Copyright © 2005, The European Society of Cardiology
Gender and age related differences in left ventricular function and geometry with focus on the long axis
Wallenberg Laboratory for Cardiovascular Research, Cardiovascular Institute, The Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden
Received 20 January 2005; accepted after revision 15 June 2005.
* Corresponding author. Tel.: +46 31 342 32 11; fax: +46 31 82 37 62. bert.andersson{at}wlab.gu.se
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Abstract |
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Aims To study age and gender related alterations in left ventricular (LV) long axis function.
Methods Eighty-two healthy individuals from the general population in three age groups were investigated. LV long axis and short axis function and dimensions were studied with echocardiographic M-mode and two-dimensional technique.
Results The most prominent age related differences were observed in LV long axis function, whereas only minor alterations in short axis function were noticed. Both systolic and diastolic long axis function decreased with advancing age; maximal systolic velocity (r=0.61, p<0.0001), maximal early diastolic filling velocity (r=0.87, p<0.0001). The length of the long axis decreased with age, while the relative contraction amplitude was maintained. LV global and short axis measurements revealed significant differences between genders, males having generally larger dimensions, even when correcting for body surface area. Females exhibited a more pronounced remodelling process with advancing age.
Conclusion Functional age related changes in LV function are more prominent in the long axis, while differences between genders are more pronounced in short axis and in volume measurements. These findings might be of importance when remodelling processes are evaluated, as these appear to be different in men and women and also age related.
Keywords: Age; Echocardiography; Geometry; Gender; Healthy subjects; Left ventricular function; Diastole
The heart is subjected to alterations in morphology and function with advancing age. Several age related structural and functional alterations might also be a consequence of cardiac disease, such as valvular fibrosis, reduction in the number of myocytes,1 and altered calcium transport.2 These changes contribute to the stiffening of the myocardium and influence aspects of left ventricular (LV) diastolic function,3 such as prolongation of left ventricular relaxation, and are in part responsible for a reduction in cardiovascular reserve capacity.4
Systolic and diastolic LV function is a combined action of shortening and lengthening of circumferential, oblique, and longitudinal muscle fibres.5,6 The conventional method to assess global LV function has been to measure short axis contraction, carried out preferentially by the circumferentially arranged muscle fibres, orientated in the middle layer of the left ventricular wall. Less attention has been paid to contraction of the longitudinal muscle fibres in subendocardial and deep layers7,8 that contribute to shortening of the long axis. However, the movement of the mitral annulus – or atrioventricular plane (AVP) – towards apex plays a major role in LV pumping function. Indeed, these movements encompass the largest amplitudes and fastest myocardial velocities in the heart. Although AVP movements have been observed for many years,9 a recent increase in interest has occurred through the introduction of new echocardiographic techniques, using tissue Doppler imaging.10–12
As information about normal LV long axis function is scarce in the literature, the aim of the present study was to investigate the influence of age and gender on changes in systolic and diastolic LV function as well as geometry with focus on the LV long axis.
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Study group
An equal number of healthy men and women were recruited, in three different age groups: 20–29 years, 50–59 years, and 60–69 years. By random number generation, one day of birth per month was selected. From the county registry of the city of Göteborg, and the adjacent community Mölndal (in total 475 000 residents) data for all persons born on that selected day on the corresponding year were obtained. From this list one man and one woman were chosen by random number generation. By telephone interview the person was asked about concomitant diseases and medications and was asked to participate in the study. If the subject could not be reached, or was unwilling to participate, or had a disease that might influence cardiovascular function, another person on the list born on the same day was chosen. In total 108 persons accepted to participate in the study. They were subjected to a physical examination, including an ECG, and filled out a questionnaire regarding background data and symptomatology. Persons older than 50 years had a chest X-ray and routine blood tests taken (regarding haematology, kidney, liver, and thyroid function). Those individuals who had a history or signs indicating cardiovascular disease or another disease that might influence cardiac function were excluded. Twenty-six persons were excluded due to the following reasons: hypertension (15), ischemic heart disease (4), significant aortic regurgitation (4), a previously undiscovered pulmonary malignancy (3), thyroid disease (3), and diabetes mellitus (1). In all, 82 subjects met the inclusion criteria and none of the exclusion criteria. The majority of the excluded persons were in the age above 60, in whom as much as one third of the examined persons displayed signs of disease. None of the aforementioned exclusion conditions had been diagnosed by a physician prior to our investigation. The study was approved by the Ethical Committee of Göteborg University, and informed consent was obtained from all individuals. Anthropometric data are presented in Table 1.
