What you Need to Know About your Atherogenic Particle Number (LDL-P or ApoB)

While most of us have heard of cholesterol and maybe even triglycerides, many people are not familiar with the lipoprotein particles that are the containers that carry these fats in the blood. Understanding how these particles work is important to understanding your own test results past “good” cholesterol and “bad” cholesterol. Spoiler alert: cholesterol is neither really good nor bad; the particles carrying cholesterol are what matters.

First, cholesterol and triglycerides are fats (“lipids”) that circulate in your blood. If you’ve heard of the term “lipid panel” when having your routine physical, this means that your doctors is having a test run to assess these important lipid values. Because cholesterol and triglycerides can't dissolve in blood, they circulate throughout your body inside these lipoprotein particle “containers”.

 

Lipoprotein particles that carry cholesterol and triglycerides

Atherogenic particles.png

As you can see in the diagram above, some lipoprotein particles, like low-density lipoprotein (LDL) and high-density lipoprotein (HDL), carry mostly cholesterol. Other lipoprotein particles, like Chylomicrons and VLDL (very-low-density lipoprotein), carry mostly triglycerides.1

 
 

Note: HDL is often miscategorized as “good” cholesterol and LDL is often miscategorized as “bad” cholesterol. The particles carrying these cholesterols are what are “good” and “bad”. The cholesterol itself is neutral.

 
 

LDL and HDL Particles vs. Chylomicrons and VLDL Particles

Cholesterol & Triglycerides.png

Some lipoprotein particles lead to plaque formation in your arteries. These particles are called “atherogenic” particles. Atherogenic particles share a common characteristic: they all have one apolipoprotein B (ApoB) molecule on their outer surface.2,3 Over 90% of all of these atherogenic particles are LDL particles.4 Whether small or large, all LDL particles are equally bad and capable of driving arterial plaque formation.5-7

 

Atherogenic lipoprotein particles with apolipoprotein B (“ApoB”) molecules

 
Atherogenic Lipoprotein Particle-2.png
 

As atherogenic particle levels increase in your bloodstream, more particles deposit in the artery wall and promote plaque formation.2,3 The higher the atherogenic particle number, the greater the risk for you having a cardiovascular event.2,3,8

Low-density lipoprotein cholesterol (LDL-C) is the cholesterol carried in your LDL particles, while non-high-density lipoprotein cholesterol (non HDL-C) is the cholesterol carried in all potentially atherogenic particles. Similarly, your LDL particle score is the number of LDL particles in your bloodstream while your ApoB score is a measurement of the number of all potentially atherogenic particles.14

Although a cholesterol test can estimate a value, a nuclear magnetic resonance (NMR) lipoprotein particle number test directly quantifies your atherogenic particle value.

  • Atherogenic particle number values with ApoB above 90 mg/dL or LDL-P above 1200 nmol/L significantly increase long-term cardiovascular risk.9-12
  • Atherogenic particle number above 130 mg/dL or LDL-P above 2000 nmol/L is considered a “risk enhancing factor” when determining your overall risk for suffering a cardiovascular event.13

If the amount of cholesterol per particle was always the same, measurements of your cholesterol values (LDL-C and non-HDL-C) and your particle numbers (LDL-P and ApoB) would give very similar results. However, because the amount of cholesterol carried inside lipoprotein particles is highly variable, cholesterol tests and particle number tests frequently show conflicting values with regard to your cardiovascular risk.14-16 In statin intervention trials, apoB levels on therapy are a significantly stronger predictor of cardiovascular event reduction versus LDL-C or non HDL-C.19 Your LDL-P and ApoB particle score is your best reference point to track your cardiovascular risk.

Data from multiple insurance providers shows that individuals with high cardiovascular risk managed to low LDL-P (mean 860 nmol/L) during their usual medical care, experience significantly fewer cardiovascular events versus statin treated patients attaining low LDL-C (mean 79 mg/dL) at 12-, 24-, and 36-months of follow up.20,21 Additionally, cost-effectiveness analysis demonstrated that attaining low LDL-P was cost neutral at 24 months and cost savings at 36 months versus standard of care statin therapy.21

 

What you should remember:

1. Cholesterol is generally neither good or bad; the particles carrying cholesterol and triglycerides are what are important for you to track.

2. When cholesterol and particle number tests disagree, your risk for a cardiovascular event is more accurately assessed using your particle number, rather than cholesterol.10,12,14,17,18

3. Achieving a low particle number (LDL-P) significantly improves your risk of not suffering future cardiovascular events and brings down your overall cost of healthcare.

 

Your Potential Next Steps

High cardiovascular risk trends with high atherogenic particle values, whether measured by LDL-P or ApoB. The higher the scores for a longer time, increases your risk. The lower the scores for a longer time, decreases your ASCVD risk.

Here are actions you may consider taking under the care of a licensed physician in your area:

  1. If your LDL-P > 1600 mg/dL or your ApoB > 110 mg/dL your physician can help you rule out secondary causes of disease by checking your thyroid status (TSH or thyroid cascade), liver status (AST, ALT, bilirubin ‐ components of a Comprehensive Metabolic Panel), and renal status (creatinine and urine protein ‐ components of a Comprehensive Metabolic Panel and urinalysis).

  2. You should definitely see a provider if you have Extremely High Atherogenic Particle values meaning LDL-P > 2400 mg/dL or ApoB > 160 mg/dL. These are clear signs of subclinical ASCVD (Atherosclerotic Cardiovascular Disease).

