High cholesterol early in life can predispose to atherosclerosis in adulthood

• Higher levels of low-density lipoprotein (LDL) cholesterol in the blood is linked to an increased risk of atherosclerosis, the buildup of fatty plaques in the blood vessels.
• These are linked to cardiovascular disease as they narrow the blood vessels, and can block them.
• Researchers have shown that early exposure, particularly intermittent exposure to a high-fat Western-style diet is linked to greater development of plaques in mice than later continuous exposure, despite overall exposure being similar.
• They also showed that exposure to low density lipoprotein cholesterol early in life influenced risk of atherosclerosis in midlife, in an analysis of a cohort of people in Finland.

Childhood exposure to cholesterol can have an impact on future risk of atherosclerosis, which has been linked to increased risk of cardiovascular disease.

Recently an international team of researchers has looked at cholesterol levels in mice and people in Finland and found that early exposure to low-density lipoprotein (LDL) cholesterol accelerated the risk of atherosclerotic plaques in the arteries in mid-life, compared to later continuous exposure.

The authors of the study — whose results appeared in Nature — argue that their findings support earlier cholesterol testing in order to determine who could be at risk of heart disease in future, to allow earlier treatment of high cholesterol.

Ziad Mallat, MD, PhD , corresponding author of this study, and BHF Professor of Cardiovascular Medicine at the University of Cambridge in the U.K., told Medical News Today that:

“The concentration in the blood and the exposure duration to cholesterol over time is a determinant of cardiovascular disease. So in terms of cholesterol, cardiovascular disease incidence increases with increasing LDL cholesterol concentration and with increasing exposure duration.”

Does the timing of cholesterol exposure affect atherosclerosis risk?

In this new study, the researchers wanted to look at the impact of the timing and duration of cholesterol exposure.

“[I]f the body is exposed to cholesterol for the same duration, let’s say, but starting at 30 [years old] versus starting late, [we wanted to see] whether this has any impact on the development of the disease later on,“ explained Mallat. This is important, he noted, because everyone is exposed to cholesterol throughout their lives.

“However, you know people who care about cholesterol only when they are old all the screening programmes start very late in life, generally after the age of 50, because what we think is that atherosclerosis is something that affects old people and is related to age,” he added.

Mallar and fellow researchers set out to determine if the timing of the exposure had an effect on later development of atherosclerosis.

Why do arterial plaques progress?

When a person’s cholesterol is tested, the ratio of high-density lipoprotein (HDL) cholesterol to LDL cholesterol can be used to calculate a person’s risk of heart disease .

This is as fat accumulation, or “plaques” in the arteries, known as atherosclerosis, is associated with greater risk of heart disease as it can narrow and block the blood vessels.

When LDL cholesterol cell receptors are lost, the cells are less able to take them up, increasing LDL cholesterol in the bloodstream, leading to the formation of these plaques.

Researchers initially looked at mouse models of familial hypocholestrolemia , a condition driven by genetics in which a person’s LDL cholesterol is too high due to the loss of these receptors, leading to atherosclerosis at a young age.

They gave male mice 6 weeks of a late continuous high-fat, Western-type cholesterol-rich diet versus 6 weeks of an early intermittent Western-type diet.

The cholesterol levels of the mice were frequently measured, and the researchers found that the overall cholesterol load was similar between the two groups of mice as were weight, heart rate, blood pressure, and plasma corticosterone levels.

However, the size of the atherosclerotic plaques detected were larger in the mice who had followed the early intermittent Western diet. This was also the case in female mice. This trend persisted in mice that received the two different diets for 12 weeks.

The researchers then found that the behavior of immune cells called macrophages in the aorta of these mice are altered during the progression of atherosclerosis, and this led to further disease progression.

Early cholesterol raises risk of atherosclerosis in mid-adulthood

Next, the researchers looked at whether these patterns also appeared in humans. To do this, they analyzed data from ultrasounds of the carotid artery taken as part of the Cardiovascular Risk in Young Finns Study (YFS)35. Participants entered the study in the 1980’s between the ages of 3 and 18.

The researchers looked at data collected from two groups of over 2,000 participants, one observed around age 30 and the other around age 50.

They found that not only was higher LDL-cholesterol exposure across different life stages associated with higher risk of plaque presence in the carotid artery, they also found that higher LDL-cholesterol levels before adulthood contributed to the development of atherosclerosis in mid-adulthood.

Cheng-Han Chen, MD , a board-certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA, who was not involved in the research, explained to MNT that:

“​​Intermittent early exposure to high cholesterol appears to affect the function of the macrophage cells that live in the walls of our arteries, at an important time in their development, causing them to increase the accumulation of atherosclerosis/blockages in the future.”

However, he cautioned that “long-term longitudinal controlled studies would be necessary in order to link early intermittent exposure to high cholesterol to development of atherosclerosis in adults.”

What role does diet play in plaque formation?

Jayne Morgan,MD , a cardiologist, and Vice President of Medical Affairs at Hello Heart and Adjunct Associate Professor of Medicine at The Morehouse School of Medicine, not involved in this research, told MNT that ”children, with early exposure [to high cholesterol], may be most at risk [of cardiovascular problems].”

”We also know this from autopsy results of children in Western countries who often can already show ‘streaking’ in their aortas, which are early signs of fatty deposits beginning, even at such a young age. We see here as well that early exposure was more atherogenic when mice exposed at 6 weeks of age were compared to mice exposed at 22 weeks of age for the intermittent Western diet,” she detailed.

The main reason why the Western-like diet the mice were put on resulted in atherosclerosis was due “to the type of fat, [that is,] saturated vs unsaturated, [and] processed foods vs unprocessed or minimally processed foods,” explained Morgan.

”This is important because diets that are high in saturated fats and processed foods can decrease the number of LDL receptors in the liver, which are responsible for removing cholesterol from the blood. A decrease in LDL receptors translates into a rise in LDL levels in the blood and an increase in fatty deposits within the arteries,” she noted.