Abstract
BACKGROUND
Changes in left ventricular (LV) systolic and diastolic properties may generate variations in left atrial (LA) size and function in many pathophysiological models of LV overload. Besides these states, increasing age may independently influence and magnify LA changes.
OBJECTIVE
To investigate the relation of LA size and function to increasing age in hypertensive patients, and to evaluate whether this relationship is influenced by LV function.
METHODS
Three hundred thirty-six patients were evaluated using Doppler echocardiography. Maximal LA volume and ejection force were used as indexes of LA size and performance, respectively.
RESULTS
Age was positively associated with LA ejection force (r=0.34, P<0.001) and maximal volume (r=0.25, P<0.001). The effect of age was independent of LV mass and LV concentric geometry, which independently influenced LA parameters. The relationship between age and LA ejection force was maintained in patients with and without LV systolic dysfunction, and in those with normal diastolic function, whereas it was lost in those with LV diastolic dysfunction. The relationship between age and LA size was not influenced by either LV systolic or diastolic function. LA ejection force was associated with LV mass and LV concentric geometry in all groups of patients 56 years or older, while no association was found between these variables in patients younger than 56 years. LV mass was systematically linked to maximal LA volume in all classes of age, together with LV end-diastolic volume in all groups of patients 56 years of age or older, and LV concentric geometry in patients 68 years of age or older.
CONCLUSIONS
There is a positive relationship between age and LA size and performance in hypertensive patients, which is independent of LV mass and geometry. The effect of age on LA performance is insignificant when diastolic dysfunction occurs.
Keywords: Echocardiography, Left atrial size and function, Left ventricular function, Systemic arterial hypertension
The Frank-Starling mechanism is operative in the left atrium of human hearts, and depends on left ventricular (LV) systolic and diastolic properties, which may change in many pathophysiological conditions, including systemic arterial hypertension and other models of LV overload (1,2). The increase in left atrial (LA) size and function is an important compensatory behaviour to prevent critical changes in mean LA pressure whenever LV diastolic pressure or LA preload increases (3–5); moreover, increases in LA size and funtion occur in parallel with the degree of LV dysfunction (6–9). Besides these pathological states, increasing age, independently of its positive relation to LV mass and diastolic dysfunction (10), may influence and magnify these LA changes. In fact, several population-based studies and observations conducted on healthy, older subjects have unquestionably documented that LA volume and performance progressively increase with advanced age (11–14). For patients with systemic arterial hypertension (9,15,16), an independent relation of age to LA size and function has recently been found in several studies (15,16); however, this relationship has never been characterized, and whether it is influenced by LV function has never been examined in detail.
Accordingly, we investigated the relation of LA size and function to increasing age in a large cohort of patients with systemic arterial hypertension based on the hypothesis that age influences LA performance independently of LV function in these patients. Furthermore, we sought to verify whether the possible association between age and LA size and function was independent of other clinical and echocardiographic variables, particularly with respect to arterial blood pressure and LV mass.
METHODS
The present study enrolled subjects older than 18 years of age in sinus rhythm with essential hypertension (defined as pharmacologically treated high blood pressure of unknown etiology) who presented to the authors’ laboratory for assessment of the impact of echocardiography on global cardiovascular risk stratification (17). All subjects were free of symptoms and had normal functional capacity, evaluated as New York Heart Association functional class I. Patients receiving stable therapy during the six months before recruitment were selected. Exclusion criteria were a diagnosis of coronary artery disease (based on a history of myocardial infarction, or on the results of exercise and stress echocardiography or coronary angiography), LV wall motion abnormalities, more than mild valvular regurgitation or any grade of valvular stenosis, or documented episodes of sustained atrial arrhythmias occurring within one month before the echocardiogram. Patients taking medications to prevent recurrences of atrial arrhythmias were also not eligible.
Echocardiography
Standard transthoracic echocardiographic studies were performed using a Megas Esaote Biomedica machine (Esaote Biomedica, Italy) equipped with a 2.5 MHz to 3.5 MHz annular array transducer. LV chamber dimensions, and septum and posterior wall thickness were measured according to the American Society of Echocardiography (18) using motion M-mode tracings. The Penn convention was only used to calculate LV mass from two-dimensional guided M-mode echocardiograms (19). Therefore, LV mass was normalized for height to the 2.7th power, and LV hypertrophy was defined as an LV mass of 51 g/m2.7 or greater (20). Wall LV mechanics were assessed by computation of midwall fractional shortening, according to previously reported methods (21,22). To predict expected mid-wall shortening for observed end-systolic stress in hypertensive patients, midwall shortening was related to circumferential end-systolic stress, as previously reported (21,22). The ratio of observed to predicted midwall shortening was used as an index of LV systolic performance, independent of afterload conditions. A value less than 0.78 (78% of predicted) identified patients with depressed LV systolic function (21,22).
