Author : Edward J McNulty Kaiser Permanente San Francisco Medical Center

2008-11-06

Coronary Artery Disease : Background and Diagnosis

This article explains what is meant by coronary artery disease, the major complications that can result (including heart attacks), what is known about the causes of the disease, and finally, how the disease is diagnosed.

Introduction

The term “coronary artery disease” most commonly refers to the build up of plaque inside the arteries that provide the heart with blood. This is something that is very common, especially as people get older. Coronary artery disease can cause complications, including angina (discomfort commonly felt in the chest or neck), heart attacks, potentially fatal irregular heart beats, and a weakened or failing heart. This Knol explains what is meant by coronary artery disease, the major complications that can result (including heart attacks), what is known about the causes of the disease, and finally, how the disease is diagnosed.

What are coronary arteries?

The heart is a muscle that pumps blood to the lungs and to the rest of the body. All muscles, including the heart, require a supply of blood in order to function. The blood carries nutrients and oxygen to the muscle, and removes the leftover “waste products.” Even th

ough the heart is filled with blood, the heart muscle does not get oxygen and nutrients directly from the blood coursing through it. Instead, the thick walls of the heart muscle require their own blood supply from “arteries.” Arteries are the vessels that carry blood from the heart to the rest of the body. They are hollow tubes that branch into smaller and smaller vessels, much as water mains branch to supply a city with water. Coronary arteries are the blood vessels that carry blood to the heart muscle itself. They are on the outside of the heart and have branches that carry blood deeper into the heart muscle, supplying it with blood from the “outside in” (see figure 1).

Figure 1. Coronary Arteries

Coronary Artery Anatomy

Most people are born with three coronary arteries (See Figure 2). These arteries arise from the main artery carrying blood out of the heart, the aorta. Two of the coronary arteries, the left anterior descending and left circumflex, usually arise from a common trunk referred to as the left main coronary artery. The third coronary artery, the right coronary artery, usually arises separately.

Figure 2. Coronary Arteries, anatomy

What is Coronary Artery Disease?

Coronary arteries can be affected by many diseases. By far the most common disease to affect the coronary arteries is atherosclerosis (literally meaning hardening of arteries due to plaque formation). In atherosclerosis, “plaque” (consisting of cholesterol and other materials) is deposited within the wall of the arteries. Atherosclerosis is a disease that can affect many arteries in the body, not just the coronary arteries (see Figure 3).

Figure 3. Severe plaque in the aorta

Atherosclerosis is a process that appears to begin even before we are born, with the precursors to plaque (“fatty streaks”) being evident in the largest artery (the aorta) in fetuses. Actual plaque can be detected in the arteries of teenagers. Plaque formation is also a process may occur gradually, or progress more rapidly, in fits and starts. Not only does this plaque cause the arteries to become hardened, but the insides of the vessels become narrowed. Once plaque has grown large enough, blockage to the flow of blood may occur. This can completely obstruct the flow of blood if the plaque becomes large enough (see Figure 4a), resulting in what is commonly referred to as a “blockage” or “clogged artery,” similar to a kitchen pipe becoming clogged with debris that prevents water from flowing through it. If there is obstruction to the flow of blood through a coronary artery, there may not be sufficient blood reaching the heart muscle beyond the obstruction. This leads to a situation referred to as “ischemia.” On a very basic level ischemia means there is not enough supply of blood to meet the demand from the heart muscle. If the obstruction is complete, then the heart muscle fed by the artery can die, a process called a myocardial infarction (“MI”) and more commonly referred to as a heart attack. Both ischemia and infarction can lead to discomfort or “angina” (see “symptoms of coronary artery disease”), difficulty breathing, a weakened heart muscle or heart failure (see “Heart Failure”), and cause irregular heart beats (“arrhythmias”) which can be fatal.

Figure 4.

     The consequences of the blockages depend not only on how severe they are, but also on how quickly they form.   Blockages that form gradually may result in a condition called “stable angina” (see “symptoms of coronary artery disease”). Blockages that develop or worsen abruptly may result in a more dangerous condition called “unstable angina,” or may cause a heart attack.

