Cholesterol & Cardiovascular Risk

Monday, 24 June 2019

Is high cholesterol is the cause of heart disease?

Part of the confusion about cholesterol and its role in disease is actually caused by dated science and by imprecise terminology. However, before I explain why a simple high total cholesterol reading is not the underlying cause of heart disease, we have to cover some basics.

What is Cholesterol?

Cholesterol is not technically a fat. Rather, it’s classified as a sterol, which is a combination of a steroid and alcohol. It’s crucial to understand that you don’t have a cholesterol level in your blood. Cholesterol is fat-soluble, and blood is mostly water, so the two don’t mix! 

The body’s solution to this problem is to bind cholesterol to certain proteins that function as transport vehicles, carrying different types of fats such as cholesterol, triglycerides (TG), apolipoproteins and phospholipids. These combinations of fats and protein are called lipoproteins.

These lipoproteins deposit cholesterol and phospholipids around the body as they are needed for SO many functions:- 

Cholesterol is essential for making the cell membrane and cell structures and is vital for synthesis of our sex hormones, vitamin D and bile acids. It forms part of our myelin sheath that protects our neurons, and 25% of the cholesterol in your body is found in your brain, where it plays important roles in such things as membrane function as well as acting as an antioxidant, -  basically, we need it! 

Lipoproteins -  the cars on the road

Firstly, it is important to emphasize, that it is lipoproteins themselves that interact with the arterial wall and can, if the environment is correct, initiate the cascade of events that leads to atherosclerosis.

As I’ve just explained, Cholesterol is only one of many components of lipoproteins. Therefore, measurements of total cholesterol provide little information about the lipoproteins that transport the bulk of cholesterol.

Lipoproteins are classified according to their density; two of the most important in cardiovascular disease are low-density lipoprotein (LDL) and high-density lipoprotein (HDL).

This can get confusing quickly, so let me use an analogy to make this more clear. Imagine your bloodstream is the M25. The lipoproteins are like cars that carry the cholesterol and fats around your body, and the cholesterol and fats are like passengers in the cars. 

Coronary arteries -  the road in our analogy - are essentially hollow tubes, and the endothelium (lining) of the artery is very thin—only one cell deep. The blood, which carries lipoproteins like LDL, is in constant contact with the endothelial lining. So why does the LDL particle leave the blood, penetrate the endothelium and enter the artery wall? The answer is that it’s a gradient-driven process. Going back to our analogy, the more cars there are on the M25 at one time, the more likely it is that some of them will “crash” into the fragile lining of the artery. It’s not the number of passengers (cholesterol) the cars are carrying that is the determining factor, but the number of cars on the highway.

Advanced Testing for Cholesterol and Lipoproteins - numbers and sizes of the cars!

We have established then, assessing for the number of cars on the road is important, but we can also assess for the size and thus the quality of these “cars”. 

Measurements of the number of LDL-particles (LDL-P) appear more predictive of risk than measurements of the cholesterol mass within these particles or standard LDL-cholesterol (LDL-C) that is obtained from the GP.

LDL, which carries cholesterol, exists either as large, more buoyant particles or as smaller, more dense particles (sdLDL).  sdLDL is more easily oxidized (basically internal rusting!), has a higher affinity for vessel walls, and remains in the circulation longer because it is less likely to be cleared by the liver, making it more atherogenic than larger LDL particles.

On the other hand, a higher number of HDL-P is considered to be more protective, since HDL removes cholesterol by transporting it to the liver. In general, people with higher levels of HDL-P are at a lower risk for CHD. 

Size matters

It is also well known that LDL particle size provides extremely important information on cardiovascular health. Small, dense LDL particles are dangerous since they contribute to plaque formation in the arterial wall. Ideally, one would want their results to show large, buoyant LDL particles. Small, dense particles are also closely associated with insulin resistance and an increased risk of developing type 2 diabetes. 

Using NMR® technology -  all these markers can we run:

  • LDL particle number (LDL-P)

  • Small LDL particle number (small LDL-P)

  • HDL particle number (HDL-P)

  • LDL particle size

  • A standard cholesterol test (LDL-C, HDL-C, triglycerides and total cholesterol)

  • LP-IR

In addition to the particle size, the NMR LipoProfile® provides a laboratory developed index called LP-IR, with a higher number increasing the probability of developing insulin resistance.

