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Sex Differences in Age-Associated Concentric Remodeling and Diastolic Dysfunction
Israel Gotsman1, Donna R Zwas1, Andre Keren1
1Heart Institute, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Insights
Sex differences in cardiac aging emerge after age 60, with females showing increased remodeling and diastolic dysfunction independent of comorbidities. This highlights the need for sex-specific heart failure prevention strategies.
Area of Science:
- Cardiology
- Gerontology
- Cardiovascular Aging
Background:
- Diastolic dysfunction is key in heart failure with preserved ejection fraction.
- Age, sex, and risk factors influence diastolic dysfunction.
- Understanding sex-specific cardiac aging is crucial.
Purpose of the Study:
- Determine the age of onset for sex-related diastolic function disparities.
- Establish intrinsic sex differences in cardiac aging.
- Inform sex-specific prevention strategies for heart failure.
Main Methods:
- Analyzed echocardiographic parameters in 42,077 individuals (18,476 females, 23,601 males).
- Used covariate-adjusted general linear models to assess age-by-sex interactions.
- Performed sensitivity analysis on a comorbidity-free subgroup (N = 14,250).
Main Results:
- Significant age-by-sex interactions found for all parameters (P < 0.001).
- Females showed increased septal thickening, reduced LV diameter, and concentric remodeling after age 60.
- Diastolic function declined in females from the sixth decade (decreased e', increased E/e').
- Older females had larger left atrial volume index and higher TR gradients.
- Sex-specific disparities in diastolic function emerged around age 60, persisting in the comorbidity-free subgroup.
Conclusions:
- Age-associated cardiac remodeling and diastolic dysfunction in older females are independent of comorbidities.
- Findings support intrinsic, sex-specific differences in cardiac aging, particularly after menopause.
- Results advocate for tailored, sex-specific prevention and treatment strategies for cardiovascular diseases.
Background:
Diastolic dysfunction is a fundamental substrate in heart failure with preserved ejection fraction, with its modulation by age, sex, and cardiovascular risk factors under active investigation.
Objectives:
The purpose of this study was to determine the age onset of sex-related disparities in diastolic function to establish intrinsic sex differences in cardiac aging.
Methods:
We analyzed key echocardiographic parameters related to left ventricular geometric remodeling and diastolic function in a large cohort (N = 42,077; females/males: 18,476/23,601) using covariate-adjusted general linear models. A sensitivity analysis was performed on a subgroup (N = 14,250) free of comorbidities.
Results:
Significant age-by-sex interactions were found for all key parameters with covariate adjustment (P < 0.001), indicating that age-associated differences diverged significantly between sexes. Females demonstrated increased age-related interventricular septal thickening, left ventricular end-diastolic diameter decline, and a marked rise in relative wall thickness after age 60 (interaction F = 18.88) indicating a shift toward concentric remodeling. Diastolic functional decline also exhibited a sex-dependent age-associated pattern: e' velocity decreased significantly and E/e' ratio increased significantly in females from the sixth decade (F = 26.32). Older females also exhibited larger left atrial volume index and higher tricuspid regurgitation pressure gradients. A composite z-score of these parameters revealed significant sex-specific disparities, pinpointing the sixth decade as the age of marked divergence in diastolic function (F = 36.86). These patterns persisted in the subanalysis of individuals without comorbidities.
Conclusions:
The age-associated cardiac remodeling and reduced diastolic function in older females were independent of comorbidities, supporting intrinsic sex-specific differences in cardiac aging emerging after the menopausal transition. These findings support the development of precise, sex-specific prevention strategies.
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