I genuinely enjoy discussing health-related topics with my patients. One of the more commonly misunderstood topics in my experience is cholesterol. For instance, did you know that all nucleated cells in our bodies can make cholesterol? And for good reason – it is really important. Let’s review some basic knowledge about cholesterol in today’s article.
Why is cholesterol important?
Cholesterol provides cell membrane support, a vital role that includes stabilizing and controlling membrane fluidity.
Cholesterol is the foundation that all steroid hormones are built from; including estrogen, progesterone, testosterone, and cortisol.
Cholesterol acts like a building block, functioning as a critical component of vitamin D, CoQ10, and Bile Acids.
You may be thinking… isn’t cholesterol bad for my cardiovascular health? If cholesterol is so important, why does it have such a bad reputation? Good question! To help clarify, let me tell you a quick story.
Once Upon a Lipoprotein
Let’s begin by meeting the main characters, incredible little particles called lipoproteins. Think of lipoproteins as trucks that carry fats (cholesterol and triglycerides) around your body using the bloodstream as a highway. Some lipoproteins deliver fats to your tissues while others take them to your liver to be processed.
The story starts when you eat a meal containing fats. The cells lining your small intestine (called enterocytes) collect these fats during digestion and load them into chylomicrons, the largest lipoprotein particle. The recently filled chylomicrons are then absorbed through the intestinal mucosa into your lymphatics and then your bloodstream, where they travel around your body to deliver fats to cells in need. As they do, they become smaller, eventually shrinking to what are called “remnant chylomicrons” that are eventually absorbed by the liver for processing.
But that’s not the end. The liver then makes Very Low-Density Lipoproteins (VLDL) that transport even more fats through the bloodstream to cells that need them. As the VLDL depleted, they also shrink, becoming Intermediate Density Lipoproteins (IDL) and eventually Low-Density Lipoproteins (LDL).
Reading Between the Acronyms
Now at this point, you may be thinking, “I recognize those acronyms, I have seen them on my bloodwork!” You are right… sort of. There is an important distinction to make here.
What we have been talking about so far are particles. Bringing back the truck analogy, the particle would be the whole truck. What you see on your bloodwork is only the cholesterol portion of the particle. So, what you see on your blood results is strictly the cholesterol the truck is carrying. Making sense so far??
A question you may ask at this point is why are we so focused on the size of these particles? This is because particle size matters! As the lipoproteins become smaller, the concentrations of the fats they carry change; the amount of triglyceride decreases, and the concentration of cholesterol increases. Also, the smaller particles can slip between the cells of your blood vessels to get between the layers of the blood vessel called the arterial intima. Once here, these smaller lipoproteins may, depending on conditions, leave their cholesterol behind.
I think you see where I am going with this… cholesterol deposits in the arteries are the early stage of plaque formation and atherosclerosis. As you are likely aware, atherosclerosis is a major risk factor for cardiovascular events like heart attacks or strokes. (I won’t go further into the formation of atherosclerotic plaques in this article to keep it succinct but let me know if it’s a topic you would like to see covered in a future blog!)
What We Are Looking For
When we doctors review your cholesterol panel in your blood results, we’re reading your cholesterol story to better understand your risk of developing atherosclerosis or cardiovascular disease.
There are certain cholesterol-containing particles that are considered atherogenic (these are the ApoB- containing lipoproteins). They are represented in the Non-High Density Lipoprotein Cholesterol (Non-HDL-C) result on your blood work. This value is determined by taking your total cholesterol and subtracting your HDL-C. LDL-C makes up, by far, the largest portion of Non-HDL-C (Ference et al. 2017).
This specific cholesterol fraction is important to understand, as research shows that elevations in LDL-C alone are associated with an increased risk of cardiovascular events (Ference et al. 2017; Cholesterol Treatment Trialists’ (CTT) Collaboration et al. 2010). Further, the longer your exposure to high LDL-C levels the higher your risk of cardiovascular events (Perak et al. 2016). Naturally, we place a lot of importance on the LDL-C result of your bloodwork.
Too Much of a "Good" Thing
I would like to sidestep for a moment now to address High-Density Lipoprotein Cholesterol (HDL-C). You have heard this referred to as “good cholesterol,” but we are trying to move away from that terminology for a few reasons.
