By C. Michael Wright, MD FACC

          1. Prevention

2. Limitations of Traditional Cardiac Risk Factor Analysis

3. How Well Are We Treating Risk Factors for CHD?

4. The Current Burden of Coronary Heart Disease

5. EBCT Scanning as a Test for Coronary Heart Disease

6. Why EBCT Scanning is Useful in People Without Known Heart Disease

7. How Easy is it to Prevent Progression of CHD?

8. HeartScore: The LifeScore® Coronary Prevention Program

•             HeartScore Scan Results
•             HeartScore RiskFactor Assessment
•             HeartScore Recommendations

9. Appendix 1: Quotations From the American Heart Association

10. Appendix 2: EBCT Compared with Spiral CT

1      Prevention

                "An ounce of prevention is worth a pound of cure."
                                                                -   Proverb

LifeScore® has developed a proprietary program, called HeartScore®, for the prevention of coronary heart disease. The Company uses electron beam CT (EBCT) scanning to diagnose coronary atherosclerosis (plaque) before the onset of heart damage. Patients are placed into risk groups based on their scanning results. Recommendations for reducing risk are made based on the patient’s risk factor profile. Patients are scheduled for follow-up scans to assess the results of risk factor interventions and initiate treatment plan changes as appropriate.

Heart disease is usually preventable. Yet each year, it kills twice as many men and women as does cancer. Indeed, women are ten times more likely to die of heart disease than breast cancer. Unfortunately, most people are diagnosed with heart disease when it is already at an advanced stage. EBCT is the only noninvasive diagnostic test that can accurately and reproducibly diagnose mild to moderate coronary plaque, and track changes in plaque over time. HeartScore® is a preventive care program that uses EBCT and risk factor modification to intervene early in the development of CHD and prevent the serious consequences of advanced disease. Dr. William B. Kannel, a principal investigator for the Framingham Heart Study, has suggested that a cardiovascular event must be regarded as a medical failure rather than the first indication for treatment. As an epidemiologist, his observation stresses the importance of predicting and preventing a cardiovascular event before it occurs.

2.     Limitations of Traditional Cardiac Risk Factor Analysis

"While high blood cholesterol is an important risk factor for heart disease, 80% of patients with heart disease have the same blood cholesterol as those who do not develop heart disease."

• H. Robert Superko, MD, Cholesterol, Genetics and Heart Disease Institute

The Framingham Heart Study has given clinicians epidemiological evidence for a number of coronary risk factors (high total and LDL cholesterol, low HDL cholesterol, high blood pressure, diabetes, cigarette smoking, family history, and age) that can predict future risk of coronary heart disease. More recently, other risk factors have been identified, including high homocysteine level, sedentary lifestyle, body mass index, certain behavioral traits, socioeconomic status, and other biochemical markers.

Unfortunately, 35% of patients with established coronary heart disease (CHD) have total cholesterol levels below 200mg/dL. Conversely, many patients with elevated cholesterol levels never develop symptomatic CHD. It has been determined that risk factor analysis will incorrectly classify as low to moderate risk about 30% of those who ultimately develop CHD. For this reason, risk factor analysis remains a crude tool for determining which patients are the best candidates for aggressive primary prevention (primary prevention seeks to lower risk for a first CHD event, while secondary prevention seeks to lower risk for future events in patients with known CHD).

 3      How Well are We Treating Risk Factors for CHD?

"An estimated 98 million American adults (52%) have total blood cholesterol levels of 200mg/dL and higher, and 20% of Americans have levels of 240mg/dL or above."

- National Health and Nutrition Examination Survey III

Risk factors are indirect determinants of CHD. Therefore, the motivation to treat high cholesterol or sedentary lifestyle or obesity is not as strong as the motivation to treat known CHD. Surprisingly enough, even people with known CHD are not being aggressively treated. A recent analysis of almost 250,000 patient encounters found that the rate of cholesterol lowering drugs being used for patients with known CHD was 13%. The National Cholesterol Education Program (NCEP) guidelines for patients with no known CHD suggest starting drug therapy to lower LDL cholesterol when the level is over 190 mg/dL if there are less than 2 other risk factors, and when the level is 160 or higher when there are 2 or more other risk factors. The National Heart, Lung, and Blood Institute Cholesterol Awareness Survey documented that only 3% of patients with high cholesterol and no CHD were receiving drug therapy.

