HDL-C Levels Are Associated with Clinical Outcomes and Hospital Mortality in Critically Ill Patients with Sepsis: A Prospective Cohort Study

Background and Objectives: 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 and is associated with high mortality in critically ill patients with sepsis. This study aimed to evaluate the association between conventional plasma lipid parameters and clinical outcomes in critically ill sepsis patients. Materials and Methods: We conducted a prospective observational cohort study of critically ill sepsis patients in Taiwan between October 2020 and July 2025. Conventional plasma lipid parameters and clinical variables were measured at intensive care unit admission. Clinical outcomes were compared between patients stratified by plasma HDL-C levels. Results: A total of 285 critically ill patients with sepsis were included. Pneumonia was the presumed source of infection in 91% of patients, and 78% met the criteria for ARDS. The overall hospital mortality rate was 37.9%. Patients with ARDS had significantly higher 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 greater organ failure severity and lower HDL-C levels compared with survivors (all p < 0.05). Patients with low HDL-C (≤17.5 mg/dL; n = 106, 37.2%) had significantly higher CRP and IL-6, greater organ failure severity, and increased 28-, 60-, 90-day, and hospital mortality, compared with those with high HDL-C (> 17.5 mg/dL; n = 179, 62.8%) (all p < 0.05). In multivariable analyses, lower HDL-C were independently associated with hospital mortality. Conclusions: Lower HDL-C levels were associated with hospital mortality in critically ill patients with sepsis, most of whom had pneumonia and concomitant ARDS. These findings suggest that HDL-C may have prognostic value in this selected critically ill population, although external validation in broader sepsis populations is warranted. An easily accessible and useful for early risk stratification.