Variation in the molecules, apolipoproteins B and A-1 (apoB and apoA-1), has been previously linked to the risk of heart disease. But the latest study is among the largest yet to assess the two markers. A report on the findings appears in the Dec. 15 issue of The Lancet.
The study was led by Gõran Walldius, a scientist with the drug firm AstraZeneca, in Mõlndal, Sweden. He and his colleagues in Sweden and Norway analyzed blood fats and heart attack risk in more than 175,000 Scandinavians between the ages of 16 and 83, most of whom were participants in cholesterol screening efforts.Of those, 864 men and 359 women suffered fatal heart attacks over the next five-and-a-half years. The risk of death was greatest for people who had elevated low-density lipoprotein (LDL, the "bad" cholesterol), apoB, and another class of blood fats called triglycerides, the study found. The risk was lowest for those with more high-density lipoprotein (HDL, the "good" cholesterol) and apoA-1.
But the people whose ratio of apoB to apoA-1 was highest (in other words, those who had high B but low A-1) were especially likely to die of a heart attack during the study period, the researchers say.
In fact, even people with normal or low levels of LDL were at risk of heart attacks if their B-to-A ratio was high. Those whose ratio was in the top 25 percent had almost four times the risk of a fatal heart attack than did people in the bottom quartile.
The two apo molecules appear to stay in approximately the same proportion as a person ages, making them particularly useful markers for people over 70, whose cholesterol levels often drop as they start eating less.
"Elderly patients with an abnormal apolipoprotein balance may also benefit from lipid-lowering treatments," Walldius says in an e-mail interview. "It is never too late."
AstraZeneca is now developing an anti-cholesterol drug, called Crestor, designed to tackle not only elevated LDL but also elevated apoB. The drug, a version of the so-called statin compounds, "has positive effects on all these lipids," Walldius says, referring to blood fats.
The key question is whether doctors can efficiently screen people for the apo molecules. The Scandinavian researcher say yes.
"The tests are a little bit more expensive than LDL and HDL, but it may well be that the prices will be lower when more physicians and laboratories ask for and perform these tests," says Walldius.
Dr. Gerald Berenson, a heart specialist at Tulane University in New Orleans, agrees that the price of an apo test would probably fall with wider use.
Berenson also agrees that the latest study shows the markers can predict future heart attack risk and would probably be a valuable adjunct to conventional cholesterol and triglyceride screening. "I think the article has merit. The apos are a little better predictive than the lipoproteins [LDL and HDL]," he says.
But, Berenson adds, it's unrealistic to expect patients to do very much with the extra information, considering they already stumble badly when it comes to their cholesterol.
Heart experts say 36 million Americans should be taking statins to lower their cholesterol, far more than in fact are on the drugs.
For those who don't want to pop another pill, a healthy diet and regular exercise can also lower total cholesterol, Berenson says. Yet the average American can't report getting either.
High cholesterol is a leading cause of heart attacks, which kill about 460,000 Americans a year, according to the National Heart, Lung, and Blood Institute.
Earlier this year, the Centers for Disease Control and Prevention reported that almost 71 percent of American adults took a cholesterol test in the last five years, up from 67 percent a decade ago. Of those, almost 29 percent got back a result that was too high. The report suggested that about 9 percent of Americans have high cholesterol that goes undiagnosed.
What To Do
For more on how to spot a heart attack early, try the National Heart, Lung, and Blood Institute.
To learn more about high cholesterol and how to keep it in check, visit the American Heart Association.
You can also try HeartInfo.