Coronary Heart Disease (CHD) is the result of a blockage or decrease in the flow of blood through the coronary arteries (i.e., the blood vessels supplying blood to the heart). Arteries resemble narrow tubes; cholesterol and other debris can build up to form material called plaque within and along the walls of the arteries, a process known as atherosclerosis. Atherosclerosis can be considered a pathological form of chronic inflammation.

Plaque build-ups can harden, narrowing the space within the artery, in a process called stenosis. Stenosis results in reduced blood flow through the arteries. This can happen in any artery, but when it happens in the coronary arteries, heart function can be severely affected. The gradual reduction in the flow of blood to the heart can lead to a chronic condition known as angina pectoris, in which patients suffer from regular symptoms of tightness, squeezing or pain in the chest as a result of diminished heart function. A heart attack, also known as an acute myocardial infarction (AMI), is a complete blockage of blood flow to a portion of the heart, which can lead to death or permanent disability.

Traditionally, cardiologists have treated angina and heart attack as a single disease with a common cause: stenosis. The existing treatment protocol using stents and angioplasty was designed to open coronary artery blockages. These treatments significantly reduced the symptoms of angina but had minimal effect on heart attack event rates, leaving cardiologists perplexed, and provoking the following, among other, questions: why do over 50% of heart attack victims have no previous symptoms; and why do many of these patients show little or no evidence of stenosis in their coronary arteries?

The answer: heart attacks and angina are often caused by very different types of arterial plaque. Angina is generally caused by hard, relatively stable plaque that visibly blocks the artery. In the case of a heart attack, the major cause is soft plaques hidden within the arterial wall that are “vulnerable” to rupture. This rupture releases a liquid pool of various types of cholesterol and other debris into the blood stream that can form a blood clot, blocking blood flow to the heart and causing a heart attack. In fact, recent data have shown that vulnerable plaque rupture causes as many as 85% of all heart attacks¹.

Further, many cardiologists have also come to recognize the pivotal role that the immune system plays in the process of plaque formation and in the prevalence of CHD and heart attacks. Evidence now suggests that chronic inflammatory processes, driven by the immune system, cause atherosclerosis and the resulting transformation of cholesterols and other debris into hard and soft plaque. Research has shown that the activity of various immune system cells and agents can lead to the deterioration of the scab-like coverings, called thin cap fibroatheroma (TCFA) which cover vulnerable plaque and act as a barrier between its contents and the blood flowing inside of the artery. In addition, these immune system processes are also believed to drive the corresponding coagulation cascade that forms blood clots and leads to heart attacks.

Dr. Paris Constantinides² was the first researcher to provide convincing evidence that plaque rupture resulted in the onset of most acute cardiovascular disease. From his pivotal publication in 1966 until 1994, evidence grew around the concept that conversion of chronic to acute coronary disease occurs when breaks in the atheroma surface become a stimulus for platelet adhesion, aggregation and mediator accumulation. By 1994, there was widespread recognition of the importance of plaque rupture, thrombosis and mediator generation in the onset of cardiovascular disease³.

This new paradigm for coronary artery disease has gained considerable momentum over the past decade, and based at its core is the concept of vulnerability. The underlying premise of a vulnerable plaque is that a single unstable coronary lesion can ignite a chain of events leading to a heart attack. While a single ruptured plaque can be identified during autopsy as the cause of an event, there is currently no way to identify a culprit lesion before it kills. Coronary angiography has represented the standard imaging modality of the coronary tree for over 40 years. Angiograms provide an overview of the arterial topography and can confirm the presence of stenotic atherosclerosis with high specificity. Their ability to provide prognostic information on future coronary events is limited; the percent diameter stenosis of a lesion does not provide reliable information concerning the risk of future myocardial infarction and death⁴.

Histopathology of culprit and ruptured plaques taken from excised tissue and cadavers have provided extensive detail about the disease state and led to an improved understanding of the progression of heart disease and the development of vascular lesions. The primary culprit lesions include rupture-prone TCFAs, eroded plaques and calcified nodules. Hypothetically, being able to assess functional parameters, such as chemical composition, may allow risk stratification of patients. However, the tools needed to discriminate the vulnerability of these lesions in living human coronary arteries and assess the progression of vascular disease are not yet commercially available.

In the US and Europe nearly 1.4 million deaths occur annually due to heart attacks^5,6, and heart attacks are the major cause of death in Japan and other developed countries. Each year, nearly 1,375,000 Americans will have a coronary event. More than half of these people have no previous symptoms, and approximately 650,000 of them will not survive.⁷ Existing technologies are capable of treating only two of every ten heart attack patients – those with gradual narrowing of the arteries caused by hardened or calcified plaques. Currently available stents have not impacted the death rate from heart attacks, and the following concerns have been raised about their use:

• Restenosis: tissue proliferates inside the artery, causing it to re-narrow. This problem is more common with bare metal stents (BMS).
• Late Stent Thrombosis: clots form inside the stent itself, months or years after implantation. This problem is more common with drug-eluting stents (DES)

For the remaining eight heart attack patients, no clinically validated detection or treatment methods exist.⁵

To learn about the strides being made to address this major cause of death, click on the topics listed to the left.

[1] Robert Langreth, “Attacking Heart Attacks,” Forbes, June 21, 2004; p154.
[2] Constantinides, P. “Plaque fissures in human coronary thrombosis.” J Atherscler Res 1966; 6:1-17
[3] Muller, J and Moreno, P;”Handbook of Vulnerable Plaque”; 2004. 1. Definition of the Vulnerable Plaque. Pgs. 1-2.
[4] Regar, E, Schaar, JA, et.al, “Invasive Detection, Quantification and Monitoring of Plaque Vulnerability: Methods and Implications for Upcoming Clinical Trials”. May 2004, EuroPCR.
[5] Heart Disease and Stroke Statistics – 2006 update, American Heart Association.
[6] European Cardiovascular disease statistics 2005. British Heart Foundation Health Economics Research Center, Department of Public Health, University of Oxford.
[7] Association for the Eradication of Heart Attack – AEHA. “Saving the Vulnerable Patient.” Vulnerable Patient Symposium, 2003.