Rosa et al Arq BrasArticle

Original Cardiol
Left ventricular diastolic function in hypertensive patients 2002; 78: 472-7.

Left Ventricular Diastolic Function in Essential Hypertensive

Patients. Influence of Age and Left Ventricular Geometry

Eduardo Cantoni Rosa, Valdir Ambrósio Moysés, Ivan Rivera, Ricardo da Cintra Sesso,
Nárcia Kohlmann, Maria Tereza Zanella, Artur Beltrame Ribeiro, Osvaldo Kohlmann Jr.

São Paulo, SP - Brazil

Purpose - To evaluate diastolic dysfunction (DD) in With the advance in noninvasive diagnostic me-
essential hypertension and the influence of age and car- thods, particularly through the use of Doppler echocar-
diac geometry on this parameter. diography, more emphasis has been given to alterations in
ventricular relaxation that occur in the course of hyper-
Methods - Four hundred sixty essential hypertensive tensive disease 1-3.
patients (HT) underwent Doppler echocardiography to ob- Recent studies have shown a significant prevalence
tain E/A wave ratio (E/A), atrial deceleration time (ADT), of diastolic dysfunction in selected hypertensive popula-
and isovolumetric relaxation time (IRT). All patients were tions 4-8, including patients who are clinically symptomatic
grouped according to cardiac geometric patterns (NG - and with normal systolic function 9,10, thus rendering its
normal geometry; CR - concentric remodeling; CH- con- recognition important for the assessment of hypertensive
centric hypertrophy; EH - eccentric hypertrophy) and to persons.
age (<40; 40 - 60; >60 years). One hundred six normoten- This fact is reinforced by the potential risk involved in
sives (NT) persons were also evaluated. the pathophysiological mechanisms of diastolic dysfunc-
tion 11-19, by the potential association with ischemic coronary
Results - A worsening of diastolic function in the HT disease and by the higher morbidity and lethality attributed
compared with the NT, including HT with NG (E/A: NT - to this condition 20.
1.38±0.03 vs HT - 1.27±0.02, p<0.01), was observed. A hi- The mechanisms controlling diastolic function are
gher prevalence of DD occurred parallel to age and cardi- complex and influenced by many variables, particularly age
ac geometry also in the prehypertrophic groups (CR). Mul- and the occurrence of ventricular hypertrophy 6,8,21-25. Ho-
tiple regression analysis identified age as the most impor- wever, recent studies have shown the occurrence of diasto-
tant predictor of DD (r2=0.30, p<0.01). lic dysfunction in incipient phases of hypertensive heart di-
sease 5-7,26 where manifest cardiac hypertrophy is not yet
Conclusion - DD was prevalent in this hypertensive present.
population, being highly affected by age and less by heart This fact is extremely important because early recogni-
structural parameters. DD is observed in incipient stages of tion of diastolic function may help in the evaluation and ma-
hypertensive heart disease, and thus its early detection nagement of the hypertensive patient.
may help in the risk stratification of hypertensive patients. Few studies, however, especially in Brazil, have glo-
bally evaluated anatomical-functional cardiac correlations
Key words: essential hypertension, diastolic function,
regarding diastolic function.
age, cardiac geometry
This study aims to evaluate the prevalence of diastolic
function alterations using Doppler echocardiography in a
reference population of essential hypertensives and the
variables involved in these alterations, including age and
ventricular geometry.
Division of Nephrology, Kidney and Hypertension Hospital, Universidade
Federal de São Paulo Methods
Mailing address: Eduardo Cantoni Rosa - Rua Borges Lagoa, 960 - 04038-002
São Paulo, SP - Brazil - E-mail: [email protected]
The study evaluated 460 patients, 129 men and 331 wo-

