"Good cholesterol also has a nasty side that can increase the risk of heart attacks," BBC News reports after a US study has suggested that labelling cholesterol either "good" or "bad" is oversimplifying a complex situation.
It has long been the received wisdom that cholesterol can act in positive and negative ways, depending on how it is carried in the blood:
The study found evidence that in certain circumstances, HDL can cause inflammation of the artery wall, which is potentially harmful. A protein called apoA1 – one of the components of HDL – can become oxidised (modified) by an enzyme found in plaques (areas in the artery walls where there has been inflammation and a build-up of fat). This modified form of apoA1 can no longer function properly and promotes further inflammation.
These findings may explain why some trials of HDL cholesterol-elevating drugs have failed to demonstrate significant benefit.
However, the results of this study do not change the current dietary advice about cholesterol intake, but may lead to the development of new tests and treatments in the future.
The study was carried out by researchers from the Cleveland Clinic, Cleveland State University, Cleveland HeartLab, Wake Forest School of Medicine, and the New York University School of Medicine.
It was funded by the US National Institutes of Health, the Leducq Foundation, and the Leonard Krieger Fund.
The study was published in the peer-reviewed journal Nature Medicine.
This research was covered well by BBC News, who did an admirable job of conveying the results of a complex study in a simple way.
This was laboratory and animal research combined with a cross-sectional study on 627 people. It aimed to find out how "good" HDLs can become "bad". HDL normally transports cholesterol to other parts of the body, where it is reprocessed. It is transported to the liver, where it is made into bile acids, and other parts of the body, where it is made into hormones.
This is in contrast to "bad" LDLs, which can deposit fat in artery walls, forming plaques (swellings made up of fats, immune cells and other tissue). Plaques can be dangerous because if they rupture (burst open), they can create a blood clot and block the flow of blood to the heart (which can trigger a heart attack) or the brain (which can trigger a stroke).
One of the main components of HDL is the fat binding protein apoA1. However, apoA1 has also been found in plaques in artery walls. The apoA1 in plaques was found to be "oxidised" – or modified – by an enzyme found in the plaque and was no longer able to bind to cholesterol.
The researchers wanted to investigate why apoA1 wasn't functioning properly (not removing fat and transporting it to the liver) and was instead located in the plaques. This is the ideal study design to address this question.
The researchers did a number of experiments to determine why oxidised apoA1 didn't function properly.
They then looked at levels of the oxidised apoA1 in a group of 627 people who were being screened for risk factors associated with heart disease and stroke (cardiovascular disease) at a cardiology unit. They wanted to see if these were correlated with an increased risk of cardiovascular disease.
The researchers found that a particular amino acid (a building block of a protein) can become oxidised. They called this oxidised form oxTrp72-apoA1.
Once oxidised, the protein no longer functions properly and cannot form HDL particles with fats, which means that HDL's protective effects against cardiovascular disease are nullified.
In addition, it causes inflammation, which can damage the walls of the arteries and could contribute towards atherosclerosis.
The majority of oxTrp72-apoA1 was found in plaques on arteries. However, the researchers found that the absolute levels of oxTrp72-apoA1 and the proportion of oxTrp72-apoA1 to total apoA1 were higher in people with cardiovascular disease or coronary artery disease.
Levels of oxTrp72-apoA1 could predict cardiovascular disease with an odds ratio of a similar size to more established risk factors for cardiovascular disease, such as blood pressure and history of smoking.
The researchers present a model in which HDL enters a plaque to pick up fat to transport to the liver (or elsewhere). However, once there, apoA1 is oxidised by an enzyme in the plaque. This modified form of apoA1 can no longer function properly and promotes further inflammation.
The researchers say that measuring oxTrp72-apoA1 levels could help identify people with coronary artery disease, and could also be the target of research into new therapies.
This research has underlined the fact that the distinction between good and bad fats may be oversimplistic. But it does not change the standard healthy eating message that we should try to prevent the formation of plaques in the first place.
We can do this by limiting the amount of foods we eat that are high in saturated fats, such as processed meats, as they increase LDL levels, while making sure we eat foods high in unsaturated fats, such as oily fish and nuts, as this should help increase your HDL levels.
This research could potentially lead to more effective tests and treatments for cardiovascular diseases in the future.