No-warning heart attacks.(Your Health)(Column)

It's a common--and unnerving--story: A man or woman who exercises diligently, doesn't smoke, and has normal weight, blood pressure, and cholesterol levels is suddenly felled by a heart attack. In fact, fully half of the people who develop coronary disease have none of those risk factors, according to a recent special article in The New England Journal of Medicine. That doesn't mean the standard risk factors--diabetes, family history of early coronary disease, smoking, hypertension, high cholesterol, inactivity, and being overweight or male--are any less risky or, if modifiable, any less crucial to control. (Note that women's risk catches up to men's by age 65 to 70.) But the finding that so many "low risk" people get heart attacks has set off a search for new biological markers.

The quest has already led to more detailed understanding of what causes heart disease and to new tests for evaluating risk. Most recently, the Food and Drug Administration approved a blood test for levels of a substance called C-reactive protein (CRP), which when elevated may triple or even quadruple the coronary risk. Other likely risk factors, such as a high level of fibrinogen, a clot-promoting protein, and of lipoprotein( a), a cholesterol subtype, are promising, but either the evidence is weaker or standardized screening tests are not yet widely available.

Tests for two other emerging risk factors--elevations in blood glucose and a waste product called uric acid--are already done fairly routinely, to screen for noncardiovascular disorders. But top researchers say they're reluctant to recommend these--or tests for elevations in CRP, an amino acid called homocysteine, and iron--as cardiovascular screening tests for all adults just yet. They worry about the national cost, the chance of ambiguous results, and the fact that none of the emerging risk factors has been studied extensively.

However, tests for elevations in CRP, homocysteine, iron, glucose, and uric acid are widely available, can already be useful for screening in certain individuals; they may become widely recommended in the future. They can offer a warning that the cardiovascular system is at risk and possibly suggest a way to reduce that risk in people with no other danger signs. They can help guide medical treatment in those "low risk" people who do have cardiovascular symptoms for no apparent reason. And they can help clarify the need for treatment, and the type of treatment required, in certain people who also have standard risk factors. Here's what you need to know about the new warning signs.

CRP RESPONDS TO ARTERIAL DAMAGE

Scientists believe that atherosclerosis, or clogged arteries, begins with an injury to the smooth lining of those vessels. The exact causes are unknown, but the usual suspects include diabetes, smoking, hypertension, and high cholesterol. Research also implicates the amino acid homocysteine and possibly the waste product uric acid (see discussion below), as well as gum disease and certain respiratory infections that can spread to the blood vessels.

The arterial assault trips a kind of biological burglar alarm--an inflammatory response that attracts white blood cells, which try to remove debris from the damaged artery. That response sends C-reactive protein cascading into the bloodstream. Eventually the white cells and CRP as well as cholesterol and other matter build up at the damaged site, forming a plaque deposit. If the plaque's cap ruptures--possibly due to hypertension, further inflammation, or other, unknown factors--a blood clot can form there, plugging the artery. That obstruction may cut off enough blood flow to the heart or brain to trigger a heart attack or stroke.