September 22, 2023

Study Links Sex With Progression and Outcomes of Early-Stage Aortic Stenosis

Differences in pace of hemodynamic change signal need for sex-specific management

illustration of aortic stenosis suggesting sex-related differences

A new study by Cleveland Clinic investigators reveals distinct longitudinal echocardiographic and clinical profiles in women versus men with mild to moderate aortic stenosis (AS), underscoring the need for sex-specific management to optimize outcomes.

Advertisement

Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

Published online in JACC: Cardiovascular Imaging, the large retrospective cohort study suggests that compared with men, women with mild to moderate AS are more likely to have:

  • Slower hemodynamic progression
  • Better-preserved left ventricular ejection fraction (LVEF)
  • Concentric left ventricular hypertrophy
  • Lower incidence of aortic valve replacement (AVR)

“The faster hemodynamic progression in men may help explain their higher incidence of AVR compared with women,” says study co-author Venu Menon, MD, Section Head of Clinical Cardiology at Cleveland Clinic. “Our findings support the need for sex-specific clinical assessment and follow-up surveillance of early-stage aortic stenosis.”

Study rationale and design

Recent studies have increased awareness of persistently poor outcomes in patients with moderate AS. Additional studies have identified various sex-based differences in patients with AS, including in clinical profiles at diagnosis, onset and severity of symptoms, valvular progression, extent of ventricular remodeling and clinical outcomes. Overall data on these differences have been inconsistent, however, and these studies’ relevance to clinical practice is impacted by factors such as small sample size and limited follow-up.

In contrast, the new study used a large group of patients followed for a long time in real-world practice, with manual data collection through chart review and relevant multivariable-adjusted and subgroup analyses.

The investigators focused on data from patients aged 60 or older with mild to moderate native valve AS in the Cleveland Clinic echocardiography database from 2008 through mid-2016, with follow-up until 2018. Inclusion required an aortic valve area of 1.0 to 2.0 cm2 on index echocardiogram, and all patients had to have at least one subsequent echocardiogram at least two years later.

After exclusion of patients with bicuspid aortic valve or prior AVR, 2,549 patients (mean [±SD] age, 74 ± 7 years) were included in the analysis — 1,465 men (57.5%) and 1,084 women (42.5%). Prevalence of mild versus moderate AS was similar between the sexes, with 68.8% of the overall cohort having mild AS.

Advertisement

Primary outcomes were all-cause mortality and AVR. AS progression was the secondary outcome, as assessed by annualized changes in echocardiographic parameters, with analysis based on sex. Median follow-up was 5.7 years.

Key findings

Primary endpoints. No differences in all-cause mortality emerged between the sexes, regardless of age, baseline disease severity, progression to severe AS or receipt of AVR.

The incidence of AVR was lower in women than in men, at 37.1 vs. 57.7 events per 1,000 person-years (incidence rate ratio = 0.64; 95% CI, 0.55-0.75; P<0.0001). That difference persisted after stratification for age and AS severity and irrespective of the presence of coronary artery disease or atrial fibrillation, which were less common in women. In multivariable-adjusted risk regression analysis, the adjusted hazard ratio for AVR at 10 years in women was 0.81 (95% CI, 0.67-0.91; P = 0.009).

AVR for symptomatic disease, such as angina, syncope or heart failure symptoms, was more likely in women than men, whereas men were more likely to undergo AVR for reduced LVEF and concomitant open-heart surgery. Hyperlipidemia, atrial fibrillation and coronary artery disease all were significantly more prevalent in men.

“The lower rate of AVR in women in our study aligns with intrinsic pathophysiologic differences between the sexes and suggests that sex-based differences in aortic stenosis progression translate into differing clinical outcomes,” notes study co-author Serge Harb, MD, staff cardiologist in the Section of Cardiovascular Imaging.

Secondary endpoint. Disease progression was significantly faster in men than in women on 1:1 propensity-matched analysis, as demonstrated by significantly greater increases in the median annualized change in mean gradient (2.10 vs. 1.15 mmHg/yr; P < 0.001) as well as maximum transvalvular velocity and left ventricular end-diastolic diameters.

Advertisement

“The annualized changes in transvalvular gradients in our study are similar to findings from previous research, but those findings were not sex-stratified,” says Dr. Harb. “Given the differences we observed in aortic stenosis progression, we hypothesize that there are sex-based variations in underlying mechanisms of ventricular adaptation to pressure overload that involve phenotypic pathways of ventricular remodeling and aortic valvular degeneration.”

Weigh sex-based differences when advising patients

“As these findings illustrate, clinicians must weigh sex-based differences when considering the potential for aortic stenosis progression,” Dr. Menon observes. “Future trials are needed to identify approaches to evaluation and management of aortic stenosis that can help mitigate the disparities in outcomes between women and men.”

“Previous studies show that, compared with men, women have less valvular calcification but more fibrosis with similar aortic stenosis severity,” adds Leslie Cho, MD, Director of the Women’s Cardiovascular Center at Cleveland Clinic. Additionally, she notes, in a study of 174 patients with moderate to severe AS followed every six months with extensive imaging and biomarkers, women were more likely to be symptomatic with the same severity of AS compared with men. “These findings, along with the current paper, call for sex-specific thresholds to define severe aortic stenosis.”

Related Articles

illustration of mitral valve with male/female symbol overlay
February 12, 2024
Long-Term Outcomes of Mitral Valve Repair for Degenerative MR Worse in Women Than Men

A call for surgical guidelines to adopt sex-specific thresholds of LV size and function

23-HVI-4424566_mitral-valve_650x450
December 13, 2023
Study Reveals Persistence of Later Surgical Referrals for Severe Degenerative Mitral Regurgitation

While mortality was unaffected, later surgery was associated with more reoperations

23-HVI-4417336 CQD 650&#215;450
December 12, 2023
Aortic Valve Reimplantation Shows Long-Term Durability in Patients With Connective Tissue Disorders

Many young patients can avoid lifelong anticoagulation with a valve-sparing approach

illustration of mitral valve transcatheter edge-to-edge repair
December 1, 2023
The Two FDA-Approved M-TEER Systems Are Comparable at 1-Year Follow-Up, CLASP IID Data Show

And substudy reveals good outcomes with PASCAL system in patients with complex mitral valve anatomy

illustration of tricuspid valve regurgitation
November 10, 2023
TRILUMINATE Health Status Analysis: T-TEER Patients Likelier to Be ‘Alive and Well’ at 1 Year

Investigators conclude that improved self-reports go beyond possible placebo effect for severe TR

23-HVI-4298711_TAVR-vs-SAVR_650x450
November 1, 2023
TAVR and SAVR Perform Similarly at 5 Years in Low-Risk Patients, PARTNER 3 Report Shows

Five-year data demonstrate convergence of outcomes from years 1 to 5

23-HVI-4078932_severe-tricuspid-regurgitation_650x450
August 2, 2023
Early Surgery for Isolated Severe Tricuspid Regurgitation Improves Outcomes

Cleveland Clinic study argues against waiting for symptoms to develop

Blood Clot Cell Artery
May 31, 2023
PROACT Xa: Apixaban Is Not a Safe Warfarin Substitute With Mechanical Aortic Valve

Details released from the trial halted due to excessive thromboembolic events

Ad