(Hypertension. 1995;25:1155-1160.)
© 1995 American Heart Association, Inc.
Articles |
From the Framingham (Mass) Heart Study, Framingham (S.M.V., M.G.L., E.J.B., D.L.); the Divisions of Cardiology and Clinical Epidemiology, Beth Israel Hospital, Boston, Mass (D.L.); the Division of Cardiology, Cleveland (Ohio) Clinic (M.S.L.); the Cardiology Section, Boston City Hospital (E.J.B.); Boston University School of Medicine (E.J.B., D.L.); the Division of Preventive Medicine and Epidemiology, Boston University School of Medicine (M.G.L.); and the National Heart, Lung, and Blood Institute, Bethesda, Md (D.L.).
| Abstract |
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.10). Multivariable linear
regression models showed the relative contributions of the pressure
variables to the prediction of left atrial size to be substantially
less than those of age and, in particular, body mass index.
Furthermore, inclusion of left ventricular mass in these multivariable
models eliminated or attenuated the associations of the pressure
variables with left atrial size. In logistic analyses, increasing
levels of the pressure variables were significantly predictive of left
atrial enlargement. Subjects with 8-year average systolic pressure of
140 mm Hg or higher were twice as likely to have left atrial
enlargement as those with values of 110 mm Hg or lower. Overall, in
this population-based study sample, increased levels of systolic and
pulse pressures (but not diastolic or mean arterial pressures) were
significantly associated with increased left atrial size. However, the
magnitude of these associations was quite modest, particularly after
controlling for age and body mass index.
Key Words: atrial function, left hypertension, essential epidemiology echocardiography
| Introduction |
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Factors most commonly associated with the presence of left atrial enlargement include aging,6 increased body size,6 7 and mitral valve disease.8 Although electrocardiographic features of left atrial enlargement have been observed in the setting of hypertensive heart disease,9 10 data conflict regarding the effect of blood pressure (BP) on echocardiographically determined left atrial size. Of the available investigations, three case-control studies found a significant association of echocardiographically determined left atrial enlargement with hypertensive status,11 12 13 whereas a larger case-control study did not.7
Further examination of the relations between BP and left atrial size may contribute to our understanding of high BP as a determinant of left atrial enlargement. In addition, evaluation of long-term BP patterns may provide insight into the effects of sustained high BP on left atrial size. The Framingham Heart Study has uniformly obtained echocardiographic information and longitudinally gathered BP data. We examined the relations of contemporary and long-term BP patterns to echocardiographically determined left atrial size in subjects of this large, population-based cohort.
| Methods |
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Subjects were excluded for any of the following conditions: (1) technically inadequate or unavailable echocardiogram at the index examination, (2) history of clinically apparent coronary heart disease, congestive heart failure, valvular heart disease, or atrial fibrillation at or before the index examination, (3) use of cardiovascular medications at the index examination, (4) age less than 20 years or greater than or equal to 90 years, (5) morbid obesity (body mass index [BMI] >35 kg/m2), and (6) incomplete BP data.
Subjects were considered to have valvular heart disease if a grade 3/6 or higher systolic murmur or any diastolic murmur was detected on physical examination or if echocardiographic evidence of valvular disease (including mitral stenosis) was found. Subjects meeting the criteria for angina pectoris, coronary insufficiency (prolonged chest pain associated with documented electrocardiographic changes), or myocardial infarction were considered to have clinically apparent coronary heart disease. The criteria for coronary heart disease end points and congestive heart failure in the Framingham Heart Study have been described previously.17 Atrial fibrillation was determined from 12-lead electrocardiograms routinely obtained on subjects at each clinic examination or through review of electrocardiograms obtained from hospitalizations or office visits to outside physicians.
Methods of Measurement and Definitions
At each examination, systolic and diastolic pressure readings
were measured in the left arm with a mercury sphygmomanometer while the
subject was seated. Systolic and diastolic pressures were determined by
the first and fifth Korotkoff phases, respectively. Two separate BP
readings were obtained by the physician examiner. The respective
averages of the two measurements of systolic and diastolic pressures
were used as the examination systolic and diastolic pressures. At the
first Offspring Study examination, only one BP measurement was obtained
by the physician examiner; consequently, the first BP reading alone was
used. Body height and weight measurements obtained at the index
examination were used to calculate BMI (kilograms per meter
squared).
