Coronary artery disease (CAD) is a chronic disease in which blood flow is obstructed through the coronary arteries that supply the heart with oxygen-rich blood. This obstruction is caused by a disease known as atherosclerosis, which is sometimes called "hardening of the arteries." An estimated 13.2 million Americans suffer from CAD. Also referred to as coronary heart disease, CAD is the most common form of cardiovascular disease in the United States today.

Atherosclerosis is gradual, often taking decades before the affected person is in danger of cardiovascular problems. First, the inner lining of the artery (e.g., the endothelium) is damaged. This causes white blood cells to gather at the site of the injury. This in turn provokes an inflammatory immune response that causes further damage to the artery wall. Over time, the endothelium is compromised and large, toxic LDL cholesterol molecules can penetrate into the artery wall. The white blood cells and cholesterol combine to form a lipid foam. In the early stages of atherosclerosis, these fatty streaks are present on the arterial wall as plaque deposits. Over time, the plaque may calcify, or form a hardened "shell." This reduces the supple artery's ability to contract and expand and narrows the artery, thus reducing the amount of blood that can flow through it. If the plaque deposit ruptures, a blood clot can form at the site of the rupture, or pieces of the plaque can travel through the arteries until they eventually cause a blockage. A heart attack and cardiac arrest may result.

Untreated, CAD usually continues to worsen. Many CAD patients have symptoms such as chest pain (angina) and fatigue, which occur when the heart isn't receiving adequate oxygen. As many as 50 percent of patients, however, have no symptoms until a heart attack occurs.

Strategies to help reduce risk factors for CAD, or slow its progression if it has already begun, include:

Treatment options for CAD include medication, balloon angioplasty (with or without stenting), atherectomy and bypass surgery.

Coronary artery disease (CAD) is a chronic disease in which the coronary arteries gradually harden and narrow (atherosclerosis). This condition is also referred to as coronary heart disease.

 CAD is the most common form of cardiovascular disease in the United States and the leading cause of heart attacks. It is the leading single killer of American men and women, responsible for one of every five deaths in 2003, according to the American Heart Association. About 83 percent of people who die as a result of CAD are 65 or older. In 50 percent of men and 64 percent of women who die suddenly from CAD, there were no previous symptoms. Most recent statistics also show CAD as a leading cause of premature and permanent disability among American workers.

CAD patients tend to have periodic episodes where the heart is not receiving enough oxygen-rich blood (cardiac ischemia). Some patients feel no symptoms during these episodes (silent ischemia), while others may experience significant chest pain, pressure or discomfort (angina). If an episode of cardiac ischemia is severe or lengthy, it could trigger cardiac arrest (in which the heart stops beating).

A number of factors have been shown to increase the risk of developing coronary artery disease. They include:

• Low levels of HDL (good) cholesterol
• Uncontrolled high blood pressure (hypertension), even in the teenage years
• Smoking
• Lack of regular exercise
• High-fat diet
• Overweight or obesity
• Uncontrolled diabetes
• Chronic stress or depression

Other risk factors that increase the risk for coronary artery disease include HIV and chronic inflammatory conditions such as rheumatoid arthritis.

Symptoms typically associated with CAD include chest pain (angina) and shortness of breath, especially after stress or exercise. Women with CAD may experience breast pain or a feeling of indigestion in the upper abdomen.

However, as many as half of patients have no symptoms, despite the presence of CAD. They may have silent ischemia or be unaware of potentially dangerous abnormal heart rhythms (arrhythmias). The absence of chest pain or other common symptoms can also set the stage for a heart attack that occurs without warning.

Patients who do experience one or more symptoms should consult with their physician as soon as possible. The physician will obtain a medical history and give a complete physical examination, which will include a coronary risk profile. A number of diagnostic tests may then be ordered to help the physician to identify blockages in the arteries before more serious complications arise. Noninvasive tests include:

A coronary angiogram is a minimally invasive test that may be done if any of the above tests are abnormal, or if the patient has a history of heart-related problems. The coronary angiogram involves the insertion of a catheter into the coronary arteries and the injection of a dye (contrast medium) that is highly visible under x-ray. This allows physician to pinpoint the number and location of blockages in the coronary arteries.

Treatments for CAD vary according to the severity of the disease, the location of any blockages in the blood vessels, the presence of any risk factors (e.g., abnormal cholesterol profile or high blood pressure) and the overall health of the patient. Options include lifestyle changes, medication, and interventional and surgical techniques. 

