High-density lipoprotein (HDL) cholesterol is known as the “good” cholesterol that helps protect against heart disease. It functions by removing excess cholesterol from the arteries and transporting it to the liver for disposal.

However, recent studies suggest that not all HDL is beneficial, and some HDL particles may have a dark side.

The Dark Side of HDL Cholesterol

It is now understood that HDL cholesterol is not a homogeneous group of particles but rather a heterogeneous group with different structures, sizes, and functions.

It was discovered that not all HDL particles have the same protective effect against heart disease. Some HDL particles may have a dark side and can even contribute to heart disease development.

HDL Subclasses

HDL cholesterol can be divided into several subclasses based on their size, shape, and composition. The two main subclasses are HDL2 and HDL3.

HDL2 is larger, more buoyant, and thought to be more cardioprotective compared to HDL3, which is smaller and denser. However, recent research suggests that some smaller-sized HDL particles may not be protective and may even have pro-inflammatory effects.

Pro-Inflammatory HDL Particles

Studies suggest that HDL particles can become dysfunctional, and their structure and function can be altered under certain conditions.

One of the main reasons for HDL dysfunction is inflammation, which can lead to the transformation of HDL particles from anti-inflammatory to pro-inflammatory. This change can increase the risk of heart disease by contributing to the formation of atherosclerotic plaques in the arteries.

Causes of HDL Dysfunction

Several factors can contribute to HDL dysfunction, including:.

Obesity
Smoking
Sedentary lifestyle
Diabetes
Metabolic syndrome

HDL dysfunction can also be caused by genetic factors, such as mutations in the genes that code for proteins involved in HDL metabolism.

The Role of HDL in Cardiovascular Disease

HDL cholesterol has long been associated with a lower risk of heart disease, and increasing HDL levels has been a therapeutic target for the prevention and treatment of cardiovascular disease.

However, recent studies suggest that the relationship between HDL and cardiovascular disease is more complex than previously thought.

Research shows that not all individuals with high HDL levels are protected from heart disease, and not all individuals with low HDL levels are at higher risk of heart disease.

Therefore, some experts argue that the focus should be on measuring the functionality of HDL rather than its quantity.

HDL Functionality Tests

Several lab tests can be used to measure HDL functionality, including:.

Ex vivo cholesterol efflux capacity assay
HDL inflammatory index
Flow-mediated dilation assay
Oxidative stress markers

These tests can provide a better understanding of the protective or harmful effects of HDL and help identify individuals who may benefit from alternative therapies, such as drugs that improve HDL function.

Treatment and Prevention

The best way to prevent HDL dysfunction is to adopt a healthy lifestyle, including a balanced diet, regular exercise, and avoiding smoking.

Individuals with metabolic disorders, such as diabetes or metabolic syndrome, should work with their healthcare providers to manage these conditions and reduce the risk of HDL dysfunction.

For individuals with low HDL levels or dysfunctional HDL particles, there are several drugs available that can help improve HDL function, such as niacin, fibrates, and HDL mimetics.

However, these drugs may have side effects, and their effectiveness in reducing the risk of heart disease is still under investigation.

Conclusion

HDL cholesterol has long been considered the “good” cholesterol, protecting against heart disease. However, recent studies suggest that some HDL particles may have a dark side and can even contribute to heart disease development.

HDL functionality tests can provide a better understanding of the protective or harmful effects of HDL, and individuals with low HDL levels or dysfunctional HDL particles may benefit from alternative therapies. Adopting a healthy lifestyle is the best way to prevent HDL dysfunction and reduce the risk of heart disease.