Pulse pressure (systolic pressure minus diastolic pressure) and mean arterial pressure (diastolic pressure plus one-third pulse pressure) also were evaluated as potential correlates of left atrial size. The following BP variables were used: (1) index examination pressures were obtained at the baseline examination, when echocardiography was performed, and (2) 8-year average pressures were the averages of pressures obtained at the index examination and at the examination 8 years before. BP information obtained from the examination 8 years before the index examination was used because of its availability in both the original cohort and offspring subjects.
Echocardiographic Methods
Subjects were studied with standard M-mode echocardiography. A
2.25-MHz, 1.25-cm diameter, unfocused transducer (KB Aerotech) and an
ultrasound receiver (model 201, Hoffrel Instruments) interfaced with a
strip-chart recorder (model 1856, Honeywell) were used.
Left atrial size was determined in accordance with American Society of Echocardiography guidelines with the use of a leading edgetoleading edge measurement of the maximal distance between the posterior aortic root wall and the posterior left atrial wall at end systole.18 Wade et al19 have demonstrated low interobserver (r=.97) and intraobserver (r=.97) variabilities in the M-mode measurements of left atrial dimension using the above guidelines. The modified cubed formula (with end-diastolic left ventricular [LV] measurements obtained in accordance with the Penn convention) was used to calculate LV mass20 : LV Mass (g)=1.04[(LV Internal Diameter+LV Septal Thickness+Posterior Wall Thickness)3- (LV Internal Diameter)3]-13.6. LV mass (in grams) was adjusted for body size by dividing it by the height of the subject (in meters).21
Data Analysis and Statistical Methods
All analyses were sex specific. The relations of BP variables to
left atrial size were initially examined with simple and partial
(adjusted for age and BMI) Pearson correlation
coefficients.22 Linear regression analyses were used for
evaluation of the relative influences of BP variables, age, and BMI on
left atrial dimension.22
Left atrial enlargement was defined as left atrial dimension greater than or equal to 43 mm in men and greater than or equal to 38 mm in women, respectively. These cut points were the 90th percentile values in a younger (age <65 years), normotensive (systolic pressure <140, diastolic pressure <90 mm Hg), and nonobese (BMI <75th percentile) subset of our study sample. Age-adjusted prevalences of left atrial enlargement according to BP groups were calculated using direct age adjustment with age groups of 20 to 29, 30 to 39, 40 to 49, 50 to 59, 60 to 69, and 70 years or older. Logistic regression modeling23 was used for assessment of the probability of left atrial enlargement according to BP levels. Additional models adjusted for age and BMI.
All statistical analyses were performed with the Statistical Analysis System24 on a SUN SPARC station 2. A two-sided significance level of .05 was used for each statistical test.
| Results |
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Simple and Partial Correlation Analyses
Results of analyses correlating BP variables, age, and BMI with
left atrial size are provided in Table 3. BMI was a
stronger correlate of left atrial size (men, r=.47; women,
r=.49) than were other measures of body size such as body
weight (men, r=.42; women, r=.42) and body
surface area (men, r=.33; women, r=.30). Age was
more highly correlated with left atrial size in women
(r=.37) than men (r=.17). The simple Pearson
correlation coefficients for each of the BP variables suggested modest
but statistically significant relations with left atrial dimension.
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After controlling for age and BMI, only systolic and pulse pressure variables remained significantly related to left atrial size. The magnitude of the correlation coefficients for each BP variable markedly diminished after controlling for age and BMI. This effect was greater in women than men. Notably, after adjustment for age and BMI, the partial correlation coefficients were similar in men and women. Differences between the sexes in the relations of the BP variables with age and BMI may partially account for this observation. In both sexes, age correlated strongly with systolic pressure (men, r=.40; women, r=.58) and pulse pressure (men, r=.47; women, r=.62); the correlations in women were appreciably stronger than in men. Similarly, the correlations of BMI with systolic pressure (men, r=.18; women, r=.27) and pulse pressure (men, r=.0003; women, r=.21) were stronger in women than men. Interestingly, age was more strongly correlated with the BP variables than was BMI.
