The lipoproteins: HDL and LDL

Lipoproteins are classified according to their density.
Lipoproteins are classified according to their density.

Body components, including lipids (fats), are continually being formed, used, degraded and replaced. This process involves the transport of biological compounds between tissues, using the blood plasma as the main highway. For lipids, this poses a problem as they’re not water-soluble.

This “transport problem” is, however, solved by incorporating cholesterol and triglycerides (two different types of fats) into the lipoproteins. These lipoproteins are classified according to their density, which is determined by the proportion of lipid to protein – hence the names low-density lipoprotein (LDL) and high-density lipoprotein (HDL).

LDL and HDL are the two varieties of lipoproteins that are most strongly associated with vascular disease. An increased level of HDL cholesterol is associated with a lower risk of coronary artery disease (CAD). Conversely, low levels of HDL cholesterol are associated with an increased risk. This is why HDL is thought of as the "good" type of cholesterol.

It appears that the HDL particle can clean out excess cholesterol – including that which came from the “bad” low-density lipoprotein (LDL) cholesterol and accumulated in the walls of arteries – and take it back to the liver for reprocessing. It also performs antioxidant activities, which help protect arteries against atherosclerosis.

The HDL concentration is partly under genetic control, but is also influenced by lifestyle factors.

Most cholesterol carried in LDL

LDL is very rich in cholesterol and, in excess, is the main cause of coronary and other artery disease.

Most of the cholesterol in the blood is carried in LDL, so your total cholesterol level is usually a reflection of the amount of LDL cholesterol in your blood.

The LDL particle comprises a protein called apolipoprotein B (apoB) and cholesterol, as well as minor amounts of phospholipid (lecithin being one) and triglyceride. The apoB in LDL recognises a specific receptor (LDL-R) on liver cell walls to which it docks for importation into the liver cells.

This importation mechanism is important since it can be genetically faulty. This can lead to high levels of LDL in the bloodstream, and give rise to an inherited disorder called familial hypercholesterolaemia (FH). If you have this condition, your total cholesterol exceeds 7mmol/L, while your LDL cholesterol exceeds 5mmol/L. Adults with FH also often display a thick Achilles tendon, or a white arc on the cornea of the eye.

When levels of LDL are high, the lipoprotein penetrates the lining of the blood vessels, leading to the development of atherosclerosis. The condition initially affects the wall, but later can affect the flow of the blood, when the atherosclerotic plaque causes narrowing of the arteries. This situation can lead to a heart attack or stroke, among other complications.

While other lipoproteins are removed within hours or minutes, LDL remains in the bloodstream for nearly three days. Eventually it’s cleared, mostly by the liver.

Ongoing research

The lipoproteins have historically been the focus of research into the causes of atherosclerosis and CAD.

As so many different factors (some still unknown) are involved in the development of atherosclerosis and CAD, it’s difficult to accurately predict a person’s risk for a heart attack or stroke. But determining the “cholesterol numbers” is certainly an important part of the process.

Armed with information about lipoproteins, and their role in atherosclerosis and CAD, techniques have been developed to measure HDL and LDL cholesterol separately.

Over time, research has also pointed to other factors that determine levels of these two plasma lipoproteins. Levels of LDL cholesterol, for example, are directly linked to those of apoB – which is almost entirely carried by LDL. So, instead of measuring LDL cholesterol, scientists realised that measurement of apoB would give similar (but not identical) information.

It was also discovered that the LDL packages themselves became smaller and denser in people with certain disorders, including hypertriglyceridaemia – the medical term for raised triglyceride levels. Smaller LDL is usually associated with higher triglycerides and lower HDL, but other risk factors such as obesity, smoking and diabetes form part of the bigger picture. These factors can all lower “good” HDL levels even further. Small LDL at the same cholesterol value than large LDL is more likely to cause atherosclerosis.

The good news is that, by making certain lifestyle changes, LDL and triglyceride levels can be kept in check, while HDL levels can be improved. Talk to your doctor about the best course of action if your cholesterol numbers aren’t quite what they should be.

Reviewed by Prof David Marais, FCP(SA), Head of Lipidology at Groote Schuur Hospital and the University of Cape Town, February 2018

Image credit: iStock

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