Medications used to treat CAD fall into the following categories:

There are several main procedures used in the treatment of CAD:

• Balloon angioplasty. A procedure in which the physician guides a balloon-tipped catheter into the blocked coronary artery, then rapidly inflates the balloon. This crushes the plaque against the artery wall, thus allowing more blood to flow through the widened vessel. A major problem with this approach is the gradual reclosure of the vessel (restenosis). The recent introduction of stents has somewhat helped this problem. These tiny wire mesh tubes are implanted in the artery after angioplasty. They hold the plaque against the wall and help prevent the vessel from closing again. Newer stents, known as drug-eluting stents, are available. These drug-eluting stents have been coated with special drugs that further help reduce restenosis. Drug-eluting stents were initially rapidly accepted by physicians and used in the majority of situations. However, new research has revealed that drug-eluting stents may increase the risk of blood clots in certain situations and physicians are currently studying the best applications for both drug-eluting stents and the older bare-metal stents. 

• Atherectomy. Another catheter-based procedure in which the physician guides a special catheter into the blocked coronary artery. This catheter is equipped with a blade that cuts away the soft plaque deposits, or a grinding burr that pulverizes harder, calcified plaque
  
  
• Coronary artery bypass graft (CABG). A surgery that increases blood flow to the heart by creating a detour and re-routing the blood flow around the blocked portion of the artery. A section of a blood vessel from another part of the body (e.g., the leg or chest) is relocated and grafted above and below the damaged portion of the coronary artery to form an open channel around the blockage. Traditionally, this surgery is performed with use of the heart-lung machine, which supports the patient’s circulation while the surgeon operates on the heart. Today, however, about 25 percent of CABG surgeries are performed as off-pump bypass procedures. In this case, portions of the beating heart are held still with special stabilizers while the surgeon performs the operation through a traditional incision. This reduces side effects associated with the use of the heart-lung machine.
  
  
• MIDCAB (minimally invasive bypass surgery). This is a less traumatic form of the traditional bypass graft surgery that relies on smaller incisions to gain access to the chest cavity. While MIDCAB is effective in some situations, such as patients who have limited disease in one or two main coronary arteries, the procedure is not commonly used. MIDCAB is sometimes used in conjunction with coronary angioplasty to treat multi-vessel disease.

Because coronary artery disease tends to develop gradually, effective strategies exist to help prevent or control it. Individuals should become well informed about how changes in lifestyle and behaviors can reduce the speed at which atherosclerosis or other heart-related problems develop. Some of the most common strategies for preventing CAD, or slowing its progression, include:

These strategies may help to preserve health and prolong life, and are particularly important for those of advanced age and those with a family history of heart disease. Even someone who has suffered a cardiac event (e.g., heart attack) can reduce the risk of having another one by changing unhealthy behaviors and stopping all high-risk activities.

While there are many risk factors for coronary artery disease that patients can control, they can’t change their genes – at least not yet. Scientists have identified more than 250 genes that may play a role in the development of CAD. Research has shown that atherosclerosis often begins in childhood with subtle damage to the interior lining of arterial walls (e.g., the endothelium). Studies have also shown that atherosclerosis is more widespread than was once thought. A person with atherosclerosis in their coronary arteries is more likely to have the condition in other arteries also. These findings suggest a genetic component to atherosclerosis, although researchers have yet to uncover the complex interaction between a person’s genetic make-up and their likelihood of developing coronary artery disease and atherosclerosis.

Some progress has been made, however, concerning the relationship between genes and cholesterol. Cholesterol is carried through the bloodstream by proteins called apolipoproteins. When these proteins wrap around cholesterol and other types of fats (lipids) to transport them through the bloodstream, the resulting “packages” are called lipoproteins. There are five different types of lipoproteins:

The primary cholesterol-related genes that scientists are exploring as a means of better understanding and combating CAD include:

• Apolipoprotein A1 (APOA1). APOA1 is the major component of HDL, or protective cholesterol. Scientists have discovered that variations in the gene that codes for APOA1 can affect HDL levels, thus affecting overall risk for heart attack and stroke.
  
  
• CETP, or cholesterol ester transfer protein. This protein is involved in transforming cholesterol from the protective HDL form to the damaging LDL form. Research has shown that certain variations in the genes that code for CETP may result in higher HDL levels. Additionally, CETP is the target of newer drugs, which have not yet been approved, that seek to inhibit transformation of HDL into LDL cholesterol.
  
  
• LDL Receptor (LDLR). LDL receptors are present mostly in the liver cells, where they are responsible for recognizing LDL in the bloodstream and removing it. About one in every 500 people, however, has a mutation in the gene that controls the LDL receptors and inhibits their function, allowing LDL to build up in the blood. This condition is known as familiar hypercholesterolemia (FH). FH is the most widespread inherited cholesterol disorder, with affected individuals having cholesterol levels as high as 550 milligrams per deciliter. This is almost four times the desired level, thereby significantly increasing the risk for early heart attack, regardless of the presence of other risk factors. Researchers have also discovered that high-fat diets can also create subtle alterations in the LDLR gene even among people with normal LDLR genes. If too much dietary fat is present, too much LDL cholesterol is absorbed into the liver. In response, the liver cells repress the LDLR gene, which results in fewer LDL receptors and less LDL removed from the bloodstream. As a result, LDL levels rise in the bloodstream and can contribute to heart disease.
  
