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Cardiac Structure and Function and Dependency in the Oldest Old David Leibowitz, MD, Jeremy M. Jacobs, MD,w Irit Stessman-Lande,w Aharon Cohen, MD,w Dan Gilon, MD, Eliana Ein-Mor, MA,w and Jochanan Stessman, MDw

OBJECTIVES: To examine the association between cardiac function and activities of daily living (ADLs) in an agehomogenous, community-dwelling population born in 1920 and 1921. DESIGN: Cross-sectional analysis of a prospective cohort study. SETTING: Community-dwelling elderly population. PARTICIPANTS: Participants were recruited from the Jerusalem Longitudinal Cohort Study, which has followed an age-homogenous cohort of Jerusalem residents born in 1920 and 1921. Four hundred eighty-nine of the participants (228 male, 261 female) from the most recent set of data collection in 2005 and 2006 underwent echocardiography at their place of residence in addition to structured interviews and physical examination. MEASUREMENTS: A home-based comprehensive assessment was performed to assess health and functional status, including performance of ADLs. Dependence was defined as needing assistance with one or more basic ADLs. Standard echocardiographic assessment of cardiac structure and function, including ejection fraction (EF) and diastolic function as assessed using early diastolic mitral annular tissue velocity measurements obtained using tissue Doppler, was performed. RESULTS: Of the participants with limitation in at least one ADL, significantly more had low EF (o55%) than the group that was independent (52.6 % vs 39.1%; P 5.01). In addition, participants with dependence in ADL had higher left ventricular mass index (LVMI) (129.3 vs 119.7 g/m2) and left atrial volume index (LAVI) (41.3 vs 36.7 mL/m2). There were no differences between the groups in percentage of participants with impaired diastolic function or average ratio of early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity (11.5 vs 11.8; P 5.64).

From the Heart Institute and wDepartment of Geriatrics and Rehabilitation, Hadassah-Hebrew University Medical Center and Hebrew University Hadassah Medical School, Jerusalem, Israel. Address correspondence to David Leibowitz, Coronary Care Unit, HadassahHebrew University Medical Center, Mount-Scopus, Jerusalem 91240, Israel. E-mail: oleibo@hadassah.org.il DOI: 10.1111/j.1532-5415.2011.03534.x

JAGS 59:1429–1434, 2011 r 2011, Copyright the Authors Journal compilation r 2011, The American Geriatrics Society

CONCLUSION: In this age-homogenous cohort of the oldest old, high LVMI and LAVI and indices of systolic but not diastolic function as assessed according to Doppler were associated with limitations in ADLs. J Am Geriatr Soc 59:1429–1434, 2011.

Key words: oldest old; echocardiography; activities of daily living; ventricular function

P

eople aged 85 and older (the ‘‘oldest old’’) are the world’s most rapidly growing age group, and many of the oldest old experience significant disability, with high social and economic costs.1–3 Identifying potentially treatable predictors of functional decline is important to assist in designing preventive strategies. This population has a high frequency of cardiovascular morbidity, which presumably affects disability, and mortality.4 Most previous studies addressing disability in the oldest old focus on diseases and social factors and not on measures of cardiac function.5–9 Studies of cardiac function using echocardiography performed in the geriatric population have generally included a broad range of ages and been performed in the hospital or clinic setting, possibly contributing to a biased study population in this age group because older adults find it harder to leave their homes.10–12 The recent introduction of portable echocardiography machines has made it possible to study people in the home and thereby include a more-representative population of the oldest old. The aim of this study was to examine the association between indices of cardiac structure and function and disability in an age-homogenous, community-dwelling population of participants born in 1920 and 1921.

