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LDL cholesterol particles

Ashley Rivers, MD

As we all know cholesterol is a fat and does not dissolve in water. A blood test for cholesterol samples the water half of the blood, the serum. Clearly a conundrum — we test the water half of the blood for a substance that cannot dissolve in water.

This puzzle was solved in 1985 by two scientists in Texas who received the Nobel Prize for their work. Their discovery was that animal livers, including humans, solve this problem by wrapping cholesterol in a protective shell made of cell membrane to make an “LDL particle.” The particles can dissolve in the serum whereas the cholesterol molecules inside the particle cannot.

This is a totally different concept. Think of it, your serum has enormous numbers of microscopic “LDL particles,” each containing one to two thousand cholesterol molecules, but there is not a single cholesterol molecule dissolved by itself in the serum.

Next new concept: atherosclerotic plaque is not caused by LDL cholesterol molecules crossing from the blood into the arterial wall, since there are no LDL-C molecules in the serum. Instead plaque is formed by LDL cholesterol particles crossing from the blood into the arterial wall.

Large amounts of clinical research studies have now shown that LDL cholesterol levels do a very poor job of predicting the risk of a cardiovascular event. In fact these studies show that all of the risk tracks with how high your LDL-cholesterol particle (LDL-P) level is, and very little with a simple LCL-C cholesterol (LDL-C) level.

A relevant clinical study was published in 2009 by four Cardiologists from UCLA. They measured LDL-C levels on admission in over 100,000 Medicare patients presenting with a heart attack. The data showed that over three out of four of these MI patients had an LDL-C of less than 100, and one third had an LDL-C of under 70.

Clearly if you have an LDL-C of 100, and want to believe that you are unlikely to have an MI (myocardial infarction), maybe you should think harder.

Many of the patients seen in my office have low LDL-C levels and very high LDL-P. The patients we see who have had an MI, or needed a stent or CABG, or have carotid artery or peripheral arterial vascular disease rarely have an LDL-P of under 500. Many have LDL-P levels near the national average of 800, but often the LDL-P level is much higher, such as 1500 to 3000.

You might ask why do people end up with elevated LDL-P levels, make plaque and have heart attacks or strokes? Research studies have shown that the explanation for an elevated LDL-P particle is generally not due to overproduction of particles. The real reason for an elevated particle level is the presence of any of numerous genetic DNA defects that alter the code for the complex mechanism for LDL-P removal, such as the LDL-P receptor which is responsible for pulling excess LDL particles back into the liver cells. If the removal system does not work the particle level rises.

It should be clear that an elevated cholesterol particle level is due to a genetic disorder of liver metabolism. It is inherited from one’s parents, requires aggressive medical treatment, and is not caused by a bad diet or lack of exercise.

Over the past six months I have treated three patients below the age of 30, who presented to the ER with an MI. All had extensive family histories of MI or stroke at a very young age. All three of these patients had an LDL-C of less than 100, and an LDL-particle level of close to 2000.

Although the ACC and the AHA pretty much ignore LDL particle levels, the two lipid specialty societies strongly urge physicians to screen patients at high risk, such as those with an extensive family history, diabetics and smokers, with an LDL particle test, and use it to guide treatment.

If you would like more information about particle testing or any other heart issue you may have please call my office at 624-0400 to make an appointment.


Ashley Rivers, MD is with Eastern New Mexico Medical Group-Heart, Vascular and Vein Specialists. The advice offered in this column is that of the author.