Researchers develop a genetic test for the early detection of high cardiovascular risk

Clonal hematopoiesis is a phenomenon caused by mutations in hematopoietic stem cells and can lead to blood cancer. We now know that it also occurs in people with normal blood counts, where it is associated with an increased risk of life-threatening atherosclerotic cardiovascular disease.

A research team at the Medical University of Vienna has now developed a genetic testing procedure to detect clonal hematopoiesis that, when used in combination with an ultrasound examination of the carotid artery, can identify patients at high cardiovascular risk . The study was published in the Journal of the American College of Cardiology.

One of the most promising topics in cardiovascular research is the role of clonal hematopoiesis in cardiovascular diseases. Recent work has shown that clonal hematopoiesis is common in the population with an increasing prevalence in advanced age, detectable in up to 15% of individuals over 70 years of age.

It can lead to blood malignancies, but most importantly it greatly reduces life expectancy by increasing the risk of atherosclerotic cardiovascular disease. At an advanced stage, atherosclerosis can lead to the blockage of arterial blood vessels, thus causing heart attacks and strokes.

An interdisciplinary team at MedUni Vienna led by Christoph Binder, Robert Kralovics and Roland Jäger from the Clinical Institute of Laboratory Medicine and Matthias Hoke from the Department of Internal Medicine II has now investigated the potential effects of clonal hematopoiesis in patients with demonstrated carotid , but asymptomatic. stenosis (atherosclerotic narrowing of the carotid artery).

For this, a new assay based on high-throughput DNA sequencing was developed to perform targeted genetic testing, in order to identify causative mutations. This method was applied to approximately 1,000 blood samples derived from the Inflammation and Carotid Artery-Risk for Atherosclerosis Study (ICARAS).

ICARAS represents a prospective cohort study that has been carried out in the Angiology Division of the Department of Internal Medicine II since 2002, which aims to identify risk factors for atherosclerosis and the effects cardiovascular events such as myocardial infarction, stroke and cardiovascular death.

Detection of increased risk before the onset of symptoms

The current study describes a sharp increase in mortality in patients with carotid stenosis and simultaneous clonal hematopoiesis. “The targeted design of the genetic testing procedure allowed us to reliably identify patients affected by clonal hematopoiesis,” says lead author Roland Jäger.

By jointly detecting clonal hematopoiesis and carotid atherosclerosis, a combined biomarker could be discovered that may contribute to a personalized cardiovascular risk profile. High-risk patients can now be identified at an early stage, allowing appropriate adaptation of therapies and prevention of the progression of atherosclerotic disease, thereby reducing the risk of stroke and heart attacks.

“With the help of ultrasound-based duplex ultrasound in combination with the new genetic testing procedure, high cardiovascular risk can be detected long before symptoms of the disease appear,” explains co-author Matthias Hoke.

Corresponding authors of the study, Christoph Binder and Robert Kralovics, emphasize that “the results of this study provide the basis for future studies to investigate the role of clonal hematopoiesis in cardiovascular diseases”, with the aim of ‘to implement this type of genetic diagnosis in laboratory medicine.