Background

Background

Coronary artery disease (CAD), also known as coronary heart disease (CHD) is the main cause of death and morbidity in the western world and is projected to be the number one killer globally by 2020. In the European Union, it accounts for nearly 1 million deaths per year, with as many as 1 in 5 men and women dying from CAD and as many as 1 in 2 men or women experiencing a cardiac event during lifetime.

The burden to the European economy has been estimated to be over 28 billion Euro per year in direct healthcare costs, 7 billion Euro in informal healthcare costs, and another 10 billion Euros in loss of productivity costs. However, these numbers may be underestimations as in the USA the total direct and indirect costs for CAD for 2009 have been calculated to be 165 billion USD. Globally, more than 7 million deaths per year can be attributed to CAD and are estimated to reach 11.1 million by 2020. Despite major progress in reducing mortality from CAD and major efforts in controlling risk factors that contribute to the development of CAD, the disease is on the rise and is expected to grow further in the coming decades as obesity and metabolic disease are still increasing in the western countries and as more developing countries adopt the western way of life and diet. This establishes CAD as a major epidemic of our time requiring immediate action for the development of novel preventive and/or therapeutic strategies for its management.

CAD is a progressive disease process that generally begins in childhood and manifests clinically in the middle to late adulthood. Most individuals show no signs or symptoms of the disease for decades as the disease progresses, and are often diagnosed by chest pain, shortness of breath or a "sudden" heart attack. The underlying cause of CAD is the development of vulnerable atherosclerotic plaques in the coronary arteries that at some stage rupture, causing thrombosis and myocardial infarction. The net result is deprivation of the heart muscle from oxygen and essential nutrients which, in severe cases, leads to heart failure. However, not all coronary atherosclerotic plaques rupture, and a large number of CAD patients remain asymptomatic for a long time, often during their whole lifetime. Therefore, distinguishing which patients are likely to exhibit acute cardiovascular complications such as myocardial infarction and heart attack is critical to the management of CAD.

In the past 30 years, considerable effort has been put and significant advances have been achieved in our understanding, diagnosis and management of CAD. This has led to a significant reduction (up to 30%) in mortality from this disease. Many factors have contributed to this, including the introduction of coronary care units, coronary artery bypass grafting (CABG), thrombolytic therapy, percutaneous coronary intervention (PCI), and a renewed emphasis on lifestyle modification. Despite that, 70% of clinical events cannot be prevented with available drug therapy including statins, and at least 10% of coronary events occur in apparently healthy individuals in the absence of traditional risk factors. In addition, a plateau may have been reached in terms of the reduction in mortality that can be achieved with these approaches. Thus, only a modest portion of the total cardiovascular risk burden has actually been eliminated, and the full potential of disease control remains unrealized.

It is now widely accepted that further reduction of the cardiovascular disease burden and mortality goes through the more accurate prediction of cardiovascular risk, the more appropriate classification of coronary atherosclerosis patients and the optimal selection of treatments in accordance to the individual patient’s disease profile. Primary prevention, and if possible primordial prevention, offers the greatest chances of success as it is much more difficult to control disease once established and especially after clinical events have occurred.
 

The most significant bottlenecks in the field are:

• Lack of potent biomarkers for the accurate prediction of CAD risk
• Suboptimal classification of CAD patients for supporting clinical decision leading to unfocused use of limited health care resources.
• Gap of knowledge on the mechanistic link between biomarkers and disease pathogenesis
• Minimal availability of appropriate and predictive preclinical human models of coronary atherosclerosis
• Suboptimal preclinical mouse models of coronary atherosclerosis and coronary plaque vulnerability
• Inadequate diagnostic or prognostic approaches for asymptomatic patients of risk for major atherosclerotic events
• Nascent translational research in the field of diagnostics and prophylactic interventions to prevent major atherosclerotic events.
• Lack of personalized therapeutic strategies ‘customized’ to selected high risk patient groups or individual patients