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Echocardiographic recordings
All examinations were performed by one technician, one physician and in one laboratory, using an Acuson 128 XP with a 2.5-MHz or 3.5-MHz transducer. The study subjects were investigated in the left lateral position and all recordings were obtained during relaxed end-expiratory apnoea and recorded on videotape and on strip-charts at 100mm/s. ECG was recorded continuously. To enable detection of the second heart sound, a phonocardiogram was connected with a microphone placed across the second right intercostal space. LV short axis diameter and function were measured in the parasternal view in accordance with the recommendations of the American Society of Echocardiography,13 while measurement of chamber volumes were evaluated from paired apical views.14 From an optimal apical chamber view, the movement of the AVP was recorded with the M-mode beam positioned to the insertion of the mitral valve, using zoom function. Recordings of the septal and lateral portions of the AVP-displacement were obtained from the apical four-chamber view in all individuals, while additional registrations of the anterior and inferior portions from apical two-chamber view were performed in the age group of 20–29 years. The success rate of long axis registration was complete, whereas adequate short axis registrations were obtained in 74 subjects. The failure to obtain adequate short axis registrations in six subjects was mostly attributed to that parasternal registrations yielding an oblique view of the left ventricle.
Analysis
Atrioventricular plane movements
The systolic AVP amplitude was measured from the onset of systole, after the isovolumic contraction time, until the point that coincides with the aortic closure.15 A minimum of three cardiac cycles were analysed and averaged. The curves were traced on a digitising table and processed with a computer software program, Cardiac Analysis Software (CAS), Sahlgrenska University Hospital, Göteborg. Maximal velocities were calculated by the program from the steepest parts of systolic and diastolic movements. Amplitudes, time intervals, and velocities were analysed as illustrated in Fig. 1. In order to normalise function to the size of the heart, the AVP-fractional shortening (FS) was calculated by dividing the systolic amplitude with the length of the long axis, measured from the epicardial apex to the end of diastasis in the AVP recording.16,17 The intra-observer coefficient of variation in our laboratory regarding long axis recordings was: 4.7% (r=0.99), systolic amplitude (mm); 9.7% (r=0.92), systolic velocity (mm/s); and 9.2% (r=0.92), early diastolic filling velocity (mm/s).
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Short axis dimensions and ejection fraction
Calculations of LV short axis dimensions, mass and ejection fraction (EF)18 were digitised and analysed using CAS, generating data of dimensions, time intervals, and maximal wall motion velocities.
Left ventricular volumes
Two-dimensional bi-plane recordings (four- and two-chamber views) were performed for calculations of LV end-diastolic and end-systolic volumes. Ejection fraction was calculated with the method of disc, modified Simpson rule, in one representative heart beat.
Statistical methods
Data are presented as mean values±SD, or as median (interquartile range). The relation between age and different variables was evaluated by linear regression and ANOVA. Mann–Whitney U-test was performed for comparisons between genders. A multivariate logistic regression analysis was used to evaluate possible clinically predictors of echocardiographic variables. Variables included into the regression were: age, gender, heart rate, systolic blood pressure, and body surface area. Owing to the number of statistical comparisons, statistical significance was considered if p-value was <0.01. Data were analysed on SPSS software, Chicago, Ill, USA.
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LV long axis and short axis function
The majority of systolic as well as diastolic parameters of LV long axis recording were significantly correlated to age (Table 2). With increasing age, a significant decrease in systolic amplitude (r=0.45, p<0.0001) and maximal systolic velocity (r=0.61, p<0.0001) was observed, whereas AVP-FS was not related to age. The closest association with age was observed in diastolic parameters, including LV early diastolic filling amplitude (r=0.82, p<0.0001), and early diastolic filling velocity (r=0.87, p<0.0001). Concomitantly, left atrial (LA) contribution to diastolic filling increased with advancing age. There was an increase in LA amplitude, LA systolic velocity, and LA filling fraction, all p<0.0001. Further, there were gender related differences regarding long axis function (Table 3). AVP-FS was significantly larger in females, while LA function measurements were significantly larger in males. Age had only minor influence on systolic function, as expressed by relative functional measurements like FS or EF (Fig. 2). To evaluate different clinical factors that could affect systolic and diastolic function, a multivariate logistic regression analysis was performed (Table 4). Age was independently associated with several variables, including maximal systolic velocity, and maximal early diastolic filling velocity. In this analysis, gender was independently associated with long axis length. Systolic blood pressure or body surface area was not independently predictive of variables from long axis recordings.
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Data from short axis recordings in the different age groups are shown in Table 5. Systolic velocity of the posterior wall was the only functional parameter from LV short axis function that displayed a relation with gender. No independent associations were observed between clinical data and other measurements from short axis functional data (Table 6).
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LV geometry
We observed a significant association between age and decrease in end-diastolic long axis length in both genders (Fig. 3). Two-dimensional recordings revealed age related decrease in LV end-diastolic volumes in both genders, while a significant decrease in end-systolic volumes only was observed in women (Fig. 4). These associations concerning LV volumes and gender also persisted after correction for body surface area (Table 7). In the total study group LV mass did not change with age. However, a significant increase was observed in women with advancing age, also if LV mass was corrected for body surface area (Table 7). However, in the multivariate logistic regression analysis (Tables 4 and 6
), there was a significant independent correlation between gender and two-dimensional and short axis measurements, respectively. Likewise, gender was associated with LV external and internal diameters. Sphericity (short axis external diameter/long axis length) was related to age, but not to gender (Table 4). Thus, the study demonstrated that males had nominally larger LV dimensions, and also when controlling for body size, gender differences were apparent (Table 7).
