Cardiac structure and function as predictors of mortality in persons 85 years of age.

Abstract

Individuals aged > 85 years are the world's most rapidly growing age group and have a high incidence of cardiovascular mortality. The objective of this study was to prospectively determine the prognosis of abnormal cardiac structure and function in an age-homogenous, community-dwelling population of subjects born in 1920 and 1921. Subjects were recruited from the Jerusalem Longitudinal Cohort Study. Echocardiography was performed with a portable echocardiograph at the subjects' places of residence. Standard echocardiographic assessment of cardiac structure and function was performed. Five-year mortality was assessed through a centralized government database. Five hundred two subjects (235 men, 267 women) were enrolled in the study, of whom 107 (21%) had died at the time of 5-year follow-up. Subjects who died had significantly higher left atrial volume indexes (42.3 ± 16.5 vs 36.6 ± 12.5 ml/m2, p < 0.01) and left ventricular mass indexes (133.1 ± 47.6 vs 119.8 ± 30.6 g/m2, p < 0.05). Ejection fractions were significantly lower in subjects who died (52.5 ± 11.5% vs 56.4 ± 9.4%, p < 0.003), but indexes of left ventricular diastolic function were not significantly different between the 2 groups (E/e' ratio 13.0 ± 5.3 vs 12.2 ± 4.9, p = 0.18). In conclusion, elevated left atrial volume index and left ventricular mass index and decreased LV systolic function predicted 5-year mortality in a community-dwelling population of subjects aged 85 years, even after correction for possible confounders. Left ventricular diastolic dysfunction did not predict 5-year mortality in this cohort.

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Cardiac Structure and Function as Predictors of Mortality in
Persons 85 Years of Age
David Leibowitz, MDa,*, Irit Stessman-Lande, BSca, Jeremy M. Jacobs, MBBSb, Aaron Cohen, MDb,
Eliana Ein-Mor, MAb, Jochanan Stessman, MDb, and Dan Gilon, MDa
Individuals aged >85 years are the world’s most rapidly growing age group and have a
high incidence of cardiovascular mortality. The objective of this study was to prospectively
determine the prognosis of abnormal cardiac structure and function in an age-homogenous,
community-dwelling population of subjects born in 1920 and 1921. Subjects were recruited
from the Jerusalem Longitudinal Cohort Study. Echocardiography was performed with a
portable echocardiograph at the subjects’ places of residence. Standard echocardiographic
assessment of cardiac structure and function was performed. Five-year mortality was
assessed through a centralized government database. Five hundred two subjects (235 men,
267 women) were enrolled in the study, of whom 107 (21%) had died at the time of 5-year
follow-up. Subjects who died had significantly higher left atrial volume indexes (42.3 ? 16.5
vs 36.6 ? 12.5 ml/m2, p <0.01) and left ventricular mass indexes (133.1 ? 47.6 vs 119.8 ?
30.6 g/m2, p <0.05). Ejection fractions were significantly lower in subjects who died
(52.5 ? 11.5% vs 56.4 ? 9.4%, p <0.003), but indexes of left ventricular diastolic function
were not significantly different between the 2 groups (E/e= ratio 13.0 ? 5.3 vs 12.2 ? 4.9,
p ? 0.18). In conclusion, elevated left atrial volume index and left ventricular mass index
and decreased LV systolic function predicted 5-year mortality in a community-dwelling
population of subjects aged 85 years, even after correction for possible confounders. Left
ventricular diastolic dysfunction did not predict 5-year mortality in this cohort.
Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:901–905)
© 2012
Individuals aged ?85 years are the world’s most rapidly
growing age group and provide an increasing challenge for
cardiovascular care given the relatively high frequency of
cardiac death in this population.1,2Prospective data exam-
ining the relation of abnormal cardiac structure and function
to mortality in this population are limited. Previous studies
that have used echocardiography in elderly patients to ex-
amine prognosis included a broad range of ages, with rela-
tively few patients aged ?80 years.3–5In addition, existing
studies have been performed in the hospital or clinic setting,
possibly contributing to a biased study population in this
elderly age group, as subjects may have difficulty leaving
their homes.6The recent introduction of portable echocar-
diographic machines has made it possible to study patients in
their homes and therefore to assess a more representative
population of the oldest old. The aims of this study were to
prospectively examine the association between echocardio-
graphic measures of cardiac structure and function performed
atsubjects’homesand5-yearmortalityinanage-homogenous,
representative community-dwelling population born in 1920
and 1921.