METHODS Study Population Participants were recruited from the Jerusalem Longitudinal Cohort Study, which was initiated in 1990 and has followed an age-homogenous cohort of West Jerusalem residents born between June 1920 and May 1921. The

0002-8614/11/$15.00


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methodology has been described elsewhere in detail.13,14 The present study examines data from the third-most-recent phase of data collection, which took place during 2005/06. Participants identified from the electoral register were randomly chosen from the total sample of people born in 1920 and 1921 and living in Jerusalem in 2005. Participants were interviewed and examined in their homes on two separate occasions, each session requiring the completion of a structured interview that lasted approximately 1.5 hours. Information was collected from sociodemographic, medical, functional, and cultural domains. The institutional ethics committee of the Hadassah Hebrew University Medical Center approved the study design, and written informed consent was obtained from all participants. Sex, education, and marital status were assessed, and body mass index was calculated. Diagnosis of ischemic heart disease (IHD) was based on a history of hospitalization for myocardial infarction (MI), acute coronary syndrome, coronary catheterization with evidence of significant coronary artery disease, MI on electrocardiogram, a history typical for angina pectoris on exertion, a positive stress test, or previous percutaneous revascularization or coronary artery bypass surgery. The examining physician generally defined hypertension as treatment with antihypertensive medications or blood pressure higher than 140 mmHg systolic or 90 mmHg diastolic on examination. Diabetes mellitus (DM) was determined according to a composite of hypoglycemic medications, personal history, and a medical record diagnosis. Congestive heart failure (CHF) was determined according to hospital discharge diagnosis and according to the diagnosis of the examining research physician at the time of the home examination. Self-related health was assessed according to the question ‘‘How do you rate your health compared with others your age?’’ A cognitive assessment was performed according to a standardized Mini-Mental State Examination (MMSE), with cognitive impairment defined as a score of 24 or less out of 30.15 Dependence in functional status was defined as requiring the help of another person in one or more of the following activities of daily living (ADLs): eating, dressing, bathing, personal hygiene, toileting, and transfer.16

Echocardiography Participants had assessment of ADLs and standard twodimensional (2-D) and Doppler echocardiography at their place of residence using a portable echocardiograph (Vivid I, GE Healthcare, Haifa, Israel). All participants underwent 2-D and Doppler echocardiography with m-mode measurements of the interventricular septum, posterior wall, and left ventricular (LV) end-systolic and end-diastolic diameters according to the recommendations of the American Society of Echocardiography.17 Participants with inadequate visualization of the endocardium in apical views were excluded from assessment of ejection fraction (EF). Measurements were performed for three consecutive cardiac cycles and averaged. Participant height and weight at the time of the study were recorded and body surface area calculated. LV mass was calculated according to a necropsy-validated formula of LV mass (g) 5 0.8  (1.04  ((septal thickness1LV internal diameter1posterior wall

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thickness)3  (LV internal diameter)3))10.6 and indexed to body surface area (BSA).18 The presence of LV hypertrophy was defined as a LV mass index (LVMI) greater than 125 g/ m2 in men and 110 g/m2 in women.19 Four hundred twentytwo participants had technically adequate measurement of LVMI. Left atrial volumes were calculated at end-systole from the apical four-chamber view using the area–length method and indexed to BSA.20 EF was calculated by measuring end-diastolic and endsystolic volumes from the apical four-chamber view using the area–length method. Four hundred participants (82%) had technically adequate measurement of EF. Normal systolic function was defined as EF of 55% or greater. Diastolic parameters were measured from the apical four-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), deceleration time of E velocity, and isovolumic relaxation time. Early (e 0 ) and late (a 0 ) diastolic mitral annular tissue velocities were obtained and the ratio of E:e 0 calculated as an index of diastolic function.21–23 Normal E:e 0 was defined as 13 or less.24 Participants with atrial fibrillation were excluded from these measurements; 423 participants had adequate E:e 0 measurements.

Data Analysis Descriptive statistics were performed, and means, standard deviations, and percentages were calculated as appropriate. Baseline data was examined using chi-square tests for univariate analysis of categorical variables and the t-test for continuous variables. To control for confounding when analyzing the relationship between cardiac indices and ADLs, multiple logistic regression analysis was used with sex, history of hypertension, diabetes mellitus, ischemic heart disease, history of peripheral vascular or cerebrovascular disease, chronic obstructive pulmonary disease, renal function, New York Heart Association (NYHA) class, MMSE score, depression, education level, comorbidity index, and self-rated health assessment as covariates. Odds ratios (ORs) and 95% confidence intervals are presented. The data storage and analysis was performed using SAS version 9.1e (SAS Institute, Inc., Cary, NC). RESULTS Of the 489 participants, 228 were male and 261 female. Baseline clinical characteristics of the study group are noted in Table 1. The average body mass index of the cohort was 27.1 kg/m2, slightly lower than that noted in other Western populations but consistent with previous data reported in the Israeli population.25 One-third of the study population exhibited dependence in at least one ADL (Table 1). Echocardiographic findings in the cohort as a whole and in the independent and dependent groups are depicted as categorical and continuous variables in Tables 2 and 3. Participants with dependence in ADLs had a significantly lower LVEF than participants who were independent in ADLs (52.5% vs 56.9%; Po.001). In addition, dependant participants had significantly higher LVMI and LAVI. There were no significant differences between the groups in any of the Doppler parameters of diastolic function examined.