How Does Plaque Lead to a Heart Attack?
     Over the past few decades a greater understanding of the role of plaque in causing heart attacks has emerged.   Sometimes the plaque can “rupture” into the inside of the artery, resulting in a blood clot forming on the plaque that completely obstructs the flow of blood and causes a “heart attack” (see Figure 4b). While plaques associated with severe blockages can rupture and lead to heart attacks, there are often many less severe plaques scattered throughout the arteries.   Although these are often not associated with severe narrowing, they are also prone to rupture (see Figure 4c).

Figure 5. Microscopic cross section of atherosclerotic plaque within a coronary artery

Other Diseases Affecting Coronary Arteries

While atherosclerosis is the most common disease to affect coronary arteries, other diseases can affect the coronary arteries and interfere with the normal flow of blood. In some individuals the arteries have a tendency to narrow abruptly, or “spasm,” and this can interfere with blood flow much like obstructing plaque. Sometimes the lining on the inside of the coronary artery (the “endothelium”) can become damaged. This is especially common in smokers. Blood clots can form on this damaged surface, which in turn may lead to obstruction of flow and a heart attack (see “heart attack”). Other, much less common conditions, include congenital abnormalities (abnormalities in number and location of coronary arteries that patients are born with), abnormal communications with other blood vessels (“fistulas”), aneurysm formation, and damage to the arteries as a consequence of radiation or other diseases affecting blood vessels throughout the body. All of these conditions can lead to obstruction of the flow of blood down the coronary artery, either by narrowing the space inside, causing a blood clot to form, or both.

How Common is Coronary Artery Disease?

Since plaque forms over time it is more common later in life. Autopsy data from Olmstead County in Minnesota revealed that 27% of patients aged 20-59 years had significant plaque build up in their coronary arteries. Among individuals aged 60 years and older, over half had significant plaque (1). It is important to note that many individuals have plaque in their coronary arteries but never experience symptoms or clinical manifestations of the disease.

What problems can plaque in coronary arteries cause? (Clinical Consequences of Coronary Artery Disease)

It is estimated that one half of men in the US and one third of women will develop angina or suffer a heart attack in their lifetimes (2). In round numbers, this amounts to approximately 8 million heart attacks per year in the United States, and an additional 9 million people who will suffer from angina (3). Fatal complications of coronary artery disease (primarily heart attack) are the most common cause of death in the United States, killing approximately half a million people per year. While coronary artery disease has long been a leading killer in most developed countries, it has rapidly grown as a problem in developing nations and is now the leading cause of death in lower income countries (4). The rise in heart disease seems to be due developing countries adopting diets higher in animal fat, increasing use of tobacco as well improved treatment of other causes of death in these countries (i.e. improved treatment of infections means people are now dying of heart disease instead).

What Causes Coronary Artery Disease? “Traditional” Risk Factors for Developing Coronary Artery Disease

See Table 1. Traditional Risk Factors for CAD

Table 1. “Traditional Risk Factors” For Coronary Artery Disease

Age

Male Gender

Diabetes

High Blood Pressure

Tobacco Use

High LDL (“Bad”) Cholesterol

Low HDL (“Good”) Cholesterol

Family History of Premature Coronary Artery Disease

     Risk factors are things that make it more likely that someone will develop a certain condition. Over the past half a century, there have been tremendous research efforts aimed at identifying the risk factors for developing complications of coronary artery disease. Most patients with coronary artery disease have high blood pressure, abnormal cholesterol, diabetes, or a history of tobacco use (5,6). These risk factors, along with older age, male gender, and a family history of premature coronary artery disease comprise the “traditional” risk factors for developing complications of coronary artery disease, and are each discussed below.

Gender
     Coronary artery disease is more common in men, but becomes common in women following menopause. One explanation for this has been that the female hormone estrogen provides some protection from coronary disease. However, taking estrogen after menopause does not appear to protect women from coronary disease and may in fact increase the risk (7).

Age
     Since plaque in coronary arteries forms over time it is more common later in life. Autopsy data from Olmstead County in Minnesota revealed that 27% of patients aged 20-59 years had significant plaque build up in their coronary arteries disease.   Among individuals aged 60 years and older, over half had significant plaque (1).

High Blood pressure
     The higher the systolic blood pressure (the higher of the two blood pressure readings) and the higher the diastolic blood pressure (the lower of the two readings) the greater the risk of death from coronary artery disease. Guidelines for treatment usually define elevated systolic blood pressure as above 140 mm Hg, and elevated diastolic blood pressure as above 90 mm Hg. Studies including literally hundreds of thousands of people have shown that the risk of suffering a heart attack or developing other complications from coronary artery disease decrease the lower one’s blood pressure (systolic and diastolic) is (8,9). The risk of dying from coronary artery disease is reduced by roughly half for every 20 mm Hg decrease in the systolic blood pressure or 10 mm Hg decrease in diastolic blood pressure (10).