Methods
Subjects were recruited from the Jerusalem Longitudinal
Cohort Study, which was initiated in 1990 and has followed
an age-homogenous representative cohort of West Jerusa-
lem residents born from June 1920 and May 1921. The
methods have been described elsewhere in detail.7,8In the
present study, we examined data from the third most recent
phase of data collection, which took place during 2005 and
2006. Subjects were interviewed and examined in their
homes on 2 separate occasions, each session requiring the
completion of a structured interview that lasted about 1.5
hours. Information was collected in socioeconomic, demo-
graphic, medical, functional, cultural, and cognitive do-
mains. The institutional ethics committee of the Hadassah-
Hebrew University Medical Center approved the study
design, and written informed consent was obtained from all
participants.
Subjects identified from the electoral register were ran-
domly chosen from the total sample of individuals born
1920 in 1921 and living in Jerusalem in 2005. As reported
previously, we performed an examination of death certifi-
cates and hospital admission records 3 years after the initi-
ation of the study and compared the study group to other
subjects of the sample frame in Jerusalem who either re-
fused or were not invited to enroll in the cohort study.7,8
Subjects of the study group, those who declined to partici-
aHeart Institute andbDepartment of Geriatrics and Rehabilitation, Ha-
dassah-Hebrew University Medical Center and Hebrew University Hadas-
sah Medical School, Mount Scopus, Jerusalem, Israel. Manuscript received
September 18, 2011; revised manuscript received and accepted October 31,
2011.
This work was supported by funds from the Ministry of Labor and
Social Affairs of the State of Israel, Jerusalem, Israel; ESHEL (the Asso-
ciation for the Planning and Development of Services for the Aged in
Israel), Jerusalem, Israel; the National Insurance Institute, Jerusalem, Is-
rael; and various private charitable donors.
*Corresponding author: Tel: 972-2-5844530; fax: 972-2-5817360.
E-mail address: oleibo@hadassah.org.il (D. Leibowitz).
0002-9149/12/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
doi:10.1016/j.amjcard.2011.10.055
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pate, and those baseline cohort members not enrolled had
near identical mortality and disease-specific hospital mor-
bidity, thus demonstrating the representative nature of the
initial study group in comparison to the total same age
stratum of the Jerusalem population. Echocardiography was
performed in 502 randomly selected subjects, evenly dis-
tributed between new recruits and subjects participating
from previous phases. Survival status at 5-year follow-up
was assessed through the centralized Ministry of Interior
database. Follow-up was available for all study subjects.
Diagnosis of ischemic heart disease (IHD) was based on
a history of hospitalization for myocardial infarction or
acute coronary syndromes, coronary catheterization with
evidence of significant coronary artery disease, positive
stress test results, myocardial infarction on electrocardiog-
raphy, a history typical for angina pectoris on exertion, or
previous coronary artery bypass grafting surgery. Hyperten-
sion was assessed by the examining study physician and
generally was defined as treatment with antihypertensive
medications or subjects’ self-reports. Hyperlipidemia was
defined as use of cholesterol-lowering medications. Diabe-
tes mellitus was a composite of hypoglycemic medications,
personal history, or a medical record diagnosis. Congestive
heart failure (CHF) was based on hospital discharge diag-
Table 1
Baseline clinical characteristics
VariableTotal Population
(n ? 502)
Survivors
(n ? 395)
Nonsurvivors
(n ? 107)
p Value
Men
Education (0–12 years)
Married
Current smokers
Former smokers
Diabetes mellitus
IHD
Hypertension
Hyperlipidemia
Atrial fibrillation
Abnormal renal function (glomerular filtration rate ?60 ml/min/1.73 m2)
Abnormal Mini Mental State Examination score (?24/30)
CHF
Dependence in activities of daily living
Poor self-rated health
Body mass index (kg/m2), mean ? SD
New York Heart Association functional class
I
II
III
IV
46.8%
51.4%
48.8%
3.4%
37.6%
19.1%
36.8%
71.3%
51%
4.3%
10.2%
17.4%
11.2%
28.8%
31.2%
27.2 ? 4.4
45.6%
54.9%
47.6%
3.6%
25.6%
15.5%
33.6%
70%
52.4%
3.5%
8.4%
13.8%
7.6%
20.9%
26.4%
27.3 ? 4.4
51.4%
38.2%
51.4%
2.9%
44.8%
32.4%
48.6%
76.2%
45.8%
6.5%
17.4%
31.6%
24.8%
58.8%
50%
26.7 ? 4.5
0.25
0.014
0.41
0.72
0.18
?0.0001
0.0042
0.24
0.22
0.17
0.0042
?0.0001
?0.0001
?0.0001
?0.0001
0.27
90.7%
7.7%
1.4%
0.2%
92.1%
7.2%
0.8%
0%
85.7%
9.5%
3.8%
1%
0.0002
Table 2
Echocardiographic measurements (n ? 502)
VariableSurvivors Nonsurvivorsp Value
Measurements of cardiac morphology
Left atrial volume index (ml/m2)
LV end-diastolic volume index (ml/m2)
LV end-systolic volume index (ml/m2)
LV mass index (g/m2)
Measurements of cardiac systolic function
LV EF (%)
Tissue Doppler lateral s wave (cm/s)
Tissue Doppler septal s wave (cm/s)
Measurements of cardiac diastolic function
Mitral valve E wave (cm/s)
Mitral valve A wave (cm/s)
E/A ratio
Deceleration time (m/s)
Tissue Doppler lateral E wave (cm/s)
Tissue Doppler lateral A wave (cm/s)
Tissue Doppler septal E wave (cm/s)
Tissue Doppler septal A wave (cm/s)
E/E= ratio
Data are expressed as mean ? SD.
