Soluble Angiotensin-Converting Enzyme 2, Cardiac Biomarkers, Structure, and Function, and Cardiovascular Events (from the Atherosclerosis Risk in Communities Study)

Authors

Aliza Hussain
Olive Tang
Caroline Sun
Xiaoming Jia
Elizabeth Selvin
Vijay Nambi
Aaron Folsom
Gerardo Heiss
Faiez Zannad
Thomas Mosley
Salim S Virani
Josef Coresh
Eric Boerwinkle
Bing Yu
Jonathan W Cunningham
Amil M Shah
Scott D Solomon
James A de Lemos
Ron C Hoogeveen
Christie M Ballantyne

Publication Date

5-1-2021

Journal

The American Journal of Cardiology

DOI

10.1016/j.amjcard.2021.01.017

PMID

33539861

PMCID

PMC8038970

PubMedCentral® Posted Date

5-1-2022

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Aged, Angiotensin-Converting Enzyme 2, Atherosclerosis, Biomarkers, Female, Follow-Up Studies, Heart Ventricles, Humans, Male, Middle Aged, Renin-Angiotensin System, Risk Factors, Time Factors, Ventricular Function, Left, ACE2, biomarkers, cardiac structure, cardiovascular disease

Abstract

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.

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