LA and LV volumes were calculated using the area-length method in two-dimensional apical two- and four-chamber views (23,24), and were then normalized for body surface area. LA ejection force was used an index of LA systolic function and was calculated according to the formula previously validated by Manning et al (25).
To evaluate LV diastolic function, transmitral flow velocities were recorded using pulsed-wave Doppler scanning from the apical four-chamber view, positioning the sample volume between the mitral leaflets at the level of their tips. The following measurements were averaged from five consecutive cycles: maximal velocity of the early diastolic wave (E wave), maximal velocity and duration of the late diastolic wave (A wave), the E/A ratio and the deceleration time of the E wave. LV isovolumic relaxation time was obtained from the apical five-chamber view with the sample volume placed between the LV outflow tract and the anterior mitral leaflet, and was defined as the time between the closing click of the aortic valve and the opening click of the mitral valve. According to the Doppler criteria recently proposed by Redfield et al (26), the study was dichotomized into two groups: patients with normal LV diastolic function, defined as an E/A ratio between 0.75 and 1.5 and an E wave deceleration time greater than 140 ms; and patients with diastolic dysfunction (all other conditions). The reproducibility of M-mode, two-dimensional-mode and pulsed-wave Doppler echocardiographic measurements from the authors’ laboratories has been previously reported (1,9,27,28).
Statistical analysis
Data are reported as mean ± 1 SD. Unpaired Student’s t test and χ2 statistics were used for descriptive statistics. Between-group comparisons of continuous and normally distributed variables were performed by ANOVA. Least squares simple regression analyses were used to investigate the relation of age to LA size and ejection force. The relations of age to LA ejection force and size, LV mass, and parameters of LV systolic and diastolic function were also investigated by multiple regression analyses. Variables that were significantly related to LA size and ejection force in simple regression analysis were included in this statistical model. A further analysis was performed stratifying patients according to LV diastolic and systolic echocardiographic patterns: relations of age to LA ejection force and maximal volume were tested in both patients with normal and impaired LV diastolic and systolic function. Moreover, using random repartition, the patients were stratified into three groups according to the tertiles of age: group 1 was comprised of patients younger than 56 years of age; group 2 was comprised of patients between 56 and 68 years of age; and group 3 was comprised of patients older than 68 years of age. A two-tailed value of P<0.05 was considered to be statistically significant.
RESULTS
During the enrolment period (from March 2001 to March 2002), 336 subjects met criteria established in the protocol and were entered into the study. The mean age of the subjects was 62±13 years; 166 patients (49%) were men; and echocardiographic LV hypertrophy was detected in 111 patients (33%). Systemic arterial blood pressure was 150±18 mmHg (mean systolic value) and 90±9 mmHg (mean diastolic value). Mean maximal LA volume and ejection force were 20±6 mL/m2 and 8.6±4.9 Kdynes, respectively. Based on Doppler criteria, 227 patients (67%) exhibited normal LV diastolic function, while 110 (33%) had LV diastolic dysfunction. LV systolic performance was normal in 266 patients (79%) and depressed in 70 patients (21%). Diuretics were prescribed for 30%, angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers for 60%, calcium antagonists for 32%, beta-blockers for 30% and miscellaneous medications for 12% of patients.
The relation of age to LA size and function
The relations of LA ejection force and maximal volume to age, LV mass, and parameters of LV systolic and diastolic function were investigated by univariate regression analyses, and the results are reported in Table 1. Age was significantly and positively associated with LA ejection force and maximal volume (Figure 1), together with LV mass, LV concentric geometry and systolic arterial blood pressure. As expected, LA ejection force was strongly correlated to indexes of diastolic function, whereas no relation was found with indexes of LV systolic function. On the contrary, a weak positive correlation emerged between these indexes and maximal LA volume, which was not linked to parameters of diastolic function.
TABLE 1.
