Stem cell study offers clue to South Asians’ increased risk of cardiovascular disease

A growing body of data show that South Asians are at greater risk of developing heart disease than white people, and they tend to get complications at younger ages, but it’s not been fully clear what explains this disparity.

A new study suggests one potential reason is that South Asians have a decreased ability to repair blood vessels that get injured from cardiovascular problems.

In a small trial comparing people of South Asian and white European descent, researchers found that South Asian people had lower levels of certain stem cells that are critical in regenerating blood vessels, according to the study, published Monday in the Journal of the American College of Cardiology.

The study comes amid greater awareness of the increased cardiovascular risk that South Asians face. Research has found that this group — which makes up about a quarter of the world’s population and is rapidly growing — has double the heart disease risk of people of European descent. Some of this increased risk could be attributed to the fact that South Asian people are more likely to develop type 2 diabetes, which often leads to heart disease, but even then, South Asians with diabetes appear to more frequently develop heart disease than white people with diabetes.

“We need to understand the biological underpinnings of what is going on in this population,” said Subodh Verma, a co-author on the study and a cardiovascular surgeon at Unity Health Toronto. “Younger South Asians are developing cardiovascular disease. Their trajectory for heart disease is accelerated. Their complication rates are higher.”

If the findings of the study are proven out in further research, they could provide a biological explanation for the increased risk among South Asians and guide decisions on how to tailor treatments for this population, such as prioritizing the use of medications that can particularly help with repairing blood vessels.

The group of researchers behind this study previously found that Jardiance, a type of diabetes drug known as an SGLT2 inhibitor, increased levels of stem cells that help with vessel regeneration in people both with and without diabetes. They’ll soon be starting a study seeing if the drug will be effective in doing this specifically in South Asians.

The researchers are also running a trial to see if semaglutide, the active ingredient in the popular diabetes and obesity drugs Ozempic and Wegovy, can help increase stem cell levels. Semaglutide was recently shown in a large trial to reduce the risk of cardiovascular complications among people with obesity and heart disease.

The trial enrolled 60 people of South Asian descent and 60 of white European descent. By analyzing blood samples, they found that South Asians had lower levels of two types of stem cells important in repairing blood vessels. One type, the progenitor cells, can be thought of as the “conductors of the orchestra,” since they direct other cells, said David Hess, a co-author and an adjunct professor at University of Toronto. The other type of stem cell, the monocyte cells, are the “musicians,” since they carry out the details of the repair process.

Monocyte cells can mature into playing either an inflammatory role in the body or a reparative role. The researchers found that the few monocytes that the South Asian people in the study did have were more inclined to mature into an inflammatory role compared to the cells of white Europeans.

The findings also suggest that impaired kidney function may play a role. Worse kidney function, captured through a measure called eGFR, was linked to lower stem cell levels in South Asians, but the researchers did not see this relationship in white Europeans.

Krishnan Ramanathan, a clinical professor of medicine at the University of British Columbia who was not involved in the study, said that the study is small and further research is needed to prove that the lower level of stem cells does actually cause less healing of blood vessels and an increased risk of heart complications.

Ramanathan, who has conducted research on heart disease in South Asians, also noted that most of the participants in the study — about 60% of the white Europeans and 90% of the South Asians — had diabetes, and he’d want to know if the findings still hold true in people without diabetes.

Still, the study points to “a novel approach” to trying to understand South Asians’ increased risk, he said. “Our current understanding — more risk factors, more disease. But is it more risk factors combined with inability to heal that leads to more events?”

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