Study protocol: a randomised controlled trial investigating the effect of exercise training on peripheral blood gene expression in patients with stable angina

Liam Bourke, Garry A Tew, Marta Milo, David C Crossman, John M Saxton, Timothy J A Chico, Liam Bourke, Garry A Tew, Marta Milo, David C Crossman, John M Saxton, Timothy J A Chico

Abstract

Background: Exercise training has been shown to reduce angina and promote collateral vessel development in patients with coronary artery disease. However, the mechanism whereby exercise exerts these beneficial effects is unclear. There has been increasing interest in the use of whole genome peripheral blood gene expression in a wide range of conditions to attempt to identify both novel mechanisms of disease and transcriptional biomarkers. This protocol describes a study in which we will assess the effect of a structured exercise programme on peripheral blood gene expression in patients with stable angina, and correlate this with changes in angina level, anxiety, depression, and exercise capacity.

Methods/design: Sixty patients with stable angina will be recruited and randomised 1:1 to exercise training or conventional care. Patients randomised to exercise training will attend an exercise physiology laboratory up to three times weekly for supervised aerobic interval training sessions of one hour in total duration. Patients will undergo assessments of angina, anxiety, depression, and peripheral blood gene expression at baseline, after six and twelve weeks of training, and twelve weeks after formal exercise training ceases.

Discussion: This study will provide comprehensive data on the effect of exercise training on peripheral blood gene expression in patients with angina. By correlating this with improvement in angina status we will identify candidate peripheral blood transcriptional markers predictive of improvements in angina level in response to exercise training.

Trial registration: Clinicaltrials.gov identifier: NCT01147952.

Figures

Figure 1
Figure 1
Flow diagram indicating participant's involvement throughout the course of the study.

