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

Int J Cardiol. 2019 Sep 15:291:168-172. doi: 10.1016/j.ijcard.2019.04.008. Epub 2019 Apr 2.

Abstract

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 ADM levels were measured. The index of microcirculatory 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 (β = 0.79; p < 0.01) and between ET-1 and IMR (β = 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 pmol/L; p = 0.07) were higher.

Conclusions: Plasma ET-1 and ADM were associated with measures of coronary microvascular and coronary conduit vessel function, respectively. Increased cFMD and elevated plasma ADM were associated with a cardioprotective effect.

Keywords: Adrenomedullin; Coronary flow mediated dilatation; Coronary microcirculation; Endothelin.

MeSH terms

  • Adrenomedullin / blood*
  • Aged
  • Biomarkers / blood
  • Chest Pain / blood
  • Chest Pain / diagnostic imaging
  • Cohort Studies
  • Coronary Angiography / trends*
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / diagnostic imaging*
  • Coronary Circulation / physiology*
  • Endothelin-1 / blood*
  • Female
  • Follow-Up Studies
  • Fractional Flow Reserve, Myocardial / physiology
  • Humans
  • Male
  • Middle Aged

Substances

  • Biomarkers
  • Endothelin-1
  • Adrenomedullin