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)
What is the background to this research?Edit
Coronary Artery Disease (CAD) can be defined as the progressive decline in the arteries ability to transport blood, due to the 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 the 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?Edit
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 regard to the composition of this original research article, however most co-authors have developed other research associated with cardiovascular complications and the impact of genetics and exercise training. Such wealth of knowledge in the area across most co-authors is also considered advantageous, considering the degree of difficulty in conducting such invasive research.
What kind of research was this?Edit
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, however, it is important to consider how the research is conducted and what causes are concluded to create what effects. 
What did the research involve?Edit
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 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 of various coronary arteries. The exercise group then engaged in a high intensity training program for 4 weeks, involving 10-minutes cycling (excluding warm up and cool down), 6 times per week at 80% of their average peak heart rate reached during the initial exercise test.  This was aimed at determining whether (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?Edit
- 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/ApproachEdit
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 therefore effected the initial testing (peak heart rate), which was used to determine intensity for the exercise program. Results were then interpreted based on means of such data and then deemed "high intensity endurance training", and "vigorous exercise", yet the participants were working at an average heart rate much lower than the actual data measured for a 10-minute period, 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; pending the question as to whether responsiveness to ACH has any direct application it on daily life. It is also therefore important to also consider that bias may arise from the measures taken in the testing protocol if the practitioner was aware of which group the participant belonged too. (experimental blinding).
Furthermore, the relatively small study could possibly be attributed to the invasiveness of the procedures necessary to carry out the research. It was also only conducted on older males, further narrowing the population, eliminating the possibility of determining any gender specific differences and restricting younger population applicability.
Lastly, perhaps the 4-week training program and the exercise type/intensity may not have been the most appropriate way to determine whether "high intensity" exercise specifically improves coronary endothelial function.
On the contrary, they did recruit participants carefully. For example, participants were only suitable providing they had a coronary-artery stenosis requiring a nonsurgical revascularisation, no existing co-morbidities and a stabilised condition. Overall, the conclusions that are made aren't necessarily not over-emphasised either, as the statistical data supports the qualitative deductions. 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 is unclear in research in general. 
What conclusions can we take from this research?Edit
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-inside 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.  
- 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.  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.
- 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 and decrease susceptibility of developing other life-threatening co-morbidities.
If this articled sparked further interest or you need support, below are extra resources to provide additional information:
- 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).
- Sandrone, Giulia, (1994)Effects of Beta Blockers (atenolol or metoprolol) on Heart Rate Variability after Acute Myocardial Infarction, American Journal of Cardiology, (74, 340-345).
- 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).