Soluble angiotensin-converting enzyme 2 in human heart failure: relation with myocardial function and clinical outcomes

J Card Fail. 2009 Sep;15(7):565-71. doi: 10.1016/j.cardfail.2009.01.014. Epub 2009 Mar 17.

Abstract

Background: Angiotensin-converting enzyme 2 (ACE2) is an endogenous counterregulator of the renin-angiotensin system. The relationship between soluble ACE2 (sACE2), myocardial function, and clinical outcomes in patients with chronic systolic heart failure is not well established.

Methods and results: We measured sACE2 activity in 113 patients with chronic systolic heart failure (left ventricular ejection fraction [LVEF] <or=35%, New York Heart Association Class II-IV). Comprehensive echocardiography was performed at the time of blood sampling. We prospectively examined adverse clinical events (death, cardiac transplant, and heart failure hospitalizations) over 34 +/- 17 months. Patients who had higher sACE2 plasma activity were more likely to have a lower LVEF (Spearman's r = -0.36, P < .001), greater right ventricular systolic dysfunction (r = 0.33, P < .001), higher estimated pulmonary artery systolic pressure (r = 0.35, P = .002), larger left ventricular end-diastolic diameter (r = 0.23, P = .02), and higher plasma NT-proBNP levels (r = 0.35, P < .001). sACE2 was less associated with diastolic dysfunction (r = 0.19, P = .05), and was similar between patients with ischemic and nonischemic cardiomyopathies. There was no relationship between sACE2 activity and markers of systemic inflammation. After adjusting for NT-proBNP and LVEF, sACE2 activity remained an independent predictor of adverse clinical events (HR = 1.7 [95% CI: 1.1-2.6], P = .018).

Conclusions: Elevated plasma sACE2 activity was associated with greater severity of myocardial dysfunction and was an independent predictor of adverse clinical events.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiotensin-Converting Enzyme 2
  • Biomarkers / blood
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Heart Failure, Systolic / enzymology*
  • Heart Failure, Systolic / mortality
  • Heart Failure, Systolic / physiopathology*
  • Humans
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / biosynthesis
  • Peptidyl-Dipeptidase A / blood*
  • Predictive Value of Tests
  • Prospective Studies
  • Severity of Illness Index
  • Survival Rate / trends
  • Treatment Outcome
  • Ventricular Function / physiology*

Substances

  • Biomarkers
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2