Arq Bras Cardiol, volume 78 (nº 5), 472-7, 2002

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Arq Bras Cardiol Rosa et al
2002; 78: 472-7. Left ventricular diastolic function in hypertensive patients

men, with a diagnosis of essential hypertension. Patients with Spearman’s correlation test was used for analysis of
secondary hypertension, diabetes mellitus, coronary in- simple correlations.
sufficiency, congestive heart failure, and renal failure were Also, the participation of cardiac morphometric (LV
excluded from the study. MI, septum, and posterior wall) and demographic parame-
All patients were evaluated with bidimensional Dop- ters as diastolic function determinants were evaluated using
pler echocardiography, excluding those with valve lesions multiple regression analysis.
or low quality examinations. Values of p <0.05 were considered significant.
In addition, 106 normotensives, 51 men and 55 women,
whose blood pressure measurements on 3 consecutive oc- Results
casions in a 1-week interval were lower than 140/90mmHg,
were evaluated. The values of means of demographic, blood pressure,
On the day echocardiography was performed, demo- and ventricular structure parameters in normotensive and
graphic parameters and pressure measurements were taken hypertensive patients and hypertensive subgroups are
with the patient in the sitting position and after a 5-minute shown in Table I.
rest. Among the hypertensive patients, 84.4% of the men Comparative analysis of diastolic function parameters
and 86.3% of the women were receiving the usual antihy- (E/A, ADT, IRT) in hypertensives and normotensives may
pertensive treatment. be seen in Figure 1, where significantly lower E/A ratios and
For the echocardiographic evaluation, Escote Biomé- higher IRT values can be observed in the hypertensives.
dica, model SIM5000 equipment, with a mechanical 2.5 MHz Figure 2 shows the comparison of diastolic function
transducer, allowing bidimensional M mode evaluation with
parameters between the hypertensive population with nor-
pulse and continuous Doppler, was used.
mal geometry and the normotensive group. It can be seen
Measurements of left ventricular mass (LV mass) were
that even in the initial phases, when still no morphometric
calculated with the modified Devereux formula 27: 0.8 [1.04
alterations are observed, significant changes already exist
(DIVS + DLVPW)3-DLVD3]+0.3, where DIVS, DLVPW, and
DLVD correspond to measurements of diastolic left inter- in the E/A ratio.
ventricular septum, left ventricular posterior wall, and left Table II shows the mean values of diastolic parameters
ventricular diameter. For calculation of the ventricular mass in hypertensive and normotensive subgroups stratified ac-
index (LVMI), correction by body surface area was used. cording to age and cardiac geometry. Figure 3 separately
Measurements of relative thickness of the septum (RST) evaluates the prevalence of patients who presented an E/A
and wall (RWT) were obtained by 2DIVS/DLVD and ratio <1 in each subgroup studied.
2DLVPW/DLVD, respectively 17. In the first place, it can be observed that the 3 parame-
For the definition of hypertrophy, the usually adopted ters were influenced by age, independently of the ventricu-
criteria for men and women were used 28: LVMI - 134g/m2 lar geometry pattern. A progressive worsening of diastolic
and 110g/m2. According to these criteria, the patients were
classified into 4 cardiac geometry groups: normal geometry
- normal LVMI and RST and RWT <0.45; concentric remo- Table I - Demographic, blood pressure, and heart structural
parameters in hypertensives and normotensives
deling - normal LVMI and RST and/or RWT ≥ 0.45; concen-
tric hypertrophy - LVMI ≥ limits and RWT ≥ 0.45 and eccen- Normotensives Hypertensives p
tric hypertrophy - LVMI ≥ limits and RWT <0.45.
106460
Diastolic function was evaluated with the following Age (years) 41.8 ± 1.8 49.7 ± 0.6 <0.01
parameters: 1 - early ventricular filling (E wave) and late ven- Sex
male 55 (51.9%) 129 (28.1%) <0.01
tricular filling (A wave) and by the E/A wave ratio, whose
female 51 (48.1%) 331 (71.9%) <0.01
normality criterion, for practical purposes, was considered BMI (kg/m2) 25.3 ± 0.5 27 ± 0.2 <0.01
≥1.0; 2 - measurement of the isovolumetric relaxation time Race
white 57 (54%) 244 (53.1%) NS
(normal IRT - <110 msec); 3 - atrial deceleration time (normal
nonwhite 49 (46%) 216 (46.9%)
ADT - <240 msec). SBP (mm Hg) 116.9 ± 1.5 148.1 ± 1 <0.001
The obtained data were evaluated using the Sigma DBP (mm Hg) 77.6 ± 0.9 94.9 ± 0.6 <0.001
HR (bpm) 73 ± 0.8 76.2 ± 0.4 <0.01
Stat program. For the global evaluation of the demographic,
DIVS (mm) 9 ± 0.2 10.7 ± 0.1 <0.001
blood pressure, structural, and functional heart parameters, DLVPW (mm) 8.7 ± 0.2 10.3 ± 0.1 <0.001
the values of means ± standard error of the respective DLVD (mm) 47.1 ± 0.5 46.6 ± 0.3 NS
LA (mm) 33.5 ± 0.5 35.1 ± 0.2 <0.01
variables were considered.
LVM (g) 142 ± 5.5 176.1 ± 2.9 <0.001
Comparison between means of normotensive and hy- LVMI (g/m2) 80.3 ± 3 103.2 ± 2.5 <0.001
pertensive groups and between groups with different remo-
NS - not-significant; BMI- body mass index; SBP- systolic blood
deling patterns was performed using covariance analysis pressure; DBP- diastolic blood pressure; HR - heart rate; DIVS- diastolic
after adjustment for age, sex, and body mass index (BMI) be- interventricular septum; DLVPW- diastolic left ventricle posterior wall;
cause of the demographic differences between the evalua- DLVD- diastolic left ventricle diameter; LA- left atrium; LVMI- left
ventricular mass index.
ted groups.

