{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:09:23Z","timestamp":1790014163922,"version":"4.0.1"},"reference-count":44,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania","award":["511\/7\/17 January 2022"],"award-info":[{"award-number":["511\/7\/17 January 2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are characterized by high morbidity and mortality. We retrospectively analyzed 468 hospital admissions from 80 patients to evaluate the prognostic value of inflammation-based hematologic indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil-percentage-to-albumin ratio (NPAR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII). All biomarker\u2013outcome associations were specified a priori as exploratory in this hypothesis-generating design. In PAH, both NPAR and SII were associated with in-hospital mortality (odds ratio [OR] 1.129, 95% confidence interval [CI] 1.011\u20131.261, p = 0.031; OR 1.001, 95% CI 1.000\u20131.002, p = 0.002), post-discharge mortality (NPAR OR 1.181, 95% CI 1.062\u20131.313, p = 0.002), and poorer overall survival (log-rank p = 0.002 and p = 0.012, respectively). Higher LMR was associated with reduced in-hospital mortality (OR 0.291, 95% CI 0.108\u20130.790, p = 0.015), while NLR predicted increased in-hospital mortality. In CTEPH, NLR and LMR were the strongest predictors, correlating with worse survival (log-rank p = 0.007 and p = 0.044) and higher post-discharge mortality (NLR OR 1.289, 95% CI 1.029\u20131.615, p = 0.027). Receiver operating characteristic (ROC) analysis suggests the potential value of SII in PAH and the promising performance of NPAR in CTEPH. Inflammation-based hematologic indices, particularly NPAR, SII, and NLR, may provide valuable prognostic information and may serve as practical, non-invasive tools for predicting hospitalization duration and mortality in PAH and CTEPH.<\/jats:p>","DOI":"10.3390\/ijms262210940","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T10:56:47Z","timestamp":1762945007000},"page":"10940","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Inflammation-Based Hematologic Indices as Prognostic Markers in Pulmonary Arterial and Chronic Thromboembolic Pulmonary Hypertension: A Hypothesis-Generating Registry Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5372-6227","authenticated-orcid":false,"given":"Dragos-Gabriel","family":"Iancu","sequence":"first","affiliation":[{"name":"Doctoral School, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"},{"name":"Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5570-3502","authenticated-orcid":false,"given":"Razvan Gheorghita","family":"Mares","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6956-3037","authenticated-orcid":false,"given":"Liviu","family":"Cristescu","sequence":"additional","affiliation":[{"name":"Doctoral School, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"},{"name":"Department of Cardiology I, The Emergency Institute for Cardiovascular Diseases and Transplantation, 540136 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7098-0042","authenticated-orcid":false,"given":"Radu-Adrian","family":"Suteu","sequence":"additional","affiliation":[{"name":"Department of Cardiology I, The Emergency Institute for Cardiovascular Diseases and Transplantation, 540136 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6395-9476","authenticated-orcid":false,"given":"Andreea","family":"Varga","sequence":"additional","affiliation":[{"name":"Faculty of Medicine in English, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3828-1499","authenticated-orcid":false,"given":"Ioan","family":"Tilea","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1093\/eurheartj\/ehac237","article-title":"ESC\/ERS Scientific Document Group. 2022 ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension","volume":"43","author":"Humbert","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e024969","DOI":"10.1161\/JAHA.121.024969","article-title":"Mortality in Pulmonary Arterial Hypertension in the Modern Era: Early Insights From the Pulmonary Hypertension Association Registry","volume":"11","author":"Chang","year":"2022","journal-title":"J. Am. Heart Assoc."