36.6 ? 12.5
67.6 ? 16.8
30 ? 12.3
119.8 ? 30.6
42.3 ? 16.5
71.6 ? 23.1
35.1 ? 18.3
133.1 ? 46.6
0.003
0.13
0.016
0.014
56.4 ? 9.4
7.8 ? 2
6.8 ? 1.8
52.5 ? 11.5
7.6 ? 2.4
6.2 ? 2.2
0.003
0.38
0.025
75.9 ? 20.9
90.2 ? 24.2
0.97 ? 1.1
207.4 ? 63.8
7.2 ? 2.1
10.2 ? 3.2
6.1 ? 2
8.3 ? 2.6
12.2 ? 4.9
79.4 ? 25.1
87.3 ? 25.6
1.1 ? 0.7
191.1 ? 71.4
7.2 ? 2.5
8.8 ? 4
5.8 ? 2.1
7.8 ? 3.2
13 ? 5.3
0.22
0.33
0.17
0.034
0.99
0.0025
0.18
0.14
0.18
902
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nosis and according to examining research physician diag-
nosis at the time of examination at home. Body mass index
was calculated and dichotomized as low (?25 kg/m2) or
high (?25 kg/m2).
Self-rated health was assessed according to the question
“How do you rate your general health?” Possible responses
were “good” and “poor.” A cognitive assessment was per-
formed according to a standardized Mini Mental State Ex-
amination, with cognitive impairment defined as ?24 of
30.9Dependence in functional class was defined as requir-
ing the help of another individual in ?1 of the following
activities of daily living: eating, dressing, bathing, personal
hygiene, toileting, and transfer.10
Five hundred two subjects underwent standard 2-dimen-
sional and Doppler echocardiography at their places of
residence using a portable echocardiograph (Vivid I; GE
Healthcare, Haifa, Israel). All subjects underwent 2-dimen-
sional and Doppler echocardiography with M-mode mea-
surements of the interventricular septum, posterior wall, and
left ventricular (LV) end-systolic and end-diastolic diame-
ters according to the recommendations of the European
Association of Echocardiography and the American Society
of Echocardiography.11Measurements were performed for
3 consecutive cardiac cycles and averaged. Subject height
and weight at the time of the study were recorded and body
surface area was calculated. LV mass was calculated ac-
cording to a necropsy-validated formula as LV mass (g) ?
0.8 ? {1.04 ? [(septal thickness ? LV internal diameter ?
posterior wall thickness)3? (LV internal diameter)3]} ?
0.6 and indexed to body surface area.12Given the high
prevalence of basal septal hypertrophy in this population,
septal thickness measurements were taken below the level
of the basal septum. Left atrial volumes were calculated at
end-systole from the apical 4-chamber view using the area-
length method and indexed to body surface area.13Mea-
surement of tricuspid regurgitation velocity was performed
in standard fashion and converted to right ventricular–to–
right atrial pressure gradient using the modified Bernoulli
equation.
