Association of body size metrics with left atrial phasic volumes and reservoir function in the elderly

Association of body size metrics with left atrial phasic volumes and reservoir function in the... Abstract Aims General obesity, defined by increased body mass index (BMI), is associated with left atrial (LA) enlargement, a marker of cardiovascular risk in the general population. The association between abdominal adiposity, defined by increased waist circumference (WC) or waist-to-hip ratio (WHR), and LA phasic volumes and reservoir function is not well known. The aim of this study was to evaluate the association between different body size metrics and LA phasic volumes and reservoir function in the elderly. Methods and results Participants from the CABL (Cardiovascular Abnormalities and Brain Lesions) study underwent measurement of BMI, WC, and WHR. The LA maximum (LAVmax) and minimum (LAVmin) volumes, and LA reservoir function, measured as total emptying volume index (LAEVI), total emptying fraction (LAEF), and expansion index (LAEI), were assessed by real-time 3D echocardiography. The study population included 629 participants (mean age 71 ± 9 years, 61% women). Mean BMI was 27.9 ± 4.6 kg/m2, WC was 95.0 ± 11.7 cm, WHR was 0.91 ± 0.08. After adjusting for multiple potential confounders (demographics, cardiovascular risk factors, left ventricular mass index, and diastolic function), higher WC was significantly associated with higher LA phasic volumes (LAVmax, β = 0.10, P = 0.007 and LAVmin, β = 0.12, P = 0.002) and reduced reservoir function (LAEVI, β = −0.15, P = 0.001 and LAEI, β = −0.09, P = 0.027). WHR was significantly associated only with reduced reservoir function (LAEVI, β = −0.11, P = 0.012), whereas BMI was not associated with either LA phasic volumes or reservoir function. Conclusion In the elderly, WC may have more impact on LA phasic volumes and reservoir function, and therefore risk for cardiovascular events, than WHR and BMI. left atrial volume , reservoir function , three-dimensional echocardiography , obesity , abdominal adiposity Introduction Analysis of population-based studies suggests that obesity is the main risk factor for left atrial (LA) enlargement during aging.1 Increased LA size is associated with higher mortality and cardiovascular events.2 The strength of the association between LA remodelling and cardiovascular risk in various clinical studies is influenced by the characteristics of the studied population, and the method used to evaluate LA enlargement. Among different measures of LA size, LA volume has shown the strongest association with adverse outcomes.3 Growing evidence suggests that the analysis of LA volume in different phases of the cardiac cycle (LA phasic volumes) may provide additional, clinically relevant information regarding LA remodelling and dysfunction.4 The introduction of real-time 3D (RT3D) echocardiography has made it possible to measure the change in LA volume throughout the cardiac cycle, and to assess the LA reservoir function which have been identified as important predictors of atrial fibrillation (AF) occurrence, and of its recurrence after catheter ablation, in overweight/obese patients.5 Body mass index (BMI) has been identified as an independent predictor of LA size in adults.1 Recent studies have shown that measures of abdominal adiposity such as waist circumference (WC) and waist-to-hip ratio (WHR), which take into account body fat distribution, may be more important for prognosis than general obesity measured by BMI.6 WC is strongly associated with cardiovascular risk factors and metabolic abnormalities, and is a strong predictor of incident cardiovascular events, especially in the elderly.7 Previously, we looked at the association of general and abdominal adiposity with subclinical left ventricular (LV) systolic dysfunction in the elderly.8 Abdominal adiposity was independently associated with subclinical LV systolic dysfunction in all BMI categories (normal, overweight, or obese), whereas BMI was not associated with LV dysfunction. More recently, another study found that abdominal adiposity is associated with several measures of impaired LV systolic and diastolic functions, independent of BMI, and even in non-obese individuals.9 Most studies that looked into the relationship between obesity and LA enlargement used BMI as an indicator of obesity. One recent study found and association between LA dilatation and visceral adiposity in the general population, however it is not known whether, and to what extent, parameters of LA volume and function are associated with abdominal adiposity in the elderly population.10 The aim of this study was to investigate the relationships of LA phasic volumes and reservoir function measured by RT3D echocardiography with the presence of general obesity, quantified by BMI, and abdominal adiposity, quantified by WC and WHR. Methods Study population The study population was derived from the CABL (Cardiac Abnormalities and Brain Lesion) Study, a community-based epidemiological study whose primary aim was to investigate the possible cardiac predictors of silent brain disease in the community. The CABL study based its recruitment on the NOMAS (Northern Manhattan Study), a population-based prospective study that enrolled 3298 participants from the community living in northern Manhattan between 1993 and 2001. The study design and recruitment details of NOMAS have been described previously.11 Participants were invited to participate in an MRI sub-study beginning in 2003 and were eligible for the MRI cohort if they: (i) were at least 55 years of age; (ii) had no contraindications to MRI; and (iii) did not have a prior diagnosis of stroke. From September 2005 to July 2010, NOMAS MRI participants who voluntarily agreed to undergo a more extensive cardiovascular evaluation were included in the CABL study. The 1004 CABL participants underwent transthoracic echocardiography, and 854 had complete datasets for RT3D, 148 of whom were excluded because of suboptimal image quality for LA volume measurements. Subjects with a history of AF, LV ejection fraction < 50% and more than mild mitral regurgitation were also excluded from the study, leading to a final study sample of 629 participants. Written informed consent was obtained from all study participants. The study was approved by the institutional review boards of Columbia University Medical Center and of the University of Miami. Risk factors and body