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhao, H., Song, J., Li, X., Xia, Z., Wang, Q., Fu, J., Miao, Y., Wang, D., and Wang, X. (2024). The Role of Immune Cells and Inflammation in Pulmonary Hypertension: Mechanisms and Implications. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1374506"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"402","DOI":"10.31083\/j.rcm2511402","article-title":"From pulmonary embolism to chronic thromboembolic pulmonary hypertension: A pathophysiological approach","volume":"25","author":"Shahidi","year":"2024","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ruaro, B., Baratella, E., Caforio, G., Confalonieri, P., Wade, B., Marrocchio, C., Geri, P., Pozzan, R., Andrisano, A.G., and Cova, M.A. (2022). Chronic thromboembolic pulmonary hypertension: An update. Diagnostics, 12.","DOI":"10.3390\/diagnostics12020235"},{"key":"ref_6","first-page":"57","article-title":"Usefulness of neutrophil-to-lymphocyte ratio in risk stratification of patients with advanced heart failure","volume":"1","author":"Hernandez","year":"2015","journal-title":"Am. J. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1177\/0300060515589394","article-title":"Prognostic value of neutrophil-to-lymphocyte ratio in pulmonary arterial hypertension","volume":"43","author":"Akdeniz","year":"2015","journal-title":"J. Int. Med. Res."},{"key":"ref_8","first-page":"480","article-title":"Prognostic Value of Platelet to Lymphocyte Ratio (PLR) and Neutrophil to Lymphocyte Ratio (NLR) in Patients with Pulmonary Hypertension","volume":"21","author":"Shahmoradi","year":"2022","journal-title":"Tanaffos"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ye, G.L., Chen, Q., Chen, X., Liu, Y.Y., Yin, T.T., Meng, Q.H., Liu, Y.C., Wei, H.Q., and Zhou, Q.H. (2019). The prognostic role of platelet-to-lymphocyte ratio in patients with acute heart failure: A cohort study. Sci. Rep., 23.","DOI":"10.1038\/s41598-019-47143-2"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e026326","DOI":"10.1161\/JAHA.122.026326","article-title":"Heart Failure Investigators. Combination of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as a Novel Predictor of Cardiac Death in Patients with Acute Decompensated Heart Failure with Preserved Left Ventricular Ejection Fraction: A Multicenter Study","volume":"3","author":"Tamaki","year":"2023","journal-title":"J. Am. Heart Assoc."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lin, Y., Lin, Y., Yue, J., and Zou, Q. (2022). The neutrophil percentage-to-albumin ratio is associated with all-cause mortality in critically ill patients with acute myocardial infarction. BMC Cardiovasc. Disord., 18.","DOI":"10.21203\/rs.3.rs-877233\/v1"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yu, Y., Liu, Y., Ling, X., Huang, R., Wang, S., Min, J., Xiao, J., Zhang, Y., and Wang, Z. (2020). The Neutrophil Percentage-to-Albumin Ratio as a New Predictor of All-Cause Mortality in Patients with Cardiogenic Shock. BioMed Res. Int., 26.","DOI":"10.1155\/2020\/7458451"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Sun, T., Shen, H., Guo, Q., Yang, J., Zhai, G., Zhang, J., Zhang, B., Ding, Y., Cai, C., and Zhou, Y. (2020). Association between Neutrophil Percentage-to-Albumin Ratio and All-Cause Mortality in Critically Ill Patients with Coronary Artery Disease. BioMed Res. Int., 2020.","DOI":"10.1155\/2020\/8137576"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"701","DOI":"10.2147\/JIR.S349996","article-title":"The Neutrophil-to-Albumin Ratio as a New Predictor of All-Cause Mortality in Patients with Heart Failure","volume":"2","author":"Hu","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"ref_15","first-page":"9","article-title":"Innate Immune Mechanisms in Myocardial Infarction\u2014An Update","volume":"26","author":"Mares","year":"2018","journal-title":"Rev. Rom. Med. Lab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"31926","DOI":"10.18632\/oncotarget.7876","article-title":"Prognostic Role of Lymphocyte to Monocyte Ratio for Patients with Cancer: Evidence from a Systematic Review and Meta-Analysis","volume":"7","author":"Gu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ma, W.T., Gao, F., Gu, K., and Chen, D.K. (2019). The Role of Monocytes and Macrophages in Autoimmune Diseases: A Comprehensive Review. