Plasma endothelin-1 and adrenomedullin are associated with coronary artery function and cardiovascular outcomes in humans

Background: Endothelin-1 (ET-1) is a vasoconstrictor associated with cardiovascular disease, whereas adrenomedullin (ADM) is a vasorelaxant with cardioprotective properties. We sought to determine the relationship between plasma ET-1 and ADM with coronary circulatory function and long-term major adverse cardiovascular events (MACE). Methods: Thirty-two patients undergoing coronary angiography for chest pain were recruited. Baseline plasma ET-1 and ADMlevels were measured. The index ofmicrocirculatory resistance (IMR), coronary flow mediated dilatation (cFMD) and coronary flow reserve (CFR) were measured in a non-obstructed coronary artery. Patients were assessed for MACE over a median period of 8.8 years. Results: Plasma ET-1 levels correlated with IMR (r = 0.57; p = 0.01) and ADM levels correlated with CFR (r = 0.50; p= 0.04) and cFMD (r= 0.62; p= 0.01). After adjustment for age, gender and cardiovascular risk factors, the association between ADM and cFMD (beta = 0.79; p = 0.01) and between ET-1 and IMR (beta = 5.7; p = 0.01) remained significant. IMR was higher, although not statistically significant, in patients with long-term MACE (17.9 +/- 5.3 vs. 13.1 +/- 6.0 units; p = 0.14). In patients free of MACE, cFMD (9.3 +/- 7.6 vs. 2.8 +/- 5.0%; p = 0.01) and plasma ADM levels (7.6 +/- 5.3 vs. 4.0 +/- 1.9 pmolL; p = 0.07) were higher. Conclusions: Plasma ET-1 and ADMwere associated with measures of coronary microvascular and coronary conduit vessel function, respectively. Increased cFMD and elevated plasma ADM were associated with a cardioprotective effect. (C) 2019 Elsevier B.V. All rights reserved.