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Observations

Opinion, arguments & analyses from the editors of Scientific American

The HDL Conundrum: What's Bad about Drugs for Good Cholesterol?

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graphic showing normal interior view of artery w/red blood cells and cholesterolAfter federal officials announced on May 26 the halting of a trial probing whether Abbott Laboratories' formulation of the B vitamin niacin can help prevent heart disease and strokes, scientists and physicians were left with an  immediate follow-on question. Specifically, was this event just another nail in the coffin of the premise on which that trial was based, the so-called HDL Hypothesis?


On the surface, the basic conjecture, the idea that raising high-density lipoprotein cholesterol (HDL-C) can help prevent cardiovascular disease, is well-grounded in science. Studies have shown that people with high levels of HDL experience less heart disease. So that should mean that raising HDL, which shuttles cholesterol from artery walls back to the liver for excretion, should prevent cardiovascular problems as well. In recent years, that notion has become a big maybe, what might be re-titled as the HDL Conundrum.


The AIM-HIGH trial using Abbott’s drug Niaspan in conjunction with a statin that lowers LDL cholesterol—LDL “bad,” HDL “good,” probably a macro in some health reporters’ laptops—showed that the drug worked as billed. It raised HDL, but it didn’t prevent cardiovascular risk any better (actually it may have registered a slightly worse result) than a statin alone. This is not the first hit for the famed good lipid. A Pfizer drug that increased levels of HDL by a different biological mechanism was halted in 2006 because it upped the risks of deaths. Still, Merck is putting big money behind another HDL.


So what’s going on here? Nobody knows for sure, but there are a few ideas kicking around. A review article published in 2010 in the Journal of Lipid Research by a group of scientists from the University of Amsterdam underlined that the HDL hypothesis remains just that, a hypothesis. The scorecard for HDL on a variety of standard measures is mixed. Yes, the epidemiology shows that high HDL is protective. And a series of lab dish studies indicate that HDL has properties that guard against cardiovascular disease, but none of these things have been validated in humans. Animal studies indicate the same, but other blood lipids were changing along with the increase in HDL, possibly muddying the picture. Genetic studies looking at whether HDL is protective remain unconvincing. So what sounds good on paper is sketchy at best, particularly in light of this most recent study. So to quote Stephen Jay Gould when he appeared on The Simpsons: Much more research is needed.

In the meantime, maybe those reporters should think about changing the macros in their computers.


Image: U.S. National Library of Medicine

The views expressed are those of the author and are not necessarily those of Scientific American.

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