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01140"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1007\/s10067-017-3815-2","article-title":"The association between the lymphocyte-monocyte ratio and disease activity in rheumatoid arthritis","volume":"6","author":"Du","year":"2017","journal-title":"Clin. Rheumatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1097\/MCA.0000000000000857","article-title":"Association of Lymphocyte-to-Monocyte Ratio with Total Coronary Plaque Burden in Patients with Coronary Artery Disease","volume":"31","author":"Si","year":"2020","journal-title":"Coron. Artery Dis."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wang, L., Gao, J., Liu, B., Fu, Y., Yao, Z., Guo, S., Song, Z., Zhang, Z., He, J., and Wang, C. (2024). The Association between Lymphocyte-to-Monocyte Ratio and All-Cause Mortality in Obese Hypertensive Patients with Diabetes and without Diabetes: Results from the Cohort Study of NHANES 2001\u20132018. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1387272"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhou, Y.X., Li, W.C., Xia, S.H., Xiang, T., Tang, C., Luo, J.L., Lin, M.J., Xia, X.W., and Wang, W.B. (2022). Predictive Value of the Systemic Immune Inflammation Index for Adverse Outcomes in Patients with Acute Ischemic Stroke. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.836595"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5189165","DOI":"10.1155\/2019\/5189165","article-title":"Predictive Value of Novel Inflammation-Based Biomarkers for Pulmonary Hypertension in the Acute Exacerbation of Chronic Obstructive Pulmonary Disease","volume":"2019","author":"Zuo","year":"2019","journal-title":"Anal. Cell Pathol."},{"key":"ref_23","first-page":"231","article-title":"Systemic immune-inflammation index as a potential biomarker for predicting acute pulmonary embolism: A systematic review","volume":"62","author":"Suwadi","year":"2024","journal-title":"Rom. J. Intern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"229","DOI":"10.5761\/atcs.oa.14-00190","article-title":"Neutrophil\/Lymphocyte Ratio Can Predict Postoperative Mortality in Patients with Chronic Thromboembolic Pulmonary Hypertension","volume":"21","author":"Yanartas","year":"2015","journal-title":"Ann. Thorac. Cardiovasc. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Harbaum, L., Baaske, K.M., Simon, M., Oqueka, T., Sinning, C., Glatzel, A., L\u00fcneburg, N., Sydow, K., Bokemeyer, C., and Klose, H. (2017). Exploratory analysis of the neutrophil to lymphocyte ratio in patients with pulmonary arterial hypertension. BMC Pulm. Med., 26.","DOI":"10.1186\/s12890-017-0407-5"},{"key":"ref_26","first-page":"PA2479","article-title":"Neutrophil- to-lymphocyte ratio as a prognostic parameter in pulmonary arterial hypertension","volume":"48","author":"Foris","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.healun.2021.10.018","article-title":"Risk Assessment in Pulmonary Hypertension Based on Routinely Measured Laboratory Parameters","volume":"41","author":"Yogeswaran","year":"2022","journal-title":"J. Heart Lung Transplant."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wu, C.C., Wu, C.H., Lee, C.H., and Cheng, C.I. (2023). Association between neutrophil percentage-to-albumin ratio (NPAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and long-term mortality in community-dwelling adults with heart failure: Evidence from US NHANES 2005\u20132016. BMC Cardiovasc. Disord., 23.","DOI":"10.1186\/s12872-023-03316-6"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3000605231178512","DOI":"10.1177\/03000605231178512","article-title":"Association between neutrophil percentage-to-albumin ratio and 28-day mortality in Chinese patients with sepsis","volume":"51","author":"Hu","year":"2023","journal-title":"J. Int. Med. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e039860","DOI":"10.1136\/bmjopen-2020-039860","article-title":"Association between neutrophil-to-albumin ratio and mortality in patients with cardiogenic shock: A retrospective cohort study","volume":"19","author":"Peng","year":"2020","journal-title":"BMJ Open"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e255","DOI":"10.1097\/01.hjh.0000539728.65245.a2","article-title":"The Lymphocyte-to-Monocyte Ratio\u2014A novel independent predictor of all-cause mortality in patients with heart failure","volume":"36","author":"Delcea","year":"2018","journal-title":"J. Hypertens."