Apolipoprotein CIII and N-Terminal Prohormone B-type Natriuretic Peptide as Independent Predictors for Cardiovascular Disease in Type 2 Diabetes Marco Colombo 1 *, Helen C Looker 2 *, Bassam Farran 1 , Felix Agakov 1,3 , M Julia Brosnan 4 , Paul Welsh 5 , Naveed Sattar 5 , Shona Livingstone 6 , Paul N Durrington 7 , D John Betteridge 8 , Paul M McKeigue 1 , Helen M Colhoun 1,9 ** 1 University of Edinburgh, 2 Diabetes Epidemiology and Clinical Research Section, National Institutes of Health, 1550 E Indian School Road, Phoenix, AZ 85014, 3 Pharmatics Ltd, Edinburgh Bioquarter, 9 Little France Road, Edinburgh, EH16 4UX, UK, 4 Pfizer Inc., 5 University of Glasgow, 6 Diabetes Epidemiology Unit, University of Dundee, Mackenzie Building, Kirsty Semple Way, Dundee DD2 4BF, UK, 7 Cardiovascular Research Group, University of Manchester, 46 Grafton Street, Manchester, M13 9NT, UK 8 University College London Hospitals, London, UK, 9 NHS Fife, Kirkcaldy, UK * These authors contributed equally to this work **Corresponding author (present address): Prof. Helen M. Colhoun, AXA Chair in Medical Informatics and Life Course Epidemiology, MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Crewe Road, Edinburgh, UK, EH4 2XU, Tel : +44 (0) 131 651 8770, Email: [email protected]Clinical and Population Original Research Paper 1
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Apolipoprotein CIII and N-Terminal Prohormone B-type Natriuretic Peptide as Independent Predictors for Cardiovascular Disease in Type 2 Diabetes
Marco Colombo1*, Helen C Looker2*, Bassam Farran1, Felix Agakov1,3, M Julia Brosnan4, Paul
Welsh5, Naveed Sattar5, Shona Livingstone6, Paul N Durrington7, D John Betteridge8, Paul M
McKeigue1, Helen M Colhoun1,9**
1University of Edinburgh, 2 Diabetes Epidemiology and Clinical Research Section, National
Institutes of Health, 1550 E Indian School Road, Phoenix, AZ 85014, 3Pharmatics Ltd, Edinburgh
Bioquarter, 9 Little France Road, Edinburgh, EH16 4UX, UK, 4Pfizer Inc., 5University of Glasgow, 6Diabetes Epidemiology Unit, University of Dundee, Mackenzie Building, Kirsty Semple Way,
Dundee DD2 4BF, UK, 7Cardiovascular Research Group, University of Manchester, 46 Grafton
Street, Manchester, M13 9NT, UK 8University College London Hospitals, London, UK, 9NHS
Fife, Kirkcaldy, UK
* These authors contributed equally to this work
**Corresponding author (present address): Prof. Helen M. Colhoun, AXA Chair in Medical
Informatics and Life Course Epidemiology, MRC Institute of Genetics and Molecular Medicine,
Western General Hospital, Crewe Road, Edinburgh, UK, EH4 2XU, Tel : +44 (0) 131 651 8770,
research support, travel expenses and is on the Steering Committee for Novo Nordisk. HMC is a
shareholder of Roche Pharmaceuticals and Bayer. HMC has received speaker fees from Pfizer.
All other authors declare that there is no duality of interest associated with their contribution to
this manuscript.
Financial support: This work was funded by the Innovative Medicine Initiative under grant
agreement n° IMI/115006 (the SUMMIT consortium). The original CARDS Trial was funded by
Diabetes UK, the UK Department of Health, Pfizer UK and Pfizer Inc. (manufacturers of
atorvastatin).
Author contributions: MC carried out the primary statistical analyses and reviewed/edited the
manuscript, HCL wrote and revised manuscript, BF researched data and reviewed/edited the
manuscript, MJB researched data and reviewed and edited the manuscript, FA contributed to
the design of the study and revised the manuscript, PW and NS undertook the biomarker assays
and reviewed/edited the manuscript, SJL ,PND, DJB researched data and reviewed/edited the
manuscript, PMM and HMC designed the study, researched the data and revised the
manuscript. All authors have approved the final version of the manuscript.
Acknowledgements: We wish to acknowledge the patients who participated and the
investigators of the Collaborative Atorvastatin in Diabetes Study (CARDS): Helen Colhoun, John
Betteridge, David DeMicco, Paul Durrington, John Fuller, Graham Hitman and Andrew Neil.
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Table 1: Baseline Demographics and Biomarker Concentrations of CARDS Study Participants by Incident CVD status (n=2105)
No CVD Event
(n=1961)CVD Event (n=144) p-value
adjusted
for age
and sex
Median/
Frequency
Interqua
rtile
range
Median/
Frequency
Interquartile
range
Age (years) 62.7 55.7, 67.9 65.0 61.1, 69.4 <0.001a