We need to think about cholesterol from an earlier age, say University of Cambridge researchers

We need to keep cholesterol levels low even when we are young, University of Cambridge scientists say, as our risk of developing atherosclerosis – the ‘furring’ of the arteries – can begin much earlier in life than previously thought.

The researchers also suggest that those people on lipid-lowering drugs such as statins to lower cholesterol levels should remain on them even if their cholesterol levels have fallen, as stopping treatment could increase their risk of atherosclerosis.

One of the major causes of heart and circulatory disease, atherosclerosis involves the hardening and narrowing of vessels that carry blood to and from the heart.

It is caused by the build-up of abnormal material called plaques, which are collections of fat, cholesterol, calcium and other substances circulating in the blood.

Most screening, prevention and intervention programmes primarily target those with high cholesterol levels, and generally after the age of 50, as atherosclerosis has been largely considered a disease of the elderly.

But the new study, published in Nature, shows high cholesterol levels at a younger age – particularly if those levels fluctuate – can be even more damaging than high cholesterol levels that only begin in later life.

While scientists have previously given mice high fat diets for several weeks as adults to see if it leads to a build up of plaques, Prof Ziad Mallat and colleagues at the Victor Phillip Dahdaleh Heart and Lung Research Institute at the University of Cambridge tried a different approach. They gave mice the same amount of high fat food spread over their lifetime to see how it affected their atherosclerosis risk.

“When I asked my group and a number of people who are experts in atherosclerosis, no one could tell me what the result would be,” said Prof Mallat, a British Heart Foundation (BHF) professor of cardiovascular medicine.

“Some people thought it would make no difference, others thought it would change the risk. In fact, what we found was that an intermittent high fat diet starting while the mice were still young – one week on, a few weeks off, another week on, and so on – was the worst option in terms of atherosclerosis risk.”

The team then turned to the Cardiovascular Risk in Young Finns Study, one of the largest follow-up studies into cardiovascular risk from childhood to adulthood.

It recruited participants in the 1980s, who returned for follow-ups over the subsequent decades. More than 2,000 of them had ultrasound scans of their carotid arteries when they were aged around 30 years and again at around 50 years.

Analysing the data, the team discovered those participants who had been exposed to high cholesterol levels as children tended to have the biggest build of plaques, confirming the findings in mice.

“What this means is that we shouldn’t leave it until later in life before we start to look at our cholesterol levels,” Prof Mallat said. “Atherosclerosis can potentially be prevented by lowering cholesterol levels, but we clearly need to start thinking about this much earlier on in life than we previously thought.”

Fluctuating levels of cholesterol appeared to cause the most damage, which Prof Mallat said could explain why some people on statins who do not take them regularly remain at an increased risk of heart attack.

“If you stop and start your statin treatment, your body is being exposed to a yo-yo of cholesterol, which it doesn’t like, and it seems this interferes with your body’s ability to prevent the build-up of plaques,” he explained.

The damage caused by this may relate to the effect that cholesterol has on types of immune cells known as ‘resident arterial macrophages’, which are found in our arteries and help them to clear damaged cells and fatty molecules known as lipids, which include cholesterol, and stop the build-up of plaques.

In the mouse models, high and particularly fluctuating cholesterol levels changed these macrophages physically and altered the activity of their genes, so that the cells were no longer protective, but were instead detrimental, accelerating atherosclerosis.

The research was funded by the British Heart Foundation.