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May 17, 2012
Is HDL Always "Good Cholesterol"?
The failure of Roche's dalcetrapib has a lot of people wondering just what's going on with HDL as a cardiovascular drug target. And this isn't the first time - there have been a number of puzzling findings in the lipoprotein field that point out to us that we don't know nearly as much about this area as we might think. Many promising therapeutic ideas in it have turned out disastrously.
Now there's a new paper in The Lance that underscores this, and how. The authors have done large genome-wide association studies looking for polymorphisms that affect lipoproteins, and they're following those up with clinical data on cardiovascular outcomes. Untangling the effects of HDL, LDL, triglycerides and other factors isn't easy, but they did find one mutation that appears to raise HDL alone. Looking at the people carrying that one, they find that there's no amelioration of risk in them at all. That's as opposed to the mutations that lowered LDL levels, which were consistently associated with lower risks.
This doesn't (necessarily) mean that HDL is useless as a predictor of cardiovascular risk, but it definitely means that it isn't as simple as "HDL = Good Cholesterol!". What this means for things like CETP inhibition is anyone's guess.
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