ACE2: Canadian Study Shows Plasma ACE2 levels Linked To increased Risk Of Cardiovascular Events

ACE2: Canadian researchers from the Population Health Research Institute, Hamilton Health Sciences, and McMaster University-Ontario, along with support from experts from Bayer Pharmaceuticals-Germany in a news study have discovered that increased plasma ACE2 (Angiotensin-converting enzyme 2) levels in the blood could indicate a higher risk of major cardiovascular events.


 
In brief, the study showed that increased concentration of plasma ACE2 was associated with increased risk of total deaths (hazard ratio [HR] 1·35 per 1 SD increase [95% CI 1·29–1·43]) with similar increases in cardiovascular and non-cardiovascular deaths.
 
Plasma ACE2 concentration was also associated with higher risk of incident heart failure (HR 1·27 per 1 SD increase [1·10–1·46]), myocardial infarction (HR 1·23 per 1 SD increase [1·13–1·33]), stroke (HR 1·21 per 1 SD increase [1·10–1·32]) and diabetes (HR 1·44 per 1 SD increase [1·36–1·52]).
 
These study findings were independent of age, sex, ancestry, and traditional cardiac risk factors. With the exception of incident heart failure events, the independent relationship of ACE2 with the clinical endpoints, including death, remained robust after adjustment for BNP. The highest-ranked determinants of ACE2 concentrations were sex, geographic ancestry, and body-mass index (BMI).
 
Significantly when compared with clinical risk factors (smoking, diabetes, blood pressure, lipids, and BMI), ACE2 was the highest ranked predictor of death, and superseded several risk factors as a predictor of heart failure, stroke, and myocardial infarction.
 
The study findings were published in the peer-reviewed journal: Lancet. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31964-4/fulltext#%20
 
Early studies have already shown that the ACE2 (Angiotensin-converting enzyme 2) receptors act as the entrance of the SARS-CoV-2 coronavirus into the cells by binding with the virus spike proteins. There are various ongoing research efforts to better understand the ACE2 and the key roles in plays in the human body.
 
The findings of this study would also have repercussions on current studies underway that are using synthetic or soluble ACE2 to act as a prophylaxis against the COVID-19 disease. https://www.thailandmedical.news/news/covid-19-research-japanese-researchers-engineer-high-affinity-ace2-receptors-to-serve-as-decoys-to-neutralize-sars-cov-2
 
It is known that ACE2 is a known regulator of cardiac function, and once the system becomes dysregulated, it could lead to health consequences. It is essential to know more about the role of ACE2 and how it can affect the cardiac health of patients infected with the SARS-CoV-2 coronavirus. https://jamanetwork.com/journals/jamacardiology/fullarticle/2763524
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Past smaller clinical studies have suggested that elevated levels of circulating ACE2 activity and concentration may serve as a marker of poor prognosis in people with a multitude of cardiovascular diseases. https://pubmed.ncbi.nlm.nih.gov/32388565/
https://pubmed.ncbi.nlm.nih.gov/31607667/
https://pubmed.ncbi.nlm.nih.gov/27738071/
https://pubmed.ncbi.nlm.nih.gov/29897923/
https://pubmed.ncbi.nlm.nih.gov/19700132/
 
To date, no study has provided evidence in a large cohort in the general population.
 
This Canadian study, called the Prospective Urban Rural Epidemiology (PURE) study, opens the door to explore the link between ACE2 levels with future cardiovascular disease events and deaths in a global community-based cohort.
 
The study team aimed to see the role of demographic and clinical characteristics as possible determinants of the concentration of ACE2 in the plasma and described the link between plasma ACE2 levels and cardiovascular events and mortality, and also explored the importance of ACE2 in the plasma as a risk marker.
 
In order to arrive at the study findings, the PURE study involved participants in 27 low-income, middle-income, and high-income countries.
 
The study team developed a biobanking initiative for the participants to assess genomic and proteomic markers of chronic disease risk. Further, they collected blood samples from the countries, and 14 countries even shipped samples, including Bangladesh, Brazil, Argentina, Canada, Colombia, Chile, India, Philippines, Pakistan, Iran, South Africa, Tanzania, Sweden, the United Arab Emirates, and Zimbabwe.
 
The study team included cardiovascular events, such as stroke, heart failure, diabetes, myocardial infarction, and death.
 
Upon collecting blood samples from all over the globe, the research team measured proteins and plasma concentration using an immunoassay based on proximity extension assay technology. Further, genotyping and genetic analysis were also conducted by the study researchers.
 
The team found that sex accounted for the most variation in plasma ACE2 levels, followed by geographic ancestry, body mass index (BMI), diabetes, age, systolic blood pressure, smoking status, and low-density lipoprotein (LDL) cholesterol levels.
 
The research findings add to the previous one noting that men are at a higher risk of developing severe COVID-19. The study shows that men had higher plasma ACE2 levels than women, while concentrations varied broadly by geographic ancestry. https://pubmed.ncbi.nlm.nih.gov/32388565/
https://pubmed.ncbi.nlm.nih.gov/23535224/
https://pubmed.ncbi.nlm.nih.gov/19700132/
 
Significantly, a higher BMI, older age, diabetes, higher blood pressure, higher LDL cholesterol levels, and smoking were all tied to elevated levels of circulating plasma ACE2.
 
When compared with clinical risk factors, such as diabetes, smoking, blood pressure, BMI, and lipid levels, ACE2 was the highest-ranked predictor of death.
 
Sukrit Narula, one of the co-researchers in the team told Thailand Medical News, “The ACE2 receptor facilitates viral entry for SARS-CoV-2. In patients with COVID-19, the ACE2 receptors might play a role in leading to cardiovascular complications such as thrombosis, cardiac injury, and heart failure. ACE2 is a possible link between SARS-CoV-2 and the cardiac presentations described in findings that have emerged from global data during the COVID-19 pandemic.”
 
The study team noted that the plasma concentration of ACE2 exhibits an independent link with cardiovascular disease, including death.
 
The team added, “Compared with established clinical risk factors, ACE2 consistently emerges as a strong predictor of cardiovascular disease or death.”
 
The study team also added, “Regardless of cause, plasma ACE2 might present a readily measurable indicator of renin–angiotensin system dysregulation. Our primary means of modulating the renin–angiotensin system cascade has focused on therapies dampening the pressor arm using agents such as ACE inhibitors and angiotensin receptor blockers. Modulation of ACE2 and the counter-balancing arm might represent an important therapeutic frontier, and clinical trials are underway to this effect.”
 
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