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/m 2 , p <0.01) and left ventricular mass indexes (133.1 ± 47.6 vs 119.8 ± 30.6 g/m 2 , 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.
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. Prospective data examining 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 examine prognosis included a broad range of ages, with relatively few patients aged >80 years. In 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. The recent introduction of portable echocardiographic 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 echocardiographic measures of cardiac structure and function performed at subjects’ homes and 5-year mortality in an age-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 Jerusalem residents born from June 1920 and May 1921. The methods have been described elsewhere in detail. In 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, demographic, medical, functional, cultural, and cognitive 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.
Subjects identified from the electoral register were randomly 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 certificates and hospital admission records 3 years after the initiation of the study and compared the study group to other subjects of the sample frame in Jerusalem who either refused or were not invited to enroll in the cohort study. Subjects of the study group, those who declined to participate, and those baseline cohort members not enrolled had near identical mortality and disease-specific hospital morbidity, 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 distributed 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 electrocardiography, a history typical for angina pectoris on exertion, or previous coronary artery bypass grafting surgery. Hypertension 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. Diabetes mellitus was a composite of hypoglycemic medications, personal history, or a medical record diagnosis. Congestive heart failure (CHF) was based on hospital discharge diagnosis and according to examining research physician diagnosis at the time of examination at home. Body mass index was calculated and dichotomized as low (≤25 kg/m 2 ) or high (>25 kg/m 2 ).
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 performed according to a standardized Mini Mental State Examination, with cognitive impairment defined as ≤24 of 30. Dependence in functional class was defined as requiring the help of another individual in ≥1 of the following activities of daily living: eating, dressing, bathing, personal hygiene, toileting, and transfer.
Five hundred two subjects underwent standard 2-dimensional and Doppler echocardiography at their places of residence using a portable echocardiograph (Vivid I; GE Healthcare, Haifa, Israel). All subjects underwent 2-dimensional 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 European Association of Echocardiography and the American Society of Echocardiography. Measurements 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 according to a necropsy-validated formula as LV mass (g) = 0.8 × {1.04 × [(septal thickness + LV internal diameter + posterior wall thickness) − (LV internal diameter) } + 0.6 and indexed to body surface area. Given 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. Measurement 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 fibrillation (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/s .
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. A normal E/e′ ratio was defined as ≤13. Patients with atrial fibrillation were excluded 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 models were adjusted for gender, education, self-rated health, physical activity, diabetes, IHD, hypertension, renal disease, 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, subjects 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 subjects who died, but indexes of diastolic function were not significantly different between the 2 groups.
| Variable | Total Population (n = 502) | Survivors (n = 395) | Nonsurvivors (n = 107) | p Value |
|---|---|---|---|---|
| Men | 46.8% | 45.6% | 51.4% | 0.25 |
| Education (0–12 years) | 51.4% | 54.9% | 38.2% | 0.014 |
| Married | 48.8% | 47.6% | 51.4% | 0.41 |
| Current smokers | 3.4% | 3.6% | 2.9% | 0.72 |
| Former smokers | 37.6% | 25.6% | 44.8% | 0.18 |
| Diabetes mellitus | 19.1% | 15.5% | 32.4% | <0.0001 |
| IHD | 36.8% | 33.6% | 48.6% | 0.0042 |
| Hypertension | 71.3% | 70% | 76.2% | 0.24 |
| Hyperlipidemia | 51% | 52.4% | 45.8% | 0.22 |
| Atrial fibrillation | 4.3% | 3.5% | 6.5% | 0.17 |
| Abnormal renal function (glomerular filtration rate ≤60 ml/min/1.73 m 2 ) | 10.2% | 8.4% | 17.4% | 0.0042 |
| Abnormal Mini Mental State Examination score (≤24/30) | 17.4% | 13.8% | 31.6% | <0.0001 |
| CHF | 11.2% | 7.6% | 24.8% | <0.0001 |
| Dependence in activities of daily living | 28.8% | 20.9% | 58.8% | <0.0001 |
| Poor self-rated health | 31.2% | 26.4% | 50% | <0.0001 |
| Body mass index (kg/m 2 ), mean ± SD | 27.2 ± 4.4 | 27.3 ± 4.4 | 26.7 ± 4.5 | 0.27 |
| New York Heart Association functional class | ||||
| I | 90.7% | 92.1% | 85.7% | 0.0002 |
| II | 7.7% | 7.2% | 9.5% | |
| III | 1.4% | 0.8% | 3.8% | |
| IV | 0.2% | 0% | 1% |
| Variable | Survivors | Nonsurvivors | p Value |
|---|---|---|---|
| Measurements of cardiac morphology | |||
| Left atrial volume index (ml/m 2 ) | 36.6 ± 12.5 | 42.3 ± 16.5 | 0.003 |
| LV end-diastolic volume index (ml/m 2 ) | 67.6 ± 16.8 | 71.6 ± 23.1 | 0.13 |
| LV end-systolic volume index (ml/m 2 ) | 30 ± 12.3 | 35.1 ± 18.3 | 0.016 |
| LV mass index (g/m 2 ) | 119.8 ± 30.6 | 133.1 ± 46.6 | 0.014 |
| Measurements of cardiac systolic function | |||
| LV EF (%) | 56.4 ± 9.4 | 52.5 ± 11.5 | 0.003 |
| Tissue Doppler lateral s wave (cm/s) | 7.8 ± 2 | 7.6 ± 2.4 | 0.38 |
| Tissue Doppler septal s wave (cm/s) | 6.8 ± 1.8 | 6.2 ± 2.2 | 0.025 |
| Measurements of cardiac diastolic function | |||
| Mitral valve E wave (cm/s) | 75.9 ± 20.9 | 79.4 ± 25.1 | 0.22 |
| Mitral valve A wave (cm/s) | 90.2 ± 24.2 | 87.3 ± 25.6 | 0.33 |
| E/A ratio | 0.97 ± 1.1 | 1.1 ± 0.7 | 0.17 |
| Deceleration time (m/s) | 207.4 ± 63.8 | 191.1 ± 71.4 | 0.034 |
| Tissue Doppler lateral E wave (cm/s) | 7.2 ± 2.1 | 7.2 ± 2.5 | 0.99 |
| Tissue Doppler lateral A wave (cm/s) | 10.2 ± 3.2 | 8.8 ± 4 | 0.0025 |
| Tissue Doppler septal E wave (cm/s) | 6.1 ± 2 | 5.8 ± 2.1 | 0.18 |
| Tissue Doppler septal A wave (cm/s) | 8.3 ± 2.6 | 7.8 ± 3.2 | 0.14 |
| E/E′ ratio | 12.2 ± 4.9 | 13 ± 5.3 | 0.18 |
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