Very Low LDL 'Bad' Cholesterol May Cut Heart Risk Even if HDL 'Good' Cholesterol Is Also Low
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Reviewed By Laura J. Martin, MD
July 23, 2010 -- Patients on statin drugs who reduce their LDL "bad" cholesterol to very low levels may not need to be so concerned about boosting their HDL "good" cholesterol levels for protection against cardiovascular disease, according to a new study.
"Once we get the levels of LDL down to very low levels, it becomes unclear whether HDL is an important determinant of [cardiovascular] risk," says researcher Paul Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham & Women's Hospital, and professor of medicine at Harvard Medical School, Boston.
Ridker led the JUPITER trial (Justification for the Use of Statins in Primary Prevention), which previously found that the statin drug Crestor reduced heart attacks and strokes by 44% in men and women with average to low LDL at the study start and no history of cardiovascular disease. In this follow-up analysis, Ridker and colleagues divided the JUPITER participants into four groups depending on their HDL levels.
The question, Ridker tells WebMD, is: "Does HDL remain an important predictor of risk when we drop the LDL to low ranges?" Based on this new analysis, he says, "the answer looks to be no."
The findings are published online in The Lancet.
The JUPITER trial was funded by AstraZeneca, which makes Crestor. Ridker reports receiving research grants from AstraZeneca, Novartis, Merck, Abbott, Roche, and Sanofi-Aventis.
Reducing LDL With Statins
As studies of statin therapy have accumulated, the drugs have been established as the "intervention of choice" for most patients with cardiovascular disease or at risk of it, the researchers write.
The statin Crestor reduces LDL up to 52%, according to the manufacturer. It also raises HDL, but not as much as it reduces LDL. Typically, Crestor increases HDL by up to 14%.
But a "residual" risk for cardiovascular disease remains in the patients on statin therapy even after they have lower LDL levels, and the researchers wanted to see if it was due to the HDL levels.
Because low HDL levels are a strong predictor of heart disease risk in the general population, Ridker says, he wanted to see if boosting it might take care of this residual risk for the patients on statin therapy with low LDL levels.
In the new analysis, Ridker says, those on placebo with high HDL levels were protected from cardiovascular events, with those in the highest group having about half the risk of cardiovascular events as those in the group with the lowest HDL levels.
Despite the finding, Ridker says the issue must be further studied. Studies of new drugs to boost HDL are under way, he says.
And despite his finding that HDL may not matter in those with very low LDL levels, he emphasizes that "HDL remains an important predictor of risk in the general population." The LDL levels of the JUPITER participants on drug therapy, he says, are very low and not typically achieved in Western populations without intensive drug treatment.
In the study, the median LDL for those on Crestor was 55 mg/dL.
Lifestyle matters, too, he tells WebMD. "If you are at increased risk [of cardiovascular disease] due to increased LDL, a low HDL, or an elevated high sensitivity C-reactive protein [another marker for heart disease], the real message should be to go to the gym, throw out the cigarettes, and lose some weight. Next, talk to your doctor about statin therapy."
The new finding supports what cardiac specialists believe about treatment of heart disease risk factors, says Sidney C. Smith, Jr., MD, professor of medicine and director of the Center of Cardiovascular Science and Medicine at the University of North Carolina, Chapel Hill, who reviewed the findings for WebMD.
"The primary focus of our treatment strategies should be reduction of LDL, and this article certainly supports that," says Smith, a past president of the American Heart Association.
However, he had a caveat. "I do not think that the evidence in this study is sufficient to say that addition of therapy focusing on HDL would not help. I think the jury is still out on whether there might be therapies which increase HDL that could have additional benefit."
In a comment accompanying the study, Derek J. Hausenloy MD, PhD, of the University College London Hospital and two co-authors point out that other research has found that even in patients with very low LDL levels, HDL cholesterol was still predictive of heart attack and stroke risk. So why the new findings didn't reach this conclusion is unclear, he writes.
He, too, called for more research. And he writes that paying attention to HDL remains "a major treatment strategy for the reduction of cardiovascular risk in the large majority of patients who do not have very low LDL cholesterol."
SOURCES: Paul Ridker MD, MPH, Eugene Braunwald Professor of Medicine, Harvard Medical School; director, Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston.
Ridker, P. The Lancet, published onlineJuly 22, 2010.
Hausenloy, D. The Lancet, published online July 22, 2010.
Sidney C. Smith Jr., MD, professor of medicine and director, Center of Cardiovascular Science and Medicine, University of North Carolina, Chapel Hill.
Crestor.com: "What Crestor Does."
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