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Comment by mrfusion | Hacker News Reader

It mentions statins as something obviously good but is there any evidence they're actually beneficial? I thought cholesterol was good now?

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LDL cholesterol and triglycerides are harmful. Higher values of those cause higher risk of coronary artery disease and earlier death. HDL cholesterol ("good cholesterol") appears to have no effect, at least the scalar quantity that we measure with current lab tests.

Statins reduce risk of death in proportion to their reduction of LDL cholesterol, so most likely this effect is a consequence of decreased LDL cholesterol.

Not sure why you say HDL has no effect. Ratios of "bad" to "good" markers have been shown to be much better predictors of risk than any one number on its own, even LDL.

https://www.youtube.com/watch?v=YRFRRqe0vrE&t=924s

You should also take a look at the latest risk calculator derived from the Framingham Heart Study. It's basically a multivariate regression of various risk factors against CVD risk. Total cholesterol and HDL are inputs, while trigs and LDL aren't used. They do of course factor into total cholesterol, but the researchers specifically stated that "The use of low-density lipoprotein cholesterol did not improve model fit or performance."

http://circ.ahajournals.org/content/117/6/743.long

Some doctors and researchers believe the benefit from statins is more to do with the decrease in inflammation caused by them. Possibly widespread use of statins has beneficial effects on other disease processes too.

Yeah I think there was a large study done comparing a newer cholesterol lowering drug with statins. The result was the new non-statin drug wasn't effective at all even though it lowered cholesterol levels.

You might be thinking of CETP inhibitors. This class of drug modifies cholesterol levels to numbers associated with better health, but so far none of them have conclusively improved health outcomes:

https://en.wikipedia.org/wiki/CETP_inhibitor

Anacetrapib is still in stage III trials so it's too early to consider the concept a failure, but I think the bad results so far are evidence that hyperlipidemia is a symptom not a cause of cardiovascular disease, and that statins have some mechanism of action beyond just modifying cholesterol levels (eg. anti-inflammatory, as some people have suggested).

Yes those drugs. Hard to say conclusively, but the failure of most of CETP inhibitors is troubling news for the hyperlipidemia theory. Meaning possible hyperlipidemia has multiple causes and in and of itself isn't bad.

AKA

Cause A results in hyperlipidemia.

Cause B results in hyperlipidemia.

Cause C results in hyperlipidemia and arterial plaques.

Cause D results in hyperlipidemia.

Numerous lines of evidence, including randomized controlled trials, single gene studies, and Mendelian randomization studies, are not consistent with your interpretation.

Multiple agents that reduce cholesterol, including ezetemibe and statins, reduce cardiovascular disease outcomes and death.

Multiple cholesterol-related genes, including HMGCR, LDLR, APOB, PCSK9, and ANGPTL3, contain variants which influence both LDL cholesterol and the risk for coronary artery disease, myocardial infarction, and death.

And Mendelian randomization studies that rely upon a dose-response relationship between genes that influence cholesterol and the cardiovascular outcomes that they cause have also demonstrated a link between genetically driven cholesterol levels and hard endpoints.

So, one set of drugs (CETP inhibitors) that don't seem to follow the story are more likely to be the exception, rather than the rule. Interesting biology awaits us in the explanation of why the CETP inhibitors don't do what we imagined they would with hard outcomes.

> reduce cardiovascular disease outcomes and death.

Only in small selected populations.

However, non-steroidal antiinflamatories are linked to cancer.

LDL is still "bad" and HDL is still "good", but that means in your blood, not your diet. The evidence linking dietary cholesterol and saturated fat to cardiovascular disease is weak.

Dr. Peter Attia provides an excellent summary of the topic here: https://www.youtube.com/watch?v=nhzV-J1h0do

Citation?

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