Tobacco use
     Tobacco use is considered the strongest potentially “modifiable” risk factor for coronary artery disease (a modifiable risk factor is one that can be changed, unlike one’s age or gender). Cigarette smoking increases the risk of dying from complications of coronary artery disease by two to three times (11). Furthermore, an estimated 35,000 nonsmokers die yearly in the United States from complications of coronary artery disease as a result of exposure to “second hand” tobacco smoke (12).

Link to CDC tobacco factsheet www.cdc.gov/tobacco/factsheets/Tobacco_Related_Mortality_factsheet.htm

Cholesterol

     The higher one’s total cholesterol level, the greater the risk of dying or developing other complications from coronary artery disease (13). Total cholesterol greater than 200 mg/dl is considered elevated. There are many types of cholesterol, and modern guidelines establish goal levels according to the various components of cholesterol. The higher the “Low Density Lipoprotein (LDL) cholesterol” (often referred to as “bad” cholesterol), the greater the chance of developing plaque in the coronary arteries and dying as a result of complications from coronary artery disease. On the other hand, “High Density Lipoprotein (HDL) cholesterol” (often referred to as “good” cholesterol”) seems to protect individuals from coronary artery disease. HDL levels tend to be higher in women than in men. A low HDL cholesterol level (< 40 mg/dl) therefore, is not a good thing, and is considered a risk factor for developing complications of coronary artery disease according to current guidelines. An HDL cholesterol of > 60 mg/dl is considered a “negative” risk factor; that is, having a high HDL level protects one from coronary artery disease. Triglycerides are another type of cholesterol that appear to increase the risk of coronary artery disease, especially in women. Normal triglyceride levels are < 150 mg/dl. Whether other types of cholesterol, as well as ratios of various components, are more accurate at measuring risk is a subject of much current research and debate.

Diabetes

Diabetes is considered a “coronary artery disease equivalent.” This means that adults with diabetes carry a risk of developing either symptoms from coronary artery disease or dying from complications of coronary artery disease that is as high as individuals with established coronary artery disease. They are therefore treated as if they have coronary artery disease in terms of recommendations for diet, lifestyle and medications.

Family History of Premature Coronary Artery Disease

Coronary artery disease is common, especially as one gets older, so the majority of individuals with coronary artery disease will have a blood relative who also developed coronary artery disease. Early or premature coronary artery disease refers to women having complications of coronary artery disease (a heart attack, angina, or a coronary procedure such as an angioplasty or bypass surgery) before the age of 65 or a man before the age of 55. A “family history of premature coronary artery disease” means that one has a first degree relative (mother, father, brother, or sister) with premature coronary artery disease, and this increases ones risk for developing coronary artery disease (14).

Traditional Risk Scores - Combining Risk Factors

These risk factors are considered “traditional” risk factors. Much of the work in identifying these factors came from following the population of Framingham, Massachusetts for many years (14). A limitation of this work was that most of the population studied was Caucasian. Subsequent studies have confirmed the role of these same risk factors in more diverse populations (15,16). There are many “risk scores” that can be used to calculate an individual’s risk of having a heart attack or dying from complications of coronary artery disease. One commonly used calculator is the Framingham Risk Calculator:

Link to Framingham risk calculator http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=pub Framingham Risk Calculator

Other Risk Factors for Coronary Artery Disease

While there is abundant evidence linking the above risk factors to coronary artery disease, many (up to 20%) of individuals can develop complications of coronary artery disease without any of the identified “traditional risk factors.” Much effort has been devoted to identifying other risk factors for coronary artery disease.

Peripheral Artery Disease

As with diabetes, individuals with peripheral artery disease (severe plaque in arteries in the neck or extremities), or abdominal aortic aneurysms have similar risks of developing complications from coronary artery disease as do individuals with established coronary artery disease, and therefore are treated as if they have coronary artery disease.

Physical inactivity/lack of exercise

Physical activity appears to reduce the risk of heart attack and death from coronary artery disease. Conversely, physical inactivity and poor conditioning increases the risk of these complications (16). Among its beneficial effects, exercise reduces weight (and the risk of developing diabetes), blood pressure, and improves cholesterol.

