Author + information
- Jay Ramchand, MBBS, BMedScia,b@DrJRamchand,
- Sheila K. Patel, BSc, PhDa,
- Leighton G. Kearney, MBBS BMedSci, PhDb,
- George Matalanis, MBBS, MSc,
- Omar Farouque, MBBS, PhDa,b,
- Piyush M. Srivastava, MBBSa,b and
- Louise M. Burrell, MBChB, MDa,b,∗ (, )@LouiseBurrell3
- aDepartment of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
- bDepartment of Cardiology, Austin Health, Heidelberg, Victoria, Australia
- cDepartment of Cardiac Surgery, Austin Health, Heidelberg, Victoria, Australia
- ↵∗Address for correspondence:
Dr. Louise M. Burrell, Department of Medicine, Austin Health, University of Melbourne, Level 7, Lance Townsend Building, 145 Studley Road, Heidelberg, VIC 3084, Australia.
Objectives This study investigated the relationship between plasma angiotensin-converting enzyme 2 (ACE2) activity levels and the severity of stenosis and myocardial remodeling in patients with aortic stenosis (AS) and determined if plasma ACE2 levels offered incremental prognostic usefulness to predict all-cause mortality.
Background ACE2 is an integral membrane protein that degrades angiotensin II and has an emerging role as a circulating biomarker of cardiovascular disease.
Methods Plasma ACE2 activity was measured in 127 patients with AS; a subgroup had myocardial tissue collected at the time of aortic valve replacement.
Results The median plasma ACE2 activity was 34.0 pmol/ml/min, and levels correlated with increased valvular calcification (p = 0.023) and the left ventricular (LV) mass index (r = 0.34; p < 0.001). Patients with above-median plasma ACE2 had higher LV end-diastolic volume (57 ml/m2 vs. 48 ml/m2; p = 0.021). Over a median follow-up of 5 years, elevated plasma ACE2 activity was an independent predictor of all-cause mortality after adjustment for relevant clinical, imaging, and biochemical parameters (HR: 2.28; 95% CI: 1.03 to 5.06; p = 0.042), including brain natriuretic peptide activation (integrated discrimination improvement: 0.08; p < 0.001). In 22 patients with plasma and tissue, increased circulating ACE2 was associated with reduced myocardial ACE2 gene expression (0.7-fold; p = 0.033) and severe myocardial fibrosis (p = 0.027).
Conclusions In patients with AS, elevated plasma ACE2 was a marker of myocardial structural abnormalities and an independent predictor of mortality with incremental value over traditional prognostic markers. Loss of ACE2 from the myocardium was associated with increased fibrosis and higher circulating ACE2 levels.
This work was supported by a National Health and Medical Research Council Program Grant (APP1055214) to Dr. Burrell. Dr. Ramchand is supported by a postgraduate scholarship co-funded by the National Heart Foundation of Australia and National Health and Medical Research Council (APP1132717). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received June 25, 2019.
- Revision received August 13, 2019.
- Accepted September 6, 2019.
This article requires a subscription or purchase to view the full text. If you are a subscriber or member, click Login or the Subscribe link (top menu above) to access this article.