Global cohort study: increased plasma ACE2 tops list of CV risk factors

  • Narula S & al.
  • Lancet
  • 03.10.2020

  • von Emily Willingham, PhD
  • Clinical Essentials
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Takeaway

  • 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.

Key results

  • 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.

Study design

  • Case-cohort analysis from the Prospective Urban Rural Epidemiology study, 14 countries, 5 continents.
  • Funding: Canadian Institute of Health Research; Bayer; others.

Limitations

  • Unmeasured confounding, reverse causality possible.