Anti-inflammatory medications may help prevent heart disease in people with an age-related blood condition

Inflammation-reducing medications could be an effective way to prevent heart disease in people with a common age-related blood condition, according to a new study from researchers at Columbia University College of Physicians and Surgeons Vagelos.

The researchers identified how the blood condition, known as clonal hematopoiesis, causes atherosclerosis, and their findings show that previously proven anti-inflammatory drugs may have potential this in a wider population of people with cardiovascular disease if used only in those with clonal hematopoiesis.

“The key message from our research is that anti-inflammatory therapies for atherosclerotic heart disease may be particularly effective in patients with clonal hematopoiesis,” says Alan Tall, MD, Professor of Medicine Tilden Weger Bieler, co-author the study by Nan Wang, MD, associate professor of medical sciences (in medicine).

Their study was published online March 17 in Nature.

Aging contributes to heart disease

Although great strides have been made in reducing atherosclerotic heart disease with medications such as cholesterol – lowering statins, many people have still developed more disease despite these conventional treatments.

Over the years, researchers have found that the aging process significantly contributes to cardiovascular disease. But how aging can lead to heart disease – and how it can prevent it – is not well understood. “

Trevor P. Fidler, PhD, Allied Research Scientist in Medicine, First Author of the Study

A common blood condition increases heart disease

In the new study, the researchers looked closely at a common blood condition, called clonal hematopoiesis, that is associated with aging.

Clonal hematopoiesis is thought to occur in about 10% of people older than 70, and most people have no symptoms. But researchers recently realized that the condition – for unknown reasons – raises the risk of heart disease by 40%.

Clonal hematopoiesis occurs when hematopoietic (blood) stem cells undergo mutations. As people age, all hematopoietic cell gases undergo genetic mutations, although most of these mutations have no effect. But in clonal hematopoiesis, some mutations cross the gas shaft so that it produces a larger number of blood cells compared to other stem cells.

Examination of mice reveals an additional source of heart risk

Clonal hematopoiesis usually arises when one of four specific genes is suppressed. The Columbia team looked specifically at JAK2, which presents the strongest risk for premature coronary artery disease.

In atherosclerosis, white blood cells called macrophages accumulate in plaques and expand as the plaque grows.

In studies on mice, the researchers found that JAK2 mutations caused a number of changes in macrophages that increased macrophage proliferation, increased inflammation in the atherosclerotic plaques, and contributed to the necrotic heart of the plaque.

“We know in humans that such regions are associated with unstable records, which can collapse, causing heart attacks or strokes,” Fidler says.

The researchers also monitored the molecular mechanisms that led to these changes, including increased activity of the inflammasome AIM2, a complex of inflammation-inducing proteins.

Flammasome targeting may reduce cardiovascular risk

By blocking various parts of the inflammasome improved the stability of the plaques, as did IL-1ß, a product of influenza.

Although an IL-1ß inhibitor called canakinumab reduced cardiovascular events in a clinical trial, the drug was associated with a low risk of infection and was not marketed to reduce cardiovascular disease.

“If we instead use a precision treatment approach and use canakinumab alone to treat patients with JAK-guided clonal hematopoiesis,” Fidler says, “we may increase the cardiovascular benefit. Even if infectious risk has not changed, we may take full advantage of this.