Counting coronary calcium: Are the new scans right for you?

(This article was first printed in the February, 2004 issue of the Harvard Men's Health Watch. For more information or to order, please go to http://health.harvard.edu/men.)

Coronary artery disease is a dynamic process that begins with damage to the lining of an artery. The usual culprit is the oxidized form of low-density lipoprotein (LDL, or "bad") cholesterol, often acting in combination with other harmful influences such as high blood pressure, diabetes, and smoking. The injury triggers inflammation in the artery wall, which perpetuates the damage.

As the process continues, the plaques of atherosclerosis enlarge and begin to block the artery. If the obstruction is severe, it limits blood supply to the heart muscle, causing the pain of angina. That's bad enough, but a fibrous cap usually covers large plaques so they don't rupture. Smaller plaques don't cause angina, but since they are not capped, they can break open. Blood clots form on the ruptured plaque, resulting in a completely blocked artery - and a heart attack.

Doctors are very good at diagnosing heart attacks and angina. But nearly 70% of heart attacks and 50% of sudden deaths due to coronary artery disease occur in people who have never been diagnosed with the disease. If doctors could detect plaques before they cause symptoms, they might be able to start effective treatment in time to prevent damage.

Tried and true

At present, doctors depend on risk factor screening to identify people who may have silent coronary artery disease. The idea is to detect individuals at risk, treat them to reduce that risk, and monitor them to see how they're doing.

Coronary artery disease is complex, and more than 300 risk factors have been proposed. But you don't need hundreds of tests to find out if you are vulnerable. Many of the potential risk factors have a minor impact, and many cluster together, so measuring one is as informative as testing for all of them. See sidebar for a list of the most important risk factors.

Every man should know where he stands with regard to modifiable risk factors - and since coronary disease begins early in life, that goes for men age 20 and up. If correctable risk factors are identified, they should be treated; the stronger the factors, the stronger the treatment.

Most men are familiar with the standard risk factors, but they should also understand two of the newer ones.

Homocysteine is an amino acid. Elevated blood levels can damage arteries, but routine testing is not yet recommended. That's because a high consumption of three B vitamins (B₆, B₁₂, and especially folic acid) from a good diet (and a daily multivitamin) will usually keep homocysteine under control. As a result, people can be "treated" without first being tested.

C-reactive protein (CRP) reflects inflammation. Atherosclerosis involves vascular inflammation, and elevated levels of CRP can help identify people at risk. In some studies, CRP is an even better indicator of trouble than cholesterol. There is no treatment for CRP itself, but elevated levels should spur aggressive treatment of other risk factors; for example, statin therapy often lowers CRP as it reduces LDL cholesterol (see Harvard Men's Health Watch, January 2002). Similarly, studies suggest that two newer markers of inflammation - myeloperoxidase and glutathione peroxidase 1 - may outperform CRP, but these will need to be tested on more patients before they become widely used.

Risk factor screening is very important - but up to 50% of cardiac events can't be explained or predicted by the known factors. How can doctors improve their batting averages?

Tried and tricky

Stress testing is another way to evaluate a man's coronary arteries. The theory is sound: Make the heart work hard in the safe confines of an exercise lab to detect abnormalities before they cause trouble in the unprotected real world.

Cardiologists can stress the heart with exercise on a treadmill or bike or by administering a drug such as dobutamine or adenosine. They then monitor the patient's symptoms, blood pressure, and EKG, and they can add an echocardiogram or nuclear heart scan for extra precision.

Stress testing is an excellent way to evaluate people with chest pain, shortness of breath, or other symptoms that may indicate heart disease. It's also an important way to track the progress of patients who already have the disease. Unfortunately, though, stress testing has not succeeded in screening apparently healthy people to see if they have silent coronary artery disease. There are simply too many false positive and false negative results.

Tried and tough

Coronary angiography is the gold standard for detecting coronary artery disease; it's the essential test for patients who may need angioplasty or bypass surgery. It involves threading a catheter into the heart and injecting dye so that x-rays can detect blockages. Because angiography is an invasive, expensive test with risks of its own, it has no place in screening people who seem healthy. But newer techniques now permit doctors to obtain high-quality cardiac images without risk. The tests are here - but are they right for you?

Trying hard

Since the early days of cardiac pathology in the late 19th century, doctors have known that c alcium is deposited in the plaques of atherosclerosis. Calcium does not seem responsible for this damage, but these deposits are part of the body's reaction to ongoing inflammation in arteries (as well as in other tissues). Calcium puts the hardness in "hardening of the arteries."

Ordinary x-rays can detect calcium deposits if they're large enough. But early atherosclerosis is another matter. The coronary arteries are small, just 2-4 mm in diameter, and take many twists and turns as they travel through the heart muscle. And they are in constant motion, gyrating with each heartbeat.

