation. 2012 Apr-Jun;2(2):229-40. PubMed PMID: 22837864. Pubmed Central PMCID: 3401877. DOI: https://doi.org/10.4103/2045-8932.97613

Tian W, Jiang X, Tamosiuniene R, Sung YK, Qian J, Dhillon G, et al. Blocking macrophage leukotriene b4 prevents endothelial injury and reverses pulmonary hypertension. Science translational medicine. 2013 Aug 28;5(200):200ra117. PubMed PMID: 23986401. Pubmed Central PMCID: 4016764. DOI: https://doi.org/10.1126/scitranslmed.3006674

Rodriguez-Carrio J, Alperi-Lopez M, Lopez P, Alonso-Castro S, Carro-Esteban SR, Ballina-Garcia FJ, et al. Red cell distribution width is associated with endothelial progenitor cell depletion and vascular-related mediators in rheumatoid arthritis. Atherosclerosis. 2015 Mar 10;240(1):131-6. PubMed PMID: 25778627. DOI: https://doi.org/10.1016/j.atherosclerosis.2015.03.009

Ozsu S, Abul Y, Gulsoy A, Bulbul Y, Yaman S, Ozlu T. Red cell distribution width in patients with obstructive sleep apnea syndrome. Lung. 2012 Jun;190(3):319-26. PubMed PMID: 22310880. DOI: https://doi.org/10.1007/s00408-012-9376-x

Can MM, Tanboga IH, Demircan HC, Ozkan A, Koca F, Keles N, et al. Enhanced hemostatic indices in patients with pulmonary arterial hypertension: an observational study. Thrombosis research. 2010 Oct;126(4):280-2. PubMed PMID: 20673969. DOI: https://doi.org/10.1016/j.thromres.2010.06.020

Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, et al. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation. 2010 Jul 13;122(2):156-63. PubMed PMID: 20585011. DOI: https://doi.org/10.1161/CIRCULATIONAHA.109.911818