Unmasking hearts at risk: Indicators can be hidden

Who is a candidate for a heart attack in the next year, or two or three? Wouldn't we all like to know. The best predictors identified thus far can determine with a fair amount of certainty only who will have a heart attack within the next decade.

Can't modern medicine do better?

Yes it can, many say. And a search has been on for the past several years for new signals that go beyond the traditional markers of cholesterol levels, hypertension, diabetes, smoking and family history.

A handful of novel risk factors has emerged, and some of them could have a place in a physician's toolbox.

But physicians are divided concerning their use. Some support the value of testing for such risk factors as C-reactive protein, fibrinogen, homocysteine or lipoprotein(a) and LDL particle size and number. Coronary calcium scans also are considered by some to be useful tests to flag a heart in imminent danger.

Other physicians hesitate to use these measures, while a middle camp uses them only selectively.

"Our research suggests that if you have a patient with a family history of heart disease and they are age 40 and over if a man, or age 45 and over if a woman, a physician might want to think about getting a coronary calcium scan," says Roger Blumenthal, MD, director of the Ciccarone Preventive Cardiology Center at the Johns Hopkins School of Medicine in Baltimore.

"They may also want to think about getting a C-reactive protein blood test in addition to the standard cholesterol profile and checking their patient's blood pressure and blood sugar," he says.

Gerald Fletcher, MD, a cardiologist at the Mayo Clinic in Jacksonville, Fla., and a spokesman for the American Heart Assn., is less certain that the tests reveal more than already can be determined by measuring conventional risk factors. "We may be getting to the era where we are looking at borderline measures," he says. "But a thorough analysis of blood cholesterol is probably the best way to pick out these people who may just topple over and die suddenly."

"At this point in our understanding of the role of CRP testing in primary evaluation, the test can be considered for use in patients who fall in the 'intermediate risk' category by prediction scores such as the Framingham risk score," says Mary Cushman, MD, associate professor of medicine and a hematologist at the University of Vermont College of Medicine in Burlington.

Family physician Russell White, MD, professor of medicine at the University of Missouri in Kansas City, notes that he uses the CRP test to gather additional information on patients who have had a first myocardial event and, after modifying their risk factors, go on to have another.

Testing the mid-risk group

He uses exercise stress tests or a calcium score from a CT scan for patients whose risk factors place them at middling risk for a heart attack as measured by the Framingham risk score. Results from those tests could help identify a patient as being at low risk or high risk, and treatment can commence appropriately.

"The tests aren't in the mainstream," Dr. White says. "If it's not a mainstream idea or concept from the American Heart Assn. or American College of Cardiology, I don't feel that I, as a primary care physician, need to use them on each patient."

Family physician Corey Evans, MD, MPH, director of medical education at St. Anthony's Hospital in St. Petersburg, Fla., agrees. High-risk patients, those who are at a 20% or greater risk for having a heart attack within the next 10 years, already should be treated aggressively, and those whose risk is 6% or less don't need treatment, he says.

It's the patients who fall between 6% and 20% on the risk scale who might need additional tests, says Dr. Evans, who keeps a global risk assessment calculator on his PDA. "Let's say your risk was 14% and I put you on a treadmill and you had a positive test," he explains. "I would move you to the high-risk group and begin aggressive treatment."

Dr. Evans also considers an individual's insurance coverage and the test's availability. C-reactive protein tests are usually covered by insurance, Dr. Blumenthal says, but coronary calcium scans generally are not.

Statistics, statistics

To help weigh the need to order any one of these new tests, physicians also should consider the validity of a statistic that has been circulating for the past few years -- 20% of people who have heart attacks have none of the traditional risk factors.

Such a statistic would seem to propel the need to employ novel risk factors to ferret out these vulnerable patients. Plus, that's a large number of people, considering that more than 163,000 out-of-hospital sudden cardiac arrests occur each year in the United States, according to the American Heart Assn.

But questions have been raised concerning just how many of these people actually had no identifiable risk factors.

Many now believe that the figure should be much lower than 20%, which had been preceded by the even higher figure of 50%.

It was the 50% figure that prompted Philip Greenland, MD, a professor of preventive medicine at Northwestern University's Feinberg School of Medicine in Chicago, and colleagues to look into the matter.

The results of their study, published in the Aug. 20, 2003, Journal of the American Medical Association, challenged the claim that coronary heart disease commonly occurs in individuals without at least one traditional risk factor.

A second study in the same issue found that 80% to 90% of patients with coronary heart disease had conventional risk factors.

So where did that 20% figure come from? It might have come from Dr. Greenland's study. One of the many population samples examined did show that 20% of the people studied had no traditional risk factors. But for the vast majority of the studies examined, the number was more like 5% or 10%, he notes.

"How big is this number of people who don't appear to have a traditional risk factor?" Dr. Greenland asks. "I have a sense that the number is actually pretty small."

The risk factor or factors likely were present all along, they just weren't identified, several physicians say.

Leslie Cho, MD, director of the Cleveland Clinic's Cardiovascular Center, would put her money on the lower figure. "There are plenty of data that point to the traditional risk factors as being at the root of the problem."

It's not that the various novel markers hold no interest. "I'm an interventional cardiologist, and I like to play with toys," she says. "I like new things. But we do such a poor job of controlling traditional risk factors."

While much remains unknown about the newer tests, the traditional risk factors have been well studied, Dr. Fletcher adds. "Each year we are looking at lower and lower blood cholesterol levels." And optimal blood pressure is now placed at 115 over 75. "If it's running 138 over 82, that's abnormal."

Even though most patients probably do have traditional risk factors, there remain a small number who have heart attacks in the absence of these factors, says Iftikhar J. Kullo, MD, associate professor of medicine at Mayo Clinic College of Medicine in Rochester, Minn.

Five of the novel risk factors that are close to being accepted by the mainstream medical community include C-reactive protein, fibrinogen, lipoprotein(a), homocysteine, LDL particle size and number, Dr. Kullo adds.

"There is clearly a lot of interest in trying to figure out who is really at high risk of heart disease and who isn't," Dr. Blumenthal says. "Because you can't tell by looking at a person on the outside, but knowing more about what their arteries look like on the inside or whether their arteries are inflamed, we think it is going to turn out to be a much better way to pinpoint who is at higher risk and who isn't."

How predictive are the predictors?

Dr. Greenland has thought a lot about risk factors and risk scores and their overall predictive ability. "I happen to think it is way more complicated than most people give credit."

He equates determining an individual's risk of having a heart attack with predicting the weather. "I can tell you 100% of the time what the weather is like right now. But 24 hours ago, how good a prediction would I have been able to make of today's weather? No matter how much we study the weather, we still miss a fair amount of the time."

Looking at risk factors for heart attacks follows much the same path. Measurements often are taken for each patient at one point in time rather than three, four or five times, and some measures are self-reported, such as smoking. "And the events we are trying to predict are five, 10 or 20 years from now," he points out.

"What people have totally missed sight of is, if you take all of the risk factors that are in the Framingham risk score and ask yourself how good are these risk factors at predicting heart attacks in the next 10 years, the answer is 80%," he says. That's not bad. But "what we want to get to is 100%."

When Dr. Greenland adds the new risk factors to the traditional risk factors, however, he sees only a small movement in the 10-year risk score to perhaps 81%. "For the practicing doc, what that means is adding the new risk factors doesn't make you much more confident of your predictive ability than what you knew from the traditional risk factors."