The disease risk associated with blood lipids appears to be in cardiovascular disease, such as heart attack and stroke. I think that atherosclerosis (arterial plaques) is the mechanism here, but I don't actually have anything laying that out.

Abbreviations:
  • the "coronary arteries" are the arteries serving the heart muscle itself -- apparently shaped like a crown.
  • CHD: coronary heart disease.
  • CVD: cardiovascular disease, including not in the coronary arteries.

So, how do blood lipids compare with other risk factors for CVD?

The Framingham study is a cohort study of some thousands of people in Framingham, Massachusetts, tracking CVD development. See a 1998 American Heart Association summary of findings, which I have only skimmed.

Framingham has generated handy tables by which you can add up points and estimate your risk of "general CVD", "hard coronary heart disease" (heart attack or sudden coronary death), whatever's your pleasure. It's an interesting exercise.

Any additive point scale like this is going to be an approximation of the study's underlying data (the AHA article comments on this), but let's say it's reasonable. Then we can compare the point difference (low HDL - high HDL) vs. (smoking - nonsmoking), for example, to get an idea of whether low HDL is "as bad as smoking" in terms of modeled risk ratio.

For 10-year CVD risk in men (they have data for women, too, but I'm focusing on the data that covers me):
  • HDL, 30 vs. 65: 4 points. (Points are bad, mkay.)
  • Total cholesterol, 290 vs. 150: 4 points.
  • Systolic blood pressure (pre-treatment), 165 vs. 110: 5 points.
  • (And they have a factor for post-treatment blood pressure. I think you add in just one or the other, but I'm not certain.)
  • Smoking: 4 points.
  • Diabetes: 3 points.
  • Aging from 32 to 42: 5 points.
  • Aging from 42 to 62: 6 points.
We can probably pool the "Total cholesterol" and "HDL" factors and call that LDL/HDL ratio. It's a significant factor, but it's far from all of the non-aging risk variation: it's 40% of it. Blood pressure is a big deal -- and bigger in women.

Or for 10-year hard CHD risk in men:
  • HDL, 30 vs. 65: 3 points.
  • Total cholesterol, in 40-45 age range, 290 vs. 150: 8 points.
  • Systolic blood pressure (pre-treatment), 165 vs. 110: 2 points.
  • Smoking: 5 points.
  • Diabetes: excluded from the population for this model, for some reason.
Here, once we discard smoking as a bad idea, the Big Ugly is total cholesterol. (Or maybe it's really LDL, or triglycerides, which would correlate highly and are not reported separately here.)

Big disclaimer #1: I believe all of this is about observed risk association -- outcomes in subpopulations with various values of each factor. That doesn't say anything about causality, at all. Or about how intervening to change a factor might affect outcomes. (These risk numbers are still interesting to me, though, because they're a rough upper bound on the causal impact of each factor: for a factor's caused risk to exceed its observed risk, you'd need to have it correlated with a counteracting factor, which just doesn't sound terribly prevalent.)

Big disclaimer #2: I haven't looked into any systemic issues with the Framingham study itself.

Notes for future posts:
  • CVD outcomes from lipid interventions, e.g. fibrates vs. statins.
  • poking into mechanism and intermediate processes: inflammation, lipid peroxidation, blood glucose level.
  • rancidity, homocysteine, exercise.

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Eli

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