- In this large global cohort study, increased plasma angiotensin-converting enzyme 2 (ACE2) bested smoking, diabetes, BP, lipids, and BMI as a predictor of death.
- ACE2 values also bested other risk factors as predictive of myocardial infarction, stroke, and heart failure.
Why this matters
- This association is independent of traditional cardiovascular (CV) risk factors, even after adjustment for brain natriuretic peptide.
- This study captured data for people of 7 different ancestral groups and also found associations of 2 loci with increased ACE2 expression.
- A total of 10,753 people were included.
- Median follow-up, 9.42 (interquartile range, 8.74-10.48) years.
- Genetic analyses were confined to those of Latin, European, and Persian ancestry.
- For every increased standard deviation in plasma ACE2, risk (HRs, 95% CIs) was increased for:
- Total death: 1.35 (1.29-1.43).
- CV death: 1.40 (1.27-1.54).
- Non-CV death: 1.34 (1.27-1.43).
- Incident heart failure: 1.27 (1.10-1.46).
- Myocardial infarction: 1.23 (1.13-1.33).
- Stroke: 1.21 (1.10-1.32).
- Diabetes: 1.44 (1.36-1.52).
- These effects were separate from age, sex, ancestry, other CV risk factors.
- Case-cohort analysis from the Prospective Urban Rural Epidemiology study, 14 countries, 5 continents.
- Funding: Canadian Institute of Health Research; Bayer; others.
- Unmeasured confounding, reverse causality possible.