High density lipoproteins, disease severity and clinical outcomes in patients with idiopathic pulmonary fibrosis

Dysregulation of lipid metabolism is implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). We assessed associations between circulating levels of high-density lipoprotein-cholesterol (HDL-C) and its components apolipoprotein A-1 (ApoA1) and paraoxonase-1 (PON-1) and disease severity and outcomes in patients with IPF. The cohort comprised 284 patients enrolled in the IPF-PRO Registry. We analyzed associations between HDL-C, ApoA1 and PON-1 levels at enrollment and measures of disease severity at enrollment (using linear regression) and outcomes during follow-up (using Cox models). Models were adjusted for demographic and clinical variables, including cardiovascular disease and statin use, assessed at enrollment. In unadjusted models, higher ApoA1 and lower PON-1 were associated with higher FVC % predicted at enrollment. Median follow-up was 40 months. In unadjusted models, higher ApoA1 at enrollment was associated with lower risks of all-cause mortality (hazard ratio [HR] 0.32 [95% CI: 0.16, 0.64] per unit higher log2 ApoA1) and respiratory hospitalization (HR 0.25 [0.11, 0.57] per unit higher log2 ApoA1). In analyses adjusted for demographic and clinical variables, the association with respiratory hospitalization remained significant (HR 0.30 [95% CI: 0.10, 0.88; p = 0.029]), but the association with all-cause mortality was no longer significant (HR 0.44 [95% CI: 0.18, 1.08; p = 0.074]). Levels of PON-1 or HDL-C were not associated with all-cause mortality or respiratory hospitalization. In a real-world cohort of patients with IPF, a higher circulating level of ApoA1 was associated with a lower risk of respiratory hospitalization. ApoA1 is a potential prognostic biomarker in patients with IPF.