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
Chest

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

Keywords

Cardiovascular diseases Spirometry Multi-detector computed tomography Smoking Mass screening 

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

Notes

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.

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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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