Do Blood Types Predict the Risk of Early Onset Stroke in Younger People?

Background 

Stroke is one of the leading causes of death and a major contributor to age-related cognitive decline, disability, and dementia. Nearly 80% of strokes are ischemic in nature and belong to specific subtypes¹. Identification of the underlying mechanisms contributing to stroke risk has been challenging owing to the involvement of multiple genes that interact with environmental risk factors¹.

Genetic variants that predispose to stroke risk factors have been shown to predispose to ischemic stroke in genome-wide association studies (GWAS)¹. While classical risk factors account for only a small portion of stroke risk, the majority of ischemic stroke GWAS have concentrated on late-onset disease². It is therefore imperative to investigate the role of common genetic variants in the risk of early-onset ischemic stroke.

ABO gene variants and stroke risk

The ABO blood system determines our blood type according to the carbohydrate functional groups found on RBCs³. While most research of ABO variants has focused on transfusion and organ transplantation, there is considerable evidence that supports the link between ABO blood type and cardiovascular diseases (CVDs)³.

Previous reports have demonstrated the association of stroke risk and the ABO gene variants⁴. One study even established that the B allele is associated with an increased risk of ischemic stroke in hypertensive or perimenopausal women⁵.

Risk factors for early-onset stroke (EOS)⁶

With consistent associations, atrial fibrillation, CVDs, and both type 1 and type 2 diabetes mellitus emerge as strong risk factors for early-onset ischemic stroke.

Apparently, a history of stroke in the family has been found to be a significant risk factor for EOS in the younger population. This finding supports the hypothesis that genetic factors may play a larger role in EOS as compared to the later-onset stroke (LOS).

Gaps in stroke research

So far, genetic associations with specific stroke subtypes have been identified, implying that each subtype has different risk factor profiles and pathophysiological mechanisms¹.

To fully understand the relationship between blood type and stroke risk, more research in diverse populations, including both young and elderly patients, is required. This can also be used to determine whether more aggressive risk factor modification is necessary in these individuals³.

Evidence from clinical trials

In the REasons for Geographic and Racial Differences in Stroke (REGARDS) study³, blood type AB was associated with stroke risk in a large, biethnic population, and factor VIII levels mediated 60% of the association. Furthermore, racial differences in ABO blood type mediated some of the excess stroke risk seen in black people in the United States.

To date, GWAS in ischemic stroke have used small discovery populations. The METASTROKE collaboration¹ was the first to combine GWAS data from over 12,000 stroke cases and showed that common genetic variation was a major determinant of ischemic stroke pathogenesis.

Which blood types are at a higher risk?

A new study analyzed 16,730 stroke cases and 599,237 non-stroke controls from 48 different studies to conduct a meta-analysis of GWAS². According to the findings, type A and type O gene variants were linked to EOS, where venous thromboembolism was more strongly associated with EOS than LOS⁴. Besides, people with blood type A may be at a greater risk if they smoke or have hypertension^2,4.

As a risk factor for stroke in younger people, blood type cannot be implied for prevention of heart diseases. While blood groups cannot be changed, identifying the high-risk population allows for a more aggressive risk factor reduction. This could be critical in preventing ischemic strokes with early preventive strategies and interventions, especially in young people who are not generally considered at risk of having a stroke.

Conclusion

The 2020 study² has taken over the internet, sparking numerous discussions and speculations about how blood groups affect a person’s chances of having a stroke. This opens up new avenues for EOS pathophysiology research while also filling a gap in stroke research on the younger population. More young patients suffering a stroke must therefore be included in clinical trials to identify new risk factors that are not found in older people⁴.

References

1. Traylor M, Farrall M, Holliday EG, Sudlow C, Hopewell JC, Cheng YC, Fornage M, Ikram MA, Malik R, Bevan S, Thorsteinsdottir U. et al. Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis of genome-wide association studies. The Lancet Neurology. 2012 Nov;11(11):951-62.
2. Jaworek T, Xu H, Gaynor BJ, Cole JW, Rannikmae K, Stanne TM, Tomppo L, Abedi V, Amouyel P, Armstrong ND, Attia J. Contribution of common genetic variants to risk of early onset ischemic stroke. Neurology. 2022 Aug 31.
3. Zakai N, Judd S, Alexander K, McClure L, Kissela B, Howard G, Cushman M. ABO blood type and stroke risk: the REasons for Geographic And Racial Differences in Stroke Study. Journal of Thrombosis and Haemostasis. 2014 April;12(4):564-570.
4. Blood Type Linked to Higher Risk for Early-Onset Stroke [Internet]. Medscape. 2022 [cited 2022 Sep 15]. Available from: https://www.medscape.com/viewarticle/980048?src=soc_fb_220908_mscpedt_news_mdscp_bloodtype&faf=1#vp_2
5. Wiggins K, Smith N, Glazer N, Rosendaal F, Heckbert S, Psaty B, Rice K, Lumley T. ABO genotype and risk of thrombotic events and hemorrhagic stroke. Journal of Thrombosis and Haemostasis. 2009 Feb;7(2):263-269.
6. Kivioja R, Pietilä A, Martinez‐Majander N, Gordin D, Havulinna A, Salomaa V, et al. Risk factors for early‐onset ischemic stroke: A case‐control study. Journal of the American Heart Association. 2018 Nov;7(21):e009774.