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You dutifully keep track of your HDL ("good") and LDL ("bad") cholesterol levels, but some experts say this paints only a partial picture of your overall heart health. A new test, called apoB, gives you and your doctor a more precise way of figuring out whether your arteries are in danger of clogging by measuring blood levels of a component of LDL called apolipoprotein B. LDL comes in different-size particles, some large and some small. It's the smallest ones that are most harmful, in part because they're capable of penetrating and lodging in the inner walls of coronary arteries, forming dangerous plaque (whereas large particles "float" on by). Because one molecule of apoB sits on every LDL particle, a high apoB count relative to your LDL cholesterol number would suggest that you have more small, damaging particles than large ones and therefore may be at greater risk of developing heart disease.
"Most physicians haven't tuned in to apoB testing yet," says Ronald M. Krauss, MD, a spokesman for the American Heart Association and director of atherosclerosis research at Children's Hospital Oakland Research Institute, in California, "but an increasing number of cardiologists and endocrinologists view it as a clearer measure than the standard cholesterol test of a patient's heart-attack risk and how she should be treated." Current medical guidelines call for drug therapy to lower LDL to below 100 if you're at high or moderately high risk of heart disease -- that is, if you have a strong family history of heart attack, you smoke, are overweight or have diabetes or metabolic syndrome, a disorder that includes a constellation of risk factors such as high blood lipids, insulin resistance, and excessive abdominal fat. However, your apoB results could prompt your doctor to consider other forms of treatment.Do You Know Your Heart Disease Profile?
For example, if you take two women who each have an LDL of 120 and the same heart-disease profile, a doctor may not recommend medication for patient A if she has mostly large particles, while patient B's mostly small particles might warrant a prescription. "There are probably a lot of women taking cholesterol-lowering statins who don't need them and a lot who should be on these drugs but aren't," says Lewis H. Kuller, MD, chair of epidemiology at the University of Pittsburgh Graduate School of Public Health and a researcher who has studied the relationship between LDL particles and heart attacks in women. In fact, 19 percent of the participants in a 2003 heart study would have a different treatment recommendation if apoB results were used to guide treatment rather than LDL alone.
ApoB testing isn't for everyone. "We measure particle size only in carefully selected patients," says Ladies' Home Journal medical adviser Marianne J. Legato, MD, director of the Partnership for Gender-Specific Medicine at New York City's Columbia University. "It's often done when you have someone who's at relatively low risk of heart disease in all respects except that she has a high total cholesterol and/or LDL level." For people with borderline or high cholesterol but no other risk factors and no family history of early heart disease (under the age of 55 for men, 65 for women), finding out that their LDL particles are the large kind can be reassuring news (even though LDL levels over 130, regardless of particle size, are always cause for concern). However, you may be given the test even if your LDL isn't high but you have other cardiovascular risk factors, such as high blood pressure or metabolic syndrome.
The American Heart Association does not currently recommend routine apoB testing because researchers have not yet come up with guidelines for interpreting test results across the general population. You're not likely to come across the blood test at your annual physical but may get it if your internist refers you to a cardiologist for a more thorough risk assessment. ApoB is often used as part of cholesterol screening at heart centers such as the famed Cleveland Clinic. "The standard lipid profile -- a count of total cholesterol, HDL and LDL -- is sufficient for most people, but we use apoB for patients with high triglycerides for whom the standard test may not be adequate," explains Byron Hoogwerf, MD, an endocrinologist in the Cleveland Clinic's preventive cardiology and rehabilitation section.Some Doctors Question the apoB Test
To complicate matters further for patients, some doctors challenge the value of apoB tests and cholesterol lowering in general. Nortin M. Hadler, MD, professor of medicine and microbiology/immunology at the University of North Carolina at Chapel Hill, cautions that high cholesterol ups your lifetime heart-disease risk by only 1 to 2 percent and feels it isn't a meaningful threat unless you have a family history of early heart attacks. He believes that the evidence for taking steps to lower cholesterol (either with diet, exercise, or drugs) is weak and that these measures make no real difference in preventing heart attacks. Others, such as John Abramson, MD, a family physician and clinical instructor at Harvard Medical School and author of Overdosed America, question the value of cholesterol testing when the resulting treatment -- statins -- has not been shown to actually prevent heart disease in otherwise-healthy women. A 2004 Journal of the American Medical Association review of 13 studies on statins found that they reduce the risk of heart attacks only for patients who already have heart disease.
Most doctors, however, remain firm proponents of controlling cholesterol and will generally recommend improving diet and exercising more as first steps. By losing weight, you can shift the balance of LDL particles, lowering the levels of small ones while increasing the number of large particles, Dr. Krauss points out. If that doesn't improve your cholesterol profile enough, your doctor may prescribe cholesterol-lowering drugs. Fibrates, which were first introduced late in the 1960s, raise HDL, lower LDL and apoB levels, and alter the size and composition of LDL from small, dense particles to large ones. Prescription-strength niacin, an even older cholesterol-lowering drug, has similar effects. Either treatment may be given alone or, if your LDL is especially high, in combination with a statin. While statins do not affect LDL particle size, they are particularly effective at lowering total LDL particle levels, and in the last two decades they've become the most widely used of all cholesterol-lowering medications.
All of these drugs have side effects, which, though rare, you should discuss with your doctor. Fibrates can cause nausea, stomach upset, diarrhea and, after long-term use, gallstones. Niacin can cause flushed or itchy skin, headaches, and heart palpitations. And statin side effects include stomach upset, constipation, abdominal cramps and muscle pain, and weakness. Finally, taking any of these medications requires close monitoring of your liver function by your doctor.The Future of Cholesterol-Lowering Drugs
While most cholesterol drugs target "bad" LDL by blocking the liver enzyme needed to produce it, researchers at several drug companies, including Pfizer and Roche, are now racing to create drugs to boost HDL and rev up the body's ability to whisk excess cholesterol out of arteries and to the liver for elimination.
In 2003, Cleveland Clinic researchers found that a newly formulated drug called recombinant ApoA-1 Milano (a synthetic version of a naturally occurring "super" HDL component found among inhabitants of a small coastal town in Italy) significantly reversed hardening of arteries caused by cholesterol in just a matter of weeks. Patients who took ApoA-1 Milano saw benefits about 10 times greater than the plaque removal that statins produce over a period of years. ApoA-1 Milano remains a priority for the Cleveland Clinic, and a version of the drug is under development by Pfizer.
Another HDL-boosting medication in the wings is Pfizer's torcetrapib, which trials have shown raises good cholesterol by as much as 55 percent and may help stop the buildup of plaque. Torcetrapib could be on the market in the next several years.