Relations of left atrial (LA) ejection force and maximal volume to age, systemic blood pressure, left ventricular (LV) mass, and parameters of LV systolic and diastolic function (least squares simple regression analysis)
| LA ejection force
|
Maximal LA volume
|
|||||
|---|---|---|---|---|---|---|
| Variable | r | Slope | P | r | Slope | P |
| Age | 0.34 | 0.13 | 0.0000001 | 0.25 | 0.11 | 0.000006 |
| Body mass index | 0.06 | 0.05 | NS | 0.08 | 12.5 | NS |
| Systolic blood pressure | 0.17 | 0.04 | 0.003 | 0.13 | 0.04 | 0.02 |
| Diastolic blood pressure | −0.10 | −0.07 | NS | −0.05 | −0.03 | NS |
| LV midwall FS | 0.11 | −0.18 | NS | 0.20 | −8.10 | 0.0001 |
| Afterload-corrected LV midwall FS | 0.13 | −4.10 | NS | 0.22 | −0.39 | 0.0001 |
| LV ejection fraction | 0.07 | 0.05 | NS | −0.11 | 0.10 | NS |
| LV mass | 0.26 | 0.09 | 0.000003 | 0.53 | 0.22 | 0.0000001 |
| LV relative wall thickness | 0.28 | 19.8 | 0.000001 | 0.28 | 22.9 | 0.000001 |
| LV end-diastolic volume | 0.01 | 0.09 | NS | 0.22 | 0.05 | 0.00003 |
| LV isovolumic relaxation relaxtion time | 0.07 | 0.01 | NS | 0.16 | 0.03 | 0.005 |
| Peak E wave velocity (mitral flow) | 0.06 | 0.01 | NS | 0.02 | 0.005 | NS |
| E wave deceleration time | 0.06 | 0.02 | NS | 0.10 | 0.01 | NS |
| Peak A wave velocity (mitral flow) | 0.78 | 0.25 | 0.00000001 | 0.05 | 0.15 | NS |
| A wave duration (mitral flow) | 0.14 | 0.04 | 0.02 | 0.07 | 0.02 | NS |
| E/A wave ratio of mitral flow | −0.42 | −5.50 | 0.0000001 | 0.01 | 0.1 | NS |
E/A Ratio of maximal velocity of the early diastolic wave to maximal velocity and duration of the late diastolic wave; FS Fractional shortening; NS Not significant; Peak A Peak late diastolic flow velocity of mitral flow; Peak E Peak early diastolic flow velocity of mitral flow
Figure 1.
Relationship between age and left atrial ejection force (left panel), and between age and maximal left atrial volume (right panel) in the study population (336 hypertensive patients). Scatter plot of linear correlation and 95% CIs are shown
The independent relations of these clinical and echocardiographic variables to LA parameters were subsequently tested in a multivariate logistic model. As shown in Table 2, both LA size and function depended on age, with a similar positive relationship. The effect of age was independent of LV mass and LV concentric geometry, which independently influenced both LA ejection force and maximal volume. However, in the statistical model, LA ejection force was mainly linked to LV diastolic properties, epitomized in the E/A ratio of mitral flow; this result was not evident for maximal LA volume, which instead was independently related to end-diastolic LV volume.
TABLE 2.
Multiple regression analyses applied to the study population: Variables independently associated with left atrial ejection force and maximal volume
| Exp (beta) | P | |
|---|---|---|
| Left atrial ejection force | ||
| Older age | 0.12 | 0.04 |
| Relative wall thickness | 0.18 | 0.0006 |
| Left ventricular mass | 0.15 | 0.004 |
| E/A wave ratio of mitral flow | −0.32 | 0.000001 |
| Multiple r=0.46, r2=0.21, adjusted r2=0.20, intercept= −10.9, SEE=4.3, F=21.3, P<0.0000001 | ||
| Maximal left atrial volume | ||
| Older age | 0.21 | 0.0002 |
| Left ventricular mass | 0.42 | 0.0000001 |
| Left ventricular end-diastolic volume | 0.18 | 0.00009 |
| Relative wall thickness | 0.11 | 0.02 |
| Multiple r=0.60, r2=0.36, adjusted r2=0.35, intercept=3.6, SEE=4.7, F=43.4, P<0.0000001 | ||
E/A Ratio of maximal velocity of the early diastolic wave to maximal velocity and duration of the late diastolic wave
Age and LV diastolic function
Considering the power that LV diastolic function has to affect LA performance, the models of regression analysis were therefore applied to the different LV diastolic patterns to verify whether the effect of age on LA parameters was independent of LV diastolic function. The correlation coefficients (r) of age to LA ejection force, evaluated by simple regression analysis, were 0.34 (P=0.0000001) in patients with normal LV diastolic function and 0.08 (P = not significant) in those with LV diastolic dysfunction. Multiple regression analysis confirmed that the independent positive relation of age to LA ejection force was maintained only in patients with normal diastolic function, whereas it was lost in the presence of LV diastolic dysfunction. Conversely, the influence of age on maximal LA volume was evident in patients both with and without LV diastolic dysfunction (simple regression analysis: r=0.26 and r=0.30, respectively; all P=0.001), and was independent of LV mass and geometry (Table 3).
TABLE 3.