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Table 1. Baseline Characteristics of the Whole Group n (%)

Characteristic

Total (N 5 489)

Independent (n 5 348, 71.2%)

Dependent (n 5 141, 28.8%)

P-Value

Male Education 0–12 years Married Pack-years of smoking, mean  SD Diabetes mellitus Ischemic heart disease Hypertension Glomerular filtration rate 60 mL/min Cerebrovascular disease Peripheral vascular disease Chronic obstructive pulmonary disease Depression Mini-Mental State Examination score 24 Poor visual acuity Poor hearing High comorbidity index (43) Dependent Dressing Toileting Bathing Eating Incontinence Self-rated health poor Body mass index, kg/m2 mean  SD New York Heart Association class 1 (not symptomatic) 2 (symptoms with normal activity) 3 (symptoms with minimal activity) 4 (symptoms at rest)

228 (46.6) 233 (47.7) 236 (48.7) 8.3  19.6 90 (18.4) 177 (36.2) 350 (71.6) 50 (10.2) 76 (15.5) 56 (11.5) 24 (4.9) 127 (26.9) 82 (17.3) 199 (41.7) 324 (66.5) 100 (20.5)

172 (49.4) 144 (41.4) 178 (51.5) 3.9  13.3 54 (15.5) 58 (41.1) 248 (71.3) 28 (8.1) 34 (9.8) 30 (8.6) 4 (14) 18 (62) 49 (19.4) 121 (34.9) 219 (62.9) 50 (14.4)

56 (39.7) 89 (63.1) 58 (41.7) 13.9  24.6 36 (25.5) 119 (34.2) 102 (72.3) 22 (15.6) 42 (29.8) 26 (18.4) 10 (7.1) 65 (50.8) 33 (14.9) 78 (60.0) 105 (75.5) 50 (35.5)

.05 o.001 .05 o.001 .01 .15 .81 .01 o.001 .002 .15 o.001 .20 o.001 .008 o.001

92 (18.8) 43 (8.8) 132 (27.0) 63 (12.9) 55 (11.3) 147 (30.8) 27.1  4.4

51 (19.5) 25 (9.6) 83 (31.8) 13 (34) 32 (12.3) 93 (36.6) 27.4  4.8

41 (18.0) 18 (7.9) 49 (21.5) 29 (12.7) 23 (10.1) 54 (24.1) 26.8  3.9

.66 .51 .01 .92 .45 .003 .15

443 (90.8) 38 (7.8) 6 (1.2) 1 (0.2)

329 (94.8) 16 (4.6) 2 (0.6) 0 (0.0)

114 (80.9) 22 (15.6) 4 (2.8) 1 (0.7)

o.001

SD 5 standard deviation.

For participants dependent in at least one ADL, there were no significant differences in EF, E:e 0 or LVMI between those with hypertension alone; hypertension and diabetes mellitus; or hypertension, diabetes mellitus, and ischemic heart disease. When echocardiographic parameters were assessed categorically, a significantly larger number of participants with dependence in ADLs had an abnormal EF (52.6% vs 39.1%; P 5.01) (Table 3). Although absolute numbers were low, as demonstrated in Table 3, when EF was less than 45%, the relative difference in percentage of dependent participants and independent participants was greater (20.7% vs. 9.8%). There was a trend toward more participants in the dependent group with LV hypertrophy. Because 90% of the participants had a high LAVI, these dichotomous data are not presented. There were no significant differences between the dependent and independent groups in the numbers of participants with abnormal diastolic function as assessed by measurement of E:e 0 . When the population was subdivided into four groupsFnormal systolic and diastolic function, abnormal systolic and diastolic function, normal systolic and abnormal diastolic

