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Diet and lifestyle

The myth of "good" cholesterol

HDL being “good” cholesterol is a myth. New research shows that both high and low concentrations of HDL in the blood are associated with an increased risk of both infectious disease and death.

Until very recently, doctors and researchers talked about “good” cholesterol. They meant HDL (high-density lipoprotein), and higher levels of HDL cholesterol in the blood seemed certain to be better for the heart and the rest of the circulatory system.

However, this assumption is obsolete, and the fact that the associations are not that simple has become increasingly clear in recent years. Having low levels of HDL in the blood certainly seems to be associated with a greater risk of cardiovascular diseases, but this does not necessarily mean that having high levels is healthy.

New Danish research provides even more evidence that we should stop calling HDL “good” cholesterol. The study, carried out on 116,000 people in Denmark, shows that both high and low levels of HDL in the blood are associated with significantly increased risk of both infectious disease and death.

“A few years ago, people rejected us researchers who were not so certain that HDL is as healthy as everyone said it was. Eventually, however, the situation has changed, and having high levels of HDL in the body is now clearly not beneficial – on the contrary. Many pharmaceutical companies have burned through a great deal of money trying to develop medicines that increase the levels of HDL,” says Børge Nordestgaard, Clinical Professor, Copenhagen University Hospital and Department of Clinical Medicine, University of Copenhagen.

Børge Nordestgaard and Christian Medom Madsen recently published an article in European Heart Journal about their findings, which link high levels of HDL with an increased risk of infectious disease.

The body produces HDL

HDL is a fat-soluble lipoprotein.

Unlike the other types of cholesterol, LDL (the “bad” cholesterol) and triglycerides, which should also be at a low level, we do not get HDL through food. We produce it ourselves, so our genes are one factor determining the levels of HDL.

HDL plays a crucial role in transporting essential fatty acids and vitamins round the body, so HDL is crucial for keeping us alive.

Previous studies have shown that people with low levels of HDL have an increased risk of cardiovascular disease, but these people also often have high levels of triglycerides.

Further, studies in mice have shown that the level of HDL influences how the bone marrow produces immune cells.

“We therefore think that the level of HDL can affect the risk of getting an infectious disease,” says Børge Nordestgaard.

Data from 106,000 Danes

In the new research, Christian Medom Madsen and Børge Nordestgaard used HDL measurements from 106,000 Danes who participated in the Copenhagen General Population Study.

The researchers compared the HDL measurements with the registered hospitalizations for infectious diseases in the Danish National Patient Registry.

The researchers followed up the participants for 6 years on average and thus could determine the association between the level of HDL and the risk of getting an infectious disease.

Significantly higher risk of hospitalization for infection

The study showed that people with low levels of HDL had a 75% greater risk of hospitalization during the study period compared with people with average levels of HDL.

In addition, people with high levels of HDL had a 43% greater risk of hospitalization for infectious diseases.

So having high or low levels of HDL was not associated with improved health rather than the opposite.

Of the 106,000 participants, 21% had low levels of HDL, and 8% had high levels of HDL.

“So more than one quarter of Denmark’s population has HDL levels associated with an increased risk of infectious disease. This should not be neglected,” says Børge Nordestgaard.

Dysfunctional HDL could be the cause

Børge Nordestgaard says that, for now, he can only speculate on why having either high or low levels of HDL is associated with a higher risk of infectious disease.

The obvious possibility is that low levels of HDL lead to the bone marrow producing fewer immune cells, and thus low levels of HDL increase the risk of infectious disease.

The second possibility is that HDL affects the body’s defence against toxins, and low levels of HDL can therefore also contribute to the severity of infections.

The quality of the HDL might explain the fact that high levels of HDL appear to have the same association with infections as low levels. Børge Nordestgaard speculates that the levels of HDL may only be high because the HDL particles do not function as well as they should.

“This is all speculation, but the simplest explanation is that, even though we find high levels of HDL, the quality may be so low that these people have a similar increased risk of infectious diseases for the same reason as people with low levels of HDL,” says Børge Nordestgaard.

High HDL is also associated with an increased risk of death

This study is the first major epidemiological study to associate the levels of HDL and the risk of infectious diseases, but it is not the first to show that high levels of HDL can be dangerous.

Another study by Børge Nordestgaard performed in 2017 using data from the Copenhagen General Population Study showed that high levels of HDL are also associated with an increased risk of death.

Thus, men with the highest levels of HDL were twice as likely to die during the study as subjects with moderate HDL. For women, the risk was 68% higher.

“These results imply that some of us are genetically predisposed to have high levels of HDL and that this may increase the risk of both death and infectious diseases. We can use this knowledge to advise people with high levels of HDL that they should focus intensely on a healthy lifestyle and avoid too many of the factors that would otherwise lead to a shorter life and cardiovascular disease, such as smoking, insufficient physical activity and an unhealthy diet,” says Børge Nordestgaard.

U-shaped relationship of HDL and risk of infectious disease: two prospective population-based cohort studies” has been published in European Heart Journal. In 2016, the Novo Nordisk Foundation awarded a grant to Børge Nordestgaard for the project Low High-density Lipoprotein as a Cause of Infectious Disease.

Børge Nordestgaard
Clinical professor
We analyse data for 116,000 subjects from the Copenhagen City Heart Study and the Copenhagen General Population Study, in combination with mortality data from the Danish Civil Registration System. They have followed the subjects for an average of 6 years, and based the study on just over 10,500 deaths. The researchers were able to calculate the mortality rate based on these deaths and medical information on the subjects. The results showed that men with extremely high HDL levels in the blood had a 106 per cent higher mortality rate than men with a normal HDL level. Among women, those with extremely high levels of HDL had a 68 per cent higher mortality rate than the normal group. Men in the next group, with very high levels, also had a 36 per cent higher mortality rate.