Preclinical Atherosclerosis is Widespread in 50+ Year Old People

Atherosclerosis is the growth of fatty, inflamed deposits in blood vessel walls, narrowing and weakening them. It results from processes that are universal, present in every older individual. The oxidative stress and inflammation of aging lead to a raised amount of oxidized lipids and lipid carriers such as LDL particles, and these produce a growing dysfunction in the macrophage cells responsible for clearing unwanted lipids from blood vessel tissue.

It is not surprising to see the data presented in today's research materials, showing that near half of older adults in their 50s and 60s age have measurable atherosclerotic lesions in their blood vessels despite exhibiting no clinical symptoms. This is consistent with past studies using imaging to determine the burden of atherosclerosis in large patient populations. Those lesions grow over time to kill at least 25% every older person via stroke, heart attack, or other cardiovascular disease. A way to reverse atherosclerotic lesions is desperately needed, but the research and development of new therapies remains near entirely focused on lowering of LDL cholesterol in the bloodstream, an approach that can only slow the condition, and is incapable of producing sizable reversal of atherosclerosis.

To make real progress towards reversal of atherosclerosis, macrophage cells must be made resistant to the aged environment, enabling these cells to continue their beneficial maintenance of blood vessels as they did in youth. Researchers recently demonstrated sizable reversal in mice via targeting antioxidants to the lysosomes of macrophages to suppress the harm done by oxidized LDL particles, for example. Other approaches exist, such as sequestration of harmful 7-ketocholesterol, under development at Underdog Pharmaceuticals, or providing macrophages with the ability to break down excess cholesterol in situ, under development at Repair Biotechnologies.

More than 40% of adults with no known heart disease had fatty deposits in heart arteries

Atherosclerosis, or the buildup of fatty deposits in blood vessels that supply blood to the heart, is a major cause of heart attacks. A widely used approach to screen people who are at risk for heart disease but who do not yet have symptoms is cardiac computed tomography, commonly known as a cardiac CT scan, for coronary artery calcification (CAC) scoring. The scan creates cross-sectional images of the vessels that supply blood to the heart muscle to measure the presence and density of calcium-containing plaque in the coronary arteries. However, CAC scoring can miss a percentage of people who are at risk for heart attack even though they have a zero CAC score. "Measuring the amount of calcification is important, yet it does not give information about non-calcified atherosclerosis, which also increases heart attack risk. Non-calcified atherosclerosis is believed to be more prone to cause heart attacks compared with calcified atherosclerosis."

Researchers randomly recruited participants aged 50-64 years old from the Swedish census register from 2013 to 2018 as part of the Swedish CArdioPulmonary BioImage Study (SCAPIS). They report on data from 25,182 participants with no history of a prior heart attack or cardiac intervention who underwent both CAC scans and coronary computed tomography angiography (CCTA) scans. CCTA is a radiologic technique that gives a very detailed image of the inside of the arteries that supply the heart with blood. The researchers wanted to determine the prevalence of atherosclerosis in the general population without established heart disease, and how closely the CCTA findings correlated to CAC scores.

CCTA detected some degree of atherosclerosis in more than 42% of the study participants. CCTA found that in 5.2% of those with atherosclerosis, the build-up obstructed blood flow through at least one coronary artery (out of three) by 50% or more. In nearly 2% of those found to have artery build-up, the atherosclerosis was even more severe. Blood flow was obstructed to the main artery that supplies blood to large portions of the heart, and in some cases, all three coronary arteries were obstructed. Atherosclerosis started an average of 10 years later in women compared to men. Atherosclerosis was 1.8 times more common in people ages 60-64 vs. those ages 50-54. Participants with higher levels of atherosclerosis seen by CCTA also had higher CAC scores. Of those with a CAC score of more than 400, nearly half had significant blockage, where more than 50% of the blood flow was obstructed in one of the coronary arteries. In those with a CAC score of zero, 5.5% had atherosclerosis detected by CCTA, and 0.4% had significant obstruction of blood flow.


How about gene therapy with the LAV-BPIFB4 gene? see: Dossena, M., et al. & Puca, A. A. (2020). New Insights for BPIFB4 in Cardiovascular Therapy. International Journal of Molecular Sciences, 21(19), 7163. PMC 7583974
How about prevention and therapy with UDP-003? see: Oconnor, M. S. , et al. & Sadrerafi, K. (2021). Cyclodextrin dimers: A pharmaceutical engineering approach to the therapeutic extraction of toxic oxysterols. Atherosclerosis, 331, e130-e131. doi:10.1016/j.atherosclerosis.2021.06.390
How about prevention and therapy with ApoE-Based Peptides (such as AEM-28)? see: Benitez Amaro (2021). Apolipoprotein and LRP1-Based Peptides as New Therapeutic Tools in Atherosclerosis, J. Clin. Med. 10, 3571. PMC8396846

Posted by: Dmitry Dzhagarov at October 2nd, 2021 1:43 AM

Everyone should receive statins freely.

Posted by: thomas.a at October 2nd, 2021 7:01 AM

Thank god for Repair Biotechnologies and Underdog Therapeutics.

Also, why haven't any other bioetechs or big pharma taken a look at removing this type of damage?

Posted by: jimofoz at October 4th, 2021 12:28 AM

"Trimethylaminuria (TMAU) is an uncommon condition that causes an unpleasant, fishy smell. It's also called "fish odor syndrome". Sometimes it's caused by faulty genes that a person inherits from their parents." This condition is thought to protect against atherosclerosis.

Posted by: Tj Green at October 6th, 2021 10:32 AM
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