17
May
12

Chasing indicators, HDL edition

Derek Lowe wonders:

Spoiler warning: Not so much.

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.

My mental model for lipoproteins and atherosclerosis is very much a simple-minded thing, but I’ve never come across a mechanism for HDL lowering risk.  Seems to me, then, that high HDL levels (or more likely low LDL:HDL ratios) are correlated with improved CV health, and the elevated HDL is an indicator of some other mechanism.  Trying to replicate the indicator — raising HDL, as with this mutation — doesn’t necessarily replicate the causal mechanism.

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