Linear Regression Analyses
Since systolic and pulse pressures remained statistically
significantly related to left atrial size after adjustment for age and
BMI in the correlation analyses (see Table 3), their relations with
left atrial size were the focus of further analyses. Multivariable
linear regression analyses confirmed the statistically significant
associations of the individual systolic and pulse pressure variables
with left atrial size as demonstrated in the previous correlation
analyses. For each index examination and 8-year average pressure
variable, the association with left atrial size was highly
statistically significant after age and BMI were taken into account
(P<.01); however, the magnitudes of these associations were
negligible. In both men and women, the coefficients for the 8-year
average pressure variables were slightly greater than the coefficients
for the index examination pressure variables.
These multivariable models showed the relative contributions of the pressure variables to the prediction of left atrial size to be substantially less than those of age and in particular BMI. Increments in left atrial size for each 1-SD increment of age, BMI, and individual BP covariates were calculated. The effect of a 1-SD increment of BMI on left atrial size (men, 1.9 mm; women, 1.7 mm) was approximately sixfold greater than the influence of a 1-SD increment of 8-year average systolic pressure on left atrial size (men, 0.3 mm; women, 0.3 mm). Similarly, the influence of a 1-SD increment of age on left atrial size (men, 0.5 mm; women, 0.9 mm) also was greater than was a 1-SD increment of 8-year average systolic pressure.
Effect of LV Mass on Left Atrial Size
In our study sample, the correlation between left atrial size and
LV mass was substantial (men, r=.42; women,
r=.50). With inclusion of LV mass in the multivariable
linear regression models, the relations between the pressure variables
and left atrial size were in general no longer statistically
significant. In women, however, the relations of the pulse pressure
variables with left atrial size were not significantly altered after
adjustment for LV mass.
Prevalence of Left Atrial Enlargement According to BP Levels
Age-adjusted prevalences of left atrial enlargement according to
8-year average systolic pressure and 8-year average pulse pressure are
presented in Figs 1 and 2,
respectively. In both men and women, a stepwise increase in the
prevalence of left atrial enlargement occurred with increasing levels
of systolic and pulse pressures. In both sexes, subjects with 8-year
average systolic pressure greater than or equal to 140 mm Hg were
twice as likely to have left atrial enlargement as those with values
less than or equal to 110 mm Hg.
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Logistic Regression Analyses
In multivariable logistic regression analyses, the relations of
each of the pressure variables to the prediction of left atrial
enlargement were statistically significant before and after adjustment
for age and BMI. These associations were greater in women than in men
and were attenuated after adjustment for age and BMI. Results are
shown in Table 4. The odds ratios are expressed in terms
of 1-SD increments.
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| Discussion |
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Comparison With the Literature
The results of this population-based investigation contribute to
the understanding of the relations of systemic BP to left atrial size
and extend the work of previous investigators. In a study of 31
hypertensive subjects without clinically evident coronary heart
disease, Dunn et al11 found that hypertensive subjects
with evidence of left atrial abnormality by electrocardiogram or LV
hypertrophy by either electrocardiogram or chest roentgenogram had
significantly greater left atrial indexes (left atrial size/body
surface area) than 14 age-matched normotensive subjects. Miller et
al,12 in an evaluation of 14 hypertensive and 10
normotensive subjects with normal coronary angiography, demonstrated
significantly increased left atrial dimension and left atrial index
(left atrial size/body surface area) among the hypertensive subjects. A
recent study by Pearson et al13 of 144 participants of the
Systolic Hypertension in the Elderly Program (SHEP) trial and 55
age-matched normotensive control subjects found significantly increased
left atrial index (left atrial size/body surface area) in the
hypertensive group. However, among 234 subjects with mild to moderate
hypertension in a study by Savage et al,7 only 5% of
hypertensive subjects were found to have abnormal left atrial
dimensions (defined as values above the 95% prediction interval
derived from 124 normotensive control subjects).
