Blood Test Predicts Coronary Disease Death Risk

Cardiovascular (CV) disease is a major cause of morbidity and mortality, and is associated with activation of the renin-angiotensin system (RAS). 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).


Scientists at the University of Melbourne (Parkville, Australia) and their international colleagues prospectively recruited 79 consecutive patients aged >18 years between November 2004 and January 2006 after referral to a tertiary cardiovascular center for a coronary angiogram to investigate suspected CAD. Fasting blood samples were collected at the time of admission for measurement of kidney function, lipids, and troponin. The Access AccuTnI assay was used to measure plasma troponin.

For plasma ACE2 measurement, blood was collected within 48 hours of presentation into lithium heparin tubes, and plasma was obtained by centrifuging blood at 3,000 rpm at 4 °C for 10 minutes and stored at –80 °C until tested. Plasma ACE2 activity was measured within two years after all samples were collected. The catalytic activity of ACE2 was measured using a validated, sensitive quenched fluorescent substrate-based assay. The rate of substrate cleavage was determined by comparison to a standard curve of the free fluorophore.

The scientists reported that the median (IQR) plasma ACE2 activity was 29.3 pmol/mL/min (range: 21.2–41.2). Over a median follow up of 10.5 years, MACE occurred in 46% of patients (36 events). Above median levels of ACE2 (>29.3 pmol/mL/min) were significantly associated with a higher incidence of MACE and HF hospitalization compared with those with below-median ACE2. Over the follow-up period, there were 18 deaths, 19 myocardial infarcts and 16 hospitalizations with HF. The primary endpoint of MACE, a composite of CV mortality, HF hospitalization or MI occurred in 36 patients.

The authors concluded that their study demonstrated that elevated plasma ACE2 activity is an independent predictor of MACE in patients with obstructive CAD. Louise M. Burrell, MBChB, MRCP, MD, FRACP, a professor of Cardiology and senior author of the study, said, “We have come a long way in treating coronary artery disease but certain patients continue to be at high risk of dying. This new blood test helped identify such patients who may derive benefit from more aggressive treatment.” The study was published on June 13, 2018, in the journal Public Library of Science ONE.

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