Prognostic value of elevated plasma angiotensin-converting enzyme 2 in cardiometabolic diseases: A review

Angiotensin-converting enzyme 2, as an internal anti regulator of the renin-angiotensin hormone cascade reaction, plays a protective role in vasodilation, inhibition of fibrosis, and initiation of anti-inflammatory and antioxidative stress by degrading angiotensin II and generating angiotensin (1-7). Multiple studies have shown that plasma angiotensin-converting enzyme 2 activity is low in healthy populations without significant cardiometabolic disease, and elevated plasma angiotensin-converting enzyme 2 levels can be used as a novel biomarker of abnormal myocardial structure and/or adverse events in cardiometabolic diseases. This article aims to elaborate the determinants of plasma angiotensin-converting enzyme 2 concentration, the relevance between angiotensin-converting enzyme 2 and cardiometabolic disease risk markers, and its relative importance compared with known cardiovascular disease risk factors. Confronted with the known cardiovascular risk factors, plasma angiotensin-converting enzyme 2 (ACE2) concentration uniformly emerged as a firm predictor of abnormal myocardial structure and/or adverse events in cardiometabolic diseases and may improve the risk prediction of cardiometabolic diseases when combined with other conventional risk factors. Cardiovascular disease is the leading cause of death worldwide, while the renin-angiotensin system is the main hormone cascade system involved in the pathophysiology of cardiovascular disease. A multi-ancestry global cohort study from the general population by Narula et al revealed that plasma ACE2 concentration was strongly associated with cardiometabolic disease and might be an easily measurable indicator of renin-angiotensin system disorder. The association between this atypical hormone disorder marker and cardiometabolic disease is isolated from conventional cardiac risk factors and brain natriuretic peptide, suggesting that a clearer comprehending of the changes in plasma ACE2 concentration and activity may help us to improve the risk prediction of cardiometabolic disease, guide early diagnosis and feasible therapies, and develop and test new therapeutic targets.