Some experts argue that if we only treat people who fit the NCEP guidelines, many with so-called normal cholesterol levels will develop heart disease. A recent study showed that risk of developing CHD could be lowered by over 30% in people with average cholesterol levels by giving cholesterol-lowering drugs.

LifeScore® recognizes a significant opportunity for reducing the burden of heart disease. People at risk for developing heart disease can be more accurately identified with EBCT scanning. As described below, our program identifies early stages of coronary plaque build-up and tracks the plaque to ascertain that lifestyle and/or medication interventions are working. We believe that CHD prevention will be improved by the ability to visualize coronary artery plaque. Our program combines risk factor analysis and plaque visualization to provide the most complete assessment of an individual.

4     The Current Burden of Coronary Heart Disease

"Coronary heart disease caused 1 of every 4.9 deaths in the United States in 1996."

- American Heart Association

It is not surprising that CHD is an epidemic. As described above, many people at risk are not being treated. Many of these people progress year after year to their first coronary attack. Every 29 seconds an American suffers a coronary event, and every minute someone dies from CHD. CHD is the single largest killer of both men and women. 12 million people in America have diagnosed CHD, and each year there are 650,000 heart attacks and deaths in people who had no idea they had coronary plaque. Once people develop symptoms of CHD, they become candidates for various procedures, such as cardiac catheterizations to diagnose blockages, and angioplasty or bypass surgery to correct blockages. The chart below shows the growth of these procedures since 1979. The total cost for treating heart disease in 1999 will be over $100 billion.



 

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5    BCT Scanning as a Test for Coronary Heart Disease

"This is vastly more accurate than any other way of identifying apparently healthy people who are at risk for the development of CHD. Our findings suggest that this could become the primary screening tool for CHD."

- Alan Guerci, MD, Director of Research, St. Francis Hospital, Roslyn, NY

Prior to the development of EBCT scanning, CHD could only be diagnosed in two ways. The most accurate technique is angiography. A plastic tube must be inserted into the body and placed at the entrance to a coronary artery. Dye is injected and a picture called an angiogram is taken. The picture reveals areas of narrowing in the artery. This procedure, known as coronary angiography, is invasive and costly. The second, less sensitive technique involves stressing the heart with exercise or drugs and then looking for signs of decreased blood flow to the heart muscle. This technique requires that a functionally significant narrowing be present in the artery. Generally speaking, narrowings over 60-70% will cause abnormalities on a stress test, but not always.



EBCT scanning is a noninvasive x-ray procedure using a high-speed CT (coaxial tomography) scanner. Pictures are taken when the heart is between beats. During a single breath hold, twenty to forty images can be acquired, spanning the entire heart. The patient remains fully clothed in a comfortable, open environment. The images are processed in several minutes and are highly reproducible and quantifiable. Unlike any other test except for the invasive research tool known as intravascular ultrasound, EBCT shows even small amounts of plaque throughout the coronary arteries. It does so by measuring calcium, which makes up 20% of plaque. The amount of calcium is directly proportional to the amount of plaque.

EBCT received FDA approval in 1988. Since then, over 200 papers have been written validating this technology as the only noninvasive test that can accurately and reproducibly quantify coronary atherosclerosis. Academic centers such as Stamford; the Mayo Clinic; University of California, San Francisco; University of California, Los Angeles; University of Illinois; and Walter Reed Medical Center, as well as centers around the world, are actively pursuing new scientific studies, The National Institutes of Health has begun an eight year study of subclinical cardiovascular disease which will involve the recruitment of 18,000 men and women between the ages of 35 and 84. The RFP for the study states "Coronary calcium quantified by electron-beam computed tomography (EBCT) has a correlation of 0.90 or greater with histological coronary plaque area, identifies persons with 5- to 20-fold increased risk for CHD events, and is thus the best available noninvasive technique for quantifying subclinical coronary atherosclerosis." In the NIH study, EBCT will be the main technique employed for documenting early coronary heart disease.

 

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6    Why EBCT Scanning is Useful in People Without Known Heart Disease

" One of the reasons I ever got involved with EBCT scanning is to take my group into the 21^st century."

- Robert Roberts, MD, Professor of Medicine and Chief of Cardiology, Baylor College of Medicine.

