> Of 1000 people treated with a statin for five years, 18 would avoid a major CVD event which compares well with other treatments used for preventing cardiovascular disease. Taking statins did not increase the risk of serious adverse effects such as cancer. Statins are likely to be cost-effective in primary prevention.
> Fourteen trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All‐cause mortality was reduced by statins (OR 0.86, 95% CI 0.79 to 0.94); as was combined fatal and non‐fatal CVD RR 0.75 (95% CI 0.70 to 0.81), combined fatal and non‐fatal CHD events RR 0.73 (95% CI 0.67 to 0.80) and combined fatal and non‐fatal stroke (RR 0.78, 95% CI 0.68 to 0.89). Reduction of revascularisation rates (RR 0.62, 95% CI 0.54 to 0.72) was also seen.
So the evidence base is a collection of studies where most of the participants had at least one prior indicator of CVD or diabetes, and their outcome is a relatively weak benefit to all-cause mortality, CVD, CHD and stroke. For primary prevention, what you really want is a strong outcome in a study of people without any prior indication of disease [1].
I think the article posted by parent is exaggerating, but even the Cochrane review is pulling its punches here, saying specifically "cost-effective in primary prevention", instead of the stronger claim. Common jokes about putting statins in the water supply aside, there's not a ton of evidence for giving them to, say, otherwise healthy 20-somethings.
[1] Imagine the following, not-uncommon scenario: you have an otherwise healthy patient who is both pre-diabetic, as well as presenting with elevated cholesterol. Statins have a tendency to elevate blood glucose. So which risk do you choose?
The available evidence provides poor guidance.
Lack of data doesn't mean the treatment won't work. There is plenty of reason to think statins work for primary prevention even though it hasn't been proved yet. For most the side effects are acceptable, and the cost is low. Thus for most it is worth trying as primary prevention even if we don't have data to show it works. Remember you are playing with your own life here, and the best evidence we have is on the side of stains for primary prevention - this may change in the future when we get data of course.
In drug development, that is the default presumption, and rightfully so: almost nothing ever works.
> There is plenty of reason to think statins work for primary prevention even though it hasn't been proved yet.
Define "primary prevention" -- do you propose giving this to a healthy 20 year old with no other signs of illness? Younger? Should we "put it in the water", as they say? How about older patients? How old? Or, do you mean someone with symptoms? If so, then what about the case I cited (which is quite common in "primary prevention") where you have multiple things in tension?
The evidence provides no guidance here, and anyone who tells you otherwise is guessing. For what it's worth, though, we agree completely on the need for larger data. I think what drives me most batty about the "appeal to consensus" is that it's almost invariably used as a highbrow-lowbrow way of beating up on people who want to ask the question, which is the first step toward getting the answer!
Lowering cholesterol lowers the amount of oxidized cholesterol that is caused from inflammation. The fact is is that in inflammation is the fundamental disorder, not high cholesterol on its own.
pubmed.ncbi.nlm.nih.gov/18625445/
Oxidative modification of low-density lipoprotein (LDL) is one of the earliest events in atherosclerosis.
https://www.frontiersin.org/journals/cardiovascular-medicine...
The point of the original article is we should be focusing more on lowering oxidative stress (inflammation) instead of focusing on lowering cholesterol since 75% of people who have heart attacks have normal cholesterol.
Also, CVD mortality is lowered, but other causes of death increase.
We have MVMR studies that look at multiple variables
https://journals.plos.org/plosmedicine/article%3Fid%3D10.137...
https://www.thelancet.com/journals/lanhl/article/PIIS2666-75...
Some MR looking specifically at CRP actually dispute the idea of a causal link altogether
https://www.bmj.com/content/342/bmj.d548
https://www.ahajournals.org/doi/10.1161/01.atv.0000258869.48...
Factorial MR show strong evidence that the risk is additive, in the case of these that look at atherogenic particles and IL-6 signaling
https://www.ahajournals.org/doi/10.1161/JAHA.121.023277
MR looking at specific genes that reduce LDL-C through a variety of mechanisms, including some that lower inflammation, show basically identical reduction of risk per LDL-C lowered.
However, I’m not aware of any evidence showing that higher oxLDL vs higher LDL entails greater risk. IIRC there is a paper that compared oxLDL to ApoB where ApoB was more strongly associated with risk, which doesn’t seem like it would be expected on your hypothesis.
The response to retention hypothesis and the mechanistic evidence supporting it point to oxidation being inevitable once ApoB tagged lipoproteins are trapped in the arterial wall. That being the case, it would be moot whether it entered the wall in an oxidised state or not.
So yes, oxLDL is one of the early stages of atherogenesis, but I’m not aware of any evidence that having LDL pre-oxidised before it’s trapped vs regular LDL increases risk.
I’m always open to new evidence that would change my view, but that’s my understanding of the research landscape at the moment.
What the BMJ has to say on this very topic of statins:
https://www.bmj.com/campaign/statins-open-data
So no settled science here.
And remember that the largest ever study on saturated fat and cholesterol lowering was just not published by their original author because it didn't proove their hypothesis.