Blood Type Linked to Higher Risk for Early-Onset Stroke

Kelli Whitlock Burton

August 31, 2022

Dr Braxton Mitchell

Individuals with type A blood have a 16% higher risk for early-onset stroke (EOS) than those with other blood types, new research shows.

Conversely, results from a meta-analysis of nearly 17,000 cases of ischemic stroke in adults younger than 60 years showed that having type O blood reduced the risk for EOS by 12%.

In addition, the associations with risk were significantly stronger in EOS than in those with late-onset stroke (LOS), pointing to a stronger role for prothrombotic factors in younger patients, the researchers note.

"What this is telling us is that maybe what makes you susceptible to stroke as a young adult is the blood type, which is really giving you a much higher risk of clotting and stroke compared to later onset," co-investigator Braxton Mitchell, PhD, professor of medicine and epidemiology and public health at the University of Maryland School of Medicine, Baltimore, told Medscape Medical News.

The findings were published online August 31 in Neurology.

Strong Association

The genome-wide association study (GWAS) was done as part of the Genetics of Early Onset Ischemic Stroke Consortium, a collaboration of 48 different studies across North America, Europe, Japan, Pakistan, and Australia. It assessed early onset ischemic stroke in patients age 18 to 59 years.

Researchers included data from 16,927 patients with stroke. Of these, 5825 had a stroke before age 60, defined as early onset. GWAS results were also examined for nearly 600,000 individuals without stroke.

Results showed two genetic variants tied to blood types A and O emerged as highly associated with risk for early stroke.

Researchers found that the protective effects of type O were significantly stronger with EOS vs LOS (odds ratio [OR], 0.88 vs 0.96, respectively; P = .001). Likewise, the association between type A and increased EOS risk was significantly stronger than that found in LOS (OR, 1.16 vs 1.05; P = .005).

Using polygenic risk scores, the investigators also found that the greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with EOS compared with LOS (P = .008).

Previous studies have shown a link between stroke risk and variants of the ABO gene, which determines blood type. The new analysis suggests that type A and O gene variants represent nearly all of those genetically linked with early stroke, the researchers note.

While the findings point to blood type as a risk factor for stroke in younger people, Mitchell cautions that "at the moment, blood group does not have implications for preventive care."

"The risk of stroke due to blood type is smaller than other risk factors that we know about, like smoking and hypertension," he said. "I would be much more worried about these other risk factors, especially because those may be modifiable."

He noted the next step in the study is to assess how blood type interacts with other known risk factors to raise stroke risk.

"There may be a subset of people where, if you have blood type A and you have some of these other risk factors, it's possible that you may be at particularly high risk," Mitchell said.

More Research Needed on Younger Patients

In an accompanying editorial, Jennifer Juhl Majersik, MD, associate professor of neurology at the University of Utah, Salt Lake City, and Paul Lacaze, PhD, associate professor and head of the Public Health Genomics Program at Monash University, Australia, note that the study fills a gap in stroke research, which often focuses mostly on older individuals.

"In approximately 40% of people with EOS, the stroke is cryptogenic, and there is scant data from clinical trials to guide the selection of preventative strategies in this population, as people with EOS are often excluded from trials," Majersik and Lacaze write.

"This work has deepened our understanding of EOS pathophysiology," they add.

The editorialists note that future research can build on the results from this analysis, "with the goal of a more precise understanding of stroke pathophysiology, leading to targeted preventative treatments for EOS and a reduction in disability in patients' most productive years."

Mitchell echoed the call for greater inclusion of young patients with stroke in clinical trials.

"As we're learning, stroke in older folks isn't the same as stroke in younger people," he said. "There are many shared risk factors but there are also some that are there really is a need to include younger people."

The study was funded by the National Institutes of Health and the Department of Veterans Affairs. Mitchell, Majersik, and Lacaze have reported no relevant financial relationships.

Neurology. Published online August 31, 2022. Abstract, Editorial

Kelli Whitlock Burton is a reporter for Medscape Medical News who covers psychiatry and neurology.

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