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Rosa et al Arq Bras Cardiol
Left ventricular diastolic function in hypertensive patients 2002; 78: 472-7.

E/A ADT IRT

Fig. 1 - Diastolic function parameters in normotensive and essential hypertensives.

*p<0.01 vs NT; NT - normotensive; HT - essential hypertensive; E/A - E/A wave Fig. 3 - Prevalence of diastolic function in normotensive and essential hypertensive
ratio; ADT - atrium deceleration time (msec) IRT - isovolumetric relaxation time according to age and cardiac geometry. NT - normotensive; hypertensive with: NG -
(msec). normal geometry; CR - concentric remodeling; CH - concentric hypertrophy; EH -
excentric hypertrophy.

E/A ADT IRT

ficant correlation with age, and significant but lower correla-

tions with structural parameters, especially with the septum
and posterior wall were obtained.
The individual participation of morphometric cardiac
(LVMI, DIVS, DLVPW), demographic (age, gender, race,
BMI and time of hypertension), pressure (SBP, DBP, measu-
red in the office), and heart rate parameters, as diastolic
function determinants, using E/A ratio as a parameter, were
Fig. 2 - Diastolic function parameters on echocardiography in normotensive and evaluated with multiple regression analysis.
essential hypertensives with normal geometry *p<0.01 vs NT; NT-normotensive; Table III shows the obtained results, only regarding
HT-NG-hypertensive with normal geometry; E/A - E/A wave ratio; ADT-atrium de-
celeration time (msec); IRT - isovolumetric relaxation time (msec). variables with some predictive value, the septum and LVMI
being evaluated separately. As expected, age was the most
important predictive factor for alterations in the E/A ratio
function was noted with age, including in the normotensive (r2=0.3; p<0.001) with less participation by septum altera-
group, where alteration in the E/A ratio was verified in 57% tions (r2 =0.04; p<0.0001), LVMI (r2 =0.03; p<0.0001) and
of the individuals over 60 years of age (Figure 3). LVPW (r2=0.03; p <0.0001 - result not shown).
At the same time, an effect of structural alterations is
observed for all age ranges, particularly on evaluation of the Discussion
E/A ratio, where a progressive reduction in the mean values
is seen already in the group with normal geometry. This fact Evaluation of alterations in diastolic function in the
can especially be observed in the younger age ranges (<40; hypertensive population showed that alterations are pre-
40- 60 years). valent and changed in regard to normotensive patients
Figure 4 shows a correlation analysis between the E/A and, as found in other studies, were influenced mainly by
variable and age and the heart structural parameters (LVMI, age 5,5,21,22,29.
septum, and posterior wall). As expected, a close and signi- Normotensive elderly patients (>60 years) reached a

Table II - Diastolic function through E/A wave ratio, ADT, and IRT according to age range and cardiac geometry pattern.

