New tests for heart disease

Three blood tests designed to detect early heart disease show great potential, but may not quite be ready for prime time.

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By  Harvard Medical School Published  March 15, 2006

|~||~||~|Cardiologists are often asked to make predictions about a patient’s chances of having a heart attack or stroke. It’s a difficult task, since they must make do with limited information. To make matters worse, the stakes are high. An incorrect estimate could mean a person takes medications he or she doesn’t need, or doesn’t make the changes needed to prevent serious cardiovascular trouble. Everyone could have an angiogram, the cardiologist’s equivalent of a weather forecaster’s Doppler radar. This special x-ray offers a direct look at the heart’s arteries. It can show if they are flexible, clean, and open, or stiff and clogged with cholesterol-filled plaque. This kind of detail provides solid information for prognostication. There are a few drawbacks to this approach. One is the small but very real risks of angiography — infection, bleeding, a punctured blood vessel, kidney damage, even death. Another is that they are expensive. For these reasons, angiography is reserved for people with chest pain and other indicators of serious heart disease. Cholesterol levels offer a hint at what’s going on inside the arteries. They aren’t that precise, though. That’s why the search continues for other ‘bloodhound’ tests that can sniff out trouble in the arteries or the heart before it causes a heart attack, stroke, or other damage. Homocysteine once looked like it was poised to join cholesterol as a common test for heart disease risk, but its luster has faded. C-reactive protein (CRP) is an up-and-coming test. It is now recommended as an add-on when cholesterol, blood pressure, and other factors don’t yield a clear-enough picture. Three new possibilities include tests for white blood cells, a hormone made by the heart, and an enzyme that repairs cholesterol-carrying particles. Measuring white blood cells In the new view of heart disease, a key player is inflammation, the same process that triggers a fever or causes swelling around an injury. The C-reactive protein test is a new way to gauge bodywide inflammation. An older and less expensive way to do this is by checking the white blood cell count. A small body of research, mostly in men, links higher white cell counts (more inflammation) with higher chances of having a heart attack or stroke. A study that included more than 70,000 older women supports this connection. Women with the highest white cell counts at the start of the study (above 6.7 billion per liter of blood) were more likely to have had a heart attack or stroke or died of heart disease over a six-year period than those with the lowest counts. One problem with the test is that white blood cell counts jump with an infection, which could lead to alarming but incorrect predictions about heart disease. Another is that the cutoff of 6.7 billion used in this study is smack in the middle of what is now considered the normal range for white blood cells. An unrelated analysis of data from a trial of cholesterol-lowering statins showed that treatment with pravastatin (Pravachol) was more effective in people with higher white cell counts than in those with lower counts. So it is possible that this test could someday be used to identify good candidates for statin therapy. Making the grade It takes more than just a few studies showing a connection between heart disease and a particular substance in the blood in order for a test to become widely used. What does a new marker have to do before it’s admitted to the club? l It must add extra information beyond that provided by cholesterol, blood pressure, and other established risk factors l Be reliably positive in people with heart disease and reliably negative in people without it be easy, quick, and relatively inexpensive l Vary little in an individual over short periods l Offer information that can guide decisions about specific treatments. Stressed-heart hormone Heart muscle cells churn out a protein-like hormone called B-type natriuretic peptide (BNP) when overwork causes the ventricles to enlarge or in response to troublesome levels of pressure and fluid. A test for BNP is becoming widely used to diagnose heart failure. Heart cells deprived of sufficient oxygen, even temporarily, also make extra BNP. So measuring blood levels of it could reveal signs of seriously narrowed arteries before they cause chest pain or give other hints of their existence. A string of studies supports this idea. In one of them, among 500 initially healthy residents of Copenhagen who were followed for five years, those with the highest BNP levels at the study’s start were more likely than those with lower levels to develop heart trouble, have a stroke, or die. In fact, BNP predicted heart disease better than C-reactive protein. Fixit protein A repair enzyme that rides around the bloodstream attached to LDL (bad) cholesterol particles has been identified as a possible marker of atherosclerosis. This enzyme, called lipoprotein-associated phospholipase A2 (Lp-PLA2) appears to be involved in the release of substances from LDL that promote inflammation. Some (but not all) studies show a connection between high levels of the enzyme and heart disease. Whether it adds important information, however, remains to be seen. Cream rises Neither white cell counts, BNP, nor lipoprotein-associated phospholipase A2 are ready to join cholesterol and blood pressure as key tests for heart disease. Although they are interesting and promising, they don’t satisfy the requirements for such a test (see ‘Making the grade,’ above). A good test is positive in a very high percentage of people with heart disease and negative in a very high percentage of those without it. If it yields a lot of false positives or false negatives, patients could end up taking medications they don’t need or be falsely reassured when they’re at risk. Until newer tests come along, information about cholesterol, blood pressure, habits, and family history offers the best gauge of a person’s risk of having a heart attack or stroke. An online tool developed by the Harvard School of Public Health, called Your Disease Risk, can help individuals estimate their chances of having a heart attack (or developing osteoporosis or having cancer) and offer tips for reducing that risk. It can be found by visiting: www.yourdiseaserisk.harvard.edu. This article is provided courtesy of Harvard Medical International. © 2006 President and Fellows of Harvard College||**||

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