Unfortunately, these vitally important markers contained in the NMR LipoProfile® are not included in the typical cholesterol test from your doctor. Standard lipid profiles utilize inferior technology and are limited to the use of just cholesterol, LDL and HDL as a surrogate marker for your extremely important LDL particle number and the quality of these particles

The environment and other important risk factors 

Measuring cholesterol and lipoproteins without looking at the environment  - the health of the endothelium and inflammation will only tell part of the story. In our analogy, this is essentially The Road- M25

Recent evidence goes beyond lipids to suggest that inflammation within the artery wall is the primary contributor to this residual risk for heart attack and stroke. Inflammation contributes to both vulnerable plaque formation and to plaque rupture.

Inflammation can be easily measured with advanced testing that assesses a patient’s inflammatory state and cardiovascular risk. Monitoring your inflammatory status may allow you to catch the beginning, or even treat advanced stages of inflammation, in an effort to reduce your cardiovascular risk.

I use Cleveland HeartLab (they offer inflammatory and other advanced biomarker testing in the management and prevention of heart disease), as they offer unique inflammation testing which provides additional and complementary insight into cardiovascular risk beyond cholesterol testing alone. This additional information allows for targeted treatment to reduce risk over one’s lifetime. The inflammatory markers are: 

  1. F2-IsoPs - These are prostaglandin-like compounds formed from the free radical oxidation of arachidonic acid, and are the ‘gold standard’ for measuring oxidative stress in the body. F2-IsoPs also have potent biological effects associated with inflammation and therefore may mediate chronic disease initiation and progression. Additionally, F2-IsoPs may also act as potent vasoconstrictors in the endothelium, and promote platelet activation resulting in thrombus formation.

  2. OxLDL - Measures protein damage due to the oxidative modification of the LDL cholesterol. The oxidation of LDL cholesterol is one of the first steps in the development of atherosclerosis. Briefly, LDL-C enters the artery wall where it becomes oxidized. OxLDL is then recognized by scavenger receptors on macrophages which engulf OxLDL, resulting in foam cell formation, vascular inflammation and the initiation of atherosclerosis.

  3. Lp-PLA2, or lipoprotein-associated phospholipase-A2 - measures disease activity within the artery wall below the collagen or calcified cap due to the activation of macrophages-white blood cells. Lp-PLA2 also interacts with oxidized LDL, which increases inflammation and enhances a proatherogenic state, as well as plaque vulnerability. 

  4. MPO - Is a marker that measures the body’s response to a damaged endothelium that has become thinned, cracked and ultimately unstable due to cholesterol accumulation and inflammation. Your risk for a heart attack increases as your MPO levels increase.

  5. ADMA/SDMA - identifies endothelial damage due to the loss of nitric oxide, a molecule that can protect the endothelium. Microalbumin identifies endothelial damage in the kidneys. Increased levels of these markers may identify the presence of diabetes or heart disease.

  6. hsCRP - is a general marker of inflammation. The presence of a cold may increase hsCRP levels over the short-term (days to weeks). However, the accumulation of cholesterol in the artery wall may result in increased hsCRP levels over the long-term (years to decades).

Summary

As you can see, a standard lipid panel doesn’t give the full picture on whether or not you are at risk of a heart attack. In fact, we are simply touching the surface on how complicated this can be. 

A standard lipid panel simply tells us how much cholesterol is inside the lipoproteins that are carrying it. For most people, a standard lipid panel is enough to get a baseline of how your body is functioning.  However, If you see a pattern of higher lipid and cholesterol levels or have a family history of cardiovascular disease, further testing is warranted to see the exact cause of the abnormal numbers.  

This is the panel I use in clinic:

Comprehensive Cardiac Health Assessment £415

Markers:

  • Myeloperoxidase
  • Lp-PLA2 Activity
  • ADMA/SDMA
  • NMR LipoProfile with Lipids (LDL Particle Size (small), Large HDL (low levels), and Large VLDL
  • HbA1c
  • hsCRP
  • Microalbumin/Creatinine
  • Lipoprotein(a)
  • OxLDL
  • F2-Isoprostanes/Creatinine
  • Comprehensive metabolic panel 
  • TMAO
  • TSH
  • CoQ10
  • OmegaCheck
  • Vitamin D

PLUS

  • 002 Essential Nutrients £85 (Vit D, Mg, B12, Iron metabolism, Folate) 
  • 003 Comprehensive Thyroid Profile £85 (TSH, TT3, FT3, Anti-thyroglobulin, Anti-TPO, FT4, T3 Uptake)