LifeScore® will offer its program to men and women between the ages of 40 and 70 who do not have diagnosed heart disease. EBCT studies reveal that the calcium score, and therefore the total amount of coronary plaque, increases with age. 50% of men and 25% of women between 40 and 50 have calcium. This rises to 100% of men and 75% of women between 50 and 60. The higher the calcium score, the greater the likelihood of significant coronary narrowings. Coronary calcium scores can be used to determine who in a given population would most benefit from risk reduction programs. Studies have shown that those patients with the highest scores have up to 35 times greater risk than those with the lowest scores. When cholesterol testing is used, those with high cholesterol levels have only 2 times the risk of those with low levels. Therefore, the visualization and quantification of coronary plaque appears to be the most powerful predictor of future adverse events.

Most heart attacks are caused by the sudden closure of a less than 50% narrowed plaque in a coronary artery. These moderately narrowed artery segments do not cause any symptoms. Before the advent of EBCT, there was no way to identify the silent, early stages of plaque build-up. As a result, each year hundreds of thousands of people die or become disabled before initiating a preventive care program.

As mentioned above, doctors have not been successful at treating people with significant risk factors for heart disease. This is partly due to our system of health care, which is preferentially focused on treating disease episodes. It is also due to the difficulty of treating a condition such as high cholesterol that does not cause pain or disability. Finally, it is hard to motivate people to make significant lifestyle changes based on the theoretical risk of disease. EBCT scanning combined with risk factor analysis now offers a complete approach to diagnosing and managing pre-clinical CHD. Instead of using risk factors to motivate lifestyle changes, LifeScore® will use the images and calcium score to inform patients of the presence of coronary plaque. This information will provide a powerful motivation for the patient to take steps to reduce the likelihood of plaque progression. LifeScore® will use risk factor information to design a set of recommendations and will then help the patient track the results of their efforts. Follow-up scans will provide positive or negative feedback and will allow further refinements in the preventive care program.

 

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7    How Easy is it to Prevent Progression of CHD?

" Recent studies have demonstrated remarkable improvement in the clinical course of high-risk patients following aggressive modification of coronary risk factors."

- Michael Miller, Robert A. Vogel, The Practice of Coronary Disease Prevention, Williams and Wilkins, 1996.

Over the past decade, numerous studies have been done using medicine and lifestyle changes to reduce risk of coronary events and to reverse the process of plaque build-up. The lifestyle change studies have shown that very low fat diets or the so-called Mediterranean diet (high in fruits, vegetables, and mono-unsaturated fats) can lower risk by 30-50% and cause plaque to regress. The medication studies, using a class of cholesterol-lowering medications known as statins, which are very well tolerated, have shown that risk of coronary events can be lowered by 30-40%. A combination of medications and lifestyle changes can lower risk by up to 70%. A recent study in the prestigious New England Journal of Medicine showed that EBCT could be used to measure the effectiveness of statin therapy. Patients who did not receive therapy had a 50% progression in EBCT calcium scores, compared with a 5% decrease in scores in those who achieved target cholesterol levels on statin therapy. Prior to EBCT scanning, only coronary angiography could be used to assess progression or regression of plaque. Now, a painless, quick, and inexpensive exam can replace a costly, expensive, and invasive procedure, and creates an opportunity to track plaque regression/progression in the general population.

 

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8    HeartScore®: The LifeScore® Coronary Prevention Program

" LifeScore® fills a significant void by providing a complete longitudinal program for preventing coronary heart disease."

- C. Michael Wright, MD, President of LifeScore®.

LifeScore® has developed a unique program, called HeartScore®, for diagnosing and tracking coronary plaque. The program combines risk factor assessment, EBCT scanning, risk reduction recommendations (to be carried out by the client’s physician), follow-up interactions to assess lifestyle and risk factor modifications, and follow-up scans.

• HeartScore Scan Results

            Each patient will receive the following information based on his/her scan results:

• Scores for each coronary artery.
• Total coronary calcium score.
• Age/sex percentile.
• Relative/future risk.