Multiple regression analyses applied to patients divided according to left ventricular (LV) diastolic function: List of variables independently associated with left atrial ejection force and maximal volume in patients with normal diastolic function and in those with mild diastolic dysfunction
| Normal diastolic function | Exp (beta) | P | Diastolic dysfunction | Exp (beta) | P |
|---|---|---|---|---|---|
| Left atrial ejection force | |||||
| Older age | 0.31 | 0.0000001 | Older age | 0.09 | Not significant |
| Relative wall thickness | 0.19 | 0.000001 | Relative wall thickness | 0.34 | 0.0003 |
| LV mass | 0.13 | 0.002 | LV end-diastolic volume | 0.32 | 0.0008 |
| Systolic blood pressure | 0.11 | 0.002 | LV mass | 0.19 | 0.04 |
| Multiple r=0.54, r2=0.30, adjusted r2=0.29, F=50, intercept= −11.1, SEE=4.0, P<0.0000001 | Multiple r=0.43, r2=0.18, adjusted r2=0.17, F=11, intercept= −8.6, SEE=5.3, P<0.00005 | ||||
| Maximal left atrial volume | |||||
| Older age | 0.18 | 0.001 | Older age | 0.22 | 0.003 |
| LV mass | 0.42 | 0.000001 | LV mass | 0.58 | 0.0000001 |
| LV end-diastolic volume | 0.20 | 0.00002 | Relative wall thickness | 0.24 | 0.002 |
| Relative wall thickness | 0.10 | 0.03 | |||
| Multiple r=0.57, r2=0.33, adjusted r2=0.32, F=75, intercept =1.9, SEE=4.4, P<0.0000001 | Multiple r=0.71, r2=0.51, adjusted r2=0.49, F=32, intercept= −7.6, SEE=3.8, P<0.0000001 | ||||
Age and LV systolic function
By simple regression analysis, it was found that older age was significantly associated with higher LA ejection force and maximal volume, independently of the presence of LV systolic dysfunction (r=0.39 and r=0.24, respectively, in patients with normal function; r=0.32 and r=0.22, respectively, in those with depressed LV systolic performance; all P<0.005). Multivariate regression analysis revealed that this behaviour was independent of confounders such as LV mass, LV concentric geometry, LV end-diastolic volume and parameters of LV diastolic function (Table 4).
TABLE 4.
Multiple regression analyses applied to patients divided according to left ventricular (LV) systolic function: List of variables independently associated with left atrial ejection force and maximal volume in patients with normal systolic function and in those with depressed systolic performance
| Normal systolic function | Exp (beta) | P | Depressed systolic function | Exp (beta) | P |
|---|---|---|---|---|---|
| Left atrial ejection force | |||||
| Older age | 0.42 | 0.0000001 | Older age | 0.33 | 0.0004 |
| Relative wall thickness | 0.26 | 0.0003 | Relative wall thickness | 0.27 | 0.03 |
| LV mass | 0.12 | 0.02 | LV mass | 0.25 | 0.02 |
| Peak E wave mitral flow | 0.35 | 0.001 | |||
| Multiple r=0.54, r2=0.29, adjusted r2=0.27, F=25, intercept= −19.8, SEE=4.3, P<0.0000001 | Multiple r=0.52, r2=0.27, adjusted r2=0.23, F=7, intercept= −9.8, SEE=4.0, P<0.0004 | ||||
| Maximal left atrial volume | |||||
| Older age | 0.26 | 0.0003 | Older age | 0.32 | 0.001 |
| LV mass | 0.41 | 0.000001 | LV mass | 0.60 | 0.0000001 |
| LV end-diastolic volume | 0.20 | 0.0004 | Relative wall thickness | 0.21 | 0.02 |
| Peak E/A ratio of mitral flow | 0.38 | 0.0001 | |||
| Multiple r=0.54, r2=0.29, adjusted r2=0.28, F=23, intercept= −3.4, SEE=4.6, P<0.0000001 | Multiple r=0.77, r2=0.60, adjusted r2=0.57, F=23, intercept= −17.0, SEE=4.6, P<0.0000001 | ||||
E/A Ratio of maximal velocity of the early (E) diastolic wave to maximal velocity and duration of the late (A) diastolic wave
Classes of age
The main characteristics of patients, divided according to age into three groups (group 1 was comprised of those younger than 56 years, group 2 of those 56 to 68 years of age, and group 3 of those older than 68 years), are shown in Table 5. In comparison with younger patients (groups 1 and 2), older patients belonging to group 3 exhibited a lower body surface area, diastolic blood pressure and LV end-diastolic volume; higher LV mass and relative wall thickness; and more frequently depressed LV systolic performance and diastolic dysfunction. Both LA ejection force and maximal volume were significantly and progressively higher in each class with increasing age than the others. Masking the age-related effects on LA parameters, the relationships of LA ejection force and maximal volume to sex, blood pressure, body mass index and surface area, LV mass and geometry, LV end-diastolic volume and midwall fractional shortening were tested for each class of age. LA ejection force was predicted by LV mass and LV concentric geometry in groups 2 and 3, while no association was found between these variables in the younger patients in group 1. Regarding LA size, LV mass was systematically linked to maximal LA volume in all classes of age, together with LV end-diastolic volume in groups 2 and 3, and LV concentric geometry in group 3 (Table 6).
TABLE 5.
