Sex-specific structural and functional cardiac remodeling during healthy aging assessed by cardiovascular magnetic resonance (CMR)

Leonhard Grassow (Berlin)1, J. Gröschel (Berlin)1, H. Saad (Berlin)1, E. Blaszczyk (Berlin)1, T. Hadler (Berlin)1, J. Schulz-Menger (Berlin)1

1Charité - Universitätsmedizin Berlin Experimental & Clinical Research Center (ECRC) Berlin, Deutschland



As a major non-modifiable cardiac risk factor, aging contributes to an increased occurrence of cardiovascular diseases in the elderly (1,2). Since global demographic change challenges future medicine, it is essential to identify and understand physiological cardiac adaptations during the aging process, even in younger life stages. As female and male hearts differ (3), we aim to characterize age-related structural and functional ventricular remodeling between women and men in a healthy cohort with cardiovascular magnetic resonance (CMR). 


We retrospectively screened 203 heart-healthy adults that were enrolled in prospective clinical trials. Diseased participants (cardiovascular diseases and conditions affecting other organ systems) and missing or poor-quality CMR image datasets were excluded. After dividing the cohort into sex-groups (female/male), we defined further age-related subgroups (in years): 1: 19-29, 2: 30-39, 3: 40-49, 4: ≥50 (adjusted after Kawel-Boehm et al (4)). CMR examinations were performed at 1.5 or 3 Tesla scanners applying bSSFP-cine-imaging in a short axis full coverage of left (LV) and right (RV) ventricle. Image analysis was performed in a core laboratory using the software CVI42 and followed a standard approach according to current scientific recommendations (5). Quantitative assessment focused on CMR-indices: LV-mass-to-volume-ratio (LV-MVR) (concentricity), LV-stroke-volume-index (LV-SVI) (cardiac output), and RV-to-LV-volume-ratio (RV/LV-VR) (ventricular proportions). 


After exclusion, 140 healthy volunteers remained for the final analysis (77 females (55%)). Age ranged from 19-77 years (middle-age ± SD: 37.73 ± 13.71 years), other baseline characteristics are presented in Table 1. Women generally presented smaller cardiac dimensions and LV-mass (also indexed to body-surface-area (BSA) or height (H)), but higher biventricular ejection fraction (EF) compared to men. LV and RV volumes decreased significantly with increasing age in both sexes. LV and RV decreased equally, so that the RV/LV-VR remained constant over the lifetime in both sexes (Table 2,3; Figure 1,2,3). Concentricity (LV-MVR) increased significantly with rising age in both sexes (positive age-related correlation, p=0.003) (Table 2,3; Figure 1,3). The increase in concentricity, however, cannot be explained by an increase in LV-mass, but by a stronger decline of LV-end-diastolic-volume in relation to LV-mass. Comparing youngest to oldest age groups, LV-mass (and indexed to BSA/H) only decreased slightly, but insignificantly in both sexes (Table 2,3; Figure 1). LV-SVI (BSA/H) decreased significantly with age (negative age-related correlation, p<0.001), but stronger for men than for women, whereas LV- and RV-EF maintained. The sex-specific trend curves of LV-SVI/BSA crossed at an age of early menopause onset (47.12 years) (Table 2,3; Figure 1,3).  


Both sexes showed comparable age-associated ventricular adjustments, as illustrated in a similar increase in concentricity and in a general decrease of ventricular dimensions. Women, however, had higher biventricular systolic function and a smaller age-related decline in systolic LV performance, which may be related to changes in the sex-hormonal profile over the lifetime. This assessment of age-related cardiac adjustments may help distinguish between physiological and pathological adaptations, and thus prevent over-diagnosing individual patients. 


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