Each of the earlier studies was a case-control design and
involved relatively small study samples. Moreover, different criteria
were used for the definition of hypertension: elevated systolic and
diastolic pressures (
140/90 mm Hg),11 12 isolated
systolic hypertension (systolic
160 and diastolic <90
mm Hg),11 and diastolic hypertension (
95
mm Hg).7 In accordance with our findings, the studies
that included subjects with systolic hypertension11 12
found significant associations of hypertension with increased left
atrial size. Conversely, Savage et al7 evaluated subjects
with diastolic hypertension and did not find an increased prevalence of
left atrial enlargement among hypertensive subjects. Of note, among
subjects in the study by Savage et al with available resting BP
readings (n=128), systolic pressure was significantly correlated
(r=.20, P<.05) with left atrial dimension,
whereas diastolic pressure was not (r=.17,
P>.05).
Among the previous studies, body surface area was predominantly used to account for differences in body size. The appropriateness of left atrial indexation by body surface area is controversial, and correction of left atrial size is not widely used clinically. However, as has been previously demonstrated, there are significant sex-specific differences in left atrial dimension.25 In the absence of validated methods for body size correction, the analyses in the present study were all sex specific and used 90% cutoffs for unindexed left atrial dimension based on a healthy sample of Framingham Heart Study subjects.
Effects of Aging and Obesity on Left Atrial Dimension
In our analyses, the effect of age on left atrial size and on the
prevalence of left atrial enlargement was considerable. The
influence of aging on left atrial size has been previously
reported. Autopsy26 27 and
echocardiographic6 25 studies have shown modestly
increased left atrial size with aging. This effect may be related to
changes in atrial tissue composition that occur with advancing
age.27 28
BMI was the most powerful determinant of left atrial size in our study sample, proving to be a stronger correlate of left atrial size than height or body surface area. Previous echocardiographic studies have found that left atrial size increases as a function of body surface area6 25 29 and height.30 Although body surface area is body mass dependent and tends to increase in the setting of obesity, BMI is a better, though still imperfect, correlate of obesity. A small case-control study by Lavie et al31 suggested that obese subjects (defined as body weight exceeding 150% ideal weight) had increased left atrial size compared with lean control subjects. The mechanisms by which obesity may promote left atrial enlargement are unclear but are likely related to hemodynamic alterations in the obese characterized by increased intravascular volume associated with increased cardiac output and stroke volume.32 33
Mechanisms of Association Between Left Atrial Size and BP
Elevated systolic or pulse pressure may directly promote atrial
dilatation. Alternatively, the increase in left atrial size in the
hypertensive patient may reflect other factors associated with
increased systolic and pulse pressures. Previous studies have
demonstrated a positive association between systolic pressure and LV
mass.34 35 36 Moreover, several studies have demonstrated
left atrial functional abnormalities in the setting of increased LV
mass.37 38 39 In the present study, the correlation
between left atrial size and LV mass was considerable (men,
r=.42; women, r=.50), and adjustment for LV mass
negated the significant association of the pressure variables with left
atrial size. As such, it is possible that the association of BP with
left atrial size and left atrial enlargement may be mediated through
the more clearly defined association of hypertension with LV hyper-
trophy.40 41
Strengths and Limitations
The present study was based on a large, closely followed
population-based sample. Because of the elimination of clinical
referral patterns, selection bias was inherently minimized. An
additional advantage of the present investigation was the
availability of historical BP information that was used in analyses of
the long-term BP variables. In view of the frequent, routine
longitudinal surveillance of our subjects, exclusions for clinically
evident cardiac disease were likely to be more complete. Occult
coronary disease, however, cannot be excluded in this study sample.
Several limitations warrant consideration. The generalizability of these results may be limited because the study sample is overwhelmingly white; extrapolation of these results to nonwhite populations may not be applicable. In addition, the anteroposterior left atrial dimension provided by M-mode may not accurately reflect true left atrial chamber size. Although the left atrium tends to enlarge spherically, symmetrical enlargement does not always occur.42 Furthermore, distortion of the anteroposterior dimension may occur secondary to dilatation of the aortic root (which forms the anterior boundary of the left atrium) or encroachment posteriorly from enlarged posterior structures. Nonetheless, misclassification of left atrial size is unlikely to have resulted in systematic bias. A further limitation of M-mode is its insensitivity for the detection of valvular heart disease. In particular, M-mode cannot evaluate clinically significant mitral regurgitation, well known to be associated with left atrial enlargement.