General characteristics of study patients (n=336) divided according to age
| Characteristic | Group 1 (n=44) | Group 2 (n=200) | Group 3 (n=92) |
|---|---|---|---|
| Age, years | 39±9 | 60±6* | 77±5†‡ |
| Body surface area, m2 | 1.87±0.2 | 1.87±0.2 | 1.76±0.2†‡ |
| Weight, kg | 78±14 | 77±14 | 70±11†‡ |
| Height, m | 1.73±0.9 | 1.68±0.9* | 1.65±0.8†‡ |
| Body mass index, kg/m2 | 26±3 | 26±4 | 26±4 |
| Systolic arterial blood pressure, mmHg | 147±14 | 149±19 | 53±18† |
| Diastolic arterial blood pressure, mmHg | 93±9 | 91±9 | 86±8†‡ |
| Heart rate, beats/min | 69±11 | 69±11 | 69±11 |
| LV end-diastolic volume, mL/m2 | 54±10 | 53±15 | 51±13†‡ |
| LV mass, g/m2.7 | 45±11 | 52±14* | 53±14† |
| LV hypertrophy, n (%) | 10 (23) | 65 (33) | 36 (39)† |
| LV relative wall thickness | 0.40±0.06 | 0.41±0.07 | 0.43±0.07†‡ |
| LV ejection fraction, % | 64±6 | 64±8 | 64±7 |
| LV midwall fractional shortening, % | 17.5±3 | 17.1±3 | 15.7±3†‡ |
| Left atrial ejection force, Kdynes | 5.2±2 | 8.4±4* | 10.5±6†‡ |
| Maximal left atrial volume, mL/m2 | 17±4 | 19±6* | 22±5†‡ |
| Peak E wave velocity of trasmitral flow, cm/s | 71±15 | 61±14* | 53±16†‡ |
| Peak A wave velocity of trasmitral flow, cm/s | 54±10 | 67±14* | 73±16†‡ |
| Peak E/A ratio | 1.36±0.4 | 0.96±0.3* | 0.75±0.3†‡ |
| A wave duration, ms | 100±14 | 106±19* | 109±21† |
| E wave deceleration time, ms | 151±25 | 167±47* | 185±50†‡ |
| LV isovolumic relaxation time, ms | 118±26 | 132±30* | 146±35†‡ |
| LV diastolic dysfunction, n (%) | 1 (2) | 56 (28)* | 53 (58)†‡ |
| LV systolic dysfunction, n (%) | 5 (12) | 37 (19) | 28 (31)†‡ |
Group 1 was comprised of patients younger than 56 years of age; group 2 was comprised of patients 56 to 68 years; group 3 was comprised of patients older than 68 years.
P<0.05 between group 1 and group 2;
P<0.05 between group 1 and group 3;
P<0.05 between group 2 and group 3. E/A Ratio of maximal velocity of the early (E) diastolic wave to maximal velocity and duration of the late (A) diastolic wave; LV Left ventricular
TABLE 6.
Multiple regression analysis: factors independently related to left atrial ejection force and maximal volume in patients divided according to age
| Exp (beta) | P | Multiple r | SEE | |
|---|---|---|---|---|
| Independent predictors of left atrial ejection force | ||||
| Group younger than 56 years | ||||
| None | – | – | – | – |
| Group 56 to 68 years of age | ||||
| LV mass | 0.19 | 0.01 | 0.36 | 3.9 |
| LV relative wall thickness | 0.15 | 0.04 | ||
| Systolic blood pressure | 0.18 | 0.01 | ||
| Group older than 68 years | ||||
| LV mass | 0.30 | 0.006 | 0.30 | 5.9 |
| LV relative wall thickness | 0.18 | 0.04 | ||
| Independent predictors of maximal left atrial volume | ||||
| Group younger than 56 years | ||||
| LV mass | 0.35 | 0.02 | 0.35 | 4.3 |
| Group 56 to 68 years of age | ||||
| LV mass | 0.55 | 0.0000001 | 0.63 | 4.6 |
| LV end-diastolic volume | 0.18 | 0.006 | ||
| Group older than 68 years | ||||
| LV mass | 0.30 | 0.002 | 0.54 | 4.6 |
| LV relative wall thickness | 0.34 | 0.0005 | ||
| LV end-diastolic volume | 0.26 | 0.009 | ||
LV Left ventricular
DISCUSSION
Several studies have convincingly pointed out that LA size and performance increase with increasing age. This behaviour has been described both in subjects with no evidence of cardiovascular disease (11–13) and in those with systemic arterial hypertension (15,16,29). The meaning of this phenomenon has been analyzed in some of these investigations, particularly in those conducted on older patients, in which it was concluded that LA enlargement and an increase in LA systolic function may be important compensatory mechanisms against mounting LV hypertrophy and diastolic dysfunction in this age population. However, because of small sample sizes and the particular characteristics of the enrolled populations, these studies could not clarify whether age influenced LA parameters independently of LV systolic and diastolic function. This issue has important clinical implications if we consider that LA volume and LA ejection force are two important independent risk markers for the occurrence of the first cardiovascular event, including incident atrial fibrillation, myocardial infarction, stroke, congestive heart failure and death (14,30,31). Thus, the positive effects from antihypertensive treatment – inducing normalization of LA function in parallel to LV hypertrophy regression, as reported by Dernellis et al (32) – may also include favourable effects on long-term prognosis, beyond mere improvements in LV systolic and diastolic function due to reduction in LV mass.