  
• Apolipoprotein E (APOE). Apolipoprotein E is a major component of VLDL. Variations in the gene that controls APOE can cause high levels of LDL to occur, especially in people who eat a high-fat, high-cholesterol diet.
  
  
• Apo(a). A gene that creates the Apo(a) protein, which combines with LDL cholesterol to form Lp(a), a new protein that affects the ability of the blood to clot (coagulation). High Lp(a) levels in the blood have been linked to the development of CAD and to increased heart attack risk.
  
  
• Apo(b). This gene controls the production of apo(b), another component of apolipoproteins and chylomicrons. Blood test that measure apo(b), or one of its products, apoB100, are considered a very accurate risk assessment for heart attack risk.

Other genes that are being investigated as to their impact on CAD include:

• Integrin (ITGB3). Another gene that affects coagulation, variations of ITGB3 have been found in a significant number of CAD patients.
  
  
• Elastin (ELN). The blueprint for a protein component of the elastic fibers found throughout the body. These fibers affect the elasticity of body tissue such as blood vessels. For instance, arteries deficient in elastin will often take a shape that inhibits the flow of blood and contributes to CAD. Elastin is lost as a part of the aging process.
  
  
• PTGIS. The blueprint for a protein (prostacyclin) that coats the inner layers of blood vessels, keeping blood from sticking and forming clots.
  
  
• ACE. While this gene is one of the most studied in regard to CAD, very little is known about its effect on heart disease. ACE is the blueprint for a protein that affects the heart, kidneys and arterial walls.

Increasingly, inflammation has been singled out as an underlying factor that both causes and accelerates atherosclerosis. Atherosclerosis itself is an inflammatory process, characterized by activation of the body's inflammatory cascade at the level of the endothelium. This inflammatory cascade is part of a normal immune response. It is thought that atherosclerosis is characterized by a local immune response caused by damage to the arterial wall. As a result, white blood cells gather at the site of the injury and release inflammatory chemicals (such as interleukin-6 [IL-6]) that further damage the arterial wall and attract more white blood cells. Eventually, the arterial wall becomes permeable, allowing toxic LDL molecules to migrate into the inner lining of the artery. The white blood cells combine with LDL cholesterol molecules to form a lipid foam. This lipid foam is the main component of arterial plaque streaks, which appear early in the atherosclerotic process.  

During this process, the body releases a number of inflammatory markers that can be measured in the blood. These include C-reactive protein, IL-6, lipoprotein-associated phospholipase A2 and others. Currently, only C-reactive protein is regularly used as a marker of heart disease risk, while researchers are examining the role of other inflammatory markers. So far, the data on C-reactive protein has been somewhat mixed. Some studies have found that C-reactive protein is a useful independent measure of heart attack risk, while others have found conflicting results. The source of this conflict might lie in the fact that C-reactive protein is not specific: levels are raised in response to inflammation and injury anywhere in the body. Nevertheless, some physicians recommend monitoring C-reactive protein to measure inflammation in the body.

In the future, lipoprotein-associated phospholipase A2 might emerge as another important tool to measure risk of heart attack. Studies have found that elevated levels of this enzyme are a strong risk factor for heart attack, even in the presence of other normal LDL cholesterol levels.

Researchers have also been investigating the link between infection/inflammation and CAD. Based on the connection between inflammation and immune system activation, researchers have hypothesized that chronic, inflammatory conditions, such as rheumatoid arthritis and persistent bacterial infection, may contribute to atherosclerosis.

Preparing questions in advance can help patients to have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions regarding coronary artery disease:

1. I'm worried about my cardiac health because of a family history, but I don't have other risk factors. How often should I get blood work done?
   
   
2. What do you think of unconventional "risk factors" such as CRP and homocysteine measurements?
   
   
3. Will I need to take medication for life if I start on medication to control my disease?
   
   
4. Is there anything I could have done differently, or could be doing differently, to interfere with my disease?
   
   
5. Is it possible to reverse coronary artery disease?
   
   
6. What symptoms should trigger a visit to your office? What symptoms should trigger an emergency 911 call?
   
   
7. What kind of exercise do you recommend?
   
   
8. What kind of dietary choices should I make to reduce my risk of heart attack?
   
   
9. What's a good source for dietary information?
   
   
10. How will you decide if/when I need to undergo a procedure such as stenting or bypass surgery?
    
    
11. Are my children at increased risk because of my disease?