Should I be worried if my HDL is low?

High Density Lipoprotein (HDL) is often labelled as the “good” cholesterol. However, over the years it has become clear that this label is far too simple. HDL is a far more complex particle than initially thought. In this article, I will discuss everything you need to know about it.

What is HDL?

HDL is a type of cholesterol carrying particle in the blood (lipoprotein). It carries cholesterol and other fats around the body. Like other lipoproteins it has a protein backbone that packages up all the fats so they can travel in blood. The protein on HDL is called Apolioprotein A1.

These lipoproteins were historically characterized by their density, which is why this one is called high density lipoprotein (HDL). In comparison to low density lipoprotein (LDL) and very low density lipoprotein (VLDL).

Measuring HDL?

• What does the number HDL-C mean in the standard cholesterol blood work? The number HDL-C (HDL-Cholesterol) refers to the total amount of cholesterol found in all the HDL cholesterol particles in the blood.
• Are there other metrics to measure HDL? We can measure ApoA1, which gives us an approximation of the HDL particle numbers.
• Can we measure the function of HDL? HDL particles have lots of functions. We have no easy way to assess the functionality of HDL particles.

Why is HDL called the “good” cholesterol?

First off, I would like to state for the record that there is no such thing as good and bad cholesterol! All lipoporoteins have important physiological functions unrelated to their cholesterol content, and these labels are far too simplistic. So labeling LDL-C as “bad cholesterol” is far too simplistic either.

The reason why HDL is called the “good” cholesterol is because population studies ( in healthy people) found that people with low levels of HDL-C had more heart attacks.¹ Therefore higher HDL was associated with less risk of heart disease. Hence the term “good” cholesterol. However, this is not a linear relationship.  Once HDL goes above 60mg/dl there is no further reduction in risk of heart attacks.

The story doesn’t stop there. More recent studies have shown that once HDL-C gets above a certain level it is actually associated with an increased risk of death!

What is the normal HDL level?

Once HDL-C gets to 60mg/dl, there is no further reduction in the risk if heart attack. The HDL level associated with the lowest risk of death is 50mg. Above 50, the association with death increases. However, don’t get hung up on these levels, they are not targets for you! Keep reading.

What does HDL do?

HDL has a number of different functions:

1. HDL plays a key role in reverse cholesterol transport. That is transporting excess cholesterol produced by the peripheral tissues to the liver. For example, they can collect excess cholesterol found in macrophages or cell membranes and transport it to the liver. This is part of their proposed role of removing cholesterol from atherosclerotic plaques.
2. Anti-inflammatory and cyto-protective – They have potential roles in preventing monocytes from pathologically attaching to blood lining cells (endothelium) and can be involved in endothelium repair. In addition, they have effects on prevention of clot formation, cell damage and cell death.

As you can see from the way we currently measure HDL, we capture none of this functionality.

What conditions cause low HDL-C?

Low HDL-C is most commonly seen in metabolic syndrome or diabetes. In addition it can be seen in chronic inflammatory conditions, chronic kidney disease and smoking.

What lifestyle changes increase HDL-C?

A number of lifestyle measures can increase HDL-C. These lifestyle measures are also associated with reduced cardiac risk. The amount of the benefit attributable to changing HDL is not known because these lifestyle changes effect multiple other parameters that can reduce the risk of heart disease.

• Physical activity – 5-10% increase
• Weight loss – 5-20% increase
• Stopping smoking – 5-10% increase
• Reduced alcohol intake – 5-15% increase
• Mediterranean diet – 0-5% increase

Does raising HDL-C prevent heart attacks?

A number of medications influence HDL-C. Statins and fibrates both increase HDL-C marginally, however their benefits on cardiac risk are more likely due to their other effects on lipid parameters.

There were a group of compounds called CETP (Cholesterol Ester Transfer Protein) inhibitors that were specifically developed to increase HDL-C. Drug companies thought (very simplistically) that because low HDL was associated with high risk, if they raised HDL then this would reduce risk. 

However, despite raising HDL-C these drugs all failed to show an improvement in cardiac risk. In fact, one compound that I was involved with as an investigator, torcetrapib, actually increased cardiac risk!

Therefore we have no evidence that targeting and trying to raise HDL-C will lower your risk of a heart attack.

What should you do if your HDL-C is low?

If you have low HDL-C then look for metabolic or inflammatory conditions that might cause it. You should then look at your lifestyle and check for areas that could be improved. However, don’t worry about your HDL-C number, it is not a therapeutic target. Focus on your LDL-C and ApoB along with other metabolic parameters like glucose and HbA1c.

Summary

The HDL story is complex and the “good” cholesterol label is too simplistic.

• Low HDL-C is associated with increased cardiac risk.
• High HDL-C is associated with increased risk of death.
• Raising HDL-C with medication does not reduce your risk of a heart attack.
• HDL particles have multiple functions.
• The measurement of HDL-C tells us nothing about HDL particle function.

Focus on lifestyle and forget about your HDL-C, all it causes is confusion and it keeps focus away from the most important marker which is ApoB.

References

1 Gordon DJ, Probstfield JL, Garrison RJ et al (1989) High density lipoprotein cholesterol and cardiovascular disease. Four Prospective American Studies. Circulation 79:8–15

2  Bowe B, Xie Y, Xian H, Balasubramanian S, Zayed MA, Al-Aly Z (2016) High density lipoprotein cholesterol and the risk of all-cause mortality among US Veterans. Clin J Am Soc Nephrol. doi:10.2215/CJN.0073011