ApoB, plaque, and when to start treating heart disease

In this episode of The Proof, Simon Hill brings together two leading lipidologists, Tom Dayspring and Dan Soffer, to talk about primary prevention of cardiovascular disease. Atherosclerosis is close to universal: we all develop it to some degree, but at very different rates. The question is not whether you have plaque, it is how fast it builds and what to do about it.

What atherosclerosis actually is

The blood carries lipoproteins that hold the protein ApoB. Most can cross the wall of the artery, and once inside they are transformed and trigger the white blood cells in the wall to consume them. That cholesterol filled white blood cell becomes a foam cell, and that is the start of plaque. The process repeats millions of times over a lifetime, with some processes slowing it and others speeding it up. Eventually the plaque grows, changes the structure of the artery, and can narrow blood flow.

Why ApoB is the necessary ingredient

Two people with the same apparent risk factors can end up with one loaded with plaque and the other with none, because there are many susceptibility variables we still cannot measure. But the starting point is always the same. Without ApoB particles depositing cholesterol in the wall, there is no atherosclerosis, no matter how many other risk factors you carry. Clinical trials, epidemiology, and Mendelian randomization agree: lowering ApoB and LDL cholesterol reduces events, and it kept reducing them even going from 70 to 15 mg/dL. ApoB is also a very powerful risk indicator at the extremes, very high or very low.

How much do genes matter

A lot, but not everything. Familial hypercholesterolemia is an example of a single gene disorder with a large effect. Outside those cases, the single worst gene variant for atherosclerosis has a hazard ratio below 1.5, meaning less than a 50 percent rise in risk. High blood pressure, smoking, or diabetes each multiply risk by two to four. Real genetic risk is polygenic, what the guests call death by a thousand paper cuts. The clear exception is Lp(a), heavily gene driven, which should be measured at least once in a lifetime.

Primordial, primary, secondary

Dayspring proposes a ladder. Primordial prevention: clean arteries, the goal is a good lifestyle from childhood. Primary prevention: high biomarkers already show up, ApoB, blood pressure, glucose, or a bad family history, and you act harder. Secondary prevention: there is visible subclinical plaque on imaging. Tertiary prevention: a heart attack, bypass, or stroke has already happened. The label primary prevention lumps the 25 year old vegan runner with no risk factors together with the 65 year old diabetic smoker with a calcium score of 3,000, which is why the detail matters.

Reading your risk

The 2026 dyslipidemia guideline recommends the PREVENT calculator, which now covers ages 30 to 79 and gives a 30 year risk, and adds kidney function and zip code as a marker of social and economic stress. Alongside it are risk enhancing factors and imaging. A calcium score only sees calcified plaque; coronary CT angiography detects more, though a pristine coronary does not guarantee an absence of plaque in other territories. Carotid intima media thickness has fallen out of favor for poor reproducibility.

ApoB years and the 5000 threshold

An emerging tool is LDL cholesterol years or ApoB years: multiply your age by your level. When the product reaches around 5,000 mg/dL years, the plaque burden already represents real risk. A 12 year old with an LDL of 230 has already crossed that threshold, which is why they need early attention.

When to start treatment

There is no single number for everyone. The principle is lower for longer is better, and treatment intensity should match the disease burden. In a 35 year old with an ApoB of 90, a bad family history, and no plaque on imaging, Dayspring still leans toward treating with a low dose statin plus ezetimibe, very safe and cheap drugs, to take ApoB from 90 to 60. If Lp(a) is high or plaque is visible, he gets more aggressive. If the patient prefers not to medicate and there is no class one recommendation, it is reasonable to review yearly and repeat imaging in three to seven years. Statins are first line per the guideline; Dayspring first checks cholesterol synthesis and absorption to choose.

Where to begin

Check blood pressure and waist size, get a standard lipid panel, and add an ApoB and an Lp(a) at least once in a lifetime. Assess the risk, personalize it, and re-evaluate. The foundation for slowing progression is the eight pillars of Life's Essential 8, and drug therapy is chosen on top of that per case.

Bottom line

Atherosclerosis is a process almost all of us share, but not all of us have to die from it. Knowing your ApoB, your Lp(a), and your plaque burden lets you decide with data when lifestyle is enough and when adding a drug is worth it, the earlier the better if risk is high.