In the present study, we analyzed the relation of age to LA size and function in patients with systemic arterial hypertension, and evaluated whether this relationship was influced by LV systolic and diastolic function. We verified that LA size and ejection force progressively increased with increasing age in our patients, as well as the prevalence of LV concentric geometry, hypertrophy, and LV systolic and diastolic dysfunction. The presence of LV systolic dysfunction did not significantly influence the relationship between LA parameters and age. Indeed, LA ejection force and maximal LA volume depended on age with a similar positive relationship in patients with either normal or depressed LV systolic function. Of note, in both groups, older age emerged in multivariate analysis as the strongest predictor of high LA ejection force.
Conversely, the relationships between age and LA parameters were clearly affected by changes in LV diastolic properties; in our population (divided into three subgroups according to age), the prevalence of LV diastolic dysfunction ranged from 2% in younger patients to 58% in older patients, and LV hypertrophy ranged from 23% to 39%, respectively. Considering the group of patients with diastolic dysfunction, no association was found between age and LA ejection force in multiple regression analysis, and the relation of age to maximal LA volume was weak and of poor clinical significance. Otherwise, LA parameters were directly correlated to LV relative wall thickness and LV mass. Thus, in hypertensive patients with any degree of LV diastolic dysfunction, the influence of LV concentric geometry and hypertrophy is particularly important, making negligible the power of age on LA size and performance. These findings are in line with those reported by Zabalgoitia et al (10), showing that abnormalities of mitral flow pattern identified using pulsed Doppler echocardiography were particularly frequent in elderly patients with systemic arterial hypertension, and that the pathological changes due to pressure overload in these patients covered the physiological influence of aging on LV diastolic function and LA parameters.
Our results suggest that in patients with systemic arterial hypertension, establishment of normal values of LA ejection force and maximal volume for various classes of age is paradoxically appropriate and reasonable only in younger subgroups, whereas for older patients, other factors such as LV geometry and LV mass should be taken into account, being that LV concentric pattern and hypertrophy are the major causes of abnormal LV diastolic function, as well as the main conditions increasing LA performance (9). As a result, in elderly patients with systemic arterial hypertension, an accurate estimation of the appropriateness of LA parameters to LV mass and geometry could be more helpful than normalization for age in interpreting LV diastolic function and stratifying long-term prognosis.
This perspective considers the typical mechanical properties characterizing the cardiac remodelling process in systemic arterial hypertension and agrees with findings recognized in patients with chronic aortic valve disease (1,9). We previously showed that in both these models, LV mass increases in a concentric fashion in attempting to compensate for elevated wall stress, and this inexorably leads to increased stiffness of the LV (33,34). This behaviour is the strongest stimulus for the LA to change size and function, which increase with a magnitude that reflects, for the most part, the degree of LV diastolic dysfunction (1,3–5,8,9). These features are highly prevalent in the elderly population with systemic arterial hypertension, and may explain why the influence of LV mass and concentric geometry on LA parameters is independent of and stronger than age in these patients.
Study limitations
The present study has two important limitations. First, arterial stiffness was not assessed or tested, so we could not provide data about the effects of peripheral vascular structure and tone on the relationship between LA parameters and age. However, most of these effects resulted in pressure overload and led to increased LV mass, which was mainly considered in our analysis. Second, patients received pharmacological agents, such as angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers, which may improve LA function over time. To minimize the role of medications, we selected patients receiving stable therapy for six months before recruitment. However, we underline that even the changes in LA function due to pharmacological therapy are linked, and parallel LV hypertrophy regression, for which LV mass were taken into account in our analyses.
CONCLUSIONS
There is a positive relationship between age and LA size and performance in patients with systemic arterial hypertension. This relationship is independent of LV mass and geometry. The effect of age on LA performance exists both in patients with normal LV systolic function and in those with systolic dysfunction, whereas it is insignificant when diastolic dysfunction occurs.