  3. If, after 6 months of improved diet and lifestyle change, your 10-year cardiovascular risk score is > 20%.

  4. If, after 6 months of improved diet and lifestyle change, your LDL-P > 1600 mg/dL or ApoB > 110 mg/dL meeting the criteria for High Atherogenic Particle values.

  5. In men at least 34 years of age or women at least 44 years of age, if you LDL‐P is between 1600‐2000 mg/dL or ApoB 110‐130 mg/dL, then you should consider finding a center than does B‐Mode Carotid Ultrasound (looking for local plaque > 1.49 mm in size). This type of non-invasive imaging can find plaques earlier than calcified plaques identified by a Coronary Artery Calcium Score (CAC Score). However, they are also less easily available in most geographies as they are a bit more labor intensive than a CAC score.

  6. In men at least 44 years of age or women at least 54 years of age, if you LDL‐P is between 1600‐2000 mg/dL or ApoB 110‐130 mg/dL, then you should consider finding a center than does Coronary Artery Calcium Score (CAC Score) to identify calcified plaques in the arteries around your heart.

References

  1. Cromwell WC, Otvos JD. Clinical utilization of lipoprotein subfractions. In: Davidson MH, Toth PP, Maki KC, eds. Therapeutic Lipidology. Totowa: Humana Press; 2007:321-48.

  2. Ference BA, Ginsberg HN, Graham I, et al. 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. Eur Heart J 2017;38:2459-72.

  3. Boren J, Chapman MJ, Krauss RM, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2020.

  4. Sniderman A, Vu H, Cianflone K. Effect of moderate hypertriglyceridemia on the relation of plasma total and LDL apo B levels. Atherosclerosis 1991;89:109-16.

  5. Mora S, Szklo M, Otvos JD, et al. LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 2007;192:211-7.

  6. Otvos JD, Collins D, Freedman DS, et al. Low-density lipoprotein and high-density lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial. Circulation 2006;113:1556-63.

  7. Parish S, Offer A, Clarke R, et al. Lipids and lipoproteins and risk of different vascular events in the MRC/BHF Heart Protection Study. Circulation 2012;125:2469-78.

  8. Sniderman AD, Lawler PR, Williams K, Thanassoulis G, de Graaf J, Furberg CD. The causal exposure model of vascular disease. Clin Sci (Lond) 2012;122:369-73.

  9. Wilkins JT, Li RC, Sniderman A, Chan C, Lloyd-Jones DM. Discordance Between Apolipoprotein B and LDL-Cholesterol in Young Adults Predicts Coronary Artery Calcification: The CARDIA Study. Journal of the American College of Cardiology 2016;67:193-201.

  10. Otvos JD, Mora S, Shalaurova I, Greenland P, Mackey RH, Goff DC, Jr. Clinical implications of discordance between low-density lipoprotein cholesterol and particle number. J Clin Lipidol 2011;5:105-13.

  11. Davidson MH, Ballantyne CM, Jacobson TA, et al. Clinical utility of inflammatory markers and advanced lipoprotein testing: advice from an expert panel of lipid specialists. J Clin Lipidol 2011;5:338-67.

  12. Cromwell WC, Otvos JD, Keyes MJ, et al. LDL particle number and risk of future cardiovascular disease in the Framingham Offspring Study - Implications for LDL management. J Clin Lipidol 2007;1:583-92.

  13. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines 2019;73:3168-209.

  14. Sniderman AD, Lamarche B, Contois JH, de Graaf J. Discordance analysis and the Gordian Knot of LDL and non-HDL cholesterol versus apoB. Curr Opin Lipidol 2014;25:461-7.

  15. Cromwell WC, Otvos JD. Heterogeneity of low-density lipoprotein particle number in patients with type 2 diabetes mellitus and low-density lipoprotein cholesterol <100 mg/dl. Am J Cardiol 2006;98:1599-602.

  16. Cromwell WC, Otvos JD, Keyes MJ, et al. LDL Particle Number and Risk of Future Cardiovascular Disease in the Framingham Offspring Study - Implications for LDL Management. J Clin Lipidol 2007;1:583-92.

  17. Sniderman AD, Toth PP, Thanassoulis G, Furberg CD. An evidence-based analysis of the National Lipid Association recommendations concerning non-HDL-C and apoB. J Clin Lipidol 2016;10:1248-58.

  18. Mora S, Otvos JD, Rifai N, Rosenson RS, Buring JE, Ridker PM. Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipids and apolipoproteins in predicting incident cardiovascular disease in women. Circulation 2009;119:931-9.

  19. Thanassoulis G, Williams K, Ye K, et al. Relations of Change in Plasma Levels of LDL-C, Non-HDL-C and apoB With Risk Reduction From Statin Therapy: A Meta-Analysis of Randomized Trials. J Am Heart Assoc 2014;3:e000759.

  20. Toth PP, Grabner M, Punekar RS, Quimbo RA, Cziraky MJ, Jacobson TA. Cardiovascular risk in patients achieving low-density lipoprotein cholesterol and particle targets. Atherosclerosis 2014;235:585-91.

  21. Grabner M, Winegar DA, Punekar RS, Quimbo RA, Cziraky MJ, Cromwell WC. Cost Effectiveness of Achieving Targets of Low-Density Lipoprotein Particle Number Versus Low-Density Lipoprotein Cholesterol Level. Am J Cardiol 2017;119:404-9.