Abstract
BackgroundAngiotensin 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).MethodsWe 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).ResultsWe 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).ConclusionsPlasma ACE2 activity independently increased the hazard of adverse long-term cardiovascular outcomes in patients with obstructive CAD.
Highlights
Cardiovascular (CV) disease is a major cause of morbidity and mortality,[1] and is associated with activation of the renin-angiotensin system (RAS)
On Kaplan-Meier analysis, above-median plasma Angiotensin converting enzyme 2 (ACE2) activity was associated with major adverse cardiovascular events (MACE) and heart failure (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)
Summary
Cardiovascular (CV) disease is a major cause of morbidity and mortality,[1] and is associated with activation of the renin-angiotensin system (RAS). Increased ACE2 activity predicted adverse CV outcomes in heart failure,[16] but not in patients after emergency orthopedic surgery[17] or with chronic kidney disease.[13, 14] These differences may reflect the patient population, the relative cardiovascular risk of the patient population or the length of follow up. The aim of this study was to investigate the utility of plasma ACE2 activity levels to predict CV events in a high-risk cohort of patients with angiographically proven obstructive CAD with more than 10 years of follow-up. 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)
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