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

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 approximately 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.