- Their two recent studies have uncovered new information about clonal hematopoiesis and its treatment with the anti-inflammatory drug colchicine.
- Researchers from the Centro Nacional de Investigaciones Cardiovasculares (CNIC) in Spain have confirmed that clonal hematopoiesis is a risk factor for atherosclerosis, the underlying cause of most cardiovascular diseases.
- This new information could lead to the development of novel personalized treatments for patients in the future.
Clonal hematopoiesis describes how certain blood-forming stem cells in the bone marrow or bloodstream acquire genetic changes, or mutations, and start to grow and multiply more than usual.
These acquired changes occur in somatic cells, or cells in the body that are not egg and sperm cells, during a person’s lifetime.
This expansion of mutated cells can increase the risk of blood cancers and other disorders, but in many cases does not cause immediate problems and is often discovered incidentally in older adults.
Now, researchers have shown that the condition is linked to increased cardiovascular risk.
One study, published in Nature Medicine at the end of August 2024, has identified clonal hematopoiesis as a new risk factor for atherosclerosis, a condition where plaques build up in arteries.
The second study, published in the European Heart Journal at the end of August 2024, suggests that the long-used medication colchicine could play a key role in personalized treatment plans for individuals with clonal hematopoiesis linked to mutations in the TET2 gene.
José J. Fuster, PhD,, associate professor at the Laboratory of Hematovascular Pathophysiology at the Spanish National Center for Cardiovascular Research, who is lead author of both of these studies, explained his and his colleagues’ key findings to Medical News Today.
“Our study [from Nature Medicine] clarifies the relationship between clonal hematopoiesis, a new cardiovascular risk factor, and the development of atherosclerosis, the build-up of lesions on the arterial wall that underlies most cardiovascular diseases,” he told us.
“Clonal hematopoiesis occurs when a cell called a hematopoietic stem cell, which can develop into different types of blood cells, acquires a genetic mutation and therefore makes blood cells with the same genetic mutation. These mutant blood cells have a different genetic pattern than the rest of blood cells, which can affect their function. People with mutations that cause clonal hematopoiesis have a higher risk of cardiovascular problems, such as heart attacks, but the exact nature of the relationship between these mutations and cardiovascular disease remained unclear.”
– José J. Fuster, PhD
“Some earlier studies suggested that certain mutations linked to clonal hematopoiesis contribute directly to cardiovascular disease by accelerating the development of atherosclerosis,” Fuster added.
“On the other hand,” he cautioned, “others proposed that it is atherosclerosis that causes clonal hematopoiesis by increasing the proliferation of hematopoietic stem cells, thereby generating a higher proportion of mutated blood cells.”
“The Nature Medicine study clarifies the relationship between clonal hematopoiesis and atherosclerosis through a longitudinal analysis of DNA sequencing data and imaging data from a population of healthy middle-aged individuals that is being monitored over the years,” Fuster further explained.
“[The Nature Medicine] study clearly demonstrate[s] that participants who had mutations linked to clonal hematopoiesis at the start of the study were more likely to develop atherosclerosis in the following years,” said Fuster.
At the same time, he explained, “the presence and extent of atherosclerosis had no influence on the expansion of mutated blood cells.”
Thus, “together with previous research work, these findings indicate that clonal hematopoiesis contributes to the development of atherosclerosis, not the other way around,” emphasized Fuster.
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, not involved in this research, told MNT that “the study showed that increased degree of clonal hematopoiesis resulted in greater atherosclerosis, but not vice versa, thereby pointing to the direction of causality.”
“However, much more research will need to be done to better understand the mechanisms by which clonal hematopoiesis could cause atherosclerosis,” he cautioned.
The question remains as to what mechanism leads to the increased risk of arterial plaques in people with clonal hematopoiesis.
“For now, we think it may be related to the new blood cells producing increased inflammatory mediators, which then promote the buildup of atherosclerotic plaques,” Chen hypothesized.
Raj Dasgupta, MD, Chief Medical Advisor for Fortune Recommends, also not involved in the recent research, said that the Nature Medicine “paper provides important new information about clonal hematopoiesis mutations, showing that these genetic changes might be more common and significant than previously thought, even in younger, healthier people.”
“This challenges the idea that [clonal hematopoiesis] mutations are only relevant in older adults and suggests they could play a role in the development of diseases like heart disease or cancer earlier in life,” Dasgupta added.
“Clonal hematopoiesis is increasingly recognized as a potent cardiovascular risk factor and some hospitals have even developed clonal hematopoiesis clinics to monitor the health status of people with this conditions,” Fuster told MNT.
“However,” he cautioned, “identifying the presence of clonal hematopoiesis is not yet recommended for the prevention of cardiovascular disease, partly because there are no evidence-based interventions to prevent or mitigate the elevated cardiovascular risk in those who exhibit clonal hematopoiesis.”
So, when it comes to potential future treatments, the researcher suggested that, “by clarifying that these mutations are a cause of atherosclerosis, not a consequence, [the] study suggests that blocking the effects of these mutations could help to prevent cardiovascular disease.”
“Ongoing work is trying to develop personalized strategies tailored to carriers of specific mutations linked to this conditions,” Fuster added.
Chen explained that “we are still in the very early stages of understanding how clonal hematopoiesis is related to atherosclerosis and even clinical heart disease.” However, “this field of research may potentially open up new avenues of therapy to decrease the risk of cardiovascular disease in people found to have this condition.”
Dasgupta agreed, explaining that although further research is needed, “screening for these mutations could become a way to assess a person’s long-term health risks.”
“This could lead to earlier steps to prevent disease, like lifestyle changes or specific treatments, especially for those with high-risk mutations. Knowing about these genetic risks could help people take action to protect their health sooner.”
– Raj Dasgupta, MD
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