Sex Differences in the Progression of Aortic Valve Aortic Stenosis - Prognostic Implication
Virginia Nguyen MD a, d, e, Tiffany Mathieu MD a, d, e, Maria Melissopoulou MD a, Claire Cimadevilla MD a, e, Isabelle Codogno MS a, Virginie Huart PhD b, Xavier Duval MD, PhD c, Alec Vahanian MD a, d, e, David Messika-Zeitoun MD, PhD a, d, e
From (a) Department of Cardiology, (b) Centre de Ressources Biologique, (c) Centre d’Investigation Clinique 007, Assistance Publique – Hôpitaux de Paris, Bichat Hospital, Paris, France, (d) INSERM U1148, Bichat Hospital, Paris, France, (e) University Paris 7, Paris, France.
Background Female displays a lower degree of aortic valve calcification (AVC) than male for the same hemodynamic severity of valve stenosis (AS) and AS progresses faster with increasing baseline severity. However, the impact of sex on AS progression and outcome has not been specifically evaluated.
Methods Asymptomatic patients with at least mild AS enrolled between 2006 and 2013 in 2 ongoing prospective studies constituted our cohort. 203 patients underwent, the same day, a comprehensive clinical, transthoracic echocardiography (mean pressure gradient, MPG) and multislice computed tomography (AVC score) evaluation at inclusion and yearly thereafter. Asymptomatic patients were contacted every 6 months and seen at our research center every year. The occurrence of AS related events (sudden death, congestive heart failure, or new onset of symptoms) was prospectively recorded.
Results. 152 patients were male (75%). 96 patients (47%) had mild AS, 89 patients (44%) moderate AS and 18 patients (9%) severe AS. AS hemodynamic severity was similar in female and in male (p=0.28) but AVC load was significantly lower in female (p=0.0002). AVC correlated well to MPG both in male and in female but the regression curves were different according to sex (p=0.005) with lower loads of calcium in female than in male for the same hemodynamic severity. Mean follow-up was 3.2±1.2 years. Hemodynamic progression was higher in female than in male (5±5 vs. 3±3 mmHg, p=0.04) and sex was independently associated with hemodynamic progression after adjustment for age, valve anatomy and MPG (p=0.0005). As AVC was significantly lower at baseline in female, the annualized relative progression rate was significantly higher (33±32% vs. 19±16%, p=0.004) and sex was an independent predictor of AVC progression in multivariate analysis (p=0.002). 41 patients developed AS-related symptoms. AS-related events rate at 5 years was 44% in female and 23% in male (p=0.03) and sex was independently predictive of outcome (HR 2.60 [1.32–5.02], p=0.007 with MPG and HR 2.69 [1.34–5.26], p=0.006 with AVC score).
Conclusions In a prospective cohort of AS patients, female sex was an independent determinant of both AVC and MPG progression which translated into a higher AS-related events rate. These results support that AS pathophysiology may be different in female and in male and suggest that a closer follow-up time may be advised in female.