Non-HDL Cholesterol (Non-HDL-C)

Recently, non-HDL cholesterol (non-HDL-C) has become a commonly used marker for a blood lipid pattern associated with increased risk of heart disease.

To calculate non-HDL-C, you only need to know the numbers for total cholesterol and high-density lipoprotein cholesterol (HDL-C).

But why is non-HDL-C such a useful measure of future risk?

Non-HDL Cholesterol (Non-HDL-C)Atherosclerosis is the most common underlying cause of cardiovascular disease. It is due by a complex interplay between lipoproteins, white blood cells (macrophages), the immune system and the natural elements of the arterial wall.

Lipoproteins are the particles that transport cholesterol and triglycerides in the blood stream.

Lipoproteins that are directly involved in atherosclerosis are termed atherogenic. Most of these lipoproteins carry cholesterol and other types of fats such as triglycerides.

A standard lipid profile measures total cholesterol, triglycerides, and HDL-C.

These numbers are then used to calculate low-density lipoprotein cholesterol (LDL-C), according to the so-called Friedwald equation. However, calculation of LDL-C has several limitations.

Limitations of LDL Cholesterol

For historical reasons, LDL-C has become a primary goal of therapy in cardiovascular prevention. Recommendations regarding diet and drug therapy to lower cholesterol are most often based on the LDL-C number.

However, LDL is not the only lipoprotein involved in atherosclerotic heart disease. Triglyceride-rich very low-density lipoprotein (VLDL) and the so-called remnant lipoproteins are also atherogenic.

Therefore, there is a need for a lipid parameter that better reflects the amount of cholesterol within all atherogenic particles. This is of particular importance when triglyceride levels are high which is quite common, for example among people with abdominal obesity or metabolic syndrome.

What Is Non-HDL Cholesterol and Why Is It Important?

HDL and LDL particles seem to play very different roles in the pathogenesis of atherosclerosis. Therefore, measuring the amount of cholesterol within these particles tells two different stories.

While high levels of LDL-C are associated with increased risk of heart disease, elevated levels of HDL-C are associated with lower risk. HDL particles appear to be involved in clearing and removing cholesterol from arteries and atherosclerotic plaques while LDL-particles seem to participate directly in the atherosclerotic process itself.

This is the reason the cholesterol carried by HDL particles (HDL-C) is often called “good cholesterol” and the cholesterol carried by LDL particles (LDL-C) is called “bad cholesterol.” Of course, it is the same cholesterol; the difference lies within the lipoproteins that carry it.

Measuring total cholesterol provides limited information about risk because the number includes both HDL-C and LDL-C.

If we, however, subtract HDL-C from the total cholesterol we will have a measure of the amount of cholesterol carried by all lipoproteins except HDL. Doing this simple math will give us the amount of cholesterol carried within all lipoproteins that are atherogenic. In other words; a measure of cholesterol carried within all the “bad” lipoproteins but not the “good” ones (which is only HDL). This measure is termed non-HDL cholesterol (non-HDL-C).

Relying on LDL-C alone may be misleading. For example, individuals with abdominal obesity, metabolic syndrome or diabetic lipid disorders often have elevated triglycerides, low HDL-C, and relatively normal calculated LDL-C. Despite their normal LDL-C, these patients produce highly atherogenic lipoproteins such as VLDL and IDL (intermediate density lipoprotein) as well as small dense LDL particles.

A patient with low LDL-C and high non-HDL-C is an example of a patient with increased risk who may slip through the cracks because we only look at LDL-C. These patients are also likely to have high LDL particle number (LDL-P) as well as high ApoB levels.

Recent evidence suggests that non-HDL-C shows a better correlation with small dense LDL particles than do other lipid parameters including LDL-C. Clinical studies strongly suggest that a predominance of small dense LDL-C is associated with increased risk of coronary heart disease.

Non-HDL-C has been shown to be a better marker of risk in both primary and secondary prevention studies. An analysis of data combined from 68 studies, non-HDL-C was the best risk predictor of all cholesterol measures, both for CAD events and for strokes.

How to Calculate Non-HDL Cholesterol

An advantage of using non-HDL-C is that you don’t need a fasting blood sample.

Non-HDL cholesterol is your total cholesterol minus your HDL cholesterol

This is the formula:

Non-HDL Cholesterol = Total Cholesterol – HDL cholesterol

So if your Total Cholesterol is 220 mg/dL (5.7 mmol/L) and your HDL cholesterol is 50 mg/dL (1.3 mmol/L);

Non-HDL Cholesterol is 170 mg/dL (4.4 mmol/L)

If you know this simple formula, your knowledge outperforms 44 percent of providers in medical practice in the US. A survey showed that 44 percent of providers in practice could not calculate non-HDL-C when provided a standard lipid profile. Interestingly, cardiologists were just as likely as primary care physicians not to understand the calculation.

What Is a Desirable Level of Non-HDL Cholesterol?

The treatment goal for non-HDL-C is usually 30 mg/dL above the LDL-C treatment target. For example, if the LDL-C treatment goal is <70 mg/dL, the non-HDL-C treatment target would be <100 mg/dL.

Here you can see how non-HDL-C levels are looked at in terms of risk:

  • above 220 mg/dL (5.7 mmol/L) is considered very high
  • 190 – 219 mg/dL (4.9 – 5.6 mmol/L) is considered high
  • 160– 189 mg/dL (4.1 – 4.8 mmol/L) is considered borderline high
  • 130 – 159 mg/dL (3.4 – 4.0 mmol/L) is considered near ideal
  • below 130 mg/dL (below 3.4 mmol/L) is considered ideal for people at risk of heart disease
  • below 100 mg/dL (below 2.6 mmol/L) is considered ideal for people at very high risk of heart disease

How To Lower Non-HDL Cholesterol

Lowering non-HDL-C always begins with lifestyle therapy, usually aimed at lowering triglycerides. Traditionally, reduction in total calories, especially saturated and trans fatty acids, in combination with exercise is recommended. However, reducing sugar and carbohydrate consumption is often very effective in lowering triglycerides and non-HDL-C, particularly in patients with abdominal obesity or the metabolic syndrome

Foods that are high in omega-3 fatty acids may also be useful. Fatty fish such as salmon, sardines, mackerel, and herring is rich in omega-3. Omega-3 fatty acid-containing capsules or fish oils represent a reasonable alternative.

Moderate physical activity can help raise HDL-C and lower non-HDL-C.

Quitting smoking will improve your HDL-C and reduce non-HDL-C. Several studies have shown that male and female smokers have significantly lower HDL-C levels than non-smokers.

Successful reduction of elevated non-HDL-C may also be achieved with medical therapy. This would include the use of a statin drug to serve as the foundation for LDL-C lowering followed by a second treatment to bring non-HDL-C to within the target range. The three categories of drugs that would fall into this group include omega-3 fatty acid preparations, fibrates, and niacin.

However, there are very few clinical endpoint studies evaluating the potential benefit of combining each of these triglyceride lowering modalities with a statin as compared with a statin, making it very hard to recommend such a combination therapy.

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