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Pulmonary function and CT biomarkers as risk factors for cardiovascular events in male lung cancer screening participants: the NELSON study

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Abstract

Objective

The objective of this study was to investigate the association of spirometry and pulmonary CT biomarkers with cardiovascular events.

Methods

In this lung cancer screening trial 3,080 male participants without a prior cardiovascular event were analysed. Fatal and non-fatal cardiovascular events were included. Spirometry included forced expiratory volume measured in units of one-second percent predicted (FEV1%predicted) and FEV1 divided by forced vital capacity (FVC; FEV1/FVC). CT examinations were quantified for coronary artery calcium volume, pulmonary emphysema (perc15) and bronchial wall thickness (pi10). Data were analysed via a Cox proportional hazard analysis, net reclassification improvement (NRI) and C-indices.

Results

184 participants experienced a cardiovascular event during a median follow-up of 2.9 years. Age, pack-years and smoking status adjusted hazard ratios were 0.992 (95 % confidence interval (CI) 0.985-0.999) for FEV1%predicted, 1.000 (95%CI 0.986-1.015) for FEV1/FVC, 1.014 (95%CI 1.005-1.023) for perc15 per 10 HU, and 1.269 (95%CI 1.024-1.573) for pi10 per 1 mm. The incremental C-index (<0.015) and NRI (<2.8 %) were minimal. Coronary artery calcium volume had a hazard ratio of 1.046 (95%CI 1.034-1.058) per 100 mm3, an increase in C-index of 0.076 and an NRI of 16.9 % (P < 0.0001).

Conclusions

Pulmonary CT biomarkers and spirometry measurements were significantly associated with cardiovascular events, but did not contain clinically relevant independent prognostic information for cardiovascular events.

Key Points

• Pulmonary CT biomarkers and spirometry are associated with cardiovascular events

• These pulmonary measurements do not contain clinically relevant independent prognostic information

• Only coronary calcium score improved cardiovascular risk prediction above age and smoking

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Abbreviations

COPD:

Chronic obstructive pulmonary disease

CT:

Computed Tomography

CVD:

Cardiovascular disease

FEV1:

Forced expiratory volume in one second (FEV1)

FEV1%predicted:

FEV1 expressed as percent predicted

FVC:

Forced vital capacity

ICD:

International Classification of Diseases

Perc15:

Density of the lungs quantified at the 15th percentile point

Pi10:

Square root of wall area for a theoretical airway with 10-mm lumen perimeter

ROC:

Receiver operating characteristic

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Acknowledgments

The scientific guarantor of this publication is Pim A. de Jong. The authors of this manuscript declare relationships with the following companies: HJ de Koning received money for being on the Member Advisory Board of Roche Diagnostics. This study has received funding by: The Netherlands Organisation for Health Research and Development (ZonMw); the Dutch Cancer Society; and the Koningin Wilhelmina Fonds; Stichting Centraal Fonds Reserves van Voormalig Vrijwillige Ziekenfondsverzekeringen (RVVZ); Siemens Germany (provided 4 digital workstations and LungCARE for the performance of 3D measurements); Rotterdam Oncologic Thoracic Steering Committee; and the G. Ph. Verhagen Trust, Flemish League Against Cancer, Foundation Against Cancer, and Erasmus Trust Fund. One of the authors has significant statistical expertise. Institutional Review Board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study.

Some study subjects or cohorts have been previously reported. This study is an ancillary study of a large lung cancer screening RCT (NELSON Study; ISRCTN63545820).

Methodology: prospective, prognostic study (original study was a randomised lung cancer screening trial), multi-center study.

Author information

Authors and Affiliations

  1. Department of Radiology, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA, Utrecht, The Netherlands, P.O. Box 85500

    Richard A. P. Takx, Firdaus A. A. Mohamed Hoesein, Willem P. Th. M. Mali, Tim Leiner & Pim A. de Jong

  2. Center for Medical Imaging – North East Netherlands, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Rozemarijn Vliegenthart & Matthijs Oudkerk

  3. Department of Radiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Rozemarijn Vliegenthart

  4. Images Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands

    Ivana Išgum

  5. Department of Public Health, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands

    Harry J. de Koning & Carlijn M. van der Aalst

  6. Department of Pulmonology, University Medical Center Utrecht, Utrecht, The Netherlands

    Pieter Zanen & Jan-Willem J. Lammers

  7. Department of Pulmonology, University Medical Center Groningen, Groningen, The Netherlands

    Harry J. M. Groen

  8. Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    Eva M. van Rikxoort & Bram van Ginneken

  9. Fraunhofer MEVIS, Institute for Medical Image Computing, Bremen, Germany

    Eva M. van Rikxoort, Michael Schmidt & Bram van Ginneken

Authors
  1. Richard A. P. Takx
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  2. Rozemarijn Vliegenthart
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  6. Willem P. Th. M. Mali
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  8. Pieter Zanen
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  9. Jan-Willem J. Lammers
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  10. Harry J. M. Groen
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  11. Eva M. van Rikxoort
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  12. Michael Schmidt
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  13. Bram van Ginneken
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  14. Matthijs Oudkerk
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  15. Tim Leiner
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  16. Pim A. de Jong
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Corresponding author

Correspondence to Richard A. P. Takx.

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Takx, R.A.P., Vliegenthart, R., Hoesein, F.A.A.M. et al. Pulmonary function and CT biomarkers as risk factors for cardiovascular events in male lung cancer screening participants: the NELSON study. Eur Radiol 25, 65–71 (2015). https://doi.org/10.1007/s00330-014-3384-6

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  • DOI: https://doi.org/10.1007/s00330-014-3384-6

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