For a study, researchers found that the heightened risk of high blood pressure (BP), coronary artery disease, and mortality were linked with exogenous administration of recombinant erythropoietin. But, whether there was any correlation between coronary artery disease and its risk factors with endogenous circulating erythropoietin remained unknown. The researchers had quantified and evaluated the epidemiological and genetic links of circulating plasma erythropoietin levels in two population cohorts. The cohorts are from the United States (N=3671) and China (N=4329). The researchers performed erythropoietin exposure in vivo smooth muscle cell responses and in vivo murine studies. There was a linear and positive correlation of erythropoietin levels with BP traits. But, an inverse correlation was found with cholesterol levels and red cell indices. Greater prevalence of high BP (odds ratio, 1.20 [95% CI, 1.12–1.29], P=4.41×10−7), and coronary artery disease (odds ratio, 1.16 [95% CI, 1.00–1.34], P=0.046) were connected with the higher erythropoietin levels. The researchers pointed out a formerly reported locus chromosome 6 (rs7776054 near HBS1L-MYB, P=4.86×10−25) and a new locus on chromosome 4 (rs172629 near PDGFRA-KIT, P=2.1×10−8) in a discovery stage genetic association study of the levels of erythropoietin. They were separately replicated. The researchers also identified a locus on chromosome 22 (rs855791 near TMPRSS6, P=3.60×10−9) in the meta-analysis of discovery and replication genetic association results. High BP in vivo and increased contraction of vascular smooth muscle cells in vitro were generated by erythropoietin administration within a physiological range of hematocrit.

Taking everything into account, regular genetic variation impacted endogenous circulating erythropoietin levels. And, these levels were linked with BP traits, high BP, and coronary artery disease. The researchers discovered a new mechanism of high BP and cardiovascular risk with probable suggestions for supporting erythropoietin in the clinic. The discovery was supported by erythropoietin’s vascular effects, which were exhibited in vivo and in vitro.