What Is Non HDL Cholesterol

 Non-HDL cholesterol is all of the cholesterol that is not included in the HDL fraction of your lipoproteins.

The reason we like to use this is that it is a "measured" cholesterol. It is non calculated from triglycerides and other formulas. It gives us a pretty close approximation of apoB, or the lipoproteins that contain the "beta" apolipoprotein. Beta lipoproteins are all of the lipoproteins that are potentially atherogenic. The apo A-1 particles are the HDL particles below. The apoB particles are any number of VLDLs, IDLs, LDLs, Lp(a), and chylomicrons.

The reason I say "potentially atherogenic, is because LDL particles spend some of their lifespan helping HDL particles return cholesterol back to the liver for elimination in a process called indirect reverse cholesterol transport. Usually, the HDL particle return cholesterol for elimination. But LDL particles can "mate" with an HDL using cholesterol ester transfer protein and exchange triglycerides for cholesterol with HDLs and return that cholesterol to the liver for elimination.

Transfer of Cholesterol From HDL To LDL

Below is a diagram showing the transfer of cholesterol from HDL particles to LDL particles in exchange for triglycerides.

Understanding Non-HDL Cholesterol: The Cardiologist's Guide

Non-HDL cholesterol has gained significant attention in cardiovascular medicine due to its robust predictive power for atherosclerotic cardiovascular disease (ASCVD). As one of the foremost cardiologists, Dr. Thomas Dayspring emphasizes the importance of non-HDL cholesterol in assessing lipid-related risk beyond traditional measures like LDL cholesterol.

Total cholesterol (TC) represents the cholesterol carried in all the circulating lipoproteins. If one subtracts the cholesterol in HDL particles (HDL-C) from total cholesterol (TC), one would have the cholesterol mass that is not in the HDL particles. This represents apoB-cholesterol and is more conveniently called non-HDL-cholesterol (non-HDL-C). It is a surrogate (guesstimate) of apoB.

Non-HDL-C can be used as a surrogate for apoB (see above graphics). Because this is easy to calculate from any lipid panel, many have advocated for its use.

As an example, your total cholesterol is 220 mg/dL and your HDL is 40 mg/dL. You take 220-40 and your number is 180 mg/dL. So, your non-HDL-C is 180 mg/dL. This is just an example of how you can calculate this yourself. Many labs now report this value in their standard lipid panel results.

What is Non-HDL Cholesterol?

Non-HDL cholesterol refers to the total cholesterol minus HDL cholesterol. It encompasses all the atherogenic lipoproteins, including:

• Low-Density Lipoprotein (LDL)
• Intermediate-Density Lipoprotein (IDL)
• Very-Low-Density Lipoprotein (VLDL)
• Lipoprotein(a) [Lp(a)]
• Chylomicron remnants

Since these particles are directly involved in the formation of atherosclerotic plaques, non-HDL cholesterol is a comprehensive marker for cardiovascular risk.

Why Focus on Non-HDL Cholesterol?

1. Broader Risk Assessment Than LDL Cholesterol

While LDL cholesterol has traditionally been the primary target for therapy, it doesn’t account for other atherogenic lipoproteins. Non-HDL cholesterol bridges this gap, making it a superior predictor of ASCVD risk.

2. Simple and Reliable

Calculating non-HDL cholesterol doesn’t require fasting, unlike other lipid parameters like triglycerides. This simplifies screening and monitoring in clinical practice.

3. Better Alignment with Outcomes

Studies show that non-HDL cholesterol correlates more closely with cardiovascular events than LDL cholesterol, particularly in patients with high triglycerides or diabetes.

More HDL Particles than LDL Particles

One thing to note is that there are about 27 times more HDL particles in circulation than LDL particles. HDL particles are much smaller and hence carry much less cholesterol. That's why your HDL cholesterol is much lower than your LDL cholesterol.

Non-HDL More Accurate As A Risk Assessment 

The benefit of using non-HDL-C is that it also includes the cholesterol that is not only in LDL particles but also VLDL particles and their smaller, cholesterol-rich remnants which can be especially prominent when triglycerides start to increase above 100 mg/dL and especially when triglycerides are > 150 mg/dL. Neither calculated nor directly measured LDL-C will evaluate VLDL remnants. A better and more accurate name for non-HDL-cholesterol is apoB-cholesterol.