Implications
The present study demonstrates statistically significant
effects of systolic and pulse pressures on left atrial size. The
influences appear to be very modest in magnitude and may be mediated by
the influence of LV mass on left atrial size. It is not known whether
antihypertensive strategies that prevent the development of LV
hypertrophy or contribute to its regression materially affect the
development of left atrial enlargement.
| Footnotes |
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Received December 29, 1993; first decision February 9, 1994; accepted November 9, 1994.
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A. M. Pritchett, D. W. Mahoney, S. J. Jacobsen, R. J. Rodeheffer, B. L. Karon, and M. M. Redfield Diastolic dysfunction and left atrial volume: A population-based study J. Am. Coll. Cardiol., January 4, 2005; 45(1): 87 - 92. [Abstract] [Full Text] [PDF] |
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A V Mattioli, S Bonatti, D Monopoli, M Zennaro, and G Mattioli Left atrial remodelling after short duration atrial fibrillation in hypertrophic hearts Heart, January 1, 2005; 91(1): 91 - 92. [Full Text] [PDF] |
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T. J. Wang, H. Parise, D. Levy, R. B. D'Agostino Sr, P. A. Wolf, R. S. Vasan, and E. J. Benjamin Obesity and the Risk of New-Onset Atrial Fibrillation JAMA, November 24, 2004; 292(20): 2471 - 2477. [Abstract] [Full Text] [PDF] |
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P. L. L'Allier, A. Ducharme, P.-F. Keller, H. Yu, M.-C. Guertin, and J.-C. Tardif Angiotensin-converting enzyme inhibition in hypertensive patients is associated with a reduction in the occurrence of atrial fibrillation J. Am. Coll. Cardiol., July 7, 2004; 44(1): 159 - 164. [Abstract] [Full Text] [PDF] |
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T. J. Wang, M. G. Larson, D. Levy, E. J. Benjamin, E. P. Leip, P. W.F. Wilson, and R. S. Vasan Impact of Obesity on Plasma Natriuretic Peptide Levels Circulation, February 10, 2004; 109(5): 594 - 600. [Abstract] [Full Text] [PDF] |
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A. M. Pritchett, S. J. Jacobsen, D. W. Mahoney, R. J. Rodeheffer, K. R. Bailey, and M. M. Redfield Left atrial volume as an index ofleft atrial size: a population-based study J. Am. Coll. Cardiol., March 19, 2003; 41(6): 1036 - 1043. [Abstract] [Full Text] [PDF] |
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E. Gerdts, L. Oikarinen, V. Palmieri, J. E. Otterstad, K. Wachtell, K. Boman, B. Dahlof, and R. B. Devereux Correlates of Left Atrial Size in Hypertensive Patients With Left Ventricular Hypertrophy: The Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) Study Hypertension, March 1, 2002; 39(3): 739 - 743. [Abstract] [Full Text] [PDF] |
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C. Stefanadis, J. Dernellis, and P. Toutouzas A clinical appraisal of left atrial function Eur. Heart J., January 1, 2001; 22(1): 22 - 36. [PDF] |
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J. A. Millar and A. F. Lever Implications of Pulse Pressure as a Predictor of Cardiac Risk in Patients With Hypertension Hypertension, November 1, 2000; 36(5): 907 - 911. [Abstract] [Full Text] [PDF] |
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J. S. Gottdiener, D. J. Reda, D. W. Williams, B. J. Materson, W. Cushman, and R. J. Anderson Effect of Single-Drug Therapy on Reduction of Left Atrial Size in Mild to Moderate Hypertension : Comparison of Six Antihypertensive Agents Circulation, July 14, 1998; 98(2): 140 - 148. [Abstract] [Full Text] [PDF] |
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