Among patients taking cholesterol-lowering drugs called statins, the higher the HDL or good cholesterol, the less likely they were to have a heart attack or other "cardiovascular event," they found.
Dr. Philip Barter of the Heart Research Institute in Sydney said the result is important because "it shows very, very clearly that the risk is real" when levels of good cholesterol, known as HDL, are too low.
"It means doctors can't ignore a low HDL even if they're treating people with statins. They need to attack the HDL as well, if the HDL remains low," Barter said.
Doctors have known for years that HDL, or high-density lipoprotein, protects against heart attacks and stroke, probably by cleaning up the bad low-density lipoprotein cholesterol, known as LDL.
"But it has not been clear whether a low HDL cholesterol level would remain a significant risk factor in people whose LDL cholesterol was reduced to very low levels," Barter and colleagues wrote in their report, published in the New England Journal of Medicine.
"Indeed, it had been argued hypothetically that if the LDL cholesterol level were reduced sufficiently, the level of HDL cholesterol might become irrelevant," they added.
No such luck.
Looking at a study of 9,700 patients taking the statin drug Lipitor in a study financed by maker Pfizer Inc., Barter and his international team of colleagues found that the higher a patient's HDL, the less likely he or she was to have a major cardiovascular event such as a stroke or heart attack.
"Even when LDL is taken down to very low levels, the kind of levels people say should be the aggressive targets, having a low HDL is still associated with a substantial increase in risk," Barter said in a telephone interview. "It surprised a lot of people and it surprised me."
But raising HDL levels is difficult. One drug that does it, niacin, has bothersome side effects.
Attempts by several companies to design drugs to raise HDL cholesterol have not yet been successful.
In April Pfizer said it was placing a hold on development of any drugs in the same class as torcetrapib, its experimental product that dramatically raised HDL but was scrapped after being linked to deaths in a large trial.
The alternative is to "become lean and become very active. That's probably as effective as anything we have at the moment. But most people who try don't succeed," Barter said. "The biggest frustration is that we don't have the magic bullet like we do for the LDL."
Barter said aggressively lowering levels of bad cholesterol probably reduces the risk of heart disease and stroke by 40 to 50 percent. Having a drug that brought up HDL levels would likely cut the remaining risk by half.
Pfizer paid for the new analysis.