Frailty is a biologic syndrome reflecting a state of decreased physiological reserve of increasing importance in cardiovascular disease given the aging of the population. The relation between frailty and indexes of cardiac structure and function remains unclear, particularly in the “oldest old.” The objective of this study was to examine the association between cardiac function and frailty in an age-homogenous, community-dwelling population of subjects aged 85 and 86 years. Subjects were recruited at ages 85 to 86 from the Jerusalem Longitudinal Cohort Study that has followed an age-homogenous cohort of Jerusalem residents. Subjects underwent echocardiography at their place of residence with standard assessment of cardiac structure and function. Frailty was defined according to the “phenotype of frailty” including at least 3 of the following: weakness, slowness, low physical activity level, exhaustion, and weight loss; 405 subjects (193 men and 212 women) were enrolled in the study. Subjects defined as frail had significantly lower ejection fraction compared with the non-frail group (53.7 ± 0.09% vs 56.4 ± 0.09%; p <0.04). In addition, frail subjects had increased LV mass index (130.6 ± 36.2 g/m 2 vs 119.2 ± 31.1 g/m 2 ; p <0.03) and LA volume index (41.9 ± 14.7 cm 3 /m 2 vs 36.7 ± 13.1 cm 3 /m 2 ; p <0.001). Indexes of diastolic function (E/e)’ were not significantly different in the 2 groups (11.5 vs 11.8; p = NS). In this age-homogenous cohort of the oldest old, structural changes and indexes of systolic but not diastolic function were associated with frailty.
People >85 years (the “oldest old”) are the world’s most rapidly growing age group. The aging of the population poses an increasing challenge for cardiovascular care given the high frequency of cardiovascular morbidity and mortality in this population. Frailty is a biologic syndrome reflecting a state of decreased physiological reserve and vulnerability to stressors common in this age group. Observational studies have shown a correlation between frailty and cardiovascular morbidity and mortality, and the presence of frailty has been shown to worsen prognosis in patients with cardiovascular disease. However, few studies have examined whether there are differences in cardiac structure and function in a frail population. Studies that are available have generally included a broad range of ages and have been performed in the hospital or clinic setting, possibly contributing to a biased study population in this elderly age group as subjects find it harder to leave their homes. The aim of this study was to examine the association between indexes of cardiac structure and function and frailty in an age-homogenous, community-dwelling population of subjects born in 1920 and 1921.
Methods
Subjects were recruited from the Jerusalem Longitudinal Cohort Study that was initiated in 1990 and has followed an age-homogenous cohort of West Jerusalem residents born between June 1920 and May 1921. The methodology has been described elsewhere in detail. The present study examines data from the third phase of data collection, which took place during 2005/2006. Subjects identified from the electoral register were randomly chosen from the total sample of people born between 1920 and 1921 and living in Jerusalem in 2005. Subjects were interviewed and examined in their homes on 2 separate occasions, each session requiring the completion of a structured interview that lasted about an hour and a half. The institutional ethics committee of the Hadassah Hebrew University Medical Center approved the study design, and written informed consent was obtained from all participants.
Gender, education (≥12 years schooling), marital status, and smoking were assessed, and body mass index (kg/m 2 ) was calculated. Diagnosis of ischemic heart disease was based on a history of hospitalization for myocardial infarction, or an acute coronary syndrome, coronary catheterization with evidence of a significant coronary artery disease, myocardial infarction on electrocardiogram, a history typical for angina pectoris on exertion, a positive stress test, or previous coronary artery bypass grafting surgery. Hypertension was defined by the study physician as either treatment with antihypertensive medications or an average of 6 measurements of sitting blood pressure >140 mm Hg systolic or 90 mm Hg diastolic. Diabetes mellitus was a composite of anti-diabetic 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.
Frailty was defined based on the presence or absence of 5 criteria as described by Fried et al : (1) “slowness”: the slowest 20% of the sample based on the time taken to get up from a chair without assistance, walk 3 m, turn back, and sit on the same chair adjusted for gender, (2) “weakness”: the lowest 20% of the sample assessed by hand grip that was measured using hand-held dynamometer, (3) “shrinking”: based on unintentional weight loss of >1 kg in the last 3 months, (4) “exhaustion”: determined by self-reported fatigue that was identified using the question “Do you feel generally tired?,” available answers being yes or no, and (5) “low physical activity level”: defined as <4 hours of weekly physical activity. Subjects fulfilling ≥3 criteria were defined as frail.
Subjects had both assessment of frailty and standard 2-dimensional and Doppler echocardiography at their place of residence with a portable echocardiography machine (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 LV end-systolic and end-diastolic diameters according to the recommendations of 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 calculated. LV mass was calculated according to a necropsy-validated formula of 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. Left atrial volumes were calculated at end-systole from the apical 4-chamber view using the area-length method.
Ejection fraction was calculated by measurement of end-diastolic and end-systolic volumes from the apical 4-chamber and apical 2-chamber views using the modified Simpson’s rule method. Normal systolic function was defined as ejection fraction (EF) ≥55%. Diastolic parameters were measured from the apical 4-chamber view using pulse-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′) and late (A′) diastolic mitral annular tissue velocities were obtained and the ratio of E/e’ calculated as an index of diastolic function. Patients with atrial fibrillation were excluded from these measurements.
Descriptive statistics were performed and means, SDs, and percentage were calculated as appropriate. Baseline data were 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 relation between cardiac indexes and frailty, we used multiple logistic regression analysis in 3 separate models: basic model including gender and education and medical models including gender, diabetes, hypertension, and ischemic heart disease or CHF. To each medical model was added either depression or cognitive function. Odds ratios and 95% confidence intervals are presented. The data storage and analysis were performed using SAS, version 9.3 (SAS Institute, Inc., Cary, North Carolina).
Results
Four-hundred five subjects of the cohort had both echocardiographic studies and assessment of frailty, of whom 212 were men and 193 women. Baseline clinical characteristics of the study group are listed in Table 1 . As noted, 17% of the study population met the study definition of frailty. The only demographic characteristic associated with frailty was education. Medical conditions significantly associated with frailty included cognitive impairment, depression, a history of congestive heart failure, and a history of cerebrovascular disease. Echocardiographic findings as continuous variables in the non-frail and frail groups are depicted in Table 2 . Frail subjects had significantly lower EFs and significantly higher left ventricular mass index (LVMI) and left atrial volume index (LAVI). There were no significant differences between the groups in any of the Doppler parameters of diastolic function examined. When subjects were divided into stages of diastolic dysfunction, there were no significant differences between frail and nonfrail subjects.
