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

A new study opens the possibility of creating a blood test that could predict the likelihood of a stroke or future cognitive decline.

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

Developing such a test would be a major step forward. Currently, cerebral microangiopathy (CSVD) is best diagnosed with 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 and autoimmune disorders, making them difficult to measure. In 2020, researchers linked five of these molecules to vascular brain damage detected in brain MRIs.

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

The final cohort of study participants consisted of 2,201 people aged 45 and over. Blood samples were available for each, as well as MRI scans. This allowed the researchers to develop a model that they could use to estimate people’s risk of stroke – higher scores meant higher risk.

For those who scored in the top 25%, the risk of having a stroke at some point in their lives was 84%. For others whose scores were less elevated, the risk was 51%.

What is cerebral microangiopathy and 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 often goes unnoticed."

"Microangiopathy typically refers to chronic and progressive damage to small arteries, called perforators, that branch off from large intracranial arteries and supply blood to deep brain structures," said Jose Morales, MD, MS, a vascular neurologist and neurointerventional surgeon at the Pacific Neuroscience Institute in Santa Monica, California, who 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 clogged or narrowed, especially with age, and cause decreased oxygen delivery to brain tissue."

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

Predicting CSVD is difficult, Morgan added, "[Given] 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 difficult because "inflammation levels rise and fall in each person."

What's new about the study, he says, 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 risk of stroke in a quantifiable way."

"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 check for small vessel disease of the brain?

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

"Small vessel disease 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 temporary or persistent and improve over time."

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

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

What a simple blood test could mean for stroke prevention The proposed blood test for individuals currently requires more research and development, Hinman said:

"To make this clinically useful, we ideally need 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 expressed hope to see cutoff values for biomarkers that would make it easy for health workers and patients to interpret tests.

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

Morgan noted that while this study shows promising results, all markers measured do not show the same degree of positive predictability, with some having a stronger correlation than others.

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

"While 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 […] vascular risk factors, maintaining a healthy lifestyle and engaging in regular exercise.”

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

The study is published in the journal Stroke.