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

This article was published in Scientific American’s former blog network and reflects the views of the author, not necessarily those of Scientific American


After 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.


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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

Gary Stix, Scientific American's neuroscience and psychology editor, commissions, edits and reports on emerging advances and technologies that have propelled brain science to the forefront of the biological sciences. Developments chronicled in dozens of cover stories, feature articles and news stories, document groundbreaking neuroimaging techniques that reveal what happens in the brain while you are immersed in thought; the arrival of brain implants that alleviate mood disorders like depression; lab-made brains; psychological resilience; meditation; the intricacies of sleep; the new era for psychedelic drugs and artificial intelligence and growing insights leading to an understanding of our conscious selves. Before taking over the neuroscience beat, Stix, as Scientific American's special projects editor, oversaw the magazine's annual single-topic special issues, conceiving of and producing issues on Einstein, Darwin, climate change, nanotechnology and the nature of time. The issue he edited on time won a National Magazine Award. Besides mind and brain coverage, Stix has edited or written cover stories on Wall Street quants, building the world's tallest building, Olympic training methods, molecular electronics, what makes us human and the things you should and should not eat. Stix started a monthly column, Working Knowledge, that gave the reader a peek at the design and function of common technologies, from polygraph machines to Velcro. It eventually became the magazine's Graphic Science column. He also initiated a column on patents and intellectual property and another on the genesis of the ingenious ideas underlying new technologies in fields like electronics and biotechnology. Stix is the author with his wife, Miriam Lacob, of a technology primer called Who Gives a Gigabyte: A Survival Guide to the Technologically Perplexed (John Wiley & Sons, 1999).

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