Image by Narupon Promvichai from Pixabay
It’s conventional wisdom that cholesterol is bad for you, because cholesterol causes heart disease, including heart attacks and strokes. That is the rationale behind the fact that statins are the most prescribed drug in America.
But, there’s plenty of evidence that while statins work to lower cholesterol levels, they do not, in fact, decrease risk of heart disease. In fact, there is apparently no evidence that cholesterol is a causative factor in heart disease… and furthermore, statins can actually cause heart disease.
If that’s true, and yet heart disease is still the number one killer in America, what’s the real cause—or, since there can be many external causes (sugar, smoking, stress, etc), what’s the real internal mechanism that all of these triggers have in common?
Cholesterol Doesn’t Cause Heart Disease
As mentioned above, there’s actually quite a bit of evidence that cholesterol doesn’t cause heart disease, after all—and we’ve known it for a long time.
This enormous study from the late 60s and early 70s demonstrates that, while decreasing saturated fat led to decreased cholesterol, this effect not only failed to decrease cardiovascular risk—it actually increased all cause mortality. The results segment reads: “There was a 22% higher risk of death for each 30 mg/dL (0.78 mmol/L) reduction in serum cholesterol.”
This study, analyzing data from the late 60s and early 70s, but only published in 2012, likewise found that removing saturated fats and increasing polyunsaturated fats from safflower oil effectively lowered cholesterol, but produced a 62% increase in all cause mortality.
The same findings appear again and again. This paper analyzed 19 studies, representing a total of over 68,000 people over 60 years of age. The conclusion was that elevated LDL-C is inversely correlated with all cause mortality, for that population at least.
What that appears to suggest is that higher cholesterol is actually, somehow, protective.
So Why Did We Think Cholesterol Was the Cause?
We thought cholesterol was the culprit for heart disease because—we thought—cholesterol was a major component of cardiovascular plaques upon analysis.
The first problem with this reasoning is that it assumes a causal relationship. The presence of cholesterol in a plaque wouldn’t necessarily mean that cholesterol caused the plaque.
The second problem is that, while there is some “cholesterol” found in plaques, it turns out that the major component in plaques is actually either cholesterol crystals (more on this below) or Lp(a)—not LDL, the “bad” cholesterol we measure on routine labs. LDL and Lp(a) are indistinguishable except for one thing: Lp(a) has an apolipoprotein on it (a protein sticking out of its membrane) called apolipoprotein a. Anybody not specifically looking for apo(a) would find what looks for all the world like LDL.
So does Lp(a) cause heart disease then? Well, not quite. Again, correlation is not causation.
Then What Does Cause Heart Disease?
We’ve known for some time that damage to the lining of an artery is the instigating factor for plaque formation. The question is, what happens in between?
When you cut your skin, the first thing that happens is formation of a clot. The same clotting cascade gets initiated if you damage your arteries. Just like when your skin heals — first you scab, and then new skin heals over it. The same is true of the arteries. As long as your body has the time in between insults to heal the damage adequately, there’s no plaque formation.
But what if you peel off a scab before it’s done healing—or worse, you re-injure that same spot when the scab has barely formed? This sets off the clotting cascade anew, and you end up with not only more damage, but more swelling and a bigger clot than you started out with. This same thing in the arteries has been shown to rapidly accelerate plaque progression in heart disease, as well as narrowing of the arteries (stenosis).
So the clotting process appears to be the primary culprit, set off by repeated injury to the endothelial (blood vessel) lining, and re-injured before it can completely heal.
How does Lp(a) factor into this? Vitamin C is necessary for repair of collagen, which (among other things) is the main building block of blood vessels. If levels of Vitamin C are too low to do the job, Lp(a) acts as a stand-in: grabbing on to amino acids exposed in the endothelial lining due to collagen damage, and initiating the clotting process. Once begun, this process pulls in all kinds of things to form part of the clot matrix, including red blood cells and platelets as well. Those with higher levels of Lp(a) are at greater risk of this process from any endothelial damage, just because more of it happens to be floating around, looking for damage to repair—and the levels of Lp(a) are genetically determined and not dietary. They’re also totally unrelated to LDL levels (and unaffected by statins).
Remember those cholesterol crystals mentioned above? They are definitely not from LDL, since LDL carries only cholesterol esters—but they are found in red blood cell membranes. And it certainly appears that the cholesterol found in plaques does come from red blood cells—which further implies that clotting is the true cause of plaque formation.
What Damages the Arteries, Leading to Clot Formation?
So if clotting (repeated, or insufficiently healed) is the real culprit for heart disease, what causes the damage that triggers the clotting in the first place?
These we’ve known for some time. Damage to the vasculature can come from chronically elevated blood sugar, such as in metabolic syndrome and diabetes.
It can occur from Advanced Glycosylated End Products (AGEs).
It can occur from increased uric acid, which is largely dietary.
It can come from aerosolized particles such as smoke (from cigarettes, wood fires, wild fires, etc), as well as excessive air pollution.
It can come from heavy metal toxicity, particularly from lead which has been shown to increase clotting in the endothelium.
It can come from increased cortisol levels—so basically, anything that induces chronic stress. Elevated cortisol occurs in response to stress, which leads to insulin resistance, which leads to high glucose (see the first cause). In addition to this, cortisol also directly increases clotting, which has been shown to lead to heart disease.
The cholesterol hypothesis has persisted as the primary cause of heart disease. Not only does the evidence not bear this out, but it instead points to clotting as an underlying cause.
We already knew most of the risk factors for the initial endothelial damage. But it appears that the emphasis upon decreasing cholesterol has been misplaced, at best.