Exercise as it relates to Disease/The small-scale effects of exercise and its large-scale implications in coronary artery disease
This article is a critical analysis of the paper: "Effect of Exercise on Coronary Endothelial Function in Patients with Coronary Artery Disease" (Rainer Hambrecht, M.D. et al. 2000)
- 1 What is the background to this research?
- 2 Where is the research from?
- 3 What kind of research was this?
- 4 What did the research involve?
- 5 What were the basic results?
- 6 Critique of Methodology/Approach
- 7 What conclusions can we take from this research?
- 8 Practical advice?
- 9 Further information/resources
- 10 References
What is the background to this research?
Coronary Artery Disease (CAD) can be defined as the progressive decline in the arteries ability to transport blood, due the to build up of fatty plaques that are deposited within the walls of tissue lining the blood vessels. 
Research into the condition of CAD and how the severity of condition can be lessened though modifiable lifestyle factors such as exercise, is critical. This can be supported by the fact that CAD is one of the leading causes of mortality in both men and women on a global scale. . Therefore, the implications of physical activity on such a disease must be examined and applied to not only to induce the positive health benefits for the individual with CAD, but on a broader level, such research can contribute to reduce the large economic burden of any cardiovascular related diseases due to physical inactivity. 
Where is the research from?
This particular research paper was published in The New England Journal of Medicine, one of the most reputable medical-related Journals worldwide. .
The primary author of this research paper, Dr Rainer Hambrecht, has been involved in the production of around 197 research articles predominantly regarding various cardiovascular dysfunctions and how exercise effects such health related issues, implying his strong reputation in this field.
Furthermore, no obvious bias exists in regards to the composition of this original research article, however most co-authors have developed other research associated with cardiovascular complications and how genetics and exercise training impacts them. Such wealth of knowledge in the area across most co-authors, is also considered advantageous considering the degree of difficulty of conducting such invasive research.
What kind of research was this?
This study was conducted in the form of a prospective Randomised Control Trial (RCT), in which one group was participating in the intervention in the form of exercise, and the other group remained the control group for later comparison. 
An RCT method of research is considered the most plausible way of determining whether or not there exists a cause and effect relationship between the intervention implemented and the overall outcome of the research. It is important however, to consider how the research is conducted and what causes are concluded to create what effects . 
What did the research involve?
The study involved the 19 male participants whom were diagnosed with CAD, and had, to some degree, dysfunction of the cell lining of blood vessels (endothelia) resulting in abnormal narrowing (vasoconstriction) in response to to the neurotransmitter acetylcholine. 10 of which were assigned an exercise training program and 9 remained the control group.
All individuals participated in an initial exercise test on a cycle ergometer to determine baseline values including peak oxygen uptake. They also underwent an invasive coronary angiogram to collect data regarding the luminal diameter and peak blood flow velocity. The exercise group then engaged in an aerobic training program for 4 weeks, consisting of 10 minutes (excluding warm up and cool down), 6 times per week at 80% of their peak heart rate reaching during the initial exercise test.  This was aimed at determining whether aerobic (high intensity) exercise corrects endothelial dysfunction in individuals with CAD.
All participant then completed a 4 week follow up, including both the exercise and invasive testing.
What were the basic results?
- After four weeks of exercise training, peak oxygen uptake during exercise increased by 12%, coronary blood-flow velocity from base line in response to higher doses of acetylcholine significantly increased (96%) and Luminal Diameter before and after exercise training remained unchanged (P>0.05).
|Bodyweight (kgs)||Peak Oxygen Uptake (ml/kg/min)||Coronary Blood-Flow Velocity (cm/sec)||Coronary blood-flow reserve (% of Change)||Flow Dependant Dilation (mm) (% of Change)|
|Pre Intervention Exercise-training Group||83.4±4||24.0±1.5||4.6±2.8||2.8±0.2||0.19±0.06|
|Post Intervention Exercise-training Group||82.5± 4||26.8±1.0||9.0±3.6||3.6±0.2 (29% ^)||0.39± 0.07 (105% ^)|
|Pre Intervention Control Group||-||23.3±1.1||-||-||-|
|Post Intervention Control Group||NOT SIGNIFICANT||NOT SIGNIFICANT||NOT SIGNIFICANT||NOT SIGNIFICANT||NOT SIGNIFICANT|
Critique of Methodology/Approach
Firstly, patients were taking normal medications throughout the process which may have altered the potential of results via (beta-blockers) as such medication influences heart rate. This therefor effected the initial testing (peak heart rate) which was used to determine intensity for the exercise program. Results were interpreted based on "high intensity endurance training", and "vigorous exercise" yet the participants were working at an average heart rate much lower then the actual data measured for a short amount of time, which may not warrant high intensity efforts in a healthy population, but in this population it may.
