Membrane-bound angiotensin-converting enzyme 2 is important in regulation of the renin–angiotensin–aldosterone system, but the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) is unclear. We evaluated the association of sACE2 with cardiac biomarkers, structure, and function and cardiovascular events in the Atherosclerosis Risk in Communities Study. sACE2 was measured in a subset of 497 participants (mean age 78±5.4 years, 53% men, 27% black); Cox regression analyses assessed prospective associations of sACE2 with time to first CVD event at median 6.1-year follow-up. sACE2 was higher in men, blacks, and participants with prevalent CVD, diabetes, or hypertension. Higher sACE2 levels were associated with significantly higher biomarkers of cardiac injury (high-sensitivity cardiac troponin I and T, N-terminal pro–B-type natriuretic peptide), greater left ventricular mass index, and impaired diastolic function in linear regression analyses, and with increased risk for heart failure hospitalization (adjusted hazard ratio per natural log unit increase [HR] 1.32, 95% confidence interval [CI] 1.10 to 1.58), CVD events (HR 1.34, 95% CI 1.13 to 1.60), and all-cause death (HR 1.26, 95% CI 1.01 to 1.57). In an elderly biracial cohort, sACE2 was positively associated with biomarkers reflecting myocardial injury and neurohormonal activation, left ventricular mass index, impaired diastolic function, CVD, events and all-cause death.
Bibliographical noteFunding Information:
The Atherosclerosis Risk in Communities study has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract numbers HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I). This work was supported by NIH grants F30-DK120160 (O.T.), K24-DK106414 (E.S.), R01-DK089174 (E.S.), R01-HL134320 (E.S. and C.M.B.), R01-HL141824 (B.Y.), R01-HL142003 (B.Y.), T32-HL094301 (J.W.C.), R01-HL135008 (A.M.S.), R01-HL143224 (A.M.S.), R01-HL150342 (A.M.S.), and K24-HL152008 (A.M.S.)]; US Department of Veterans Affairs grants 1I01CX001112-01 (V.N.), IIR 16-072 (S.V.), and IIR 19-069 (S.V.); European Union 7th Framework Programme for Research and Technological Development grant HEALTH-F7-305507 (F.Z., as part of Heart OMics in AGEing); World Heart Federation (S.V.); and American Heart Association grant 17SDG33661228 (B.Y.).
© 2021 Elsevier Inc.
- Angiotensin-Converting Enzyme 2/blood
- Follow-Up Studies
- Heart Ventricles/diagnostic imaging
- Middle Aged
- Renin-Angiotensin System/physiology
- Risk Factors
- Time Factors
- Ventricular Function, Left/physiology
PubMed: MeSH publication types
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.
- Multicenter Study
- Journal Article
- Research Support, N.I.H., Extramural