Think of trying to take a picture of a strand of spaghetti as it shimmies in boiling water, and you'll have some idea of what scientists face when they try to obtain images of the coronary arteries. It's a daunting task, but it has been accomplished.

Electron beam computed tomography

Computed tomography (CT) scanning has revolutionized the way doctors obtain pictures of the body's deepest recesses. The first scanners used x-rays produced by a generator that circled around the patient as he moved through a doughnut-shaped tube. These machines have been largely replaced by helical CTs, which are faster and more accurate because the x-ray generator moves quickly around the patient in a spiral. But as fast as they are, helical CTs are no match for the beating heart.

Enter electron beam computed tomography (EBCT, also known as ultrafast CT). EBCT uses an electronically steered electron beam to produce x-rays. The beam can rotate around the patient much faster than an x-ray generator can, so EBCT is faster than other CTs - fast enough to take a picture of a beating heart. EBCT obtains each image in just 1/20 of a second, about 20 times faster than a helical CT.

A full study can be done in about 10 minutes, and it exposes the patient to a very small amount of radiation, about a fifth of the dose he would get with an ordinary CT and just twice as much as with a simple chest x-ray. The test doesn't require medications, injections, or dye, so its risks are minimal. But EBCT is expensive, generally costing from $350 to $1,000, and it is not covered by most health insurance plans.

Testing the test

Although CTs use the latest computer technology, they ultimately depend on the same instrument as other x-ray pictures, the human eye. But EBCT is different. Instead of relying on a radiologist's subjective evaluation of a plaque, it generates a calcium score that provides a very accurate measurement of the amount of calcium in a person's coronary arteries. The more calcium, the higher the score - and the more atherosclerosis. The score can be reported as a percentile that compares an individual's result to those of other people of the same age and gender or as a simple number ranging from 0 to 1,000 or more. When the numerical Agatston score is used, numbers below 10 are excellent, numbers above 400 indicate high risk, and numbers in between have intermediate significance.

Health-conscious people like to know their scores, but does the calcium score predict actual cardiac events? It does. Many studies have been completed to date, and most agree that people with the highest scores have the highest risk.

A 2003 Illinois study of 8,855 people between the ages of 30 and 76 is a good example. None of the subjects had been diagnosed with coronary artery disease before their EBCTs. Each person provided information about his or her health and cardiac risk factors. The researchers tried to contact each subject after an average of 37 months; they were able to reach 4,155 men and 1,484 women.

Although the men were younger (average age, 50) than the women (average age, 54), the men had higher average calcium scores (137 vs. 59). Even after taking standard cardiac risk factors into account, the 25% of men with the highest scores were 4 times more likely to suffer a heart attack or die from heart disease than the 25% of men with the lowest scores; they were also 26 times more likely to need bypass operations or angioplasties. But although the calcium score did predict the need for surgery or angioplasty in women, it did not predict heart attacks or cardiac events.

This study is one of the most impressive demonstrations of the power of EBCT, but it has flaws. All the subjects referred themselves for scanning, so they may have had symptoms or other reasons to worry about their hearts. The scientists did not measure the cardiac risk factors themselves but relied on the subjects' own reports. Finally, the researchers were unable to contact more than a third of the original group. All these limitations make it hard to say that the results apply to the whole population of adults without cardiac symptoms. Still, experts agree that EBCT can detect coronary artery calcium and that high scores tend to indicate risk.

A scan for you?

Like other high-tech diagnostic tests, EBCTs are now being marketed directly to the public. For a fee, you can bypass your doctor and buy yourself a scan. But should you?

Most authorities say no. More research is needed to learn whether a high calcium score adds significantly to the information provided by much l ess expensive, better-studied risk indicators. And even if calcium scores add significantly to the risk profile, scientists will have to determine if this information leads to effective treatments and a better outcome. The large government Multi-Ethnic Study of Atherosclerosis is already under way, but it's not expected to answer these questions until around 2010.

It may not be wise for you to schedule your own scan, but should your doctor order an EBCT for you? More research is needed to answer this question, too. At present, though, the test is not likely to help low-risk individuals who would probably have low scores and are likely to stay healthy in any case. At the other extreme, high-risk individuals should receive treatment regardless of their calcium scores, so an EBCT is unlikely to help them. In the middle, however, are some folks with uncertain risk. An EBCT might help doctors decide how aggressively to treat them, particularly if stress testing is inconclusive.

EBCT is a work in progress. It's exciting progress, and it's likely to help improve the understanding and treatment of coronary artery disease. But it's also an example of a recurring dilemma in modern medicine: Technology has arrived before doctors have learned how best to use it.