It's becoming clear that your cholesterol level doesn't tell you everything you need to know about your risk of heart disease. But how do you spot heart disease risk in a person whose cholesterol level is in the normal range?
One answer may be to measure levels of Lp-PLA2, a molecule that helps LDL cholesterol do its bad thing. Earlier studies have shown that people who get heart disease despite relatively low LDL cholesterol levels tend to have relatively high Lp-PLA2 levels.
But can an Lp-PLA2 test really offer more information than a cholesterol test? Does it work in older people?
The answer to both questions is "yes," find Lori B. Daniels, MD, assistant professor of medicine at the University of California, San Diego, and colleagues. Daniels and colleagues tested blood samples from 1,077 men and women at a mean age of 72, and then looked at whether they had heart disease 16 years later.
"With increasing levels of Lp-PLA2, there was an increased risk of heart disease," Daniels tells WebMD. "This held true even after adjusting for other cardiovascular risk factors. We show this gives information beyond what we already measure."
People with the highest Lp-PLA2 levels were 89% more likely to have heart attacks, angina, or bypass/angioplasty procedures than were people with the lowest Lp-PLA2 levels. Risk quickly rose with rising Lp-PLA2 levels. The25%of patients with the second lowest Lp-PLA2 levels had a 66% higher risk of heart disease than did the 25% of patients with the lowest levels.
Lp-PLA2 Drug Now in Trials
Despite these findings, Daniels says the Lp-PLA2 test isn't yet ready for routine use.
One issue is that while studies find higher Lp-PLA2 levels are riskier than lower Lp-PLA2 levels, it's not clear exactly which levels are risky and which aren't.
"We don't know yet what cutoff level identifies risk," Daniels says. "I would not advocate going to the doctor tomorrow and asking for this. But down the line, if these results hold true, the test would be most appropriate helping individuals at intermediate risk of heart disease to find their true risk."
Steven Nissen, MD, chairman of the Cleveland Clinic's Department of Cardiovascular Medicine, agrees that the test isn't ready for prime time. Nissen was not involved in the Daniels study.
"This is a very intriguing study, but we are not ready to make this a major marker for screening outpatients -- at least not just yet," Nissen tells WebMD.
That may change in a hurry. A clinical trial now under way is testing whether a drug that blocks Lp-PLA2 can help prevent heart disease. The drug, being developed by GlaxoSmithKline, is called darapladib.
"We need to see if this inhibitor now being developed will effectively slow progression to heart disease or reduce cardiovascular events," Nissen says. "It's not enough just to see it is associated with heart disease -- we want to see if blocking this molecule prevents disease."
Cholesterol-lowering statin drugs do prevent heart disease. But results from a recent study showed that while adding a different kind of cholesterol-lowering drug to a statin cut bad LDL cholesterol even more, it didn't seem to offer more protection against buildup of arterial plaque.
"It may matter not just how far you decrease LDL cholesterol, but how you get there," Nissen says. "One of the things we are learning is that statins work by multiple mechanisms. Their ability to lower LDL is not the whole story. It remains to be seen if lowering LDL by non-statin drugs is an effective way to prevent heart disease."
Daniels and colleagues report their findings in the March 4 issue of the Journal of the American College of Cardiology. The Lp-PLA2 test used in the study is made by diaDexus Inc. While Daniels has no financial interests in diaDexus, some of her co-authors are employed by or have interests in the company.