Stroke, High Altitude, and EPO

A 2009 study from Switzerland found a 12% decrease in risk of death from stroke at 6430 ft. compared to 850 ft.  This result was more pronounced in men than women.  Since men are more physically active than women in Switzerland, it was thought the exercise at the more hypoxic conditions of higher altitude may benefit them more than for women.  The study also noted that being born at a higher altitude had a protective effect on death from cardiovascular disease1

Strokes occur when blood flow to parts of the brain is cut off causing neurons and other brain cells to die within minutes.  Strokes can either be ischemic or hemorrhagic.  80-87% of strokes are ischemic, which means that blood flow to the brain is cut off from a blood clot or other blockage of a blood vessel going to or in the brain.  Hemorrhagic strokes are caused by bleeding within the brain (intracerebral space) or in the space surrounding the brain filled with cerebrospinal fluid (subarachnoid space).  Risk of stroke is higher in individuals with previous transient ischemic attack (TIA), high blood pressure, previous heart attack, atrial fibrillation, enlarged left atria of the heart, smoking, heavy alcohol use, diabetes, obesity, high cholesterol, and stenosis of the carotid artery2.

Interestingly, on initial exposure to hypoxia at high altitude, blood flow to the brain increases which is split equally between gray and white matter.  After 4 to 5 days, blood flow to the brain decreases but is still 13% greater than at sea level.  The increased blood flow is needed to maintain adequate delivery of oxygen when the oxygen content of the blood is lower during hypoxia, until other acclimation mechanisms take effect3.

As noted in previous blog posts in response to hypoxia, erythropoietin (EPO) is also released, which increases the production of red blood cells to increase the oxygen-carrying capacity of our blood.  Other studies have found that EPO also has a protective effect on neurons.   Cerebrovascular endothelial cells have been found to have receptors for EPO and are thus able respond to EPO.  Other studies have found that EPO is also involved in brain development of a fetus in utero.  Animal studies suggest EPO not only protects neurons from cell death but may enable their regeneration as well.  If this translates into humans, it is an important effect for those at risk for stroke4.

In a small clinical trial, patients with middle cerebral artery stroke received IV EPO daily for 3 days after their stroke.  These patients had better neurological outcomes with increased physical functioning and independence as measured by Barthel index test results.  Following the EPO doses, the size of the cerebral infarct, the damaged area of the brain from blood being cut off during the stroke, was reduced as well4.

Based on this research, Ismailov hypothesized that in the United States, geographic variation in levels of EPO from altitude differences may account for the differences in risk of death from stroke.  He termed it the “stroke belt” in the Southeast, with higher rates of death from stroke compared to the Mountain states.  

The states in the “stroke belt” are Louisiana (LA), Mississippi (MI), South Carolina (SC), Alabama (AL), Georgia (GA), Arkansas (AK), Indiana (IN), North Carolina (NC), Kentucky (KY), Tennessee (TN), and Virginia (VA), and all are at lower altitude.  The mountain states have higher altitude and are North Dakota (ND), Kansas (KS), Nebraska (NE), Arizona (AZ), New Mexico (NM), Wyoming (WY), and Colorado (CO).   

Louisiana and Mississippi’s average altitudes are 100 and 300 ft. compared to Colorado and Wyoming with average altitudes of 6800 and 6700 ft4.  Since there is increased EPO released in individuals living at higher altitudes, perhaps there is more of a neuroprotective effect at higher altitudes, contributing to the observed lower risk of death from stroke seen in the Swiss study.  

Symptoms of Stroke5

Think F.A.S.T

Other signs are sudden

  • Numbness of face, arm, or leg and particularly numbness on one side of body
  • Confusion
  • Difficulty seeing out of one or both eyes
  • Difficulty walking
  • Feeling of dizziness, loss of balance, or coordination
  • Severe headache with no identified cause

For more information: https://familydoctor.org/condition/stroke/

o en Español: https://es.familydoctor.org/condicion/accidente-cerebrovascular/

Author and PA student, Stephanie Schick

Stephanie Schick is a Physician Assistant student at Rocky Vista University in Parker, CO.  She is born and raised in Fort Collins, CO.  She started off her clinical year working in pediatrics with Dr. Chris at Ebert Family Clinic.  The remainder of her clinical year will be spent closer to home in northern Colorado.   In her free time she enjoys spending time with her husband, friends, and family in the beautiful Colorado sunshine.

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