Impact of the Renin-Angiotensin System Activation on the Progression Rate of Aortic Stenosis
Mylène Shen, Lionel Tastet, Romain Capoulade, Marie Arsenault, Elisabeth Bédard, Philippe Pibarot, Marie Annick Clavel.
Quebec Heart and Lung Institute, Quebec City, QC, Canada.
OBJECTIVE: Whether AS progression is only due to the mechanical stress put on the aortic valve (due to systemic hypertension) or is also related to the activation of the renin-angiotensin system (RAS) is unknown. The objective of this study was to evaluate the impact of the ratio of angiotensinogen/angiotensin II (AGN/Ang II), which reflects the RAS activation, on the progression rate of AS.
METHODS: Asymptomatic patients with AS and preserved LVEF were recruited prospectively in the PROGRESSA study. The annualized progression of the transvalvular mean gradient (MG) was calculated based on the baseline and last follow-up data of the Doppler-echocardiography exams. AGN and Ang II plasma levels were measured at baseline, then the AGN/Ang II ratio was calculated and normalized with a logarithmic transformation.
RESULTS: In this study, 137 patients with a mean age of 65±14 years were included. There were 70% of men and 22% of bicuspid aortic valve. At baseline, median MG was 15.6 [13.0-22.1] mmHg and annualized progression of MG was 2.3 [1.0-4.9] mmHg for a median follow-up of 4.0 [2.0-5.4] years. Median AGN/Ang II ratio was 2.05 [1.66-2.66]. In univariable analyses, only baseline MG was associated with annualized progression of MG (p<0.0001). After a comprehensive adjustment (including baseline MG, age, sex, systolic blood pressure (SBP), stroke volume index, bicuspid aortic valve, dyslipidemia, diabetes, coronary artery disease and LVEF), baseline MG (p<0.0001), SBP (p=0.004) and log(AGN/Ang II) (p=0.03) were independently associated with the annualized progression of MG.
CONCLUSIONS: In this subset of patients with AS from the PROGRESSA study, AGN/Ang II ratio was independently associated with the progression rate of MG. These findings suggest that both mechanical stress and RAS activation are involved in the progression of the stenosis. Therefore, our results further support the importance of using anti-RAS medication in patients with AS.
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