I would just like to recap the lipid hypothesis for a moment. The basic idea is that an elevated level of LDL cholesterol, estimated by the Friedewald equation, makes these lipoprotein particles stick to your arterial walls, causes plaque to develop and eventually rupture. Saturated fat is the main dietary cause of heart disease because it is purported to elevate LDL cholesterol.
The key to treating heart disease is to lower LDL to below some arbitrary figure, mostly determined by the need for profit of Astra Zeneca or their ilk.
The most effective drugs to do this are the statins, which inhibit the synthesis of a basic metabolic precursor of many substances, one of which happens to be cholesterol. All tissues, particularly the liver, are then so desperate for cholesterol that they up-regulate the expression of genes coding for the LDL receptor and so pull in as much cholesterol as they can get by ingesting circulating LDL particles.
This lowering of LDL lipoproteins by statins is what is supposed to protect against, and even reverse, arteriosclerosis. Although some cardiologists accept that statins do have other effects, the lipid hypothesis says that dropping LDL is the core effect.
So, while taking a statin drug, we have cholesterol depleted cells sporting every LDL receptor they can muster to make up their deficit and this leads to a fall in plasma LDL level. Instead of there being 100 LDL particles per unit volume of blood there are now only 60 LDL particles, and hey presto, atheromatous plaque suddenly starts throwing its rancid lipids back in to those few LDL particles which still remain in the circulation!
Summary: At an LDL of 100mg/dl cholesterol packs in to arterial walls, at an LDL of 60mg/dl this very same lipoprotein becomes a magical hoover, sucking oxidised lipids out of the arterial wall.
You can even measure how good the statin is by how much oxidised phospholipid there is in your LDL lipoproteins!
If this seems to be a little far fetched, you are obviously not a cardiologist! Just check out here and here.
It is simply a fact that statinating people routinely increases the degree of oxidation of their few remaining LDL particles. Because statins are good, this change must be good too. It must be a marker of atheroma regression!
If the concept of an LDL particle sucking oxidised phospholipids out of atheroma sounds implausible, what is happening in statinated people to elevate their oxLDL? Is it good or bad?
Unadulterated LDL is non artherogenic and is taken up readily by cells which need cholesterol via their LDL receptors. Oxidised LDL is atherogenic but is NOT taken up by the LDL receptor because the glycation of the apoB100 protein, which also leads to LDL oxidation, stops it interacting with the LDL receptor.
So oxLDL tends to be left in the circulation while native LDL is taken up by cells affected by statins. There may be less oxLDL, but what is left is very sticky.
Perhaps this is good? Personally, while I think there are all sorts of considerations here, the overall answer seems to be that oxLDL is a Bad Thing. If you take a person who is exquisitely sensitive to simvastatin you can drop their TC from > 260mg/dl to < 160mg/dl. This will probably give an LDL of around 80mg/dl. And a six times greater risk of cardiovascular death than if their TC only dropped to 210mg/dl. Much of that residual LDL with be highly oxidised
An LDL of 60-80mg/dl, produced by removing ONLY the non-atherogenic component of LDL from the plasma, is going to be bad news. This is what statins do.
Never mind Nissen and his 500 victims, look at J-LIT and the 50,000. This gives a much better idea of what having a circulation with no LDL other than oxLDL does for you.
Does it seem incomprehensible that we could have made such a mistake with statins?
Yes, I think so.