Does Fat in the Blood Really Clog Arteries? Rethinking What Builds Plaque
Important: This article discusses an actively contested area of research. Mainstream cardiology continues to hold that lowering LDL reduces cardiovascular events in appropriate patients, and major guidelines reflect that. Nothing here is a reason to start, stop, or change a statin or any other prescription — those decisions belong with your physician.
The lipid hypothesis begins from a simple idea: when there is more fat — cholesterol — in the blood, it clumps together into plaque, blocks the vessel, and causes cardiovascular disease. Given the background against which the theory was built, it was a reasonable thought. But there are now a good many findings pointing the other way, and I wonder how people a hundred years from now will look back on it. As someone trained in both modern pathology and Korean Traditional Medicine (KTM), the traditional healing system of Korea also known as Hanbang (한방), what interests me most is a question the hypothesis rather skips over: what actually builds the plaque?
In Summary
- Plaque is a mass inside the vessel, associated with high blood sugar, high cholesterol, high blood pressure, and endothelial abnormality; when it blocks a vessel we call it a thrombus.
- Critics of the lipid hypothesis point to work in which cholesterol-lowering treatment lowered the numbers but did not shrink calcified plaque — in one 2003 study, plaque rose about 9.2% on average in both arms.
- In my reading, the more useful question is what builds plaque in the first place: high blood sugar and inflammation (oxidation). High sugar makes blood sticky and glycates its components.
- Cholesterol works to neutralize high blood sugar and inflammation and to maintain and protect the function of the vessel lining.
- Some LDL is altered by oxidation and glycation and deposits in the vessel wall — but it was oxidized in the vessel’s stead. Blaming cholesterol for that is like blaming a wounded child for the war they were sent to.
- The field has already conceded that one LDL number is too blunt: ApoB, lipoprotein(a), non-HDL cholesterol, small dense LDL, and remnant cholesterol are all now in use or in guidelines.
- This remains debated, and the mainstream position differs. Do not change medication on the strength of an essay.
What the Plaque Studies Asked
First, a definition. Plaque is a mass within a blood vessel; it is understood to form in the presence of high blood sugar, high cholesterol, high blood pressure, and abnormalities of the vessel lining, and when it blocks the vessel we call the blockage a thrombus.
Now the question that interested me. Suppose we step back and grant, for argument’s sake, the critics’ claim that statins do not meaningfully lower cardiovascular mortality except in a fairly narrow group. Surely, one might think, they at least shrink the plaque? Even if they do not save lives, that would be a long-term gain in quality of life. The cardiologist Stephen Sinatra, in his book on cholesterol numbers, points to a 2003 study in which 182 patients were treated either with a statin alone or a statin plus niacin, and their plaque assessed by electron-beam tomography one to two years later. As in many other studies, the cholesterol-lowering treatment did lower cholesterol. And the plaque? It did not decrease. The researchers reported that cholesterol levels improved substantially while there was no change in the development of calcified plaque — in fact plaque rose by an average of about 9.2% in both groups — and concluded that the notion of “lower is better” for LDL does not track the behaviour of calcified plaque. I should be clear that this is one study within a large and contested literature, and that defenders of LDL-lowering point to a great deal of other evidence; but it is a finding worth sitting with rather than waving away.
So What Does Build Plaque?
Here is where I think the more interesting answer lies: high blood sugar, and inflammatory (oxidative) reactions. For high blood sugar, simply think of sugar. It makes the blood sticky and glycates the components within it, and out of that process plaque is made.
Cholesterol, meanwhile, is doing something rather different from what its reputation suggests. It works to neutralize high blood sugar and the inflammatory reaction, and to maintain and protect the function of the vascular endothelium. Some portion of LDL cholesterol, as a result of oxidation and glycation, changes its form, deposits in the vessel wall, and can go on to form atheroma and thrombus. But cholesterol itself is not the villain in that story: it was oxidized in place of our blood vessels, in order to protect them. To turn around and call cholesterol itself bad, on that evidence, seems to me a mistake. A child who comes home wounded from the battlefield is not the cause of the war.
Screening Is Already Moving Beyond a Single LDL Number
The encouraging part of this story is that the field has not stood still. The complaint that one LDL-C figure is too blunt an instrument is no longer a fringe position — alternatives are already proposed, validated, and in some cases written into guidelines.
ApoB (apolipoprotein B) counts the atherogenic particles rather than the cholesterol they carry, and a 2025 body of evidence has found it a more accurate predictor of cardiovascular events than LDL-C or non-HDL cholesterol. Where the two disagree — which happens often in metabolic syndrome, diabetes, or high triglycerides — ApoB is the better predictor: in the CARDIA cohort, young adults with high ApoB but normal LDL-C had roughly 55% higher risk of coronary artery calcification 25 years later, while those with high LDL-C but normal ApoB did not. The European Society of Cardiology and the Canadian Cardiovascular Society have recommended ApoB over LDL-C for risk assessment and treatment targets.
Lipoprotein(a) is largely genetically set and is now recommended for measurement at least once in adult life, precisely for the cases where a standard lipid panel fails to explain someone’s atherosclerotic burden. Non-HDL cholesterol is long established as a target, and small dense LDL and remnant cholesterol are both recognised as carrying risk even when LDL-C reads “normal” — which is the whole point: the particle’s character matters, not just the total.
My own guess was that screening would eventually split LDL into normal versus oxidized cholesterol. Oxidized LDL remains largely a research measure rather than a routine test, so that specific split has not arrived. But the underlying direction — that a single LDL number tells you too little about what is actually happening in the vessel — is one the field has already conceded and acted on.
In Summary
The lipid hypothesis is a reasonable idea whose foundations are more contested than its confidence suggests, and at least some evidence shows cholesterol falling while plaque does not. The more useful question is what builds plaque — high blood sugar and oxidative inflammation — and in that picture cholesterol looks less like the arsonist and more like the firefighter who got burned. Encouragingly, screening is already moving past the single LDL number toward ApoB, Lp(a), non-HDL, and particle character. That said, this is a live scientific debate in which the mainstream position still favours LDL-lowering for appropriate patients, and none of it is a basis for changing your own treatment. Take the mechanism as food for thought, take the sugar seriously, and take the medication questions to your doctor.
Related reading: Cholesterol and Jing (정 精) · Why Chewing Matters
This article reflects the clinical observations and teaching practice of Professor Seungho Baek, Professor of Korean Medicine at Dongguk University College of Korean Medicine, specializing in Pathology and Oncology.