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Discussion |
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We present data from a group of healthy subjects regarding functional and geometric alterations in the left ventricle. Age and gender differently influenced LV long axis and short axis performance and geometry.
Long axis vs. short axis performance
In accordance with a previous report we noticed that the absolute systolic AVP amplitude decreased with age.19 However, a new finding was that when the contraction amplitude was normalised to LV length (AVP-FS), this association was lost (Figs. 2 and 3), attributable to a progressive age related shortening of the length of LV long axis. A parallel phenomenon is the preservation of global EF with age, in conjunction with decreasing LV volumes. Our study cannot provide data that explain the origin of this phenomenon that appear to be present during normal ageing as well as in hypertension.20 A possible reason might be that myocardial accumulation of collagen is more prominent in the subendocardial layers of the left ventricle,21 which would affect longitudinally arranged myocytes in particular.
There is a well known decrease in diastolic velocities with advancing age, a consequence of a variety of alterations in myocardial cellular function.2,25 On the contrary, it has not been equally accepted that there is a normal age related decrease in LV global systolic function. Although a decline in longitudinal systolic velocities with advancing age has been described previously – using longitudinal M-mode recordings as well as Doppler tissue imaging,12,22,23,26 we could demonstrate a striking difference comparing long axis and short axis performance in the same individuals. A possible reason for a decrease in systolic function with advancing age could be the well known increase in blood pressure observed in the Western communities, mediated by an increase in afterload.24 Although blood pressure was higher in older subjects in our study, blood pressure was not associated with myocardial velocities when controlling for other factors like age, gender, and heart rate. Our results suggest that short axis and global LV EF calculations are not sensitive enough to detect the decrease in LV systolic function with advancing age. Whether a true diastolic dysfunction might exist, or if diastolic and systolic dysfunction progress in parallel has been a debate for decades. Although this issue is beyond the scope of this report, our data support that minor systolic dysfunction can be detected in the normal heart using sensitive methods.26–29
Gender and ventricular geometry
In the present study we demonstrated an age related decrease in end-diastolic and end-systolic volumes. This reduction in LV volumes was explained by shortening of the long axis length, indicating a change from an ellipsoid towards a spherical shape, also expressed by an increased sphericity with age. A similar relation has been reported in one study using magnetic resonance imaging,30 but to our knowledge, not by echocardiography. This long axis shortening with age appeared to be more pronounced in females. Several reports have shown that LV mass increases with age in the normal human heart,31 explained by an increase in myocyte volume as a compensation for loss of function.21 We observed an increase in LV mass among women, also when correcting for body size. Generally it has been considered that cardiac dimensional data are related to body size. As men have larger bodies they ought to have larger hearts. However, when controlling for body size, dimensions of male hearts were significantly larger than female hearts, suggesting other gender related factors that explain differences in cardiac size. The dimension of long axis length was greater among men, but females had relatively longer hearts when controlling for body size. The tendency towards larger hearts in males did not appear to significantly affect functional data. Taken together, remodelling during normal ageing appeared to be more pronounced in females.
Selection of normal control subjects
We investigated subjects randomly selected from a population registry in specific age groups. This method guaranteed that the selected persons were from the general population, although it could be anticipated that non-participating persons tended to have less interest in their health. A large proportion of the older individuals exhibited different diseases, emphasising the difficulty of delineating healthy subjects in older age groups. In other studies of normal cardiac function, different selection criteria have been used for men and women, due to the high prevalence of cardiovascular disease in the male population.32 We applied equal selection criteria for both genders.
Study limitations
Our study did not include people older than 70 years. Our experience indicates that the chance to find healthy individuals in an older age group would be increasingly difficult. We did not perform exercise stress-tests to exclude silent myocardial ischemia. However, a thorough investigation disclosed symptoms or signs of disease in a large proportion of the older age group. Recently, the definition of hypertension has been changed, setting the upper limit of normal blood pressure to lower values. Our study was planned when higher values were regarded as normal, and applying the modern standards some subjects would have been considered as having possible mild to moderate hypertension. A larger group would be necessary to draw firm conclusions about gender related differences in each age group. Doppler tissue imaging would be the method most suitable for myocardial velocity studies, and measurements are not entirely interchangeable with velocity recorded from M-mode. However, Doppler cannot supply the dimensional data we present in this study.
Conclusion
We report prominent age related changes in LV long axis function. The decrease in systolic function was not observed using global or short axis measurements of LV function. Further, we observed gender differences in LV remodelling in healthy subjects. Gender differences were more prominent in the short axis, whereas age effects were more prominent in the long axis.
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Acknowledgements |
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We gratefully acknowledge Margareta Scharin Täng, Eva Lavik Olofsson and Ingela Eurenius for excellent technical assistance and fruitful discussions.
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