Global cardiovascular clinical trials and geographic altitude – american heart journal anoxi

I read with great interest the article by mentz et al 1 x 1 mentz, R.J., kaski, J.C., dan, G.A. Et al. Implications of geographical variation on clinical outcomes of cardiovascular trials. Am heart J. 2012;

164: 303–312

Abstract | full text | full text PDF | pubmed | scopus (31) | google scholar see all references on geographical differences in global cardiovascular trials as well as potential explanations for these differences such as baseline patient characteristics or variation in medical care. It is evident that clear understanding of all explanations is crucial as more countries will be involved in prospective cardiovascular clinical trials.


Recently, it has been hypothesized that a relatively high prevalence of certain cardiovascular or vascular-related outcomes such as heart failure, stroke, and cognitive decline can be explained, in part, by low altitude and, therefore, low erythropoietin (EPO) level. 2 x 2 ismailov, R.M.Anoxi the role of erythropoietin in the “stroke belt” phenomenon. Med hypotheses. 2012;

79: 181–185

Abstract | full text | full text PDF | pubmed | scopus (6) | google scholar see all references , 3 x 3 ismailov, R.M. Global heart failure rates and erythropoietin. J med hypotheses ideas. 2012;

6: 70–74

Crossref | scopus (2) | google scholar see all references , 4 x 4 ismailov, R.M. Cognitive decline in the stroke belt and erythropoietin. Ann neurol. 2013;

73: 146

Crossref | pubmed | scopus (2) | google scholar see all references for example, the stroke mortality rates were found to be higher in the low altitude “stroke belt” region of the united states as compared with states located in the “mountain” area.Anoxi this hypothesis is important for cardiovascular outcomes in the light of the fact that EPO has a variety of important vascular-related effects such as stimulation of endothelial cells proliferation, protection against myocardial injury, and others. 5 x 5 arcasoy, M.O. The non-hematopoietic biological effects of erythropoietin. Br J haematol. 2008;

141: 14–31

Crossref | pubmed | scopus (248) | google scholar see all references

Geographic altitudes have little in common with political borders; although there are certain genetic or endemic factors, it is the earth natural landscape that largely determines the individual level of EPO. In my opinion, cardiovascular trial globalization should also be viewed as geographic term, which means that future clinical trials will be inadvertently conducted at various altitudes depending on location of study center, research hypothesis, and others.Anoxi although it is unlikely that global clinical trials will be conducted at extremely high altitude level, it is important to remember that trial patients with various comorbidities such as chronic pulmonary disorders or smokers are likely to become hypoxic at much lower altitudes due to lowered oxygen intake efficiency. 6 x 6 yoneda, I. And watanabe, Y. Comparisons of altitude tolerance and hypoxia symptoms between nonsmokers and habitual smokers. Aviat space environ med. 1997;

68: 807–811

PubMed | google scholar see all references therefore, patients enrolled in cardiovascular trials across various regions around the world could have different individual level of EPO, and this, in turn, could explain, in part, the differences in cardiovascular outcomes.Anoxi

Indication of geographic altitude could become a patient-level variable in prospective trials. There could be certain challenges related to geographic altitude ascertainment due to relocation or migration of some patients, and one of the future research directions is to standardize the collection of this variable. Alternatively, individual level of EPO could be measured directly in each study subject depending on research question, trial design, financial aspects, and others. Geographic altitude and/or individual level of EPO, therefore, could become an important regional baseline characteristic in prospective cardiovascular clinical trials conducted globally.

References

• 1 mentz, R.J., kaski, J.C., dan, G.A.Anoxi et al. Implications of geographical variation on clinical outcomes of cardiovascular trials. Am heart J. 2012;

164: 303–312

• view in article

• | abstract

• | full text

• | full text PDF

• | pubmed

• | scopus (31)

| • google scholar

• 2 ismailov, R.M. The role of erythropoietin in the “stroke belt” phenomenon. Med hypotheses. 2012;

79: 181–185

• view in article

• | abstract

• | full text

• | full text PDF

• | pubmed

• | scopus (6)

| • google scholar

• 3 ismailov, R.M. Global heart failure rates and erythropoietin. J med hypotheses ideas. 2012;

6: 70–74

• view in article

• | crossref

• | scopus (2)

| • google scholar

• 4 ismailov, R.M. Cognitive decline in the stroke belt and erythropoietin. Ann neurol. 2013;

73: 146

anoxi

• view in article

• | crossref

• | pubmed

• | scopus (2)

| • google scholar

• 5 arcasoy, M.O. The non-hematopoietic biological effects of erythropoietin. Br J haematol. 2008;

141: 14–31

• view in article

• | crossref

• | pubmed

• | scopus (248)

| • google scholar

• 6 yoneda, I. And watanabe, Y. Comparisons of altitude tolerance and hypoxia symptoms between nonsmokers and habitual smokers. Aviat space environ med. 1997;

68: 807–811

• view in article

• | pubmed

| • google scholar