European Radiology

, Volume 25, Issue 1, pp 65–71 | Cite as

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

  • Richard A. P. Takx
  • Rozemarijn Vliegenthart
  • Firdaus A. A. Mohamed Hoesein
  • Ivana Išgum
  • Harry J. de Koning
  • Willem P. Th. M. Mali
  • Carlijn M. van der Aalst
  • Pieter Zanen
  • Jan-Willem J. Lammers
  • Harry J. M. Groen
  • Eva M. van Rikxoort
  • Michael Schmidt
  • Bram van Ginneken
  • Matthijs Oudkerk
  • Tim Leiner
  • Pim A. de Jong



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


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.


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).


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


Cardiovascular diseases Spirometry Multi-detector computed tomography Smoking Mass screening 



Chronic obstructive pulmonary disease


Computed Tomography


Cardiovascular disease


Forced expiratory volume in one second (FEV1)


FEV1 expressed as percent predicted


Forced vital capacity


International Classification of Diseases


Density of the lungs quantified at the 15th percentile point


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


Receiver operating characteristic



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.


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Copyright information

© European Society of Radiology 2014

Authors and Affiliations

  • Richard A. P. Takx
    • 1
  • Rozemarijn Vliegenthart
    • 2
    • 3
  • Firdaus A. A. Mohamed Hoesein
    • 1
  • Ivana Išgum
    • 4
  • Harry J. de Koning
    • 5
  • Willem P. Th. M. Mali
    • 1
  • Carlijn M. van der Aalst
    • 5
  • Pieter Zanen
    • 6
  • Jan-Willem J. Lammers
    • 6
  • Harry J. M. Groen
    • 7
  • Eva M. van Rikxoort
    • 8
    • 9
  • Michael Schmidt
    • 9
  • Bram van Ginneken
    • 8
    • 9
  • Matthijs Oudkerk
    • 2
  • Tim Leiner
    • 1
  • Pim A. de Jong
    • 1
  1. 1.Department of RadiologyUniversity Medical Center UtrechtUtrechtThe Netherlands
  2. 2.Center for Medical Imaging – North East NetherlandsUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
  3. 3.Department of RadiologyUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
  4. 4.Images Sciences InstituteUniversity Medical Center UtrechtUtrechtThe Netherlands
  5. 5.Department of Public HealthErasmus Medical Center RotterdamRotterdamThe Netherlands
  6. 6.Department of PulmonologyUniversity Medical Center UtrechtUtrechtThe Netherlands
  7. 7.Department of PulmonologyUniversity Medical Center GroningenGroningenThe Netherlands
  8. 8.Department of RadiologyRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  9. 9.Fraunhofer MEVISInstitute for Medical Image ComputingBremenGermany

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