NT NG CR CH EH

N 106 228 114 86 32

<40 anos 1.68 ± 0.06 1.57 ± 0.05 1.35 ± 0.12 *1 1.24 ± 0.13 *1+1 1.3 ± 0.16 *1
E-A 40-59 1.3 ± 0.05 1.19 ± 0.03 1.07 ± 0.04 *+1 0.94 ± 0.05 *+ 0.91 ± 0.08 *+
≥60 0.94 ± 0.09 0.85 ± 0.05 0.77 ± 0.06 0.72 ± 0.06 * 0.9 ± 0.11
<40 180.3 ± 5.6 183.7 ± 4.7 190.6 ± 10.8 214.3 ± 11*1+ 1 203.7 ± 14.3
TDA 40-59 207.5 ± 6.6 197 ±4 210.4 ± 5.4+1 229.8 ± 6.7*+# 226.4 ± 11.1+
≥60 234.1 ± 16.6 219.5 ± 9.6 254.3 ± 10.4+1 274 ± 11*1+ 281.8 ± 20.7+1
<40 81.6 ± 2.4 83.9 ±2 81.3 ± 4.7 86.9 ± 4.7 101 ± 6.2 *1+1#1@
IRIV 40-59 87.5 ± 3.1 90.2 ± 1.9 94 ± 2.6 106.5 ± 3.2*+ 102.3 ± 5.3*1+1
≥60 91.8 ± 7.8 92.5 ± 4.5 89.5 ± 4.8 117.6 ± 5.1*1+# 95.7 ± 9.6

p<0.01 vs NT; *1 p<0.05 vs NT; + p<0.01 vs NG; +1 p<0.05 vs NG; #p<0.01 vs CR; #1 p<0.05 vs CR; @ p<0.01 vs CH. E/A- E/A wave ratio; ADT (msec)- atrial
deceleration time; IRT (msec)- isovolumetric relaxation time; NT- normotensives; NG- normal geometry; CR- concentric remodeling; CH- concentric hypertrophy;
EH- eccentric hypertrophy.

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Arq Bras Cardiol Rosa et al
2002; 78: 472-7. Left ventricular diastolic function in hypertensive patients

AGE LEFT VENTRICULAR MASS INDEX

SEPTUM POSTERIOR WALL

Fig. 4 - Correlation between age and heart-structural parameters and E/A ratio.

Table III - Multiple regression analysis in essential hypertensives dy emphasized the presence of diastolic dysfunction, even
according to: dependent variable - E/A ratio; independent variables - in the absence of hypertrophy 4,6,7,26.
age, sex, time of hypertension, systolic arterial blood pressure (SBP), The study by Ren et al 8 in 1994, in particular, evalua-
diastolic arterial blood pressure (DBP), heart rate, left ventricle mass
index (LVMI), septum. ted measurements of diastolic function on Doppler echo-
cardiography according to cardiac geometry and evidenced
E/A E/A the presence of diastolic dysfunction in the prehypertrophy
Variable Coef. R 2
P Variable Coef. R 2
P phases (cardiac remodeling). However, no patients with
normal geometry were evaluated in this study.
2.36 2.34
The results of this study allowed us to recognize in
Age - 0.017 0.30 <0.0001 Idade - 0.017 0.30 < 0.0001
Septum - 0.04 0.04 <0.0001 IMVE - 0.002 0.02 < 0.0001
the population evaluated by Doppler echocardiography,
Total 0.34 <0.0001 Total 0.32 < 0.001 the early presence of diastolic dysfunction, even in the
absence of structural heart disease (normal geometry) and
Age (years); septum (mm); LVMI (kg/m2)- left ventricle mass index. also in the early phases of structural alteration (concentric
remodeling).
As has already been emphasized, in this study, the im-
prevalence of 57% in alterations in the E/A wave ratio (<1), pact of heart structural alterations on diastolic function, in
and when added to hypertension, in the groups with more contrast to findings in other studies 23,30, was not very im-
important structural alterations (CH), even a 93% inversion portant as compared to that of age. However, the partici-
of the E/A ratio could be observed. pation of these different mechanisms still remains contro-
On evaluating patients according to age range and versial, because the data obtained at that time 4,5,8,23,30, as in
cardiac geometry, we observed that in the elderly group, this study, are not uniform, there being the need for standar-
over 80% of the patients had inversion of the E/A ratio, indi- dization of methods to detect the actual participation of
cating a more permanent diastolic dysfunction, in part inde- structural mechanisms, both in the initial and the later pha-
pendent of alterations in cardiac geometry, in contrast to ses of heart disease evolution.
that in the lower age ranges. When we previously emphasized the potential patho-
On evaluating diastolic function measurements in hy- physiological mechanisms involved in diastolic dysfunction
pertensives with normal ventricular mass index, significant in hypertension, its importance caught our attention. Its pre-
incipient structural alterations as compared with the normo- sence, with or without the presence of structural alterations,
tensive group were observed. Previous studies have alrea- may certainly help in the stratification of cardiovascular risk