Obesity

Obesity increases blood pressure, lowers “good” (HDL) cholesterol, raises “bad” (LDL) cholesterol and triglycerides, and increases the risks of diabetes. In other words, obesity causes many of the other known risk factors for coronary artery disease. Obesity also appears to increase the risk of suffering complications of coronary artery disease in and of itself, "independent" of these other risk factors (17). Furthermore, the location of adipose tissue (fat) appears to be important. Having abdominal obesity (fat in the truck or “belly”) is worse than having fat that is more spread out through the body. Obesity is usually defined as having a “body mass index (BMI)” of > 30.

Link to BMI calculator:
http://www.nhlbisupport.com/bmi/

The "metabolic syndrome "

The “metabolic syndrome” refers to individuals who have three of the following: abdominal obesity, elevated fasting blood sugar (a precursor to diabetes), high blood pressure, low good (HDL) cholesterol, or elevated triglycerides. Whether this syndrome confers a risk for coronary artery disease beyond the additive risks of the individual risk factors is a subject of controversy and current research.

Diet

Coronary artery disease is more common in countries with diets higher in animal fat and processed sugar (so called “Industrial” or “Western Diets”) (18). Even among western countries there is considerable variation in the rates of coronary artery disease. In general, countries with a very high intake of animal fat have correspondingly high rates of coronary artery disease. Additional evidence for the role of diet in developing coronary artery disease comes from studying individuals migrating from areas where coronary artery disease is uncommon to areas where it is very common. For example, studies of Japanese immigrants revealed dramatic increases in the rates of coronary artery disease once individuals moved to Western countries and adopted Western diets. Finally, as countries develop and adopt “Western” diets, the incidence of coronary artery disease increases.

While the evidence linking diet to coronary artery disease is compelling, there is also much about this relationship that is poorly understood. Some fats appear to be harmful (saturated and “trans” fatty acids) while others seem to be protective (polyunsaturated and monounsaturated fats). Studies have shown lower rates of coronary artery disease in countries with diets rich in omega-3 fatty acids (found especially in fish but also in other foods such as flax, walnuts and kiwi fruit), part of the so called “Mediterranean Diet” (19).

Alcohol use

Moderate alcohol intake (1 drink per day for women and 1-2 drinks per day for men) appears to be protective against death from coronary artery disease (16). While some studies have suggested that substances in red wine could account for this protective effect, it appears that any alcohol intake is protective. It should be noted that this finding refers to individuals who have established moderate patterns of alcohol intake, not individuals who begin drinking to prevent the development of coronary artery disease. At least part of the beneficial effect of alcohol intake is due to increasing levels of good cholesterol.

Stress and Depression

Anxiety, depression, and having “type A” personality have all been shown to increase the risk of developing complications of coronary artery disease (20). The mechanisms behind these associations are not yet fully understood.

Drugs

Certain medications and illicit drugs can also lead to coronary artery disease, including cocaine and methamphetamine.

Symptoms of Coronary Artery Disease

The blockages that cause coronary artery disease can worsen gradually over time, leading to so called “stable coronary artery disease,” or more progress more rapidly, leading to “unstable disease,” which includes heart attacks. While both forms of the disease are serious, unstable disease and heart attack are much more likely to lead to serious complications, such as heart failure, or death.

The hallmark symptom of coronary artery disease is “angina” (derived from the Latin word for choking). “Typical” or “classic” angina is usually described as a sensation of pain or pressure over the middle or left side of the chest, neck or left arm, brought on by exertion or emotional distress and relieved by rest or nitroglycerin. Typical symptoms occur in only about a half of individuals with coronary artery disease, and occur more often in men than women. Other individuals can experience less typical symptoms (so called “atypical symptoms”) such as right shoulder pain, pain over the abdomen, nausea, or difficulty breathing to name just a few. Other individuals experience little in the way of symptoms despite having severe or even complete blockages, especially those with diabetes. Severe symptoms (for example, symptoms preventing one from walking up a flight of stairs or more than a few blocks), symptoms of recent onset, or symptoms occurring while at rest can be an indication of serious coronary artery disease, including a heart attack, and require emergent evaluation.

