Sex differences in cardiovascular outcome during progression of aortic valve stenosis

Abstract

Objective: Women with severe aortic valve stenosis (AS) have better LV systolic function and more concentric LV geometry than their male counterparts. However, sex differences in cardiovascular (CV) outcome during progression of AS have not been reported from a longitudinal prospective study.

Methods: Doppler echocardiography and CV events were recorded during a median of 4.0 years in 979 men and 632 women aged 28-86 (mean 67±10) years in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study. LV systolic function was assessed by EF and midwall shortening (MWS). Study outcomes were AS-related events, ischaemic CV events and total mortality.

Results: The annular cumulative incidence of AS events, ischaemic CV events and death was 8.1%, 3.4% and 2.8% in women, and 8.9%, 4.4% and 2.4% in men, respectively. Women and men had similar AS progression rate whether measured by peak jet velocity, mean gradient or valve area. In multivariate analyses, female sex independently predicted less reduction in LV MWS and EF during follow-up (both p<0.05). In time-varying Cox analyses, women had a 40% lower rate of ischaemic CV events (95% CI 21% to 54%), in particular, more than 50% lower rate of stroke and coronary artery bypass grafting, and a 31% lower all-cause mortality (95% CI 1% to 51%), independent of active study treatment, age and hypertension, as well as time-varying valve area, low systolic function and abnormal LV geometry. AS event rate did not differ by sex.

Conclusions: In the SEAS study, women and men had similar rates of AS progression and AS-related events. However, women had lower total mortality and ischaemic CV event rate than men independent of confounders.

Trial registration number: ClinicalTrials.gov identifier: NCT00092677.

Figure 1

Progression of aortic valve stenosis in women and men assessed by 4 key variables: peak aortic jet velocity, mean pressure gradient, aortic valve area and energy loss index (ELI), at 4 different study visits: baseline, 1-year visit, 2-year visit and final visit. *p<0.05 for comparison between women and men at each visit.

Figure 2

Prevalence of low midwall shortening (MWS) (continuous line) and low EF (stippled line) in women and men at different study visits. Mean values are adjusted for repeated measurements over time using full-factorial analysis of variance. p Value of significance for comparison between women and men at each visit.

Figure 3

Survival free of ischaemic cardiovascular (CV) events in women and men during progression of aortic valve stenosis with adjustment for covariates (the means of age, hypertension, active study treatment, energy loss index, low EF and midwall shortening, and abnormal LV geometry) and p value of significance based on Cox proportional hazard analyses.

Figure 4

Overall survival in women and men during progression of aortic valve stenosis with adjustment for covariates (the means of age, hypertension, active study treatment, energy loss index, low EF and midwall shortening, and abnormal LV geometry) and p value of significance based on Cox proportional hazard analysis.