HDL particles have a different function than the other particles that we have discussed. Instead of delivering fats to tissues, it picks up cholesterol from tissues and delivers it to the liver for processing. Naturally, one might be thinking “isn’t this a good thing, would that not help to manage my cholesterol??” Unfortunately, it’s not that simple…
What we see in the research is that having more HDL-C is not protective against cardiovascular outcomes! HDL-C it seems is what we call a goldilocks molecule. Researchers see an increase in cardiovascular risk in people who have both high and low HDL-C.(Madsen, Varbo, and Nordestgaard 2017; Zhong et al. 2020; Liu et al. 2022).
A Tool for Identifying Risk
Phew, that was a lot! Are you still with me? Now that you have a better understanding of cholesterol, let’s step back and review the main takeaways. We as doctors are looking to understand and communicate the risk of various health factors to you. According to the WHO, cardiovascular disease was the leading cause of death for all genders worldwide every year from 2000-2019 (“WHO Reveals Leading Causes of Death and Disability Worldwide: 2000-2019” n.d.). With that in mind, being able to assess your risk of cardiovascular disease is an important part of your ongoing healthcare.
To understand your health risks, we look at different factors, with atherosclerosis and cholesterol representing one of these risk factors. Having a clearer understanding of why doctors are concerned with these values on your blood results can help shed light on your own cholesterol story. It is my hope that you have a better picture of the importance of cholesterol in the body and the risk when these levels are out of balance. What I have outlined here is the abridged version, of course, but I do hope that you have found it helpful. If you want to dive deeper into the topic of your cholesterol, cardiovascular health, and what you can do to mitigate risk, make an appointment with your ND or your MD.
References:
1. Cholesterol Treatment Trialists’ (CTT) Collaboration, C. Baigent, L. Blackwell, J. Emberson, L. E. Holland, C. Reith, N. Bhala, et al. 2010. “Efficacy and Safety of More Intensive Lowering of LDL Cholesterol: A Meta-Analysis of Data from 170,000 Participants in 26 Randomised Trials.” Lancet (London, England) 376 (9753): 1670–81. https://doi.org/10.1016/S0140-6736(10)61350-5.
2. Ference, Brian A., Henry N. Ginsberg, Ian Graham, Kausik K. Ray, Chris J. Packard, Eric Bruckert, Robert A. Hegele, et al. 2017. “Low-Density Lipoproteins Cause Atherosclerotic Cardiovascular Disease. 1. Evidence from Genetic, Epidemiologic, and Clinical Studies. A Consensus Statement from the European Atherosclerosis Society Consensus Panel.” European Heart Journal 38 (32): 2459–72. https://doi.org/10.1093/eurheartj/ehx144.
3. Liu, Chang, Devinder Dhindsa, Zakaria Almuwaqqat, Yan V. Sun, and Arshed A. Quyyumi. 2022. “Very High High-Density Lipoprotein Cholesterol Levels and Cardiovascular Mortality.” The American Journal of Cardiology 167 (March): 43–53. https://doi.org/10.1016/j.amjcard.2021.11.041.
4. Madsen, Christian M., Anette Varbo, and Børge G. Nordestgaard. 2017. “Extreme High High-Density Lipoprotein Cholesterol Is Paradoxically Associated with High Mortality in Men and Women: Two Prospective Cohort Studies.” European Heart Journal 38 (32): 2478–86. https://doi.org/10.1093/eurheartj/ehx163.
5. Perak, Amanda M., Hongyan Ning, Sarah D. de Ferranti, Holly C. Gooding, John T. Wilkins, and Donald M. Lloyd-Jones. 2016. “Long-Term Risk of Atherosclerotic Cardiovascular Disease in US Adults With the Familial Hypercholesterolemia Phenotype.” Circulation 134 (1): 9–19. https://doi.org/10.1161/CIRCULATIONAHA.116.022335.
6. “WHO Reveals Leading Causes of Death and Disability Worldwide: 2000-2019.” n.d. Accessed January 21, 2023. https://www.who.int/news/item/09-12-2020-who-reveals-leading-causes-of-death-and-disability-worldwide-2000-2019.
7. Zhong, Guo-Chao, Su-Qun Huang, Yang Peng, Lun Wan, You-Qi-Le Wu, Tian-Yang Hu, Jie-Jun Hu, and Fa-Bao Hao. 2020. “HDL-C Is Associated with Mortality from All Causes, Cardiovascular Disease and Cancer in a J-Shaped Dose-Response Fashion: A Pooled Analysis of 37 Prospective Cohort Studies.” European Journal of Preventive Cardiology 27 (11): 1187–1203. https://doi.org/10.1177/2047487320914756.
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