Investigators Link Early Cholesterol Exposure With Faster Atherosclerosis Development

High cholesterol levels in young adults may be a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), according to a study published by scientists from the University of Cambridge. Their data showed that early intermittent exposure to cholesterol is a strong determinant of accelerated atherosclerosis, the buildup of plaque in the arterial walls. The findings may be essential for curating effective therapeutic strategies to get ahead of ASCVD in earlier years.

These findings underscore the importance of proactive management of cholesterol levels, particularly in younger individuals. Image Credit: © wuttichai1983 - stock.adobe.com

According to the American College of Cardiology, ASCVD-related conditions are the leading cause of morbidity and mortality around the world. Lifestyle modifications are key preventive strategies for ASCVD and include healthy diet, exercise, and avoidance of tobacco, as well as careful attention to blood pressure and lipid levels. The observed association between low-density lipoprotein cholesterol (LDL-C) and ASCVD indicates that reducing and maintaining lower levels of cholesterol, which can be accomplished through lifestyle changes and medical interventions, reduces the risk of ASCVD.¹

Prior studies have found strong associations between LDL-C and ASCVD events in middle-aged individuals (adjusted hazard ratio [aHR], 1.14 [95% CI, 1.04–1.24]); however, the study published in Nature expands this to younger individuals, highlighting the necessity of maintaining healthy cholesterol levels in younger populations, as well. In a mouse model, the authors discovered that early intermittent feeding of mice with a high-cholesterol, Western-type diet led to faster development of atherosclerosis compared to continuous exposure later in life.^2,3

Data from the animal model showed that early intermittent hyperlipidemia appeared to alter the balance of arterial macrophages and immune cells involved in atherosclerosis. The study authors reported that genes in these macrophages with altered expression were enriched with those linked to human ASCVD. Among their findings, LYVE1+ resident macrophages were shown to be protective against atherosclerosis, potentially revealing new biological pathways that could be targeted to slow or prevent the progression of the disease.³

To confirm their findings, the authors referred to The Young Finns Study, a major long-term investigation into cardiovascular risk from childhood to adulthood that tracked over 2,000 participants from the 1980s, most of whom received carotid artery ultrasound scans at ages 30 and 50 years. They found that participants who were exposed to high cholesterol levels as children had more significant plaque buildup.^3,4

These findings underscore the importance of proactive management of cholesterol levels, particularly in younger individuals. Pharmacists, as integral members of the health care team, can play a pivotal role in this preventive approach. By educating patients about the risks of early cholesterol exposure and the importance of maintaining healthy lipid levels, pharmacists can support lifestyle modifications and adherence to prescribed medications. Such engagement helps prevent the onset of ASCVD, mitigates its progression, and contributes to better long-term health outcomes.

“What this means is that we shouldn’t leave it until later in life before we start to look at our cholesterol levels,” Ziad Mallat, British Heart Foundation professor of cardiovascular medicine, told the University of Cambridge. “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.”⁵

REFERENCES

1. Key points from the 2019 acc/aha guidelines on the primary prevention of cardiovascular disease. American College of Cardiology. April 29, 2019. Accessed September 13, 2024. https://www.acc.org/latest-in-cardiology/articles/2019/04/29/07/42/key-points-from-the-2019-acc-aha-guidelines-on-the-primary-prevention-of-cvd

2. Mortensen M, Dzaye O, Bøtker H, et al. Low-density lipoprotein cholesterol is predominantly associated with atherosclerotic cardiovascular disease events in patients with evidence of coronary atherosclerosis: the western denmark heart registry. Circulation. January 9, 2023. doi:10.1161/CIRCULATIONAHA.122.061010

3. Takaoka M, Zhao X, Lim H.Y., et al. Early intermittent hyperlipidaemia alters tissue macrophages to fuel atherosclerosis. Nature. September 4, 2024. doi:10.1038/s41586-024-07993-x

4. The cardiovascular risk in young finns study. Young Finns Study. Accessed September 13, 2024. https://youngfinnsstudy.utu.fi/

5. High cholesterol levels at a young age significant risk factor for atherosclerosis. University of Cambridge. September 4, 2024. Accessed September 13, 2024. https://www.cam.ac.uk/research/news/high-cholesterol-levels-at-a-young-age-significant-risk-factor-for-atherosclerosis