Elevated Plasma Angiotensin Converting Enzyme 2 Activity Is an Independent Predictor of Major Adverse Cardiac Events in Patients With Obstructive Coronary Artery Disease

PLoS One. 2018 Jun 13;13(6):e0198144. doi: 10.1371/journal.pone.0198144. eCollection 2018.

Abstract

Background: Angiotensin converting enzyme 2 (ACE2) is an endogenous regulator of the renin angiotensin system. Increased circulating ACE2 predicts adverse outcomes in patients with heart failure (HF), but it is unknown if elevated plasma ACE2 activity predicts major adverse cardiovascular events (MACE) in patients with obstructive coronary artery disease (CAD).

Methods: We prospectively recruited patients with obstructive CAD (defined as ≥50% stenosis of the left main coronary artery and/or ≥70% stenosis in ≥ 1 other major epicardial vessel on invasive coronary angiography) and measured plasma ACE2 activity. Patients were followed up to determine if circulating ACE2 activity levels predicted the primary endpoint of MACE (cardiovascular mortality, HF or myocardial infarction).

Results: We recruited 79 patients with obstructive coronary artery disease. The median (IQR) plasma ACE2 activity was 29.3 pmol/ml/min [21.2-41.2]. Over a median follow up of 10.5 years [9.6-10.8years], MACE occurred in 46% of patients (36 events). On Kaplan-Meier analysis, above-median plasma ACE2 activity was associated with MACE (log-rank test, p = 0.035) and HF hospitalisation (p = 0.01). After Cox multivariable adjustment, log ACE2 activity remained an independent predictor of MACE (hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.24-4.72, p = 0.009) and HF hospitalisation (HR: 4.03, 95% CI: 1.42-11.5, p = 0.009).

Conclusions: Plasma ACE2 activity independently increased the hazard of adverse long-term cardiovascular outcomes in patients with obstructive CAD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Coronary Angiography
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / diagnosis*
  • Coronary Artery Disease / mortality
  • Coronary Occlusion / blood
  • Coronary Occlusion / complications
  • Coronary Occlusion / diagnosis*
  • Coronary Occlusion / mortality
  • Female
  • Follow-Up Studies
  • Heart Failure / blood
  • Heart Failure / diagnosis*
  • Heart Failure / etiology
  • Heart Failure / mortality
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / diagnosis*
  • Myocardial Infarction / etiology
  • Myocardial Infarction / mortality
  • Peptidyl-Dipeptidase A / blood*
  • Prognosis
  • Tomography, X-Ray Computed
  • Up-Regulation

Substances

  • Biomarkers
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2

Grant support

This work was supported by National Health & Medical Research Council project grant(APP268914) to Louise M Burrell. Dr. Jay Ramchand is supported by a postgraduate scholarship co-funded by the National Heart Foundation of Australia and National Health & Medical Research Council (APP1132717). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.