REFERENCES
- 1.Cioffi G, Stefenelli C. Comparison of left ventricular geometry and left atrial size and function in patients with aortic stenosis versus those with pure aortic regurgitation. Am J Cardiol. 2002;90:601–6. doi: 10.1016/s0002-9149(02)02563-8. [DOI] [PubMed] [Google Scholar]
- 2.Ikaheimo MJ, Palatsi IJ, Takkunen JT. Noninvasive evaluation of the athletic heart: Sprinters versus endurance runners. Am J Cardiol. 1979;44:24–30. doi: 10.1016/0002-9149(79)90246-7. [DOI] [PubMed] [Google Scholar]
- 3.Braunwald E, Frahm CJ. Studies on Starling’s law of the heart. IV. Observations on the hemodynamic functions of the left atrium in man. Circulation. 1961;24:633. [Google Scholar]
- 4.Yamaguchi M, Arakawa M, Tanaka T, Takaya T, Nagano T, Hirakawa S. Study on left atrial contractile performance –Participation of Frank-Starling mechanism. Jpn Circ J. 1987;51:1001–9. doi: 10.1253/jcj.51.1001. [DOI] [PubMed] [Google Scholar]
- 5.Stott DK, Marpole DGF, Bristow JD, Kloster FE, Griswold HE. The role of left atrial transport in aortic and mitral stenosis. Circulation. 1970;41:1031–41. doi: 10.1161/01.cir.41.6.1031. [DOI] [PubMed] [Google Scholar]
- 6.Matsuda M, Matsuda Y. Mechanism of left atrial enlargement related to ventricular diastolic impairment in hypertension. Clin Cardiol. 1996;19:954–9. doi: 10.1002/clc.4960191211. [DOI] [PubMed] [Google Scholar]
- 7.Tsang TS, Barnes ME, Gersh BJ, Bailey KR, Seward JB. Left atrial volume as a morphophysiologic expression of left ventricular diastolic dysfunction and relation to cardiovascular risk burden. Am J Cardiol. 2002;90:1284–9. doi: 10.1016/s0002-9149(02)02864-3. [DOI] [PubMed] [Google Scholar]
- 8.Simek CL, Feldman MD, Haber HL, Wu CC, Jayaweera AR, Kaul S. Relationship between left ventricular wall thickness and left atrial size: Comparison with other measures of diastolic function. J Am Soc Echocardiogr. 1995;8:37–47. doi: 10.1016/s0894-7317(05)80356-6. [DOI] [PubMed] [Google Scholar]
- 9.Cioffi G, Mureddu GF, Stefenelli C, de Simone G. Relationship between left ventricular geometry and left atrial size and function in patients with systemic hypertension. J Hypertens. 2004;22:1589–96. doi: 10.1097/01.hjh.0000125454.28861.76. [DOI] [PubMed] [Google Scholar]
- 10.Zabalgoitia M, Rahman SN, Haley WE, et al. Comparison in systemic hypertension of left ventricular mass and geometry with systolic and diastolic function in patients <65 to > or = 65 years of age. Am J Cardiol. 1998;82:604–8. doi: 10.1016/s0002-9149(98)00404-4. [DOI] [PubMed] [Google Scholar]
- 11.Nikitin NP, Witte KK, Thackray SD, Goodge LJ, Clark AL, Cleland JG. Effect of age and sex on left atrial morphology and function. Eur J Echocardiogr. 2003;4:36–42. doi: 10.1053/euje.2002.0611. [DOI] [PubMed] [Google Scholar]
- 12.Triposkiadis F, Tentolouris K, Androulakis A, et al. Left atrial mechanical function in the healthy elderly: New insights from a combined assessment of changes in atrial volume and transmitral flow velocity. J Am Soc Echocardiogr. 1995;8:801–9. doi: 10.1016/s0894-7317(05)80004-5. [DOI] [PubMed] [Google Scholar]
- 13.Spencer KT, Mor-Avi V, Gorcsan J, III, et al. Effects of aging on left atrial reservoir, conduit, and booster pump function: A multi-institution acoustic quantification study. Heart. 2001;5:272–7. doi: 10.1136/heart.85.3.272. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Tsang TS, Barnes ME, Gersh BJ, et al. Prediction of risk for first age-related cardiovascular events in an elderly population: The incremental value of echocardiography. J Am Coll Cardiol. 2003;42:1199–205. doi: 10.1016/s0735-1097(03)00943-4. [DOI] [PubMed] [Google Scholar]
- 15.Gerdts E, Oikarinen L, Palmieri V, et al. Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) Study. Correlates of left atrial size in hypertensive patients with left ventricular hypertrophy: The Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) Study. Hypertension. 2002;39:739–43. doi: 10.1161/hy0302.105683. [DOI] [PubMed] [Google Scholar]
- 16.Cuspidi C, Meani S, Fusi V, et al. Prevalence and correlates of left atrial enlargement in essential hypertension: Role of ventricular geometry and the metabolic syndrome: The Evaluation of Target Organ Damage in Hypertension study. J Hypertens. 2005;23:875–82. doi: 10.1097/01.hjh.0000163158.14493.23. [DOI] [PubMed] [Google Scholar]
