Angiotensin-Converting Enzyme Inhibitor/Angiotensin II Receptor Blocker Treatment and Haemodynamic Factors are Associated with Increased Cardiac mRNA Expression of Angiotensin-Converting Enzyme 2 in Patients with Cardiovascular Disease

Figures

• 

  Figure 1. Atrial angiotensin‐converting enzyme 2 (ACE2) mRNA expression in patients treated with angiotensin‐converting enzyme inhibitor/angiotensin II receptor blocker (ACEi/ARB). (A) Frequency distribution of ACE2 expression. Vertical lines indicate median and upper 95% confidence interval (CI). (B) Scatter and violin plots of atrial ACE2 mRNA expression stratified by patients treated with either ACEi/ARB or not and the corresponding frequency distribution underneath.

• 

  Figure 2. Univariate logistic regression analysis for atrial angiotensin‐converting enzyme 2 (ACE2) mRNA expression. Forest plot showing odds ratio (OR) and 95% confidence interval (CI) derived from univariate logistic regression analysing the risk of increased atrial ACE2 mRNA expression (>0.5478) for multiple clinical variables. ACEi, angiotensin‐converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BMI, body mass index; CCB, calcium channel blocker; LVEF, left ventricular ejection fraction; MRA, mineralocorticoid receptor antagonist; NT‐proBNP, N‐terminal pro brain natriuretic peptide; TIA, transient ischaemic attack. #Requirement of symptoms and LVEF <40% or elevated NT‐proBNP levels and either left ventricular hypertrophy (left ventricular mass index ≥115 g/m2 for male, ≥95 g/m2 for female patients), left atrial enlargement (left atrial volume index >34 mL/m2), or diastolic dysfunction. ¶>300 pg/mL for patients without atrial fibrillation, >900 pg/mL for patients with atrial fibrillation. §Glomerular filtration rate <60 mL/min.

• 

  Figure 3. The effect of angiotensin‐converting enzyme inhibitor/angiotensin II receptor blocker (ACEi/ARB) therapy on angiotensin‐converting enzyme 2 (ACE2) mRNA expression. The mean difference in ACE2 mRNA expression (and 95% confidence interval, CI) between patients treated with ACEi/ARB vs. patients not treated is shown as forest plot. The mean difference was weighted by sample size (weighted mean difference, WMD). BMI, body mass index; BNP, brain natriuretic peptide; Ca, calcium; TIA, transient ischaemic attack. #Requirement of symptoms and left ventricular ejection fraction <40% or elevated N‐terminal proBNP levels and either left ventricular hypertrophy (left ventricular mass index ≥115 g/m2 for male, ≥95 g/m2 for female patients), left atrial enlargement (left atrial volume index >34 mL/m2), or diastolic dysfunction. ¶>300 pg/mL for patients without atrial fibrillation, >900 pg/mL for patients with atrial fibrillation. §Glomerular filtration rate <60 mL/min.

• 

  Figure 4. Ventricular angiotensin‐converting enzyme 2 (ACE2) mRNA expression in failing hearts. (A) Frequency distribution of ventricular ACE2 mRNA expression at left ventricular assist device (LVAD) implantation. (B) Scatter and violin plots of ventricular ACE2 mRNA expression stratified by patients treated with either angiotensin‐converting enzyme inhibitor/angiotensin II receptor blocker (ACEi/ARB) or not. (C) Spaghetti plot of ventricular ACE2 mRNA expression at LVAD implantation and at heart transplantation (about 300 days later). (D) Scatter and violin plots of ACE2 mRNA expression at heart transplantation. HPRT, hypoxanthine ribosyltransferase.