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Rosa et al Arq Bras Cardiol
Left ventricular diastolic function in hypertensive patients 2002; 78: 472-7.

in hypertensive patients, in view of the fact that in addition ted to this entity. Therefore we have to emphasize the role of
to the participation of structural mechanisms and age, diastolic dysfunction in the mechanism of response and
ischemic alterations secondary to vascular hypertensive adaptation of cardiopulmonary reflexes to exercise maneu-
disease itself and/or atherosclerotic mechanism (coronary vers, orthostatism (tilt test), etc.33. Regarding these maneu-
plaques) may be present 13,31. vers, the vasoconstrictor response mechanisms, which
In this study, coronary disease was an exclusion fac- usually are preserved in borderline hypertensives, are more
tor for the analysis of patients, and thus we think that the impaired because of imbalance of Starling forces due to less
initial alterations present in patients with normal geometry ventricular filling. Thus, symptoms of orthostatic hypoten-
were subsequent to the hypertensive disease itself. sion and exercise intolerance in individuals with sustained
In any case, diastolic dysfunction in general hyperten- hypertension, especially the elderly, may be explained, lea-
sive populations may imply a higher prevalence of coronary ding even to anginal states, depending on the degree of co-
disease, as has already been emphasized by some authors 18, ronary perfusion.
and that may indicate a worse prognosis and demands a In view of the shown morbidity and the prognostic va-
more detailed evaluation of the hypertensive patient. lue, the presence of diastolic dysfunction may, thus, imply a
In addition, the finding of diastolic dysfunction and left treatment more directed to the hypertensive patient, avoiding
ventricular hypertrophy may imply a higher mortality 9, and unnecessary treatments, such as digitalis, diuretics, and
the presence of associated complications, such as acute vasodilators that may cause hypotension and symptoms of
pulmonary edema, may lead to more frequent hospitalizati- low output, and also trying to use drugs that potentially
ons and therefore to a higher morbidity in these patients 20. may improve the degree of diastolic dysfunction 34.
According to some studies 9,32, a significant part of he- In conclusion, diastolic dysfunction was prevalent in
art failure symptoms in the hypertensives (fatigue, exertio- the study population of hypertensives, being greatly influ-
nal dyspnea) is related mainly to mechanisms of diastolic enced by age and less so by heart structural alterations.
and not systolic dysfunction. Diastolic function occurred in incipient stages of hyper-
The worsening of diastolic function in groups with mo- tensive heart disease, indicting that its early detection may
re severe concentric hypertrophy, particularly in the elderly, lead to an additional stratification of the remodeling alte-
should also be noted. The latter, besides a greater preference rations and also guide the choice of antihypertensive drugs,
for diastolic dysfunction 25, have also more symptoms rela- avoiding those that impair the ventricular filling mechanisms.

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Iguape - SP Flavia Cardoso - SP

Editor da Seção de Fotografias Artísticas: Cícero Piva de Albuquerque

Correspondência: InCor - Av. Dr. Enéas C. Aguiar, 44 - 05403-000 - São Paulo, SP - E-mail: delcicero@incor. usp.br

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