function, and abnormal systolic and normal systolic functionFthere were no significant differences between groups, a finding that may be because of the small sample size. Multiple logistic regression analysis was performed with LVEF, E:e 0 , LVMI, and LAVI as independent variables to examine the association between cardiac function and ADLs. The association between LVEF and ADL was statistically significant (P 5.02) after controlling for sex, history of hypertension, diabetes mellitus, ischemic heart disease, history of peripheral vascular or cerebrovascular disease, chronic obstructive pulmonary disease, renal function, NYHA class, MMSE score, depression, education level, and self-rated health assessment. The addition of a comorbidity index to the model instead of individual diseases did not influence the findings. The results of the unadjusted and adjusted models are shown in Table 4.

DISCUSSION This study examined for the first time the relationship between cardiac morphology, systolic and diastolic function, and dependence in ADLs in a representative sample of a


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Table 2. Echocardiographic Measurements in the Subgroups Mean  Standard Deviation Measurement

Cardiac morphology LA volume index, mL/m2 LV end diastolic volume index, mL/m2 LV end systolic volume index, mL/m2 LV mass index, g/m2 Cardiac systolic function LV ejection fraction, % Tissue Doppler lateral S wave, cm/s Tissue Doppler septal S wave, cm/s Cardiac diastolic function Mitral valve E wave, cm/s Mitral valve A wave, cm/s E/A ratio Deceleration time, ms 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 Ratio of early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity

Independent

Dependent

P-Value

36.7  13.4 67.5  17 29.7  12.6 119.7  30.9

41.3  14.3 70.5  21.7 34.4  16.5 129.3  42.9

.004 .22 .01 .03

56.9  9.5 7.8  2 6.7  1.8

52.5  10.6 7.8  2.4 6.7  2.2

o.001 .94 .92

76.2  21.4 90.0  23.8 1.0  1.1 207.8  65.2 7.2  2.1 10.0  3.3 6.1  1.9 8.3  2.6 11.5  5.2

78.1  23.2 89.8  26.7 1.0  0.6 196.9  64.5 7.2  2.4 9.6  3.8 5.9  2.2 8.0  3.2 11.8  4.8

.40 .96 .80 .11 .87 .29 .48 .35 .64

LA 5 left atrial; LV 5 left ventricular.

community-dwelling cohort aged 85 to 86. These clinical findings correlated closely with those recently reported in a similar cohort of people born in 1920 and 1921 in Britain.5 This study demonstrates an association between high LVMI, high LAVI, and systolic but not Doppler diastolic dysfunction and ADL dependence in this age group. Few previous studies have examined the relationship between impaired ADL performance and cardiac function

Table 3. Echocardiographic Measurements Dichotomized

as assessed using echocardiography. One examined 171 participants aged 70 and older and found greater disability in participants with a low EF as measured according to m-mode echocardiography,11 findings consistent with the results of the current study. Diastolic function was not assessed in that study. Another study examined 81 nonagenarians who were able to visit the study center using echocardiography.12 There was no effect of valvular disease on functional status. The authors did not report on the association between disability and systolic or diastolic function. Previous studies in elderly populations have demonstrated an age-related increase in LVMI with preserved EF and impaired diastolic function.26–29 The reduction in

n (%) Echocardiographic Measurement

Independent

Dependent

P-Value

Table 4. Results of Unadjusted and Adjusted Models

Ejection fraction, % 55 173 (60.9) 55 (47.4) .01 45–54 83 (29.2) 37 (31.9) 35–44 20 (7.0) 17 (14.7) o35 8 (2.8) 7 (6.0) Ratio of early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity 13 198 (66.0) 73 (59.4) .20 0–8 69 (23.0) 21 (17.1) .35 9–14 173 (57.7) 79 (64.2) 15 58 (19.3) 23 (18.7) Left ventricular mass index, g/m2 125 (men) 155 (50.2) 45 (39.8) .06 110 (women)