Although, like LDL-C, non-HDL-C and apoB have high correlation, they can be discordant in which case ASCVD risk better correlates with apoB. There is no way to diagnose LDL-C / non-HDL-C discordance with apoB without obtaining all the values.

Non-HDL-C has been validated as a great risk assessment tool when apoB is not available.

Further reading:
https://pubmed.ncbi.nlm.nih.gov/30595507/
https://pubmed.ncbi.nlm.nih.gov/33736827/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9791017/

When looking at the highest tertile of apoB vs non-HDL-C, apoB was more predictive of CV risk. I highly recommend reading the original article. They corrected for all confounders and covariates.

Study:
https://www.ahajournals.org/doi/10.1161/circulationaha.104.532499

Another study examined the ability of apoB and non-HDL-C to correctly predict risk when the two values were discordant. They found that, “The result is that even with identical overall hazard ratios, apoB points to higher risk in a substantial number of individuals whereas the converse is the case for non- high-density lipoprotein cholesterol”. Risk follows apoB.

Study:
https://www.lipidjournal.com/article/S1933-2874(10)00044-9/fulltext

How is Non-HDL Cholesterol Measured?

The formula for calculating non-HDL cholesterol is straightforward:

$$\text{Non-HDL Cholesterol} = \text{Total Cholesterol} - \text{HDL Cholesterol}$$ Non-HDL Cholesterol =  Total Cholesterol −  HDL Cholesterol

For optimal cardiovascular health, the ideal level of non-HDL cholesterol is about 30 mg/dL higher than the target LDL cholesterol level. For instance, if your LDL cholesterol goal is <100 mg/dL, your non-HDL cholesterol goal should be <130 mg/dL.

Target Levels for Non-HDL Cholesterol

The American College of Cardiology (ACC) and the American Heart Association (AHA) recommend the following non-HDL cholesterol goals:

Dr. Alo's Official Lipid Targets

I prefer to be under the 20th percentile, or even under the 5th percentile depending on your risk factors and medical history.

Personally, my LDL, apoB, and Non-HDL hover in the low 40s to 50s and I have never had a cardiac event or risk factors.

Management Strategies For Lowering non-HDL Cholesterol

1. Lifestyle Modifications

• Diet: Emphasize heart-healthy foods, including vegetables, fruits, whole grains, and lean proteins.
• Exercise: Aim for at least 150 minutes of moderate aerobic activity weekly.
• Weight Management: Achieving a healthy weight can significantly lower non-HDL cholesterol levels.

2. Pharmacological Interventions

• Statins: First-line therapy for lowering atherogenic lipoproteins.
• Ezetimibe: Can be added to statin therapy for additional LDL and non-HDL cholesterol reduction.
• PCSK9 Inhibitors: Effective for individuals with genetic lipid disorders or very high cardiovascular risk.
• Bempedoic Acid: Can be added to these and is in pill formation, not an injection

The Role of Advanced Lipid Testing

For individuals with persistent cardiovascular risk despite optimal LDL cholesterol levels, advanced lipid testing can further evaluate:

• Apolipoprotein B (ApoB): Direct measure of atherogenic particle concentration.
• Lipoprotein(a): A genetically inherited lipoprotein associated with increased cardiovascular risk.

Non-HDL Cholesterol: A Paradigm Shift

As Dr. Thomas Dayspring often emphasizes, non-HDL cholesterol represents a shift towards a more inclusive and accurate approach to managing cardiovascular risk. By focusing on all atherogenic lipoproteins, clinicians can better tailor therapies and achieve superior outcomes for their patients.

How To Lower Non HDL

The way you lower non-HDL is the same way we try to lower LDL, apoB, and cholesterol in general:

1. Low saturated fat diet
2. High fiber diet
3. Statin medications
4. Ezetimibe
5. PCSK( inhibitors like Repatha, Praluent, Inclisiran
6. Bempedoic acid

Final Thoughts:

Non-HDL cholesterol is more than just a number—it’s a critical component of modern cardiovascular risk assessment. By integrating this measure into routine practice, healthcare providers can identify at-risk individuals earlier and more accurately. Whether through lifestyle changes, medications, or advanced testing, managing non-HDL cholesterol is pivotal in the fight against heart disease.

For patients and practitioners alike, understanding and addressing non-HDL cholesterol is a cornerstone of proactive, personalized cardiovascular care.

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