The ejection fraction (EF) was calculated by averaging
measurements of end-diastolic and end-systolic volumes
from the apical 4-chamber view using the area-length
method for 3 consecutive beats. In patients with atrial fi-
brillation (n ? 25), measurements were averaged for 5
consecutive beats. Subjects with inadequate imaging of the
endocardial surface in apical views were excluded. Normal
systolic function was defined as an EF ?55%. In addition,
peak systolic mitral annular function (s wave) was measured
as an additional index of systolic function. Normal tissue
Doppler s-wave velocities were defined as ?8 cm/s2.14
Diastolic parameters were measured from the apical
4-chamber view using pulsed-wave Doppler at the level of
the mitral annulus and tissue Doppler imaging of the septal
and lateral myocardial walls and included early (E) and late
(A) transmitral flow velocities, the ratio of early to late
velocities (E/A), the deceleration time of E velocity, and
isovolumic relaxation time. Early (e=) and late (a=) diastolic
mitral annular tissue velocities at the septum and lateral
walls were obtained, and the E/e= ratio using the average of
septal and lateral tissue velocities obtained was calculated
as an index of diastolic function.15A normal E/e= ratio was
defined as ?13.15Patients with atrial fibrillation were ex-
cluded from analyses of a-wave velocities.
Descriptive statistics were calculated, and because the
cardiac parameter data were normally distributed, results are
described as mean ? SD. Percentages were calculated as
appropriate. For continuous variables, differences between
means were calculated using t tests, and cumulative survival
was assessed using Kaplan-Meier analysis and log-rank
tests for statistical significance. Adjusted and unadjusted
Cox proportional-hazards models were performed. All mod-
els were adjusted for gender, education, self-rated health,
Figure 1. Kaplan-Meier survival curves: cumulative survival in (A) patients
with and without impaired diastolic function, (B) patients with EFs ?55%
and ?55%, and (C) patients with and without elevated LV mass indexes.
903
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physical activity, diabetes, IHD, hypertension, renal dis-
ease, body mass index, and cardiac measurements of the EF,
E/e= ratio, tissue Doppler s wave, LV mass index, and left
atrial volume index with each cardiac function adjusted for
separately. We produced a combined model including all
confounders and 4 cardiac functions. All p values were 2
tailed, and p values ?0.05 were considered significant. Data
storage and analysis were performed using SAS version
9.1e (SAS Institute Inc., Cary, North Carolina).
Results
Five hundred two subjects(267 women, 235 men) were
entered into the study. There was a high prevalence of
hypertension and IHD, as expected in this elderly cohort,
but most patients were in New York Heart Association
functional class I. The cohort in general had elevated LV
mass indexes and left atrial volume indexes, with a normal
mean EF and an elevated E/e= ratio, suggesting significantly
impaired diastolic function.
Of the 502 subjects, 107 (21%) had died at the time of
5-year follow-up. Clinical characteristics of the 2 groups are
listed in Table 1. As expected, compared to survivors, sub-
jects who died had a higher incidence of smoking, CHF,
IHD, diabetes, and renal insufficiency. Echocardiographic
measurements in the 2 groups are listed in Table 2. Subjects
who died had significantly higher left atrial and LV volumes
and LV mass indexes. EFs were significantly lower in sub-
jects who died, but indexes of diastolic function were not
significantly different between the 2 groups.
When parameters were dichotomized, a significantly
higher percentage of nonsurvivors had reduced EFs (54% vs
40%, p ? 0.013) and abnormal LV mass indexes (62.4% vs
50.4%, p ? 0.048). The percentage of patients with or
without elevated E/e= ratios was not significantly different
between the 2 groups. Figure 1 shows Kaplan-Meier curves
depicting cumulative 5-year survival for subjects stratified
into normal and abnormal systolic and diastolic function.
Table 3 lists the unadjusted analysis, which demonstrates
a significantly increasing risk for death with increasing left
atrial volume index as well as with a decreasing EF and
tissue Doppler s-wave velocity. Adjusted Cox proportional-
hazards models were performed controlling for each cardiac
function as well as gender, education, diabetes, IHD, hy-
pertension, kidney diseases, self-rated health, physical ac-
tivity, and body mass index. Higher left atrial volume index,
LV mass index, and tissue Doppler s wave were signifi-
cantly associated with increased mortality. An increasing
E/e= ratio did not predict death in our model. The final
complete model with the mentioned confounders and left
atrial volume index, LV mass index, the LV EF, and E/E=
ratio suggested that the LV EF was the only significant
predictor of mortality in this population. These findings
remained significant when patients with diagnoses of CHF
at baseline were excluded.