Hazard Ratio (95% Confidence Interval) Measurement

Unadjusted

Adjustedw

Ejection fraction (normal/abnormal) Ratio of early transmitral flow velocity to early diastolic mitral annular tissue velocity Left ventricular mass index Left atrial volume index

1.80 (1.15–2.80) 1.20 (0.77–1.86)

2.17 (1.21–3.87) 0.99 (0.57–1.72)

1.42 (0.91–2.21) 1.03 (1.01–1.05)

0.96 (0.53–1.74) 1.98 (0.61–6.46)

 Adjusted for sex. w

Adjusted for sex, history of hypertension, diabetes mellitus, ischemic heart disease, history of peripheral vascular or cerebrovascular disease, chronic obstructive pulmonary disease, renal function, New York Heart Association class, Mini-Mental State Examination score, depression, education, comorbidity index, and self-rated health assessment.


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myocardial relaxation seen with aging is progressive and unrelated to underlying cardiovascular morbidities.30 Reduced myocardial contraction in this population is not a purely age-related phenomenon but rather is reflective of underlying cardiac pathology and, therefore when present, may lead to worse disability, as seen in our cohort. The finding of high LVMI in the dependent group suggests but does not establish that maladaptive hypertrophy may be related to impaired systolic function in this cohort. Although clinical presentations of CHF due to systolic and diastolic dysfunction are similar, there are differences in causes of mortality in these two participant populations, suggesting that the two forms of CHF may have different clinical outcomes.31 The association between impaired EF and functional disability remained significant even when corrected for concomitant cardiovascular disease, suggesting that it is the reduction in contractile function itself that interferes with performance of ADLs. The finding of high LAVI in the dependent group is consistent with the high LVMI and impaired systolic function, because previous studies have suggested that left atrial size is a reflection of chronically high LV diastolic pressure.32 The major strengths of the current study are the use of an age-homogenous cohort to minimize variability of the clinical findings and the use of home echocardiography. Previous studies using echocardiography in the oldest old population examined participants in the hospital setting, introducing significant bias. Studying people at home ensures a more-representative sample of this age group, particularly when evaluating things such as functional impairment, given that dependent individuals are presumably less likely to participate in studies outside the home. The major limitation is the use of echocardiography in a subset of the total cohort, but this was a random subgroup, and there were no significant differences in demographics such as sex, diabetes mellitus, hypertension, and ischemic heart disease between participants who underwent echocardiography and those who did not, so that the chance of selection bias is minimal. Another limitation is the crosssectional nature of the data, which prevents conclusions regarding changes over time in the variables studied. In this cohort of the oldest old, systolic but not diastolic dysfunction as assessed using Doppler was associated with functional disability.

ACKNOWLEDGMENTS This work was supported by funds from the Ministry of Labor and Social Affairs of the State of Israel; EshelFthe Association for the Planning and Development of Services for the Aged in Israel; The National Insurance Institute; and various private, charitable donors. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Leibowitz, Stessman, Gilon, and Jacobs conceived and designed the study, acquired and analyzed the data, and drafted or revised the manuscript. Landi-Stessman designed the study and acquired and analyzed the echocardiographic data. Cohen and Ein-Mor designed the study, analyzed the data and revised the

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manuscript. All authors approved the final version of the manuscript. Sponsor’s Role: None of the funding agencies had any role in any aspects of the study or in the preparation of the manuscript.

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29. Masoudi FA, Havranek EP, Smith G et al. Gender, age and heart failure with preserved left ventricular systolic function. J Am Coll Cardiol 2003;41:217–223. 30. Shan K, Bick RJ, Poindexter BJ et al. Relation of tissue Doppler derived myocardial velocities to myocardial structure and beta adrenergic receptor density in humans. J Am Coll Cardiol 2000;36:891–896. 31. Curtis JP, Sokol SI, Wang Y et al. The association of left ventricular ejection fraction, mortality and cause of death in stable patients with heart failure. J Am Coll Cardiol 2003;42:736–742. 32. Aurigemma GP, Gottdiener JS, Arnold AM et al. Left atrial volume and geometry in healthy aging: The Cardiovascular Health Study. Circ Cardiovasc Imag 2009;2:282–289.


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