Sex Differences in Mild to Moderate Aortic Stenosis Progression

Quick Takes

  • Females had distinct echocardiographic and clinical differences and significantly higher LVEF, filling pressures, and LV septum thickness over time on follow-up echocardiograms compared to males.
  • Males had a significantly faster hemodynamic disease progression represented by greater increases in the mean gradient, maximum transvalvular velocity, and LV end-diastolic diameters.
  • There was no difference in all-cause mortality between sexes irrespective of age, baseline disease severity, progression to severe aortic stenosis (AS), and receipt of aortic valve replacement.
  • These findings provide further evidence that there are distinct sex-specific longitudinal profiles in patients with AS.

Study Questions:

Are there any sex differences in the progression and outcomes of mild to moderate native aortic stenosis (AS)?


The authors performed a retrospective single-center cohort study of patients with mild to moderate native tricuspid AS from the echocardiographic database of the Cleveland Clinic health system between 2008–2016 and followed until 2018. Patients aged ≥60 years with mild or moderate native AS, defined as aortic valve area (AVA) between 1.0–2.0 cm2 on index echocardiogram, were identified. Baseline patient characteristics including demographics, comorbidities, medications, laboratory data, and echocardiographic data were obtained from the electronic medical records based on comprehensive chart review of data. Echocardiographic and Doppler measurements were obtained by an experienced sonographer and adjudicated by an expert board-certified echocardiogram reader according to established guidelines. The primary outcome was all-cause mortality, aortic valve replacement (AVR), and the secondary outcome was disease progression assessed by annualized changes in echocardiographic parameters.


Among 2,549 included patients, the mean age was 74 years, 42.5% were female, and 89.8% were white. The median duration of follow-up was 5.7 years. In baseline characteristics, relative to females, males had a higher prevalence of chronic comorbidities as in higher hyperlipidemia (78.6% vs. 74.3%, p = 0.011), atrial fibrillation (29.9% vs. 25.2%, p = 0.009), and coronary artery disease (CAD) (57.2% vs. 36.1%, p < 0.001). There was no difference in all-cause mortality between sexes irrespective of age, baseline disease severity, progression to severe AS, and receipt of AVR.

In secondary outcomes, males had a significantly faster disease progression represented by greater increases in the median of annualized change in mean gradient (2.10 vs. 1.15 mm Hg/year, respectively, p < 0.001), maximum transvalvular velocity (0.42 vs. 0.28 m/s/year), and left ventricular (LV) end-diastolic diameters (0.15 vs. 0.048 mm/m2.7/year) (p = 0.014).

Further, females had differences in LV remodeling and filling pressures and had significantly higher LV ejection fraction (LVEF), E/e’, right ventricular systolic pressure, and LV septum thickness over time both in the overall population and in the 1:1 propensity-matched group of patients on follow-up echocardiograms compared to males.


In patients with native mild to moderate AS, males have higher burden of chronic conditions including CAD and hypertension. Males and females have distinct clinical and echocardiographic profiles of LV remodeling in response to chronic pressure overload, with females having a higher likelihood of concentric hypertrophy, higher LVEF, filling pressures, and LV septum thickness over time on follow-up echocardiograms compared to males. Males have higher mean gradient and faster progression of disease severity.


Recent genetic, molecular, and clinical data have identified sex-based differences in clinical characteristics at time of diagnosis, symptom onset and severity, valvular progression and the concomitant degree of ventricular adaptation and remodeling, and clinical outcomes in patients with AS. This is a large, real-world sample of a patient population followed for a long time. The study focuses on distinct sex-specific differences in disease progression. The recent guidelines have noted sex-specific criteria for aortic calcification based on calcium.

The study adds to the growing body of literature of distinct LV remodeling and clinical progression between the two sexes. The observed differences in AS progression between sexes in this study suggest variations in underlying mechanisms of ventricular adaptation to pressure overload via varying phenotypic pathways of LV remodeling and valvular degeneration. These differences are clinically relevant and play into progression to symptomatic disease between the two sexes.

Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Diabetes and Cardiometabolic Disease, Dyslipidemia, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Valvular Heart Disease, Atherosclerotic Disease (CAD/PAD), Atrial Fibrillation/Supraventricular Arrhythmias, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Cardiac Surgery and VHD, Acute Heart Failure, Interventions and Coronary Artery Disease, Interventions and Imaging, Interventions and Structural Heart Disease, Echocardiography/Ultrasound

Keywords: Aortic Valve Stenosis, Atrial Fibrillation, Cardiac Surgical Procedures, Coronary Artery Disease, Diagnostic Imaging, Disease Progression, Dyslipidemias, Echocardiography, Geriatrics, Heart Failure, Heart Valve Diseases, Hyperlipidemias, Hypertrophy, Sex Characteristics, Stroke Volume, Transcatheter Aortic Valve Replacement, Ventricular Pressure

< Back to Listings