The Big Picture

Apolipoprotein B (apoB) is a structural protein found in all lipid molecules that contribute to atherosclerosis developing in the body (aka. atherogenic particles). Recent research is highlighting the superiority of apoB as a cardiovascular disease risk marker over traditional cholesterol tests such as; total cholesterol, your “bad” cholesterol (LDL-C) and “good” cholesterol (HDL-C) measures. 
This is because a single apoB is present on each atherogenic lipid, meaning it gives a direct 1:1 measurement of the number of all circulating atherogenic particles in the body. In contrast, LDL-C which is the current primary measure used to assess cardiovascular risk, is estimated using an equation that can be inaccurate and does not capture the whole risk profile.

Your physician can use your apoB concentration to guide lifestyle changes or initiate pharmacological therapy to lower your risk of developing cardiovascular disease, and to track treatment progression over time.

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Apolipoprotein B’s Role in Your Body

What is a Lipoprotein Anyway?

To understand apoB (apolipoprotein B), understanding its structure is the best place to start.

Lipoproteins are molecules that transport lipids, or fats, through the bloodstream to various parts of the body. Breaking down the term helps us understand their structure further:

• LIPO = Fat (Lipid). This refers to the cholesterol and triglycerides carried within the lipoprotein's core.
• PROTEIN = The protein molecule on the exterior of the lipoprotein that provides structure and stability. These are called apolipoproteins.
  

Image Source: Journal of the American Heart Association

ApoB vs. Other Apolipoproteins

You may have heard of "good" or "bad" cholesterol, but these labels are misleading. It's not the cholesterol itself that causes issues in the body, but rather the type of lipoprotein carrying it that can affect your health [1].

ApoB is the key structural and transport protein in all major atherogenic lipoproteins— molecules that contribute to plaque buildup in your arteries. This plaque formation leads to the hardening and thickening of arteries over time, a condition called atherosclerosis. As atherosclerosis progresses and blood vessels narrow, the risk of cardiovascular disease (CVD), including heart attacks and strokes, increases [2].

Atherogenic lipoproteins include low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and lipoprotein(a) [Lp(a)]. Each of these atherogenic particles contains one molecule of apoB, making apoB a direct measure of the number of circulating atherogenic particles in the body [4, 5]. 

Is it “Good” and “Bad” Cholesterol? Or is it the apolipoprotein?

There are two main types of lipoproteins that transport cholesterol in our bodies: Low-Density Lipoprotein (LDL) and High-Density Lipoprotein (HDL). LDL is often called "bad" cholesterol because it contributes to plaque buildup on blood vessel walls. In contrast, HDL is known as "good" cholesterol because it helps remove LDL cholesterol from the bloodstream, carrying it back to the liver to be broken down and eliminated [3].

While both HDL and LDL contain cholesterol, they differ in their apolipoproteins. HDL molecules have ApoA1, while LDL contains apoB [9]. Other atherogenic particles— Lp(a), VLDL, IDL—also contain one apoB. These particles can also penetrate blood vessel walls that have been damaged by various lifestyle factors. As these particles enter the vessel walls, a cycle of inflammation and particle accumulation is triggered, leading to plaque formation and the progression of atherosclerosis [2].

So, it’s time we stop pointing the finger at cholesterol, and instead at apoB.

Why ApoB Levels Matter for Heart Health

The Limitations of Traditional Cholesterol Panels

Cardiovascular diseases are the leading cause of death worldwide, resulting in a devastating 20.1 million deaths in 2021 (WHF, WHO). While this statistic is alarming, the bright side is that most cardiovascular diseases can be prevented by addressing key lifestyle behaviours and environmental risk factors early.

Early detection of CVD risk is crucial for preventing the development of severe symptoms that worsen quality of life and can lead to death. When assessing CVD risk physicians have traditionally used a lipid panel, which takes the following values into consideration (Cleveland Clinic):

• Total cholesterol (TC)
• Low-density lipoprotein (LDL-C)
• Non-HDL Cholesterol
• Triglycerides (TG)
• Lipoprotein(a)

The Limitations of LDL-C

While HDL-C and total cholesterol are directly measured in a lipid panel, LDL-C concentration is estimated using the Friedewald equation, which is prone to inaccuracies in certain populations [10]. Additionally, LDL-C measures the amount of cholesterol within LDL particles, not the number of particles themselves. It’s possible to have normal LDL-C levels but still have a high number of LDL particles, which can increase cardiovascular risk [4].

The key takeaway here is that while traditionally LDL-C has been used to assess cardiovascular risk, many individuals with normal LDL-C levels still develop CVD. In fact, 20%(+) of all cardiovascular events occur in those without major conventional CVD risk factors, and 50% of heart attacks and strokes occur in individuals with a lipid profile which may not warrant therapeutic intervention under current guidelines [4, 8, 12].

Measuring Cardiovascular Risk with ApoB

Research investigating apoB shows it is a more accurate and specific biomarker to track in regards to your cardiovascular health because CVD risk is driven by the number of circulating apoB particles, not the cholesterol content within them [1, 4, 5, 7, 11]. ApoB is also measured more accurately by clinical laboratories because it is a direct measure, not an estimation [7], and its levels are not affected by fasting making it a more practical marker to test [1].

