Serum levels of small HDL particles are negatively correlated with death or lung transplantation in an observational study of idiopathic pulmonary fibrosis

Background: Serum lipoproteins, such as high-density lipoproteins (HDL), may influence disease severity in idiopathic pulmonary fibrosis (IPF). Here, we investigated associations between serum lipids and lipoproteins and clinical end-points in IPF.

Methods: Clinical data and serum lipids were analysed from a discovery cohort (59 IPF subjects, 56 healthy volunteers) and validated using an independent, multicentre cohort (207 IPF subjects) from the Pulmonary Fibrosis Foundation registry. Associations between lipids and clinical end-points (forced vital capacity, 6-min walk distance, gender age physiology (GAP) index, death or lung transplantation) were examined using Pearson's correlation and multivariable analyses.

Results: Serum concentrations of small HDL particles measured using nuclear magnetic resonance spectroscopy (S-HDLP_NMR) correlated negatively with the GAP index in the discovery cohort of IPF subjects. The negative correlation of S-HDLP_NMR with GAP index was confirmed in the validation cohort of IPF subjects. Higher levels of S-HDLP_NMR were associated with lower odds of death or its competing outcome, lung transplantation (OR 0.9 for each 1-μmol·L^-1 increase in S-HDLP_NMR, p<0.05), at 1, 2 and 3 years from study entry in a combined cohort of all IPF subjects.

Conclusions: Higher serum levels of S-HDLP_NMR are negatively correlated with the GAP index, as well as with lower observed mortality or lung transplantation in IPF subjects. These findings support the hypothesis that S-HDLP_NMR may modify mortality risk in patients with IPF.