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Background <p>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.</p> Methods <p>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.</p> Results <p>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 log<sub>2</sub> ApoA1) and respiratory hospitalization (HR 0.25 [0.11, 0.57] per unit higher log<sub>2</sub> 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; <i>p</i> = 0.029]), but the association with all-cause mortality was no longer significant (HR 0.44 [95% CI: 0.18, 1.08; <i>p</i> = 0.074]). Levels of PON-1 or HDL-C were not associated with all-cause mortality or respiratory hospitalization.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月17日

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  • Anna J. Podolanczuk,
  • Hillary Mulder,
  • John S. Kim,
  • Megan L. Neely,
  • Robert J. Kaner,
  • Jamie L. Todd

摘要

Background

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.

Methods

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.

Results

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.

Conclusion

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.