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Using Apolipoprotein B To Help Determine Your Risk For Heart Disease

A Better Way To Determine Cardiovascular Risk

ApoB To Help Determine Risk For Heart Disease
Using ApoB To Help Determine Risk For Heart Disease

ASCVD (atherosclerotic cardiovascular disease) is the leading cause of death in both men and women. Unfortunately, the relationship between cholesterol and heart disease turns out to be a bit more complicated than we originally thought... As far back as the 1940s, scientists established a link between cholesterol and cardiovascular disease. At first, the relationship seemed straightforward: high cholesterol equaled high risk of heart disease. But later it was discovered that there were different kinds of cholesterol, and the different kinds of cholesterol were associated with different degrees of risk. It looked like LDL was probably the bad guy, so we shifted focus on lowering him – largely with medications. But like all things related to humans, relationships are complicated. The correlation between cholesterol and ASCVD turns out to be intricate and nuanced. Yes – LDL is clearly associated with heart disease – but only in some people. In others, it is not.

As it turns out, there are many important risk factors for ASCVD: LDL- cholesterol, Lp (a), insulin resistance, hypertension, and inflammation all play a role in sticking unwanted cholesterol particles into our coronary arteries contributing to heart attacks and stroke. But it’s another biomarker that presently links one most directly to the other – and that is Apolipoprotein B. Cholesterol

  • A fat/lipid molecule produced by every single cell in the body – necessary for life.

  • Minimal percentage comes from diet (most dietary cholesterol is not in a useable form).

  • Only one kind of cholesterol – no such thing as ‘good’ or ‘bad’ cholesterol.

  • Used to produce hormones and maintain healthy cells.

  • Needs cell to cell transport but does not dissolve in blood (like oil in water).

  • Carried through the bloodstream by taxi drivers called “lipoproteins” - this makes them water soluble. Apolipoproteins are special signaling proteins on the outside of the cholesterol molecule.

  • Cholesterol is the passenger; lipoprotein is the taxi, ApoB is an offensive bumper sticker on the back of every low-density lipoprotein.

  • Lipoproteins consist of proteins and fats or lipids such as cholesterol and triglycerides – again making the cholesterol soluble in the blood and controlling its signaling with other cells.

For today’s purposes, there are TWO large classes of apolipoproteins:

  • ApoA – Think of this as good (but super complicated).

  • ApoB – Think of this as bad (still super complicated but a little bit better understood).

What Is apoB?

  • Apolipoprotein B (apoB) – A special protein that plays a key role in moving lipoproteins through the blood, facilitating interactions with other cells.

  • Several classes of apolipoproteins – apoB is the “Baddest” one.

  • ApoB is very ‘atherogenic’ meaning it can stick to and enter the blood vessel wall causing plaque to build-up and rupture (heart attacks, strokes, and other bad things).

Why Is ApoB Important?

  • ApoB is the BEST PREDICTOR of lipid associated ASCVD (atherosclerotic cardiovascular disease).

  • In simple terms – it is the NUMBER (not the total weight) of cholesterol particles that are linked to one’s risk of ASCVD. ApoB most accurately approximates the number of bad guys you got.

Wait – isn't LDL the ‘bad cholesterol’? - Yes. Kind of.

  • Sometimes ApoB and LDL are on the same team (meaning both are high or both are low) but sometimes they aren’t (i.e. one is high, the other is low).

  • If you happen to have large LDL particles, your LDL might appear high, but your total particle number (best measured by ApoB) may be low.

  • Alternatively, if you have many small LDL particles, your LDL level might look great, but your ApoB could be very high.

Large LDL particles & low ApoB levels = LOW risk for ASCVD.

What Is Atherosclerosis?

  • Disease caused by cholesterol-rich deposits called plaque which build-up within the artery wall.

How Atherosclerosis Begins & How It Can Lead To A Cardiac Event

  1. Only ApoB containing lipoproteins (mainly LDL, but also VLDL, IDL, Lp (a), and potentially chylomicrons) can stick to the blood vessel wall and become trapped inside.

