Heart Attacks Hinge on LDL Cholesterol Particle Number (LDL-P)

medical clearance, treadmill stress test

This treadmill stress test is looking for hidden heart disease

…according to Drs. Thomas Dayspring and James Underberg. I don’t know if these guys are right or not. I bet it’s more complicated than LDL particle number. I’m always skeptical of grand unification theories.

People with diabetes tend to have shorter life spans than average. One reason is a predisposition to heart disease, specifically coronary artery disease that leads to heart attacks.

Most heart attacks (aka myocardial infarctions) do indeed seem to be caused by acute rupture of an atherosclerotic plaque that’s been present for years. Two key questions are:

  1. What causes the plaque?
  2. Why causes it to rupture?

Underberg and Dayspring write:

The only absolute requirement for plaque development is the presence of cholesterol in the artery: although there are additional heart risk factors like smoking, hypertension, obesity, family history, diabetes, kidney disease, etc., none of those need to be present. Unfortunately, measuring cholesterol in the blood, where it cannot cause plaque, until recently has been the standard of risk-testing. That belief was erroneous and we now have much better biomarkers to use for CV risk-assessment. The graveyard and coronary care units are filled with individuals whose pre-death cholesterol levels were perfect. We now understand that the major way cholesterol gets into the arteries is as a passenger, in protein-enwrapped particles, called lipoproteins.

Particle entry into the artery wall is driven by the amount of particles (particle number) not by how much cholesterol they contain. Coronary heart disease is very often found in those with normal total or LDL-cholesterol (LDL-C) levels in the presence of a high LDL particle number (LDL-P). By far, the most common underlying condition that increases LDL particle concentration is insulin resistance, or prediabetes, a state where the body actually resists the action of the sugar controlling hormone insulin. This is the most common scenario where patients have significant heart attack risk with perfectly normal cholesterol levels. The good news is that we can easily fix this, sometimes without medication. The key to understanding how comes with the knowledge that the driving forces are dietary carbohydrates, especially fructose and high-fructose corn syrup. In the past, we’ve often been told that elimination of saturated fats from the diet would help solve the problem. That was bad advice. The fact is that until those predisposed to insulin resistance drastically reduce their carbohydrate intake, sudden deaths from coronary heart disease and the exploding diabetes epidemic will continue to prematurely kill those so afflicted.


 And for goodness’ sake, if you want to live longer, start reducing the amount of dietary carbohydrates, including bread, potatoes, rice, soda and sweetened beverages (including fruit juices), cereal, candy – the list is large).

Read the whole enchilada.

Offhand, I don’t recall any clinical study looking at LDL cholesterol particle number in folks who switched to a paleo diet. Given the prominence of coronary heart disease, I’m sure Dayspring and Underberg would favor a low-carb version of the paleo diet for anyone going the paleo route. Here’s my version of low-carb paleo.

Underberg and Dayspring don’t mention LDL particle size, such as small/dense and large/fluffy; the former are thought by many to be much more highly atherogenic, while the latter may not be at all. Is this idea outdated?

Whoever figures out the immediate cause of plaque rupture and how to reliably prevent it will win a Nobel Prize in Medicine.

Steve Parker, M.D.

About Dayspring and Underberg:

Thomas Dayspring MD, FACP, FNLA   Director of Cardiovascular Education, The Foundation for Health Improvement and Technology, Richmond, VA. Clinical Assistant Professor of Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School.

James Underberg MD, FACP, FNLA   Clinical Assistant Professor of Medicine in the Division of General Internal Medicine at NYU Medical School and the NYU Center for Cardiovascular Disease Prevention . Director of the Bellevue Hospital Primary Care Lipid Management Clinic.

h/t Dr. Axel Sigurdsson

3 responses to “Heart Attacks Hinge on LDL Cholesterol Particle Number (LDL-P)

  1. Charles Grashow



    The LDL-P number indicates the total number of LDL particles floating around in my bloodstream. As you can see, there has been a precipitous rise in this number peaking at 3,451 in October 2012. But check out what has happened in the past six months–the LDL-P dropped to 2,730, or 721 points! That’s a whopping 21% DECREASE.

    So – even though his LDl-P dropped it’s still WAY TOO HIGH – per Dr Dayspring it should be <1,000

    Your thoughts

  2. Here’s an animal model of atherosclerosis in a genetically hyperlipidemic mouse. It naturally produces a high small-particle LDL count (high TGs, high LDL).
    It develops atherosclerosis when the gut wall is weakened and excess LPS (cell wall fragment from gram -ve bacteria like E. Coli) enters the blood.
    i.e., inflammation plus high LDL-P = atherosclerosis.
    The atherosclerosis is prevented when a probiotic is fed, which reduces the LPS count without changing the lipid counts.
    Ergo, high LDL-P may (arguably) be a precondition for atherosclerosis, but inflammation – excessive LPS translocation from leaky gut and dysbiosis – is the trigger.
    Particulate air pollution is also associated with atherosclerosis and – guess what:
    Particulate matter air pollution causes oxidant-mediated increase in gut permeability in mice.

  3. With regard to LDL-P, Dr. Peter Attia’s personal site has a detailed, multi-part series about cholesterol, including an in-depth discussion of the different blood lipid types. It’s long, gets pretty technical, and it’s interesting. Start here: http://eatingacademy.com/nutrition/what-is-cholesterol