Discussion
Our study is the first to demonstrate that elevated left
atrial volume index and LV mass index as well as decreased
LV systolic function predict 5-year mortality in a commu-
nity-dwelling population of subjects aged 85 years. LV
diastolic parameters did not predict mortality in this cohort.
These findings remained significant in patients with and
without diagnoses of CHF at baseline and after correction
for possible confounders.
Several previous studies have examined the prognostic
value of cardiac function as assessed by echocardiography
in a “younger” elderly, community-dwelling population. In
the Cardiovascular Health Study, a community-based study
that enrolled patients aged ?65 years, an abnormal EF was
found to be a significant, independent predictor of 5-year
mortality, a finding consistent with our results.3Among
patients in this cohort with clinical diagnoses of CHF, death
rates were higher in patients with impaired systolic function,
again consistent with our findings.16Other studies examin-
ing a more general population have also demonstrated wors-
ening prognosis with even mildly impaired LV systolic
dysfunction.17,18Mogelvang et al19studied the prognostic
value of tissue Doppler imaging in a community-based
study with a mean age of 59.8 years and demonstrated that
systolic function as assessed by tissue Doppler s wave as
well as the EF was predictive of mortality. Our findings
extend this observation to a very elderly cohort examined at
home.
The prognostic impact of impaired diastolic function in
the community setting has been examined as well, although
again, generally in younger populations than in our study. In
Table 3
Unadjusted and adjusted Cox regression models for selected cardiac measurements
Variable Unadjusted* Adjusted†
Combined Model‡
Measurements of cardiac morphology
Left atrial volume index
LV mass index
Measurements of cardiac systolic function
LV EF
Tissue Doppler septal s wave
Measurement of cardiac diastolic function
E/e= ratio
Data are expressed as hazard ratio (95% confidence interval).
* Adjusted for gender.
†Adjusted for gender, education, diabetes, IHD, hypertension, kidney diseases, self-rated health, physical activity, and body mass index.
‡Additionally adjusted for left atrial volume index, LV mass index, LV EF, and E/E= ratio.
1.03 (1.01–1.042)
1.39 (0.91–2.13)
1.028 (1.012–1.044)
1.008 (1.003–1.014)
1.018 (0.997–1.04)
0.036 (0.006–0.222)
0.83 (0.730–0.947)
0.13 (0.014–1.2)
0.818 (0.703–0.95)
0.06 (0.004–0.974)
1.028 (0.990–1.067)1.033 (0.99–1.08) 1.028 (0.98–1.084)
904
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addition, the published research is limited by different
methodologies used to define abnormal diastolic function.
In the Strong Heart Study, a population-based cohort en-
rolling patients aged 45 to 74 years, findings of mitral
Doppler E/A ratio ?1.5 were independently associated with
an increase in mortality.5Mitral Doppler has well-known
limitations in the assessment of diastolic function, and tis-
sue Doppler analysis was not performed in this study, which
included a broad range of ages. In the community-based
study of Mogelvang et al,19E/e= ratio was not predictive of
mortality, a finding concordant with our study. Severe dia-
stolic dysfunction was shown to be predictive of mortality
in a hospitalized cohort of the very elderly (mean age 86.8
years).6This study enrolled hospitalized patients aged ?70
years with histories of cardiovascular disease and so does
not necessarily reflect the community-based population of
our study. Tissue Doppler was not performed, and E/e=
ratios were not reported.
Several previous studies have described an age-related
decrease in diastolic function.20–25We have previously
demonstrated that this deterioration is present independently
of concomitant cardiovascular morbidity, as evidenced by
the finding of relatively elevated E/e= ratios even in a
healthy subgroup of subjects aged 85 years.25Conversely,
systolic function as assessed by the EF has been shown to be
normal with aging.26Therefore, it seems plausible that
abnormalities of systolic function that are not part of the
innate aging process are associated with mortality in this
age group, while diastolic abnormalities which are more
common are not.
The major strengths of our study are the use of an
age-homogenous cohort to minimize variability of the clin-
ical findings and the use of home echocardiography. Study-
ing patients at home ensures a more representative sample
of this age group. The major limitation is the use of echo-
cardiography in a subset of the total cohort, but this was a
random subgroup, and there were no significant differences
in demographics between the subjects who underwent echo-
cardiography and those who did not, so the chance of
selection bias is minimal. Given baseline differences be-
tween survivors and nonsurvivors, it is possible that the
observed association between echocardiographic findings
and mortality is related to an integrated effect of these
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