  2. Once the ApoB containing particles have crossed into the vessel wall they can oxidize, cause inflammation and then plaque.

  3. Plaque consists of inflammation and cholesterol.

  4. Plaque causes stiffening of the artery wall.

  5. Stiff artery walls cause high blood pressure (independent risk factor for heart attack).

  6. Plaque can rupture through the artery wall if it becomes too large or unstable.

  7. Blood clots are caused by plaque rupture - the leading cause of most heart attacks and strokes.

  8. When inflammation is present, it makes cholesterol molecules ‘sticky’ and able to cause plaque formation and rupture. Without inflammation, cholesterol alone is harmless – it is inflammation that sets the stage for heart disease.

  9. Chronic metabolic conditions such as insulin resistance and type 2 diabetes are extremely inflammatory and accelerate the development of ASCVD.

How ApoB Determines Risk For Heart Disease

  • Low density cholesterol particle NUMBER, not total cholesterol weight, determines risk – think of this: toss enough basketballs from the free throw line with your eyes closed and your back to the basket and at SOME POINT, you’ll eventually hit the net. Simply having high numbers of sticky cholesterol particles increases the likelihood that one or more of them will cause problems.

What Studies Have Shown The ADA (American Diabetes Association), ACC (American College of Cardiology), and NLA (National Lipid Association) all endorse ApoB as superior to LDL-C for evaluating ASCVD risk:

  • “ApoB is strongly associated with ASCVD risk, while LDL-C and non-HDL-C were not significant.”

  • “ApoB was shown to be a significant predictor of fatal heart attack in both men and women, but LDL-C was insignificant in women (and only modestly associated in men).”

  • “LDL-C does not predict coronary artery disease (CAD) risk, but LDL particle number does (a surrogate marker of apoB).”

  • “Baseline LDL-C was not associated with CV events, but apoB was.”

  • “ApoB was shown to be a superior marker of CV risk than LDL-C.

  • “ApoB was determined to be a better predictor of coronary artery calcium score than LDL-C.”

  • “A large meta-analysis of twelve independent reports (including 233,455 subjects and 22,950 CV events) concluded that ApoB is the most potent marker of CV risk, LDL-C is the least, and non-HDL-C is intermediate. Based on number of CVD events at 10 years, a treatment strategy that used ApoB instead of LDL-C would prevent 500,000 – 800,000 more CV events!”

  • “ApoB is the single most significant and consistent lipid measurement to predict CV risk. It is a powerful marker of vascular disease and a better guide to the adequacy of therapy than any other lipid biomarker.”

What Doctors Are STILL Taught In Medical School

  • High cholesterol causes coronary disease

  • LDL is bad and needs to be lowered

  • Dietary cholesterol causes high LDL cholesterol

  • Low fat diets lower cholesterol

What You Need to Know

  • Cholesterol alone does NOT cause ASCVD.

  • ApoB is the best prognostic indicator of cardiovascular risk.

  • Know your ApoB level – this is an easy, inexpensive test that any lab can run.

  • Inflammation makes cholesterol particles small and sticky.

  • Insulin resistance drives inflammation (non-optimal fasting insulin, above optimal fasting glucose, HgbA1c). Talk to your doctor about fixing this.

  • Stop smoking. Smoking is one of, if not THE greatest risk factor for ASCVD.

  • Diet contributes LITTLE to total cholesterol but a LOT to inflammation – stop eating crap.

FACTS To Lower ASCVD risk

  • Eat real food.

  • Stop smoking.

  • Control your blood pressure (ACE and ARBs are ok and actually beneficial here).

  • Go for a walk.

  • Reduce stress.

  • Get good sleep – seriously.

  • Fix your insulin resistance.

  • Supplement appropriately.

  • Stop aging – optimize hormone levels. Aging is the #1 risk factor for all chronic disease.

  • Cholesterol lowering medications will lower ApoB – but at what cost?


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