U-Shaped Relationship Between Serum Lactate Dehydrogenase with All-Cause Mortality in Patients with Chronic Obstructive Pulmonary Disease

International Journal of Chronic Obstructive Pulmonary Disease Dovepress open access to scientific and medical research International Journal of Chronic Obstructive Pulmonary Disease downloaded from https://www.dovepress.com/ on 30-Mar-2023 For personal use only. Open Access Full Text Article ORIGINAL RESEARCH U-Shaped Relationship Between Serum Lactate Dehydrogenase with All-Cause Mortality in Patients with Chronic Obstructive Pulmonary Disease Lihua Huang 1, *, Zhanpeng Lu Chunsheng Zou 1 2, *, Xiaoqing Zhou 3 , Liuliu He 1 , Xiaoyan You 1 , Chunmei Chen 1 , 1 Department of Clinical Laboratory, The Second Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China; 2Department of Critical Care,The Eighth Affiliated Hospital of Sun Yat sen University, Shenzhen, People’s Republic of China; 3General Surgery Department, The Second Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China *These authors contributed equally to this work Correspondence: Lihua Huang, Department of Clinical Laboratory, The Second Affiliated Hospital of Gannan Medical University, 331 Yingbin Dadao, Xinfeng County, Ganzhou, Jiangxi Province, People’s Republic of China, Tel +86 18970771329, Email Purpose: In the anaerobic metabolic pathway, lactate dehydrogenase (LDH) plays an important role in hypoxia, inflammation, and cell damage, making it a potential biomarker for the progression of chronic obstructive pulmonary disease (COPD). We aimed to examine the relationship between LDH levels and all-cause mortality in participants with COPD. Patients and Methods: Data of participants in the US National Health and Nutrition Examination Surveys (NHANES) 2007–2012 aged ≥20 years who underwent spirometry tests were examined, and follow-up mortality data were obtained. According to serum LDH levels, participants with COPD were divided into five groups (59–111, 112–123, 124–135, 136–150, and 151–344 U/L). To evaluate whether LDH levels were independently associated with COPD mortality, we used multivariate Cox regression analysis and smooth curve fitting. Results: We included 1320 subjects, 64 with stage III or IV COPD and 541 with stage II COPD. Over a median follow-up of 9.7 years (IQR: 7.8, 11.2), 252 of the 1320 subjects died. The mean LDH level was 132.5 U/L (standard deviation [SD], 27.0). A U-shaped relationship was observed between LDH levels and all-cause mortality. Below and above the inflection point, which was approxi mately 110 U/L, we found different slopes for the correlation between LDH and all-cause mortality of patients with COPD. Below the threshold, per 1-standard deviation (1SD) increase in LDH resulted in a 68% reduced risk of all-cause mortality (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.13–0.81, P=0.016); conversely, above the threshold, per 1SD increase in LDH accelerated the risk of all-cause mortality (HR 1.23, 95% CI: 1.08–1.41, P= 0.002). Conclusion: Using the nationally representative NHANES data, we found a U-shaped association between LDH level and all-cause mortality in participants with COPD. An optimal LDH level of approximately 110 U/L was associated with the lowest risk of all-cause mortality. Keywords: lactate dehydrogenase, pulmonary disease, chronic obstructive, nutrition surveys, nonlinear, threshold Introduction Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable disease characterized by persistent respiratory symptoms and progressive airflow obstruction.1 In 2018, COPD was the fourth most common cause of death in the United States.2 COPD was diagnosed in nearly 15.7 million Americans (6.4%).3 In more than half of COPD cases, adults were unaware of their condition.4 Age-adjusted mortality rates for COPD in the United States decreased among men between 1999 and 2014 but remained stable among women during the same period.5 The International Journal of Chronic Obstructive Pulmonary Disease 2023:18 305–316 Received: 20 August 2022 Accepted: 4 March 2023 Published: 15 March 2023 305 © 2023 Huang et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Huang et al Dovepress prediction of mortality is important since it allows the identification of patients whose outcomes can be improved by implementing specific therapeutic measures. As a marker of tissue injury, necrosis, and hypoxia, lactate dehydrogenase (LDH) has an essential value in the diagnosis, treatment, and prognosis of cancer.6 Furthermore, patients with COPD have increased LDH levels. These levels indicate underlying lung damage and inflammation and show the usefulness of LDH and its isoenzymes as indicators of lung damage or inflammation.7 However, the relationship between LDH and all-cause mortality in patients with COPD has scarcely been studied. The primary aim of this study was to assess the association between LDH levels and all-cause mortality. Materials and Methods Data Source and Study Design The National Health and Nutrition Examination Survey (NHANES) is a major program of the National Center for Health Statistics (NCHS), an agency of the Centers for Disease Control and Prevention (CDC). This national survey is being conducted to assess the health of the entire United States (US) population. To generate population-level estimates, data is collected annually on a two-year cycle using a multistage probabilistic sampling design. Based on a design variable, we approximated the number of civilians (not institutionalized) using the data from the NHANES from 2007 to 2012. Demographic data, spirometry test results, disease information, and laboratory and questionnaire data related to disease definitions were also extracted and combined. We enrolled patients aged ≥ 20 years who completed spirometry and had their serum LDH levels measured (Figure 1). Data from this study are freely available on the NHANES homepage (http://www.cdc.gov/nchs/nhanes.htm) which has been approved by the NCHS Institutional Figure 1 Study flowchart. Abbreviations: NHANES, National Survey of the National Center for Health Statistics; FVC, forced vital capacity; FEV1, forced expiratory volume in the first 1 second; LDH, serum lactate dehydrogenase; BMI, body mass index; CVD, cardiovascular diseases; MCV, mean corpuscular volume; FEV1% predicted, forced expiratory volume in 1 second percent of predicted. 306 Powered by TCPDF (www.tcpdf.org) http (...truncated)