- 17.Schillaci G, de Simone G, Reboldi G, Porcellati C, Devereux RB, Verdecchia P. Change in cardiovascular risk profile by echocardiography in low- or medium-risk hypertension. J Hypertens. 2002;20:1519–25. doi: 10.1097/00004872-200208000-00014. [DOI] [PubMed] [Google Scholar]
- 18.Sahn DJ, Demaria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: Results of a survey of echocardiographic measurements. Circulation. 1978;58:1072–83. doi: 10.1161/01.cir.58.6.1072. [DOI] [PubMed] [Google Scholar]
- 19.Devereux RB, Reichek N. Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circulation. 1978;55:613–8. doi: 10.1161/01.cir.55.4.613. [DOI] [PubMed] [Google Scholar]
- 20.de Simone G, Devereux RB, Daniels SR, Koren MJ, Meyer RA, Laragh JH. Effect of growth on variability of left ventricular mass: Assessment of allometric signals in adults and children and their capacity to predict cardiovascular risk. J Am Coll Cardiol. 1995;25:1056–62. doi: 10.1016/0735-1097(94)00540-7. [DOI] [PubMed] [Google Scholar]
- 21.de Simone G, Devereux RB, Koren MJ, Mensah GA, Casale PN, Laragh JH. Midwall left ventricular mechanics. An independent predictor of cardiovascular risk in arterial hypertension. Circulation. 1996;93:259–65. doi: 10.1161/01.cir.93.2.259. [DOI] [PubMed] [Google Scholar]
- 22.de Simone G, Devereux RB, Roman MJ, et al. Assessment of left ventricular function by the midwall fractional shortening/end-systolic stress relation in human hypertension. J Am Coll Cardiol. 1994;23:1444–51. doi: 10.1016/0735-1097(94)90390-5. [DOI] [PubMed] [Google Scholar]
- 23.Lester SJ, Ryan EW, Schiller NB, Foster E. Best method in clinical practice and in research studies to determine left atrial size. Am J Cardiol. 1999;84:829–32. doi: 10.1016/s0002-9149(99)00446-4. [DOI] [PubMed] [Google Scholar]
- 24.Schiller NB, Shah PM, Crawford M, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr. 1989;2:358–67. doi: 10.1016/s0894-7317(89)80014-8. [DOI] [PubMed] [Google Scholar]
- 25.Manning WJ, Silverman DI, Katz SE, Douglas PS. Atrial ejection force: A noninvasive assessment of atrial systolic function. J Am Coll Cardiol. 1993;22:221–5. doi: 10.1016/0735-1097(93)90838-r. [DOI] [PubMed] [Google Scholar]
- 26.Redfield MM, Jacobsen SJ, Burnett JC, Jr, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: Appreciating the scope of the heart failure epidemic. JAMA. 2003;289:194–202. doi: 10.1001/jama.289.2.194. [DOI] [PubMed] [Google Scholar]
- 27.Mureddu GF, de Simone G, Greco R, Rosato GF, Contaldo F. Left ventricular filling in arterial hypertension. Influence of obesity and hemodynamic and structural confounders. Hypertension. 1997;29:544–50. doi: 10.1161/01.hyp.29.2.544. [DOI] [PubMed] [Google Scholar]
- 28.de Simone G, Greco R, Mureddu G, et al. Relation of left ventricular diastolic properties to systolic function in arterial hypertension. Circulation. 2000;101:152–7. doi: 10.1161/01.cir.101.2.152. [DOI] [PubMed] [Google Scholar]
- 29.Erol MK, Yilmaz M, Acikel M, Karakelleoglu S. Left atrial mechanical function in patients with essential hypertension. Acta Cardiol. 2002;57:323–7. doi: 10.2143/AC.57.5.2005447. [DOI] [PubMed] [Google Scholar]
- 30.Barnes ME, Miyasaka Y, Seward JB, et al. Left atrial volume in the prediction of first ischemic stroke in an elderly cohort without atrial fibrillation. Mayo Clin Proc. 2004;79:1008–14. doi: 10.4065/79.8.1008. [DOI] [PubMed] [Google Scholar]
- 31.Tsang TS, Barnes ME, Bailey KR, et al. Left atrial volume: Important risk marker of incident atrial fibrillation in 1655 older men and women. Mayo Clin Proc. 2001;76:467–75. doi: 10.4065/76.5.467. [DOI] [PubMed] [Google Scholar]
- 32.Dernellis JM, Vyssoulis GP, Zacharoulis AA, Toutouzas PK. Effects of antihypertensive therapy on left atrial function. J Hum Hypertens. 1996;10:789–94. [PubMed] [Google Scholar]
- 33.Hess OM, Ritter M, Schneider J, Grimm J, Turina M, Krayenbuehl HP. Diastolic stiffness and myocardial structure in aortic valve disease before and after valve replacement. Circulation. 1984;69:855–65. doi: 10.1161/01.cir.69.5.855. [DOI] [PubMed] [Google Scholar]
- 34.Grossman W, Barry WH. Diastolic pressure-volume relations in the diseased heart. Fed Proc. 1980;39:148–55. [PubMed] [Google Scholar]