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Binder: Coronary artery disease – new insights into an old condition

The incidence of coronary artery disease is strongly connected to our lifestyle. It is apparent that a lack of exercise, obesity, hypertension, diabetes and smoking play an important role in the development of atherosclerosis and coronary artery disease. Economic growth and globalization have contributed to the increase of these cardiovascular risk factors. Coronary artery disease is the number one cause of death worldwide. However, arteriosclerosis and cardiovascular disease are not new diseases.

Coronary artery disease has been detected in ancient populations. For example, coronary calcifications and myocardial scarring has been found in numerous Egyptian mummies1 and angina pectoris was described in the famous ‘Ebers papyrus’ (dating to 1550 bc), one of the most important sources of medical information of ancient history.2 Evidence from a computed tomography (CT) scan of a Chinese noblewoman who died over 2100 years ago with an occluded left anterior descending coronary artery3 shows that the disease was not limited to specific civilizations. Remedies for the disease can also be found in ancient writings of the Greeks and Romans. The writings of Hippocrates contain some of best descriptions of coronary artery disease in recorded history. Not only does he provide a clear description of the symptoms of coronary artery disease, but he also stresses its provocation in a cold environment and the possible fatal nature of heart failure as a consequence of myocardial infarction.

Angina is serious and rapidly fatal when no lesion is to be seen in either throat or neck, and moreover, it causes very great pain and orthopnea; it may suffocate the patient even on the first day, or on the second, third or fourth.

Prognostics XXIII4

Ancient civilizations certainly had a much healthier diet consisting of vegetables, fruit, bread, beer and only a little lean meat, a diet that we would recommend to our patients today. Therefore, why did they suffer from coronary artery disease? Is it in our genes? Observations and modern genetic studies5 truly point to the importance of inheritance. Coronary artery disease runs in families. It is well documented that first-degree relatives of people who develop coronary artery disease at young age are at a much higher risk for developing coronary lesions than the general population. We assume that the contribution of genetic factors is in the range of 40–60%, but things are not so simple. Over 250 genes that play a role in coronary artery disease have been identified but it is, as yet, unclear which of those truly are involved, how the genes interact (polygenetic effects) and how other genes might play a protective effect. There are 33 genetic risk variants, some of which mediate their risk through still unknown mechanisms and we do not know how they interact with conventional risk factors. For example, we know that human Y chromosome is associated with risk of coronary artery disease in men, but this risk also seems to be mediated through interactions of immunity and inflammation.6

We are still far from applying genetic testing for coronary artery disease in the general population and we are even further away form providing genetic therapies. Still, our knowledge has an impact in understanding the complexity of this multifactorial disease and could lead to targeted therapies in the future.

At present, we are limited to identifying high-risk patients based on their family history and conventional risk factors. Several risk scores have been established, the most common of which are the Framingham score or the Systematic COronary Risk Evaluation (SCORE) risk charts7, provided by the European Society of Cardiology, which allow the prediction of 10-year risk based on the most important risk factors [age, low-density lipoprotein cholesterol (LDL-c) levels, high-density lipoprotein cholesterol (HDL-c) levels, blood pressure, diabetes and smoking]. However, we should not forget other indicators such as renal disease, erectile dysfunction, depression, anxiety, type D personality, low socioeconomic status, lack of social support and stress at work and in family life as well as other indicators that are still under investigation.

Preventative measures starting early in life and continued throughout adulthood and senescence reduce the prevalence and mortality from coronary artery disease. Hippocrates has already recognized this; in Aphorism 44 he pointed out that the shortened life expectancy of the obese compared with slender individuals. Modification of risk factors is highly effective and it is estimated that we can achieve a reduction in risk in the range of 50%.7 Prevention is especially important in countries where risk factors are common or on the rise. If we do not undertake such measures, we will see a further increase in the disease. The World Health Organization (WHO) estimates that the prevalence of coronary artery disease will increase by 48% for men and 29% in women from 1990 to 2020 in the developed world, with even greater increases (120% for men and 137% for women) in the developing world.8 There is evidence from recent studies8 that we are well on our way to reaching these dismal numbers. The implementation of strategies that work is a difficult task and it appears as if we are fighting an uphill battle. The core objective must be to help people change their diet, exercise more, stop smoking and live a physically more active life. Public and individual initiatives, non-governmental organizations and industry must work together to achieve these goals. Furthermore, we must extend our treatment of hypertension, diabetes and hyperlipidaemia to those who are unmotivated or unaware of their risk and optimize medications to those who are undertreated. After all, medical intervention is highly effective and has been shown to reduce the risk of cardiovascular disease by as much as 40%. Thus, physicians, nurses and other medical personnel play a major role in reducing the burden of coronary artery disease. As a consequence, we need to educate those who administer the treatment to achieve the target levels recommended by societies for patients.

Early diagnosis of coronary artery disease is of equal importance. It will help identify patients at a time when treatments are most effective and help us to establish secondary preventive measures. We have come a long way since the times of the ancient Egyptians. While they recognized the symptoms of angina pectoris, and even suspected the origin of pain in the heart, they had no means of looking into the body or even seeing the abnormalities found in coronary artery disease. This has now changed, and non-invasive imaging plays an increasing role and is therefore a major topic for this issue of the Hamdan Medical Journal.

Echocardiography can be considered the backbone of cardiovascular imaging. It is cost-effective, readily available and can be applied at the bedside. One of the biggest advances in recent years is that scanners are decreasing in size. With the advent of hand-held scanners, we are now on the verge of replacing the stethoscope with cardiac ultrasound. Although this can greatly impact the care and diagnosis of heart disease in general, there is one obstacle that must be overcome: we need to train more personnel in performing ultrasound. Scanning is not easy and we need to provide expertise to those who are at the forefront.