ApoB’s 1:1 ratio with all atherogenic particles gives a direct count and a more complete picture of one’s cardiovascular risk profile, and it’s time we start testing it, instead of relying on LDL-C and HDL-C to give us all the information we need to manage our cardiovascular health [5, 6, 7]. 

Understanding Your ApoB Levels is Critical for Your Heart Health!

Read more about the science behind apoB testing and how to gain access to the best insights about your cardiovascular health through our next article here.

References 

1. Ahmad, M., Sniderman, A. D., & Hegele, R. A. (2023). Apolipoprotein B in cardiovascular risk assessment. Canadian Medical Association Journal, 195(33). https://doi.org/10.1503/cmaj.230048
   
   
2. American Heart Association. (2024, October 16). What is atherosclerosis?. https://www.heart.org/en/health-topics/cholesterol/about-cholesterol/atherosclerosis
   
   
3. American Heart Association. (2024, February 19). HDL (Good), LDL (Bad) Cholesterol and Triglycerides. https://www.heart.org/en/health-topics/cholesterol/hdl-good-ldl-bad-cholesterol-and-triglycerides
   
   
4. Behbodikhah, J., Ahmed, S., Elyasi, A., Kasselman, L. J., De Leon, J., Glass, A. D., & Reiss, A. B. (2021). Apolipoprotein B and Cardiovascular Disease: Biomarker and Potential Therapeutic Target. Metabolites, 11(10), 690. https://doi.org/10.3390/metabo11100690
   
   
5. Barter, P.J., Ballantyne, C.M., Carmena, R., Cabezas, M.C., Chapman, M.J., Couture, P., de Graaf, J., Durrington, P.N., Faergeman, O., Frohlich, J., Furberg, C.D., Gagne, C., Haffner, S.M., Humphries, S.E., Jungner, I., Krauss, R.M., Kwiterovich, P., Marcovina, S., Packard, C.J., Pearson, T.A., Reddy, K.S., Rosenson, R., Sarrafzadegan, N., Sniderman, A.D., Stalenhoef, A.F., Stein, E., Talmud, P.J., Tonkin, A.M., Walldius, G. and Williams, K.M.S. (2006), Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ten-country panel. Journal of Internal Medicine, 259: 247-258. https://doi.org/10.1111/j.1365-2796.2006.01616.x
   
   
6. Contois JH, Langlois MR, Cobbaert C, Sniderman AD. Standardization of Apolipoprotein B, LDL-Cholesterol, and Non-HDL-Cholesterol. J Am Heart Assoc. 2023 Aug;12(15):e030405. doi: 10.1161/JAHA.123.030405. Epub 2023 Jul 25. PMID: 37489721; PMCID: PMC10492988.
   
   
7. Glavinovic, T., Thanassoulis, G., de Graaf, J., Couture, P., Hegele, R. A., & Sniderman, A. D. (2022). Physiological bases for the superiority of apolipoprotein B over low‐density lipoprotein cholesterol and non–high‐density lipoprotein cholesterol as a marker of cardiovascular risk. Journal of the American Heart Association, 11(20). https://doi.org/10.1161/jaha.122.025858
   
   
8. Johns I, Moschonas KE, Medina J, Ossei-Gerning N, Kassianos G, Halcox JP. Risk classification in primary prevention of CVD according to QRISK2 and JBS3 'heart age', and prevalence of elevated high-sensitivity C reactive protein in the UK cohort of the EURIKA study. Open Heart. 2018 Nov 17;5(2):e000849. doi: 10.1136/openhrt-2018-000849. PMID: 30564373; PMCID: PMC6269641.
   
   
9. Mayo Clinic Laboratories. (n.d.). APOAB - overview: Apolipoprotein A1 and B, Serum. Test Catalogue, Clinical & Interpretive. https://www.mayocliniclabs.com/test-catalog/overview/607593#Clinical-and-Interpretive
   
   
10. Sathiyakumar, V., Blumenthal, R. S., & Elshazly, M. B. (2020, March 20). New information on accuracy of LDL-C estimation. American College of Cardiology. https://www.acc.org/Latest-in-Cardiology/Articles/2020/03/19/16/00/New-Information-on-Accuracy-of-LDL-C-Estimation
    
    
11. Sniderman, A. D., Thanassoulis, G., Glavinovic, T., Navar, A. M., Pencina, M., Catapano, A., & Ference, B. A. (2019). Apolipoprotein B particles and cardiovascular disease. JAMA Cardiology, 4(12), 1287. https://doi.org/10.1001/jamacardio.2019.3780
    
12. Vinci, P., Di Girolamo, F. G., Panizon, E., Tosoni, L. M., Cerrato, C., Pellicori, F., Altamura, N., Pirulli, A., Zaccari, M., Biasinutto, C., Roni, C., Fiotti, N., Schincariol, P., Mangogna, A., & Biolo, G. (2023). Lipoprotein(a) as a Risk Factor for Cardiovascular Diseases: Pathophysiology and Treatment Perspectives. International Journal of Environmental Research and Public Health, 20(18), 6721. https://doi.org/10.3390/ijerph20186721