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Hao, C., Bo, X., Lu, Z., Qian, H., and Chen, L. (2022). The prognostic value of admission lymphocyte-to-monocyte ratio in critically ill patients with acute myocardial infarction. BMC Cardiovasc. Disord., 22.","DOI":"10.1186\/s12872-022-02745-z"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Yang, Y.T., Jiang, J.H., Yang, H.J., Wu, Z.J., Xiao, Z.M., and Xiang, B.D. (2018). The lymphocyte-to-monocyte ratio is a superior predictor of overall survival compared to established biomarkers in HCC patients undergoing liver resection. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-20199-2"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1186\/s12872-020-01614-x","article-title":"The predictive value of lymphocyte-to-monocyte ratio in the prognosis of acute coronary syndrome patients: A systematic review and meta-analysis","volume":"20","author":"Quan","year":"2020","journal-title":"BMC Cardiovasc. Disord."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1111\/crj.12565","article-title":"Relation between lymphocyte to monocyte ratio and short-term mortality in patients with acute pulmonary embolism","volume":"12","author":"Ertem","year":"2018","journal-title":"Clin. Respir. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e20230245","DOI":"10.36660\/abc.20230245i","article-title":"The Systemic Immune-Inflammation Index Predicts In-Hospital Mortality in Patients Who Underwent On-Pump Cardiac Surgery","volume":"121","author":"Ozocak","year":"2024","journal-title":"Arq. Bras. Cardiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5283","DOI":"10.2147\/JIR.S385990","article-title":"Systemic Immune-Inflammation Index Predicts Long-Term Outcomes in Patients with Three-Vessel Coronary Disease After Revascularization: Results from a Large Cohort of 3561 Patients","volume":"15","author":"Zhao","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.2147\/JIR.S399371","article-title":"Systemic Immune-Inflammation Index and Long-Term Mortality in Patients with Stroke-Associated Pneumonia","volume":"17","author":"Xie","year":"2023","journal-title":"J. Inflamm. Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ye, C., Yuan, L., Wu, K., Shen, B., and Zhu, C. (2023). Association between systemic immune-inflammation index and chronic obstructive pulmonary disease: A population-based study. BMC Pulm. Med., 23.","DOI":"10.1186\/s12890-023-02583-5"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e3302","DOI":"10.1002\/brb3.3302","article-title":"Predictive value of the systemic immune inflammation (SII) index for stroke-associated pneumonia","volume":"13","author":"Cui","year":"2023","journal-title":"Brain Behav."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Varga, A., Tilea, I., Petra, D.N., Tilinca, M.-C., Gliga, M.L., and Demian, S. (2020). Cardiovascular Events throughout the Disease Course in Chronic Myeloid Leukaemia Patients Treated with Tyrosine Kinase Inhibitors\u2014A Single-Centre Retrospective Study. J. Clin. Med., 9.","DOI":"10.3390\/jcm9103269"},{"key":"ref_42","unstructured":"(2013). Medical Laboratories\u2014Requirements for Quality and Competence (Standard No. ISO 15189)."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"365","DOI":"10.3343\/alm.2017.37.5.365","article-title":"International Organization for Standardization (ISO) 15189","volume":"37","author":"Nah","year":"2017","journal-title":"Ann. Lab. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/0895-4356(95)00048-8","article-title":"Importance of events per independent variable in proportional hazards regression analysis. II. Accuracy and precision of regression estimates","volume":"48","author":"Peduzzi","year":"1995","journal-title":"J. Clin. Epidemiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/22\/10940\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T10:57:20Z","timestamp":1762945040000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/22\/10940"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,12]]},"references-count":44,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262210940"],"URL":"https:\/\/doi.org\/10.3390\/ijms262210940","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,12]]}}}