Can a simple blood test predict the risk of stroke and vascular problems in the brain?

New research opens the possibility of creating a blood test that can predict the likelihood of a stroke or cognitive decline in the future.

The study authors identified a network of inflammatory molecules in the blood that helps assess the risk of developing cerebral microangiopathy, a common cause of strokes and cognitive decline.

The development of such a test would be an important step forward. Currently, cerebral microangiopathy (CSVD) is best diagnosed using MRI, and the risk of stroke and cognitive decline is determined based on calculations that include family history, demographics and other risk factors, including lifestyle.

The study targets inflammatory molecules known as the interleukin-18, or IL-18, network, which includes proteins and signaling molecules to fight infections.

These molecules are associated with CSVD and strokes. However, their levels fluctuate as a result of the immune response to infections as well as autoimmune disorders, making them difficult to measure. In 2020, researchers linked five of these molecules to vascular brain damage detected in MRI of the brain.

The new study used data from the Framingham Heart Study, which has been following the medical histories of thousands of residents of Framingham, Massachusetts, since 1948.

The final study cohort consisted of 2,201 people aged 45 years and older. For each of them, blood samples were available, as well as MRI results. This allowed the researchers to develop a model with which they could estimate the risk of stroke in people—higher scores meant higher risk.

For those who scored in the top 25%, the risk of stroke at some point in life was 84%. Others whose scores were less elevated had a 51% risk.

What is cerebral microangiopathy, how does it affect brain health?

The study's first author, vascular neurologist Jason Hinman, MD, PhD, of UCLA Health, explained that: "Cerebral microangiopathy is a significant risk factor for cardiovascular disease. It increases the risk of stroke and cognitive impairment, but is often recurrent unnoticed."

"Microangiopathy typically refers to chronic and progressive damage to small arteries, called perforators, that arise from large intracranial arteries and supply blood to the deep structures of the brain," said Jose Morales, MD, MS, vascular neurologist and neurointerventional surgeon at Pacific Neuroscience Institute in Santa Monica, California, which was not involved in the study.

According to another expert, Jane Morgan, MD, a cardiologist and executive director of community health and education at Piedmont Healthcare Corporation in Atlanta, Georgia, "[these vessels can become blocked or narrowed, especially with age, and cause decreased delivery of oxygen to brain tissue."

Morgan, who was also not involved in the study, stressed that: "In turn, this can lead to decreased brain activity and cell death, leading to dementia, stroke, difficulty with movement or speech, and cognitive decline."

Predicting CSVD is complicated, Morgan added, "[g]iven that the pathophysiology of CVSD involves multiple pathways, including the blood-brain barrier, addressing predictive markers can be challenging."

Hinman noted that even after tentatively identifying five molecules associated with stroke risk, measuring any one of them can be challenging because "inflammation levels rise and fall in each person."

What's new about the study, he said, is that "those with high levels of all five of these molecules have evidence of cerebral microangiopathy and are now, thanks to this work, at future stroke risk in a quantitative way. Certain form."

"Many of the risk factors for CSVD are the same risk factors for heart disease," Hinman noted, "such as smoking, diabetes, hypertension, and high cholesterol."

"Genetics also plays a big role," Morales said.

How to Test for Brain Small Vessel Disease?

There are many indications that a person may need to be evaluated for brain small vessel disease (CSVD).

"CSVD can present as silent strokes," Morales said, "but can also cause symptoms such as one-sided weakness, facial drooping, sensory loss, cognitive impairment, or balance problems. These symptoms may be transient or persistent and improve over time."

Morgan added that difficulty using or understanding language, as well as worsening or severe headaches, should also be reported to a doctor.

"It is critical," Morales cautioned, "that patients and their families do not downplay even mild stroke symptoms and seek emergency medical care by calling 911."

What a Simple Blood Test for Stroke Prevention Could Mean For now, the proposed blood test for individuals requires more research and development, Hinman said:

"To make this clinically useful, we ideally would have to demonstrate the proactive ability of this biomarker to help prevent strokes prospectively, rather than using retrospective data as we did here," Hinman said.

He also said he hopes to see cutoff values for the biomarkers that health care providers and patients can easily interpret tests.

“Finally, understanding IL-18 network levels in a more diverse population is essential, and this work is being done as part of the DIVERSE VCID study in which we are participating.”

Morgan noted that while this study shows promise, all markers measured do not show the same degree of positive predictability, with some being more strongly correlated than others.

What to do if you have small-vascular disease of the brain?

"Although exercise has not been shown to slow the progression of CSVD," Morgan said, "studies have shown that regular exercise reduces all-cause mortality and cerebrovascular events."

Morales agreed, saying that “up to 80% of strokes can be prevented by controlling […] risk factors for vascular disease, maintaining a healthy lifestyle and regular exercise.”

He also noted that “establishing a continuum of care with a primary care physician can identify many of these risk factors early and introduce preventive measures, whether pharmacological interventions or lifestyle changes.”

The study was published in Stroke magazine.