The coronary arteries are only poorly visible on echocardiography, but this technique can be used to detect ischaemia. Wall motion abnormalities are a marker of ischaemia which can be detected by stress echocardiography. Echocardiography also plays a role in detecting risk factors for coronary artery disease such as left ventricular hypertrophy and aortic valve sclerosis. Probably the greatest impact of echocardiography is its ability to visualize the sequelae of myocardial infarction, which include myocardial damage, complications of myocardial infarction and functional mitral regurgitation; thus, echocardiography is a must in such patients. However, it should be used not only in screening patients but also in the setting of acute myocardial infarction and in the follow-up of patients. Many treatment decisions we perform today are influenced by echocardiographic findings, and it is apparent that the role of echocardiography will increase in the future. New technologies discussed in this issue, such as deformation imaging, measurements of coronary flow reserve and contrast echocardiography, already impact our ability to detect and manage coronary artery disease.9 Further refinements in these technologies, and the knowledge we gain about them, will expand our indications for echocardiography in the future.

Nuclear imaging such as single-photon positron emission computed tomography (SPECT) or positron emission tomography (PET) still plays an important role. There are extensive data that document the value of these methods that help to establish the diagnosis and assess the prognosis of patients. Nuclear imaging can determine if ischaemia is present, define the area at risk and show whether or notthe myocardium is viable. All of these factors greatly influence our approach to coronary artery disease.

Computed tomography of the heart, and specifically the coronary arteries, is a rather new diagnostic tool. Owing to recent technological improvements, CT provides spectacular images of the heart, the great vessels and coronary artery disease. The main purpose of CT is to rule out significant coronary artery disease in symptomatic patients with low to intermediate pre-test probability of coronary artery disease.10 Debates as to whether or not CT will replace coronary angiography as the primary tool to visualize the coronary arteries has now faded and opened the way to a more realistic approach in using this technology. Several limitations, such as the problem of high radiation dose or poor image quality in subsets of patients, are partially solved. It is clear that the technology will not stop here but provide even more information in the future.

Cardiac magnetic resonance (CMR) imaging has diverse applications in coronary artery disease. It provides volumetric measurements of function, is able to detect morphological abnormalities of the ventricles and allows assessment of myocardial viability. Stress CMR imaging and the technique of late enhancement can provide valuable information on myocardial perfusion, ischaemia and viability. However, the technology is still limited to specialized centres and is expensive.

Despite all of the improvements in non-invasive imaging, there has not been a significant drop in the use of coronary angiography, indicating that this technique is still the gold standard. But what has clearly changed is our approach to assessing and treating coronary lesions. Visual or quantitative assessment of stenosis alone is an approach of the past. Measurement of functional flow reserve with a catheter (pressure wire) has emerged as an important method to determine the true functional significance of a specific lesion. Optical coherence tomography (OCT) imaging is a method based on infrared light that has rapidly emerged as a breakthrough technology to assess plaque composition and monitor stent deployment.11 OCT imaging provides a 10-fold increase in image resolution compared with conventional intravascular ultrasound and provides almost microscopic visualization of coronary plaques.

The medical therapy of acute coronary syndromes and stable angina pectoris has also changed. We now have a broad array of antiplatlet and antithrombotic agents and antianginal drugs at hand. The treatment of heart failure due to myocardial infarction is still an important factor that saves lives. Large studies12 have proven the efficacy of combination therapies including beta-blockers, angiotensin-converting enzymes (ACEs) inhibitors, diuretics and angiotensin II receptor antagonists. Furthermore, we can apply numerous back-up strategies such as cardiac resynchronization therapy, left ventricular assist devices and heart transplantation to patients who are still symptomatic.

Coronary intervention in acute coronary syndromes is superior to all other forms of treatment. ‘Time is muscle’ and early intervention with reopening of the culprit lesion is the clear goal. Recommendations are less clear for patients with stable angina pectoris. Several larger studies13 have shown no survival benefit of intervention compared with optimal medical therapy. However, these results must be viewed with caution since there is an ongoing development with new stents such as drug eluting and bioresorbable stents.

Although coronary intervention has challenged the role of coronary bypass surgery, it still remains an important treatment for many patients. Despite predictions of a drop in the number of bypass surgeries, there are many centres where the number of procedures is on the rise. However, the profile of patients referred to surgery has changed. Patients are frequently older, have more complex lesions and more comorbidities. There is also an increase in ‘redo’ operations and combined procedures (e.g. valve repair and aortic root replacement). Despite these problems, bypass surgery has been shown to be highly effective and can provide long-term benefits even in patients with complex needs. This is the result of numerous refinements in surgical techniques, including new harvesting strategies of venous grafts (endoscopic), the expanded use of arterial grafts (such as the mammary artery and radial artery), minimal invasive surgery and off-pump approaches.

In conclusion, coronary artery disease must be viewed as a genetic burden with which mankind has to live. This burden is greatly influenced and modified by risk factors that are well defined, and these risk factors can be adapted if we use appropriate strategies. Our knowledge of the disease is constantly growing, as are the diagnostic tools we have at hand to detect and assess the disease. The previous decade has brought improvements to pharmacological agents as well as interventional and surgical techniques that are able to reduce the risk of death once the diagnosis has been established.

This issue of the Hamdan Medical Journal highlights the newest advances in our understanding and management of coronary artery disease. It provides a state-of-the-art overview that will ultimately aid physicians and those dealing with the epidemic of coronary artery disease to reduce the burden to patients and the health care system.



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