References

    1. Thompson PD, Buchner D, Pina IL, Balady GJ, Williams MA, Marcus BH, Berra K, Blair SN, Costa F, Franklin B. et al.Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity) Circulation. 2003;107:3109–3116. doi: 10.1161/01.CIR.0000075572.40158.77.
    1. Froelicher V, Jensen D, Genter F, Sullivan M, McKirnan MD, Witztum K, Scharf J, Strong ML, Ashburn W. A randomized trial of exercise training in patients with coronary heart disease. JAMA. 1984;252:1291–1297. doi: 10.1001/jama.252.10.1291.
    1. Jolliffe JA, Rees K, Taylor RS, Thompson D, Oldridge N, Ebrahim S. Exercise-based rehabilitation for coronary heart disease. Cochrane Database Syst Rev. 2001. p. CD001800.
    1. Taylor RS, Brown A, Ebrahim S, Jolliffe J, Noorani H, Rees K, Skidmore B, Stone JA, Thompson DR, Oldridge N. Exercise-based rehabilitation for patients with coronary heart disease: systematic review and meta-analysis of randomized controlled trials. Am J Med. 2004;116:682–692. doi: 10.1016/j.amjmed.2004.01.009.
    1. Hambrecht R, Walther C, Mobius-Winkler S, Gielen S, Linke A, Conradi K, Erbs S, Kluge R, Kendziorra K, Sabri O. et al.Percutaneous coronary angioplasty compared with exercise training in patients with stable coronary artery disease: a randomized trial. Circulation. 2004;109:1371–1378. doi: 10.1161/01.CIR.0000121360.31954.1F.
    1. Hambrecht R, Wolf A, Gielen S, Linke A, Hofer J, Erbs S, Schoene N, Schuler G. Effect of exercise on coronary endothelial function in patients with coronary artery disease. N Engl J Med. 2000;342:454–460. doi: 10.1056/NEJM200002173420702.
    1. Zbinden R, Zbinden S, Meier P, Hutter D, Billinger M, Wahl A, Schmid JP, Windecker S, Meier B, Seiler C. Coronary collateral flow in response to endurance exercise training. Eur J Cardiovasc Prev Rehabil. 2007;14:250–257. doi: 10.1097/HJR.0b013e3280565dee.
    1. Senti S, Fleisch M, Billinger M, Meier B, Seiler C. Long-term physical exercise and quantitatively assessed human coronary collateral circulation. J Am Coll Cardiol. 1998;32:49–56. doi: 10.1016/S0735-1097(98)00181-8.
    1. Billinger M, Kloos P, Eberli FR, Windecker S, Meier B, Seiler C. Physiologically assessed coronary collateral flow and adverse cardiac ischemic events: a follow-up study in 403 patients with coronary artery disease. J Am Coll Cardiol. 2002;40:1545–1550. doi: 10.1016/S0735-1097(02)02378-1.
    1. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352:1685–1695. doi: 10.1056/NEJMra043430.
    1. Schaper W, Scholz D. Factors regulating arteriogenesis. Arterioscler Thromb Vasc Biol. 2003;23:1143–1151. doi: 10.1161/01.ATV.0000069625.11230.96.
    1. Sinnaeve PR, Donahue MP, Grass P, Seo D, Vonderscher J, Chibout SD, Kraus WE, Sketch M Jr, Nelson C, Ginsburg GS. et al.Gene expression patterns in peripheral blood correlate with the extent of coronary artery disease. PLoS One. 2009;4:e7037. doi: 10.1371/journal.pone.0007037.
    1. Wingrove JA, Daniels SE, Sehnert AJ, Tingley W, Elashoff MR, Rosenberg S, Buellesfeld L, Grube E, Newby LK, Ginsburg GS, Kraus WE. Correlation of peripheral-blood gene expression with the extent of coronary artery stenosis. Circ Cardiovasc Genet. 2008;1:31–38. doi: 10.1161/CIRCGENETICS.108.782730.
    1. Meier P, Antonov J, Zbinden R, Kuhn A, Zbinden S, Gloekler S, Delorenzi M, Jaggi R, Seiler C. Non-invasive gene-expression-based detection of well-developed collateral function in individuals with and without coronary artery disease. Heart. 2009;95:900–908. doi: 10.1136/hrt.2008.145383.
    1. Chittenden TW, Sherman JA, Xiong F, Hall AE, Lanahan AA, Taylor JM, Duan H, Pearlman JD, Moore JH, Schwartz SM, Simons M. Transcriptional profiling in coronary artery disease: indications for novel markers of coronary collateralization. Circulation. 2006;114:1811–1820. doi: 10.1161/CIRCULATIONAHA.106.628396.
    1. Bye A, Tjonna AE, Stolen TO, Rosbjorgen RE, Wisloff U. Transcriptional changes in blood after aerobic interval training in patients with the metabolic syndrome. Eur J Cardiovasc Prev Rehabil. 2009;16:47–52. doi: 10.1097/HJR.0b013e32831c13a0.
    1. Lavie CJ, Milani RV, Cassidy MM, Gilliland YE. Effects of cardiac rehabilitation and exercise training programs in women with depression. Am J Cardiol. 1999;83:1480–1483. doi: 10.1016/S0002-9149(99)00127-7. A1487.
    1. Borg G. Ratings of perceived exertion and heart rates during short-term cycle exercise and their use in a new cycling strength test. Int J Sports Med. 1982;3:153–158. doi: 10.1055/s-2008-1026080.
    1. Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol. 1988;56:893–897. doi: 10.1037/0022-006X.56.6.893.
    1. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry. 1961;4:561–571.
    1. Spertus JA, Winder JA, Dewhurst TA, Deyo RA, Prodzinski J, McDonell M, Fihn SD. Development and evaluation of the Seattle Angina Questionnaire: a new functional status measure for coronary artery disease. J Am Coll Cardiol. 1995;25:333–341. doi: 10.1016/0735-1097(94)00397-9.
    1. Lancaster GA, Dodd S, Williamson PR. Design and analysis of pilot studies: recommendations for good practice. J Eval Clin Pract. 2004;10:307–312. doi: 10.1111/j..2002.384.doc.x.
    1. Vickers AJ, Altman DG. Statistics notes: Analysing controlled trials with baseline and follow up measurements. BMJ. 2001;323:1123–1124. doi: 10.1136/bmj.323.7321.1123.
    1. Sanguinetti G, Milo M, Rattray M, Lawrence ND. Accounting for probe-level noise in principal component analysis of microarray data. Bioinformatics. 2005;21:3748–3754. doi: 10.1093/bioinformatics/bti617.
    1. Packham IM, Gray C, Heath PR, Hellewell PG, Ingham PW, Crossman DC, Milo M, Chico TJ. Microarray profiling reveals CXCR4a is downregulated by blood flow in vivo and mediates collateral formation in zebrafish embryos. Physiol Genomics. 2009;38:319–327. doi: 10.1152/physiolgenomics.00049.2009.
    1. Pearson RD, Liu X, Sanguinetti G, Milo M, Lawrence ND, Rattray M. puma: a Bioconductor package for propagating uncertainty in microarray analysis. BMC Bioinformatics. 2009;10:211. doi: 10.1186/1471-2105-10-211.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する