Diagnosis of Coronary Artery Disease

1. Electrocardiogram (“ECG”)

     If unstable coronary artery disease or a heart attack is suspected, an electrocardiogram (ECG, sometimes called an “EKG”) is performed. This test entails placing electrodes (attached with simple adhesive strips) on the patient to measure the electrical activity of the heart. These can be useful in detecting signs of an ongoing or imminent heart attack as well as a prior heart attack. It is quick, easy to perform, and relatively inexpensive and is therefore useful as an initial tool in the diagnosis of coronary artery disease. It is a test that involves electrodes onto the skin (usually with small adhesive "sticker electrodes") and then plugging them in to a small machine. An electrical "picture" of the heart is obtained. This is an easy, safe test that can be done just about anywhere. However, individuals with a normal ECG can still have coronary artery disease or even a heart attack.

2. Stress Test

     A stress test can be extremely useful in diagnosing coronary artery disease. There are many different types of stress tests. The simplest involves attaching a patient to an ECG (see ECG) and then having them exercise on a treadmill. Other stress tests can use ultrasound or small doses of a radioactive chemical to actually see the heart during the "stress." These tests can be performed in an outpatient office or in a hospital and usually take from one to four hours. Stress tests can detect 70-90% of individuals with serious blockages in the coronary arteries, but are not for every patient. Stress testing can also provide useful information regarding “prognosis” or the risk that an individual will suffer fatal complications from coronary artery disease. (See "stress testing" knol - ADD LINK)

3. Blood tests

     Certain substances are released into the blood in patients having a heart attack and can be detected. These tests, especially measurement of the creatine phosphokinase (“CPK”) and troponins, are useful in determining if an individual is having a heart attack.

4. Coronary Angiography (“Cardiac Catheterization”)

     Currently, the most accurate method to detect blockages in the coronary arteries is invasive angiography.   It is performed by placing a hollow tube (called a sheath) into an artery in the groin or wrist (while the patient is sedated) and then threading small “catheters” (hollow, plastic tubes 2-3 mm in diameter) through the arteries to the coronary arteries. This is performed using X-ray guidance, so the procedure does require exposure to radiation. Once the catheters are placed into the beginnings of the coronary arteries, a substance called “contrast” is injected into the arteries while X-ray movies are taken. The contrast contains iodine so that X-rays will not penetrate it; therefore arteries with contrast inside appear dark on the X-ray picture. In this way a picture of the inside of the coronary arteries is obtained, usually from multiple positions, and blockages detected. (See figure 6). The procedure is performed in a facility called a catheterization laboratory.   It is usually recommended in patients with unstable disease or a suspected heart attack, or for patients with more severe stable angina. There are other situations in which physicians may recommend this procedure.

Figure 6. Angiography

Blockages can sometimes be treated at the same time with angioplasty and stents (see "treatment of CAD" - ADD Link).

Figure 7. Angiogram showing blockage in Left Anterior Descending Coronary Artery

While angiography is a very good technique to detect blockages in the coronary artery, it does have some risks. Because a tube must be placed into an artery in the arm or leg, there is a risk of bleeding or damage occurring to the artery that might require further treatment. There is also a risk of damage to the kidneys or an allergic reaction occurring from the contrast medium (dye). Fortunately, the risk of these complications is small, occurring in only 1-3% of patients. The risk of stroke, heart attack and death is much smaller, and tends to occur in individuals who are generally more ill.

5. CT Angiography and Electron Beam CT (Coronary Calcium Score)

Recently, CT machines have become more powerful and are now capable of producing images of almost the same quality as invasive angiography. While this procedure does not require the use of invasive catheters, it still requires the use of contrast medium and radiation. Additionally, there is limited experience with this technique, and in certain patients (patients with fast or irregular heart beats) reliable images are difficult to obtain. CT studies can also be used to detect calcium in the coronary arteries and determine a “calcium score.” Patients with severe calcium in the coronary arteries are more likely to have serious blockages and appear to have an increased chance of suffering complications from coronary artery disease.

What is the outlook for patients with coronary artery disease? (Prognosis of coronary artery disease)

The outlook for patients with coronary artery disease is variable and depends on the severity of the disease, whether the disease is “unstable” or “stable,” and other factors. In general, patients with a stable disease have a more favorable prognosis than those with unstable disease. Information obtained from the ECG, stress testing and angiography can be used guide decisions regarding treatment and to inform patients as to how likely they are to suffer further complications from the disease.

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Monday, January 30, 2012

Coronary artery disease background diagnosis