blood lipids and heart disease risk: Framingham

[eub]

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.

Comments

[bhudson.livejournal.com]

Huh; various places confirm the crown -> coronary connection (in french also). I'd have thought it would have come from the same as coeur, corazon, courage.

[mh75.livejournal.com]

My own learning on the topic, from the completely non-scientific means of listening to my co-worker who is doing her own research into the matter (smart woman, FWIW, but i'd have to get real references from her), turned up the following interesting facts:

1) People with elevated cholesterol at the time of a heart attack actually had a higher 5 year survival rate than people with normal cholesterol at the time of heart attack. (No sense of why this might be true, though.)

2) Heart problems are not as correlated to vessel congestion and they are to the quality of that congestion - you can have a severely restricted blood vessel, but it is when the plaques slough off that you run into problems. Cholesterol causes congestion, but it is not entirely clear when it converts to the type that sloughs off easily.

3) Current popular theory is that it is generalized inflammation that is the problem. High cholesterol may be a symptom of inflammation. Treatments for high cholesterol actually reduce inflammation, so the reduction of cholesterol may be coincidental to the improved outcomes.
Up and coming diet fads seem to focus on low-inflammation foods. Foods with low inflammation indices are the usual suspects (fruits, veggies, etc), and foods with high inflammation indices are also the usual suspects (animal fats, dairy).

4) The inflammation theory is being used to explain a variety of chronic diseases, including heart disease and diabetes.


Out of curiosity, do your numbers make you feel better, or worse?

[eub.livejournal.com]

Yeah, I'm going to write up something eventually about inflammation, lipid oxidation, glucose, etc.... I'd be interested in hearing a researcher's summary.

From (1) I'm not sure what can be drawn about the effect of cholesterol levels -- basically we're learning that people who have a heart attack in the absence of cholesterol must have had some other really bad news to cause that, yeah?

[mh75.livejournal.com]

To be clear, she is one of my co-workers, not a medical researcher. But she has been having bad test results, too.

It seems to me that a likely explanation is that people who have a heart attack, but no underlying diagnosable risk conditions, are less likely to make lifestyle changes or take new medication. Thus, they don't change whatever it is that led to the first heart attack. Whereas people with a diagnosable condition are encouraged to make more changes. But this doesn't seem to be a known thing.

[marzipan-pig.livejournal.com]

The inflammation thing is the hot new thing; you're supposed to floss your teeth, as there's some correlation there. My totally informal 'my public health coworker spouts off a lot' opinion is that there's a whole lot of numbers and everyone takes statins right and left, and still no one is really sure what's going on.

Don't smoke, and aim for regular exercise :)

I echo the above question but add my own spin: does looking into all of this make you feel better or worse? I wonder if finding out that recommendations aren't as based in solid science as you might have hoped will be less helpful than you've wanted?

[eub.livejournal.com]

I'm actually finding more respectable science than I thought. My baseline expectation is that we don't know crap about diet, and very little about causes of any chronic diseases. Any decent research that ties interventions to cardiac outcomes, for example, is research I actually didn't realize was out there.

My basic reason for looking into this is that if a doctor tells me "you should be healthy by doing blah blah blah stuff we all heard about on the Today show", I won't do any of that, because I know they didn't give me any new information, even if we all *already* knew, say, exercise was good for people. So this is my way of convincing myself that what I know has changed, so what I do should change too.

[3smallishmagi.livejournal.com]

I have high cholesterol, and am having trouble deciding whether statins are any good.

If you have atherosclerosis, it seems it's a good idea. Unfortunately, the most common first symptom that you have it is sudden death from a heart attack.

Statins have some negative effect. They block some chemical chain of events and stopping the production of cholesterol is only one thing it blocks.

Everyone agrees that statins lower cholesterol with relatively few side effects.

I can't find any study that shows that taking statins reduces your chance of dying. There are many studies chosen by companies who would love to have a perpetual statin drug revenue stream.

I have looked through this:
http://www.amazon.com/Fat-Cholesterol-are-Good-You/dp/919755538X/ref=sr_1_1?ie=UTF8&s=books&qid=1259741910&sr=8-1
The guys seems to be well respected and isn't quite a fanatic.

[eub.livejournal.com]

I haven't finished sorting through the research about interventions and outcomes, but I believe there is real evidence that statins reduce risk of CVD outcomes and of all-cause death. The Scandinavian simvastatin study, for example. What I don't have a sense of yet is what contradictory evidence there may be, and how it shakes out.

AFAIK there may be no evidence that any beneficial effect of statins is *because* of their effects on LDL/HDL. There may be some value to their being pharmacologically "sloppy" drugs". :)

This is in contrast to the long sad story of the fibrates, which are excellent drugs for improving LDL/HDL numbers, but after a lot of study are pretty clearly not effective drugs at saving lives. I'm not sure about niacin, but I think it may be in that boat too.

[3smallishmagi.livejournal.com]

"evaluate the effect of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease (CHD)"

The important bit is that everyone there started with heart problems. If you have heart problems, your risk of dying in 5 years goes down from 12% to 8% and your risk of having a heart attack goes down from 28% to 19%. I'd be sold on the idea of statins if I had heart disease.

(here's another study, not the one I'm looking for: http://content.nejm.org/cgi/content/full/NEJMoa0807646 )

In order to to see whether it made sense to give statins to everyone they took a bunch of Welsh men who hadn't had a heart attack and gave some of them statins. The study showed it helped. The catch though is that apparently welsh men are some of the people most likely to have heart attacks, so it was a little like taking a group of people who had heart problems (you know you're going to find a few, and you suspect from the above that you're going to help that subset by about 10%)

[eub.livejournal.com]

Ah, yeah, for people without heart disease I don't know how attractive statins look. Here's one meta-analysis, "statins in people without CV disease but with CV risk factors", that says: significant effect, but quite small reduction in absolute risk.

Here's another, "80% or more of the population without CV disease", that found significant reductions in some disease risks, but only a non-significant hint of reduction in deaths.