Introduction
Geisinger is a health organization that offers healthcare services in Pennsylvania and New Jersey. A team of Geisinger researchers discovered a new risk factor for stroke that was more common in people ages 65 and up. Dr. Abedi, a co-author of the study and genomics scientist at Geisinger, states, “Stroke is a complex multifactorial condition.” Out of the main causes for stroke, cerebral small vessel disease is among the most common reasons.
Cerebral Small Vessel Disease
Cerebral Small Vessel Disease, abbreviated as SVD, is a general term for problems related to small blood vessels in the brain. It is a common disease that is known to cause vascular dementia and around a quarter of ischemic strokes. About 87% of all strokes are ischemic, meaning that the blood supply to the brain is blocked off, causing brain cells to die. While we typically notice SVD with old age and hypertension, some of the cases are due to variants in the NOTCH3 gene. This gene variant is quite common, about 1 in 300 people worldwide. Additionally, CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a rare hereditary condition, is associated with a higher risk of stroke and SVD. CADASIL is known to cause a variety of health issues, ranging from seizures to cognitive deterioration.
Methods
The Geisinger team studied the health records of over 300 of their patients. Out of these patients, 118 of them were found to have the NOTCH3 gene variant. The researchers sought to find out if those with the NOTCH3 variant had more severe SVD as well as a higher risk of stroke and brain damage. They created a control group, consisting of patients without the NOTCH3 variant, and an experimental group, consisting of patients carrying the NOTCH3 gene variant. 4.9% of the control group had a history of stroke compared to 12.6% of the experimental group. The significant increase in the risk of stroke is likely due to the NOTCH3 gene variant. Meanwhile, the specific NOTCH3 variant that causes CADASIL was rarely found. In addition, patients over the age of 65 were noted as more prone to stroke and exhibited more damage to the brain.
This diagram displays the risk of getting a stroke as we become older through the red experimental group and green control group. From ages 0 to around 70, we notice that both groups are relatively the same percent free of stroke. However, there is a sharp decline in percentage free of stroke after the age of 70 for those carrying the NOTCH3 gene variant. The table below shows the N at risk, meaning the number of individuals at risk of stroke, and N stroke, which is the number of people with their first stroke in 10-year intervals. This shorter stroke-free survival compared to the control group reinforces the idea that the NOTCH3 gene is a significant contributor to stroke risk.
Conclusion
Due to the high number of individuals carrying the NOTCH3 variant, there is a significant risk of SVD and stroke. Additionally, the Geisinger research team has claimed that most people with the NOTCH3 variant will have SVD after the age of 65. With this new knowledge, we can continue to advance the field of medicine and prevent the strokes of individuals carrying the NOTCH3 gene variant, saving the lives of many.
Kyle Phong, Youth Medical Journal 2021
Referereces
Stroke Association, “Types of Stroke”
https://www.stroke.org.uk/what-is-stroke/types-of-stroke
Stroke: Journal of the American Heart Association, “Top-NOTCH3 Variants in the Population at Large”, 9 November 2020
https://www.ahajournals.org/doi/10.1161/STROKEAHA.120.031609
Stroke: PubMed, “Cysteine-Altering NOTCH3 Variants Are a Risk Factor for Stroke in the Elderly Population”, 9 November 2020
https://pubmed.ncbi.nlm.nih.gov/33161844/
News Medical Life Sciences, “A common genetic variant identified as risk factor for stroke”, 19 January 2021
National Institute of Neurological Disorders and Stroke, “CADASIL Information Page”, 27 March 2019
https://www.ninds.nih.gov/Disorders/All-Disorders/CADASIL-Information Page#:~:text=CADASIL%20is%20characterized%20by%20migraine,higher%20risk%20of%20heart%20attack.
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