Musings of a Dinosaur

A Family Doctor in solo private practice; I may be going the way of the dinosaur, but I'm not dead yet.

Tuesday, January 15, 2008

Another Nail in the Coffin of Correlation and Causation

Surprise: Zetia doesn't reduce heart attacks and strokes, even though it lowers cholesterol. The whole "cholesterol hypothesis" turns out to be exactly that: merely a hypothesis that now appears on its way into the stack labeled "Disproved."

It turns out that statin drugs like Zocor (simvastatin) and Lipitor (atorvastatin), the first drugs that meaningfully reduced cholesterol with a reasonable side effect profile (a patient asked me about cholestyramine last week; I asked if she really wanted to eat four packets of sand a day) can lower cholesterol significantly while also markedly reducing the risk of heart attacks and strokes. When I began reading evidence that it also had an impact on reducing the risk of Alzeimer's dementia, though, I said to myself, "There's probably more going on here than just cholesterol lowering."

Turns out to be exactly right.

Statins lower cholesterol. Statins decrease the risk of cardiovascular disease. Both of these are observations. Making the jump to "Lowering cholesterol lowers the risk of cardiovascular disease" turns out to be an error of confusing correlation with causation. The rooster crows and the sun comes up. Let's make even more noise; oh wait: it's midnight and the sun didn't come up? Something wrong with that formulation.

Now, of course, aren't all those "Cholesterol goals"' in the P4P schemes rendered meaningless? If I get someone's moderately elevated cholesterol down to "goal" with Zetia instead of a statin, have I really done them any good? Apparently not, but I can still get rewarded for it. If this doesn't highlight the perils of P4P, I don't know what does.

(I expected Orac to weigh in first on correlation-causation angle, though Dr. Centor has beaten him (and me) to it. On the other hand, I thought the good Dr. Centor would be the one jumping on the "Quality" issues. Ah well; the unexpected is what makes life interesting.)


At Tue Jan 15, 08:57:00 AM, Anonymous Anonymous said...

Today's rant does address the quality issue!

At Tue Jan 15, 11:53:00 AM, Blogger ccinnkeeper said...

I have for years wondered whether the high cholesterol/heart disease relationship was correlation or proven causation. Do you have any insight into that?

At Tue Jan 15, 01:59:00 PM, Blogger Midwife with a Knife said...

Don't people (the infamous "they") think that statins have some mysterious anti-inflammatory action? If so, it would make sense that they would have all sorts of random good side effects. There is evidence of inflammation being involved in atheroslcerotic plaques, too... all of those fat laden macrophages, maybe it's not the fat, maybe it's the macrophages...

At Wed Jan 16, 02:06:00 PM, Anonymous Anonymous said...

An interesting question that no one seems to be asking is if everyone who currently takes statins for primary prevention should really be. If statins work by reducing inflammation and not lowering LDL, would they benefit everyone with high LDL or only those who actually have this inflammation? Does everyone with high LDL have this inflammation?

Sure, in some high risk people, it is probably the case. But currently statins are often prescribed to everyone with LDL a little over some magic number.
Including healthy females for whom the studies that show benefit are difficult to find and whose 10-year risk of heart desease is in single digits. At least in the personal experience of this healthy fit slim-to-normal female. How many statins studies are there that address primary prevention in people with moderate risk, especially females? It seems like all of the results are extrapolated from studies on people with existing heart desease or at least with very high risk.

Just a completely uninformed question.

At Wed Jan 16, 04:22:00 PM, Anonymous Anonymous said...

Thanks for the info about cholestyramine! It's interesting to find out that high cholesterol can lead to Alzeimer's.


At Thu Jan 17, 04:54:00 PM, Anonymous Anonymous said...

It's interesting to find out that high cholesterol can lead to Alzeimer's.
Where did you get that from? The original entry said that statins may reduce risk of Alzheimer and that it was probably because they do something more than cholesterol lowering. Like maybe reducing inflammation. How do you deduce from it that cholesterol leads to Alzheimer?

Actually as this link suggests, the relationship between cholesterol and Alzheimer and between statins and Alzheimer is far from clear.

At Fri Jan 18, 09:51:00 AM, Anonymous Anonymous said...

Sorry if I wasn’t clear Diora. The "/teasing" at the end of my post was meant to indicate that I was just playing around, being ironical. I was simply demonstrating the same kind of confusion between correlation and causation addressed in Dino’s post in hopes it would give some folks a chuckle.

At Sun Jan 20, 06:47:00 PM, Anonymous Anonymous said...

Abby, sorry, I was a bit dense. Should've noticed it.


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