I read with great interest the article by Putaala et al.  on differences in risk factors among young population with ischemic stroke appeared in the October 2012 issue of ‘Stroke’. Fifteen study centers from 12 countries were geographically clustered into three large regions namely northern, central, and southern Europe. As authors mentioned, after controlling for gender, age, and centers heterogeneity, no statistical differences between regions with respect to such important risk factors as family history of stroke or smoking were found.
Recently, it has been hypothesized that the epidemiology of stroke can be influenced by regional differences in individual levels of erythropoietin (EPO) . The release of EPO is stimulated by hypoxia, which is, in turn, caused by higher geographic elevation. Therefore, those residents living in the low altitude regions could have lower EPO levels as compared with those residing in high-elevation areas . On the other hand, EPO has multiple neuroprotecive and vascularprotective properties such as prevention of neuronal apoptosis, improvement of neuronal functional recovery, stimulation of neoangiogenesis, etc . Such EPO benefits could result in the fact that some regions could have lower or higher prevalence of certain comorbidities and risk factors for ischemic stroke namely coronary heart disease, heart failure, family history of stroke, etc .
To the best of my knowledge, none of the study centers mentioned by authors were located at extremely high altitudes. However, study subjects with various comorbidities could become substantially hypoxic at much lower altitudes because of lowered efficiency of oxygen intake. On the other hand, oxygen intake efficiency is substantially decreased among smokers . Therefore, study subjects could have different individual level of EPO in various European study centers located at various geographic altitudes.
One of the potential future directions is to compare Europeans with ischemic stroke residing, for instance, at 800 feet above sea level or higher to those who live below this point. To the best of my knowledge, there were at least three study centers located above 800 feet above sea level (namely located at Basel, Lausanne, and Lugano) . The fact that the Central region included both moderately elevated Lausanne and ‘lowland’ Leuven (located at 1731 feet and 131 feet above the sea level, respectively) could potentially have explained the ‘no risk-factor difference’ observed in the study.
In general, ischemic stroke has complex mechanism and multiple risk factors should be used to describe its prevalence. In addition to examining well-documented vascular risk factors for ischemic stroke, future studies should also examine a complex relationship between ischemic stroke and EPO in the settings of various geographical altitudes.