Mastering Heart Health: Your Complete Guide to Prevention, Part 2 (What is Heart Disease?)

Hello and welcome to Part 2 of our email series on Heart Disease! In this post, we will take a step back and define some common terms as it relates to heart disease.  Then we will explore the process on how heart disease develops in the body.  Obviously, this is a less practical and applicable post than the others; but I find that knowing what is going on in our hearts helps us better understand how to prevent it in the first place.  So stay with me!

First off, let’s Define some Terms and Structures

• What is cholesterol?
  • Cholesterol is a molecule that can be made by every cell in the body. It is mostly involved in the creation and maintenance of cell membranes but also serves as an integral aspect of adrenal and sex hormone production, vitamin D processing, and the creation of bile.
  • Our bodies package cholesterol (and triglycerides) into little spherical balloons, shuttling them to other parts of the body that may need it. These ‘balloons’ are called lipoproteins.
  • These lipoproteins are what we often refer to as LDL and HDL. Other important lipoproteins are VLDL, IDL, Lp(a), and chylomicrons.
  • There is no such thing as “good” or “bad” cholesterol. These lipoproteins are simply transporters doing their job. The harm of these lipoproteins comes from an excessive number of particles as well as from inflamed particles. 
  • The lipoproteins that have the ability to harm the heart all carry a specific protein “name tag” on them called Apolipoprotein B (or ApoB, for short). VLDL, LDL, IDL, and Lp(a) all carry this ApoB protein. This will be important when we get to the lab work section of the series!
• Why does my cholesterol get elevated?
  • The cholesterol cycle involves 1. Creation 2. Absorption from the gut and 3. Re-absorption from the liver.
    • You can make too many cholesterol particles — this is often driven by diet and genetics
    • You can absorb too many cholesterol particles from the gut — these particles are mostly coming from bile, not food
    • Your liver can be sluggish with re-absorbing cholesterol particles from the blood stream — this is driven by genes and diet
  • In our precision program, we can use specialized blood testing to know which of these pathways is the best to target for you

Now Let’s Talk About the Blood Vessels

• The heart pumps blood through arteries to the entire body. These arteries are under high pressure and use smooth muscles to dilate (get bigger) or constrict (get smaller) to speed up or slow down blood flow.
• The blood swirls around organs and then enters into veins to travel back to the heart. This flow is slower and more passive (i.e. relies on muscle contraction to “push” blood back to the heart, similar to squeezing a tube of toothpaste)
• For all intents and purposes, arteries get disease and veins do not.
• The artery wall is made of up of layers (picture below)
  • Endothelium (tunica intima)
    • This is the inner most layer, covered by a super thin lining of cells called the endothelium. The endothelium is arguably the most important part of the artery. It is the main line of defense in keeping blood (and everything in it) separate from the rest of the body.
    • The endothelium is covered by a hair-like rug called the glycocalyx, which maintains slickness of the vessel, protects endothelium from inflammatory particles (inflamed lipoproteins, bacteria, viruses, toxins, etc), and aids in the production of nitric oxide
    • Nitric oxide is a critically important molecule that dilates blood vessels, controlling blood pressure. It also serves as a powerful antioxidant.
      • Our ability to naturally create nitric oxide declines with age, sedentary behavior, damage to the arteries themselves, and can be affected by genetics.
      • Erectile dysfunction and high blood pressure are often linked to a nitric oxide deficient state
  • Smooth muscle layer (tunica media) — this layer controls how big or small the artery opening is
  • Subendothelial space
    • The space between the endothelium and smooth muscle
    • This is the site that heart disease FIRST starts (very important when we get to the imaging section of this series)

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Ok, I’m still with you. But how do we develop heart disease?

So now to the meat of this post and a topic of growing debate, surprisingly. Heart disease starts inside the artery wall and develops over 10-30 years into a plaque that is visible within the lumen of the vessel. And it is this plaque that can rupture, stopping the flow of blood to other areas, creating a heart attack or stroke.  However, how this process even starts in the first place is hotly debated:

1. Lipid hypothesis:
   • ApoB containing particles (LDL, VLDL, IDL, Lp(a) are the reason for heart disease. Chronically elevated levels of these particles will eventually damage the glycocalyx/endothelium and start getting stuck inside the artery wall
   • This theory is the most accepted by the medical community
2. Inflammation hypothesis:
   • Inflammatory conditions in the blood (Diabetes and insulin resistance, autoimmunity, infections, toxins, etc) damage the glycocalyx and endothelium, creating weak spots in the artery that become the site for immune reactions and plaque formation
   • This is a newer proposed model but is catching steam

I’ve tried my best to understand each model and then reflect on my clinical experience as a primary care doctor as to what makes the most sense to me.  And I think both can be true at the same time. We have really good studies that support each hypothesis, and I’ve seen both play out in my practice. We should be mindful of our cholesterol levels AND conditions that create inflammation in the body. And if we are high risk, we should be monitoring labs and getting images to identify disease. 

Now, onto the process (a picture of this is shown below):

1. The glycocalyx and endothelium (the protective layer of the artery) are damaged in some way and allow lipid particles and/or inflammatory factors to slip into the wall of the artery.
2. The body’s immune system senses this as abnormal and goes to work to remove it and bring the vessel back to a state of health. In the short-term, this process works — getting the flu or eating cake on your birthday does not cause heart disease. However, if this process happens all over the body for years and decades, the immune system struggles to keep up.
3. As the immune system is activated more and more, a war ensues inside of the artery wall: lipid particles that are stuck in this space get inflamed, dead immune cells pile up or get damaged and dysfunctional, and inflammatory debris fills the area.
4. The space between the endothelium and the muscle layer continues to swell with inflammation over time (somewhat similar to an abscess) to the point that it extends into the lumen of the vessel itself — this is the first time the plaque becomes visible.
5. This newly formed plaque is soft and squishy. Since it is in the lumen,  blood swirls past it, like a river push past and around a boulder. 
6. Like a thumb over a garden hose, the plaque can grow to the point that it starts blocking flow for most of the vessel — this can cause chest pain with exercise
7. The soft plaque can also break apart, causing platelets and clotting factors to form a blood clot to “seal” it. This blood clot is what causes the heart attack or stroke.
8. If the soft plaque doesn’t rupture, the body will slowly try to cover it with a fibrous mesh of calcium as a protective mechanism. These calcified plaques are more stable and less likely to rupture.

Here’s a pretty good video on what I just described:

I hope this was helpful! Knowing what is going on in the body is key to better understanding the steps you can take to have better heart and brain health.  In the next post, we will talk about labs and imaging.

Dr. J