HDL-C levels are associated with the development of acute respiratory distress syndrome and hospital mortality in critically ill patients: a prospective cohort study

Background Metabolic perturbations frequently occur during the acute phase of critical illness and may disrupt lipid homeostasis. Acute respiratory distress syndrome (ARDS) is a severe condition that contributes to multiple organ failure and is associated with high morbidity and mortality in critically ill patients. This study aimed to evaluate the association between plasma lipid profiles and the development of ARDS, as well as clinical outcomes in critically ill patients. Methods We conducted a prospective observational cohort study of critically ill patients in Taiwan between October 2020 and July 2025. Plasma lipid profiles and clinical variables were measured at intensive care unit (ICU) admission. Clinical outcomes were compared between patients stratified by plasma HDL-C levels. Results A total of 285 critically ill patients were included, comprising 62 without ARDS and 223 with ARDS. The all-cause in-hospital mortality rates were 19.4% in patients without ARDS and 43.0% in those with ARDS. Patients who developed ARDS had significantly higher neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), and interleukin-6 (IL-6) levels, higher risk of organ failure (i.e., APACHE II and SOFA scores), and lower plasma HDL-C levels (all p  < 0.05). Non-survivors exhibited significantly higher NLR, greater organ failure severity, and lower HDL-C levels compared with survivors (all p  < 0.05). Patients with low HDL-C (≤ 22.5 mg/dL; n = 162, 56.8%) had significantly higher CRP and IL-6, greater organ failure severity, and increased 28-, 60-, 90-day, and all-cause hospital mortality, compared with those with high HDL-C (> 22.5 mg/dL; n = 123, 43.2%) (all p  < 0.05). In multivariable logistic regression analyses, elevated NLR and low HDL-C were independently associated with ARDS development and in-hospital mortality. Notably, HDL-C ≤ 22.5 mg/dL demonstrated the strongest predictive value among all variables (adjusted OR 3.383 [95% CI 1.278–8.952], p  = 0.014; adjusted OR 3.451 [95% CI 1.194–9.975], p  = 0.022, respectively). Conclusions Plasma HDL-C levels at ICU admission are independently associated with ARDS development and in-hospital mortality in critically ill patients. HDL-C may serve as a simple, accessible, and valuable early prognostic biomarker in this population.