Secondly, participants were also administered with Acetylcholine (ACH) which was used as a measure to determine the responsiveness of the health of the endothelia, which pends the question as to whether responsiveness to ACH really matters in day to day life.
Lastly, perhaps the 4 week training program and the exercise type/intensity may not of been the most appropriate way to determine whether "high intensity" exercise specifically improves coronary endothelial function.
Furthermore, the relatively small study could possibly be attributed to the invasiveness of the procedures necessary to carry out the research. Moreover, it was only conducted on older males eliminating the possibility of determining any gender specific differences and limiting younger population applicability.
Additionally, the conclusions that are made aren't necessarily not over-emphasised though, as the statistical data supports the overall findings. However, the study has made predictive claims that these results are due to the improvement of endothelial cell function without strong evidence to prove the exact mechanisms involved to create the changes in the statistical measures; something that all related research is unclear about. 
Lastly, it is important to consider that bias may arise from the measures taken in the testing, if the practitioner was aware of which group the participant belonged too (experimental blinding).
On the contrary, they did recruit participants carefully. For example, participants were only suitable providing they had coronary-artery stenosis requiring a nonsurgical revascularisation, no existing co-morbidities and a stable condition.
What conclusions can we take from this research?
As this is a smaller scale study, the degree of evidence applicability and overall conclusions made could be termed limited amongst the population as a whole. Potentially in the future, larger scale studies and more long term endurance-based exercise programs as opposed to high intensity exercise for research purposes, should be conducted. Overall, high intensity exercise training did have a beneficial effect on the endothelium in the conduit vessels as seen in the results table, though the specific mechanisms involved are not completely understood. Further, more in depth research into the working mechanisms that support this statement may also be appropriate in the future with developing technology and increased knowledge and understanding.
Nowadays, such findings outlined above do co-incide with other more current research, in that, engaging in exercise, predominantly endurance-based in nature, providing the condition is stable, can induce benefits such as improving myocardial perfusion and hindering disease progression.  
More concisely, high intensity exercise, as termed by this particular study, may not be as beneficial as endurance based training for individuals with CAD in terms of endothelial health. Therefore, exercise of an endurance based nature, within limitations, should be encouraged for individuals with stable CAD to improve not only endothelial health, but other important aspects of their cardiovascular capacity.
- As supported by more recent research, endurance based training may provoke a more advantageous response in individuals with CAD in terms of endothelial function as opposed to high intensity exercise training. 
- Due to the high current prevalence of CAD and the increasing incidence in the near future, further attention, resources and research should be dedicated to such an epidemic to increase quality of life for such sufferers and decrease susceptibility of developing other life threatening co-morbidities.
If this articled sparked further interest or you are in need of support, below are extra resources to provide additional information:
- Heart Foundation
- New England Journal of Medicine
- Allied Health Professionals Australia
- What Exercise Physiologists can do for me?
- What exercise is appropriate for CAD?
- OpenStax College, Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013.
- Hambrecht, Rainer et al. (2000) Effect of Exercise on Coronary Endothelial Function in Patients with Coronary Artery Disease, New England Journal of Medicine, (342, 454-460).
- Bhatia, Sujata K, (2010) Coronary Artery Disease, Biomaterials for Clinical Applications, (23-49).
- Oldridge, Neil B, (2008) Economic burden of Physical Inactivity: Healthcare Costs associated with Cardiovascular Disease, European Journal of Cardiovascular Prevention & Rehabilitation, (15, 130-139).
- Eugene Garfield, PhD. (2006) The History and Meaning of the Journal Impact Factor. Jama, (295, 90-93).
- Kendall, JM, (2003) Designing a research project: Randomised Controlled Trials and their Principles, Emergency Medicine Journal, (20, 164-168).
- Hambrecht, Rainer et al. (2004) Percutaneous Coronary Angioplasty compared with Exercise Training in Patients with stable Coronary Artery Disease: a Randomized Trial, Circulation, (109, 1371-1378).
- Clausen, Jan Praetorius, (1976) Circulatory Adjustments to Dynamic Exercise and Effect of Physical Training in normal subjects and in patients with Coronary Artery Disease, Progress in Cardiovascular Diseases, (18, 459-495).
- Steiner, Sabine et al. (2005) Endurance Training increases the number of Endothelial Progenitor Cells in patients with Cardiovascular Risk and Coronary Artery Disease, Atherosclerosis, (181, 305-310).