EN / DA
Body and mind

Levels of “ugly” cholesterol in the blood higher than previously thought

Danes have much higher levels of remnant cholesterol in their blood than previously thought. This discovery calls for changing the treatment of people with elevated levels of cholesterol.

New research from Denmark shows that Danes have far higher levels of remnant lipoprotein cholesterol, which researchers call “ugly” cholesterol, than previously thought.

Remnant lipoprotein cholesterol greatly increases the risk of blood clots, as does the “bad” cholesterol, low-density lipoprotein (LDL), which is one of the leading causes of death globally. Danes’ levels of this remnant cholesterol are just as high as their levels of LDL cholesterol.

This discovery indicates that the relentless focus on LDL over 25 years has allowed a potentially equally great cause of death to stay out of the public spotlight.

These surprising results were recently published in Atherosclerosis.

“Our results emphasize that solely treating people who have high LDL levels is insufficient. Medication that only reduces people’s level of LDL does not reduce the similarly high levels of remnant cholesterol and the associated high risk of developing a blood clot,” explains an author, Børge Nordestgaard, Clinical Professor, Department of Clinical Medicine, University of Copenhagen and Copenhagen University Hospital.

The body cannot break down LDL and remnant cholesterol

Human body fat comprises triglycerides and cholesterol.

Triglycerides are the main constituents of body fat in humans and of vegetable fat, and cholesterol is an essential structural component of human cell membranes. Both triglycerides and cholesterol are transported through the blood, where they bind to many other molecules in a complex process that enables fat to be transported to the places in the body where it is needed.

The human body uses cholesterol to make cell membranes and to make bile salts and as precursors of various steroid hormones, including estrogen and testosterone.

Broadly speaking, there are three types of cholesterol in the human blood.

• small particles: high-density lipoprotein (HDL), called “good” cholesterol;

• medium-size cholesterol (LDL): traditionally called “bad” cholesterol, which is associated with a significantly increased risk of atherosclerosis and blood clots because excess quantities are deposited in the walls of blood vessels, which slowly block the blood flow; and

• the largest cholesterol particles: remnant lipoprotein which, like LDL, is associated with an increased risk of atherosclerosis and blood clots.

“The problem is that the human body does not have enzymes that break down cholesterol. White blood cells can break down triglycerides and protein but not cholesterol. This is why we cannot get rid of it and why it accumulates in the arteries, where it eventually causes blood clots,” says Børge Nordestgaard.

9293 Danes studied

Børge Nordestgaard has been researching remnant cholesterol for 25 years, so the danger of having too much of it in the blood has been known.

In this study, the researchers examined the concentrations of the three types of cholesterol among 9293 participants in the Copenhagen General Population Study, which comprehensively examined the health of 140,000 Danes.

“Previous research based on the Copenhagen General Population Study has shown that overweight and obesity are the main causes of the very high concentrations of remnant cholesterol in the blood of adult Danes. Other factors include diabetes, genetics and lack of exercise,” explains another author, Mie Balling, PhD student, Department of Clinical Medicine, University of Copenhagen and Copenhagen University Hospital.

Equal quantities of remnant cholesterol and LDL in the blood

The researchers used metabolomics to identify and measure the concentrations of all metabolites in the blood of the participants, including HDL, LDL and remnant cholesterol.

These measurements showed that the concentrations of LDL and remnant cholesterol were almost equal.

“Ordinary Danes therefore have far more of the “ugly” cholesterol in their blood than previously thought. So far, both cardiologists and general practitioners have focused mostly on reducing LDL, but it will also be necessary to try to reduce the concentrations of remnant cholesterol,” says Børge Nordestgaard.

Obesity increases the concentration of remnant cholesterol in the blood

According to Børge Nordestgaard, the reason remnant cholesterol has not been in focus so far may be that there is no specific way to treat people who have high concentrations.

In contrast, people with high LDL can be effectively treated with statins, which is why the pharmaceutical industry has focused on precisely this type of cholesterol.

However, much greater focus has been placed on developing treatments to reduce the concentrations of remnant cholesterol and triglycerides in recent years, and several medicines are in clinical trials.

In addition, some studies have shown that fish oil can lower the levels of remnant cholesterol and triglycerides.

However, according to Børge Nordestgaard, everyone can act to reduce high levels of triglycerides and remnant cholesterol.

“The most important thing you can do to reduce the risk of having a blood clot is to maintain normal weight,” he explains.

In 2018, a major international randomized controlled trial showed that reducing the concentrations of triglycerides and remnant cholesterol reduced the risk of developing cardiovascular disease by 25%.

A third of nonfasting plasma cholesterol is in remnant lipoproteins: lipoprotein subclass profiling in 9293 individuals” has been published in Atherosclerosis. The Novo Nordisk Foundation awarded a grant in 2016 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.