• HeartScore Risk Factor Assessment

• HeartScore Recommendations

Appendix 1:      Quotations From the American Heart Association

Coronary Artery Calcification: Pathophysiology, Epidemiology, Imaging Methods, and Clinical Implications

A Statement for Health Professionals From the American Heart Association

1. "Electron beam CT scanning may be an appropriate first test in individuals with atypical cardiac symptoms (as) the most valuable finding in the symptomatic patient is a negative EBCT scan for coronary calcium. As discussed earlier, the negative predictive value of an EBCT calcium scan for significant (i.e., 50% or greater diameter stenosis in any major coronary vessel) is greater than 90% and perhaps closer to 95% in some circumstances."

2. "Electron beam CT and, to a lesser extent, double-helical CT have the enhanced capability to localize coronary calcification and detect smaller and less dense calcific deposits. Only EBCT can quantitate the amount or volume of calcium."

3. "EBCT has been shown to be sufficiently accurate for predicting the presence of angiographic stenoses somewhere in the coronary arteries and for predicting the likelihood of clinical end points in symptomatic patients. This evaluation should be done under the supervision of a physician knowledgeable about the significance of scan results and in management of coronary heart disease."

4. "The presence and amount of calcium detected in a coronary artery by EBCT indicates the presence and amount of associated atherosclerotic plaque."

5. "The magnitude of the calcium score can be used to a high specificity in predicting associated stenosis somewhere within the epicardial coronary system"

6. "In addition to the rationale that detection of coronary artery calcium is useful in identifying those at risk for acute coronary events, early detection of mild coronary atherosclerosis is of potential value also, particularly if the process can be slowed, arrested, or reversed. There are substantial data to indicate that lowering serum cholesterol in patients with known coronary artery disease (secondary prevention) reduces the incidence of nonfatal infarction, fatal infarction, cardiovascular mortality, and all-cause mortality."

7. "If risk increases with the amount of calcium in a continuous graded manner without a sudden, discrete step at a certain score or mass level, and the slope of this risk versus mass curve is sufficiently steep, evaluation of coronary calcium mass may be an effective method of selecting those who could benefit most from aggressive risk factor management."

8. "It can be anticipated that identifying the presence of pre-morbid coronary artery disease would influence the aggressiveness with which risk factor modification is approached."

9. "The manifest relation between calcification and atherosclerosis suggests that EBCT may have a role in establishing susceptibility (as opposed to merely quantitating risk) for coronary disease."

APPENDIX 2:  EBCT Compared with Spiral CT

Software has become available which permits coronary calcium scoring to be performed with spiral CT.  Spiral CT can acquire images in 500ms.  Thus, these images are five times slower than EBCT images.  The graph below shows that EBCT images are acquired when the heart is least mobile during the cardiac cycle.  The vertical axis is motion in milliseconds, while the horizontal axis is percent of RR interval.

In contrast, spiral CT images require at least 50% of the cardiac cycle for image acquisition.  The graph below depicts the acquisition period for a Toshiba mechanical spiral CT scanner.  As can be seen, the greater imaging time means that the coronary arteries are moving during a significant portion of the scan time.  As a result, motion artifacts are much more common.  Calcium deposits may appear blurred, and small calcifications may not be seen.

At an average heart rate of 80 beats per minute, the right coronary artery will move half its diameter in just 250ms.  This represents an unacceptable degree of motion for obtaining accurate and reproducible studies.

The above graph shows the correlation between EBCT and spiral CT scores for 31 asymptomatic patients with an average age of 51 years[1].  Using EBCT as the gold standard, spiral CT had a sensitivity of only 76% and a specificity of 70% for coronary calcification.  The false negative rate in this study was an alarming 42%.  For those with scores below 200, the inter-modality variability was 91%.   

Recent studies have demonstrated that EBCT can: 

• Non-invasively quantify coronary atherosclerosis
• Prognosticate future cardiac risk
• Measure plaque burden changes over time
• Evaluate the results of therapeutic interventions 

EBCT has been validated in over 250 research papers.  In contrast, spiral CT has only recently been introduced as a modality for measuring coronary calcium.   Virtually none of the studies comparing spiral CT scores to pathological studies, angiographic studies,  functional assessments, and future risk, have been done.  Until such studies have been performed, it is our belief that spiral CT should only be used for general qualitative assessments of plaque burden- i.e. with interpretations for moderate or severe amounts of calcium, but without the precise quantifications that remain valid at this time only for EBCT-derived scores.