8.1 PUBLICATIONS ARISING FROM THIS RESEARCH
Left ventricular hypertrophy with exercise and the angiotensin converting enzyme gene i/D poiymorphism: a randomised controiied triai with iosartan.
Myerson SG, Montgomery HE, Whittingham M, Jubb M, World MJ, Humphries SE, Pennell DJ.
Circulation 2001; 103: 226-30
The human angiotensin i-converting enzyme gene and endurance performance.
Myerson 8, Hemingway H, Budgett R, Martin J, Humphries 8, Montgomery H. Journal of Applied Physiology ^999’, 87(4): 1313-6
Human gene for physicai performance.
Montgomery HE, Marshall R, Hemingway H, Myerson 8, Clarkson P, Dollery C, Hayward M, Holliman DE, Jubb M, World M, Thomas EL, Brynes AE, Saeed N, Barnard M, Bell J, Prasad K, Rayson M, Talmud PJ, Humphries 8E
Nature 1998 May 21; 393(6682):221-2
Angiotensin-converting enzyme genotype affects the response of human skeietai muscie to functionai overioad.
Folland J, Leach B, Little T, Hawker K, Myerson 8, Montgomery H, Jones, D Experimental Physiology 2000; 85: 575-9
The assessment of ieft ventricular mass by cardiac magnetic resonance (review article)
Myerson 8G, Bellenger NG, Pennell DJ. Hypertension 2002; 39: 750-5
The relationships between MRi-determined ieft ventricular mass and body composition variables.
George KP, Myerson 8G, Birch KM, World MJ and Pennell, DJ Submitted to Am J Cardiol
8.2 SUPERVISION OF THE THESIS
Supervision was provided by:
Professor Steve Humphries
British Heart Foundation chair of cardiovascular genetics and Director, Centre for cardiovascular genetics, University College London
Dr. Hugh Montqomerv
Lecturer in cardiovascular medicine and consultant in intensive care medicine Centre for cardiovascular genetics, University College London
Professor Dudlev Pennell
Professor o f Cardiology, National Heart and Lung Institute, Imperial College and Clinical Director, Cardiovascular Magnetic Resonance unit. Royal Brompton Hospital
8.3 ETHICAL APPROVAL FOR THE RESEARCH
8.3.1 LV MASS STUDY
The study protocol was approved by the ethical committees of both the Royal Brompton Hospital and the British army. In addition, funding was obtained from the British Heart Foundation whose detailed analysis includes consideration of the ethical foundation for any approved research.
Separate consent forms were signed by the subjects for obtaining genetic samples and two further consent forms for participation in the study, once ACE genotype had been identified (one each for the Royal Brompton Hospital and the British army).
8.3.2 ACE GENOTYPE FREQUENCY DISTRIBUTION IN ATHLETES
The British Olympic Association considered the ethics of the study in detail and approved the protocol. Particular attention was paid to the anonymity of genetic data and protection of athletes’ details. The study was also approved by the UGL ethics committee.
8.4 PERSONAL CONTRIBUTION TO THIS RESEARCH
8.4.1 ACE GENOTYPING
Dr. Myerson extracted the DNA and performed the ACE genotyping for ail the subjects in these research projects.
8.4.2 CMR SCANNING
Dr. Myerson performed all the cardiac and whole body MR scans, having been trained in the technique at the Royal Brompton Hospital. Technical assistance with the running of the scanner, including transporting to and from the army base, was provided by Steve Collins, Ray Hughes and Peter Gatehouse.
8.4.3 LV HYPERTROPHY STUDY
The overall co-ordination of the study, including consenting and organising subjects, liasing with the troop commanders, other administration and data analysis, was undertaken by Dr. Myerson. Additional support was provided by Capt. Martin Whittingham who assisted with the sample collection and communication within the army base. The study was facilitated by Lt. Col. Mike World, Professor of military medicine, who organised the administration within the Army Medical College.
8.4.4 ATHLETES
Study design was by Hugh Montgomery and Dr. Myerson. The British Mountaineering Council and British Olympic Association provided contact details for the subjects. Postal packs were prepared by Dr. Myerson, Maj Mutch, Helen McGloin and Hugh Montgomery. The collation of samples, genotyping and data analysis was performed by Dr. Myerson.
8.4.5 INDEXING OF LV MASS
8.5 ACKNOWLEDGEMENTS
Grateful help was received from the following:
• The staff of the Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, in particular Steve Collins and Ray Hughes for their help with the mobile scanner. Technical assistance was also received from Peter Gatehouse and Fermi Jhooti, and G.Z.Yang and Francois Chabat provided invaluable computing expertise. Thanks too to Karen Taylor for countless administrative tasks.
• All the staff of the UCL cardiovascular genetics laboratory, in particular Ian Day, Minolas Spanakis and Ros Whittall for showing me initially how it all worked.
• Maj Mutch and Helen McGloin for their help with the postal sampling.
• The British Olympic Association and Dr. Richard Budgett, medical director.
• The British Mountaineering Council.
• Keith George, Manchester Metropolitan University, for the mathematical analysis of LV mass and body composition scaling.
I would also like to thank my friends and family who supported me through the completion of this thesis. In particular, I would like to thank:
Matthew Myerson Louise Elliott Mark Kon Danny Lawes Linda Porter
8.6 SOURCES OF FUNDING
• British Heart Foundation
Funded a junior research fellowship for Dr.Myerson for 2 years (£70, 000).
• Coronary Artery Disease Research Association (CORDA)
Provided funds to build and maintain the mobile OMR scanner.
• The British army medicai research executive
A grant of £30,000 towards the costs of the LV mass study.
• Merck Shape & Dohme pharmaceuticais
Provided initial start-up funds of £8,000 and supplied the randomised packs of losartan/placebo.
• British United Provident Association (BUPA)
An unrestricted programme grant for genetic research at UCL.
• The Post Office
8.7 INDIVIDUAL SUBJECT DATA FROM CHAPTER 3
Notes:
These tables are organised according to ACE genotype and drug status.
The number in bold in the left-most column refers to an individual subject.
Under each heading, the terms ‘pre’ and ‘post’ refer to the values for that parameter at the beginning and end of the 10-week training programme.