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Background <p>There are known associations between cardiovascular disease (CVD)-related plasma proteins and spirometry measures. Diffusing capacity for carbon monoxide (D<sub>LCO</sub>) measures gas exchange that can be impaired both by lung and heart diseases. We aimed to study the associations between D<sub>LCO</sub> and CVD-linked plasma proteins in a population-based cohort without airflow obstruction.</p> Methods <p>89 CVD-linked proteins were analysed in 427 individuals who underwent spirometry examination with D<sub>LCO</sub> measurement. Analyses were adjusted for age, gender, height, weight, smoking status and pack years, plates, storage time and cardiovascular morbidity (carotid plaques, hypertension and cardiac medication). Furthermore, a sensitivity analysis (<i>n</i> = 362) was carried out after excluding subjects with an FEV<sub>1</sub>/VC ratio &lt; the lower limit of normal (LLN) and steps were taken to ensure a false discovery rate under 5%.</p> Results <p>We found 18 proteins negatively associated with D<sub>LCO</sub>%predicted after full adjustments (GLI reference equations). Eleven of these proteins (Fibroblast growth factor 23 (estimated coefficients, (adjusted p-value)): -0.010 (&lt; 0.001), Matrix metalloproteinase-12; -0.011 (&lt; 0.001), Growth differentiation factor 15: -0.008 (&lt; 0.001), C-C motif chemokine 20: -0.013 (0.006), Interleukin-6: -0.014 (&lt; 0.001), Fatty acid-binding protein, adipocyte − 0.007 (0.001), Urokinase-type plasminogen activator receptor: -0.004 (&lt; 0.001), Interleukin-1 receptor antagonist: -0.008 (&lt; 0.001), TNF-related apoptosis-inducing ligand receptor 2: -0.005 (0.001), Renin: -0.008 (0.03) and Spondin-1: -0.003 (0.03)) remained significant after further excluding subjects with obstruction on spirometry (FEV<sub>1</sub>/VC &lt; LLN).</p> Conclusions <p>Several CVD-linked plasma proteins were associated with D<sub>LCO</sub> in subjects without airflow obstruction on spirometry and after adjustments for known cardiovascular morbidity. The likely explanations may be the pro-fibrotic and pro-inflammatory nature of many of the proteins causing changes in gas exchange. These proteins could potentially signal for early disease mechanisms leading to impaired gas exchange.</p>

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Diffusing capacity for carbon monoxide is significantly associated with cardiovascular disease-related plasma proteins, independently of obstruction

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月1日

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  • Suneela Zaigham,
  • Xingwu Zhou,
  • Magnus Dencker,
  • Sophia Frantz,
  • Morten Kraen,
  • Per Wollmer,
  • Andrei Malinovschi

摘要

Background

There are known associations between cardiovascular disease (CVD)-related plasma proteins and spirometry measures. Diffusing capacity for carbon monoxide (DLCO) measures gas exchange that can be impaired both by lung and heart diseases. We aimed to study the associations between DLCO and CVD-linked plasma proteins in a population-based cohort without airflow obstruction.

Methods

89 CVD-linked proteins were analysed in 427 individuals who underwent spirometry examination with DLCO measurement. Analyses were adjusted for age, gender, height, weight, smoking status and pack years, plates, storage time and cardiovascular morbidity (carotid plaques, hypertension and cardiac medication). Furthermore, a sensitivity analysis (n = 362) was carried out after excluding subjects with an FEV1/VC ratio < the lower limit of normal (LLN) and steps were taken to ensure a false discovery rate under 5%.

Results

We found 18 proteins negatively associated with DLCO%predicted after full adjustments (GLI reference equations). Eleven of these proteins (Fibroblast growth factor 23 (estimated coefficients, (adjusted p-value)): -0.010 (< 0.001), Matrix metalloproteinase-12; -0.011 (< 0.001), Growth differentiation factor 15: -0.008 (< 0.001), C-C motif chemokine 20: -0.013 (0.006), Interleukin-6: -0.014 (< 0.001), Fatty acid-binding protein, adipocyte − 0.007 (0.001), Urokinase-type plasminogen activator receptor: -0.004 (< 0.001), Interleukin-1 receptor antagonist: -0.008 (< 0.001), TNF-related apoptosis-inducing ligand receptor 2: -0.005 (0.001), Renin: -0.008 (0.03) and Spondin-1: -0.003 (0.03)) remained significant after further excluding subjects with obstruction on spirometry (FEV1/VC < LLN).

Conclusions

Several CVD-linked plasma proteins were associated with DLCO in subjects without airflow obstruction on spirometry and after adjustments for known cardiovascular morbidity. The likely explanations may be the pro-fibrotic and pro-inflammatory nature of many of the proteins causing changes in gas exchange. These proteins could potentially signal for early disease mechanisms leading to impaired gas exchange.