size assessment Cardiovascular risk factors were ascertained through direct examination and interview by trained research assistants. Hypertension was defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, or use of antihypertensive medication. Diabetes mellitus was defined as fasting blood glucose ≥126 mg/dL or use of diabetes medications. Hypercholesterolemia was defined as total serum cholesterol >240 mg/dL, or use of lipid-lowering treatment. Cigarette smoking, either at the time of the interview or in the past, was recorded. Coronary artery disease was defined as history of myocardial infarction, coronary artery bypass grafting, or percutaneous coronary intervention. The race–ethnicity classification was based on self-identification, and modelled after the US Census. Height and weight were measured using a standard scale. The BMI was calculated as weight (kg) divided by height (m) squared. Waist and hip circumferences were measured using flexible measuring tape with participants standing and relaxed without outer garments. The WC was measured at the level of the umbilicus, and hip circumference was measured at the level of the greater trochanters. Echocardiography Transthoracic echocardiography was performed using a commercially available system (iE 33; Philips, Andover, MA, USA) by a trained, registered cardiac sonographer according to a standardized protocol. The LV dimensions were measured from a parasternal long-axis view according to the recommendations of the American Society of Echocardiography,12 and LV mass was calculated with a validated method13 and indexed by body surface area. LV ejection fraction was calculated using the biplane modified Simpson’s rule. In addition, LV diastolic function was assessed from the apical four-chamber view by means of the peak early velocity (E) of the transmitral flow and the early diastolic velocity (e′) of the mitral annulus (average of septal and lateral site) by pulsed-wave tissue-Doppler, as described previously.14 The ratio E/e′ was calculated as an indicator LV diastolic function and filling pressure. LA phasic volume measurements were performed by RT3D echocardiography. A full volume loop was acquired from an apical window using an X3-1 matrix array transducer over four cardiac cycles. Measurements of 3D LA volumes were performed offline using commercially available software (QLAB Advanced Quantification software, V.8.1, Philips). A detailed description of the technique has been reported previously.15 Briefly, five anatomical landmarks (septal, lateral, anterior and inferior mitral annulus, and posterior wall of the LA) were manually identified by the operator, semi-automated border detection was performed by the software, and LA borders were tracked throughout the entire cardiac cycle (Figure 1). Manual correction on all possible 3D planes was performed by the reader in case of inaccurate endocardial automated detection. The parameters of LA size and function included in our analyses were: Figure 1 View largeDownload slide Left atrial phasic volumes by real-time 3D echocardiography. Arrows indicate LAVmax and LAVmin. Figure 1 View largeDownload slide Left atrial phasic volumes by real-time 3D echocardiography. Arrows indicate LAVmax and LAVmin. LA minimum volume (LAVmin): LA end-diastolic volume at the first frame after mitral valve closure. LA maximum volume (LAVmax): LA end-systolic volume right before mitral valve opening. LA total emptying volume index (LAEVI): LAVmax − LAVmin/body surface area. LA total emptying fraction (LAEF): 100 × (LAVmax − LAVmin)/LAVmax. LA expansion index (LAEI): 100 ×  (LAVmax − LAVmin)/LAVmin. Statistics Data are presented as mean ± standard deviation for continuous variables and as percentage for categorical variables. BMI, WC, and WHR were categorized in quintiles of the observed distribution, and one-way analysis of variance was used to compare the differences between mean values of LA volumes (LAVmax and LAVmin) and LA reservoir function (LAEVI, LAEF, and LAEI) across the groups. Linear regression analysis was used to assess the association of parameters of LA volume and LA reservoir function with body size measures, and unstandardized (B) and standardized (β) parameter estimates and standard errors (SE) were reported. Linear regression models were used to determine whether BMI, WC or WHR were associated with LA volumes and LA reservoir function when simultaneously entered into the same model (BMI with WC, and WHR with BMI). Covariates adjusted in multivariate models were selected based on their univariate association with body size metrics at significance level P < 0.1. For all statistical analyses, a two-tailed P < 0.05 was considered significant. Statistical analyses were performed using IBM SPSS Statistics software version 22 (IBM Corp., Armonk, NY, USA). Reproducibility of LA volumes Reproducibility of LA volume measurements was assessed in 15 randomly selected subjects. LAVmin and LAVmax were remeasured by the original reader (CR) and by a second reader experienced in 3D echocardiography (AT) in a blinded fashion. Intra-observer ICC intra-class correlation coefficients were 0.96 for LAVmin [95% confidence intervals (CI): 0.88–0.99] and 0.94 for LAVmax (95% CI: 0.85–0.98). The mean difference between two measurements was 0.23 ± 3.17 ml for LAVmin (P = 0.78) and 0.74 ± 4.05 mL for LAVmax (P = 0.49). Inter-observer ICC intra-class correlation coefficients were 0.94 for LAVmin (95% CI: 0.85–0.98) and 0.95 for LAVmax (95% CI: 0.86–0.98). The mean difference between two measurements was 0.78 ± 4.02 mL for LAVmin (P = 0.46) and 0.92 ± 4.53 mL for LAVmax (P = 0.45). Results Clinical characteristics Demographics and clinical characteristics of study participants and associations with BMI, WC, and WHR are reported in Table 1. The study population consisted of 629 participants (mean age 70.6 ± 9.2 years, 60.6% women). Mean BMI was 27.9 ± 4.6 kg/m2, mean WC was 95.0 ± 11.7 cm, and mean WHR was 0.91 ± 0.08. BMI showed a good correlation with WC (β = 0.71, P < 0.001), whereas its correlation with WHR was weaker although statistically significant (β = 0.09, P = 0.02). Table 1 Demographics and clinical characteristics of the study population and univariate relationships with body size metrics   N = 629  BMI   WC   WHR       β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  Age (years)  70.6 ± 9.2  −0.14 (0.08)  0.001  0.01 (0.03)  0.72  0.07 (4.50)  0.09  Woman, n (%)  381 (60.6)  0.16 (0.004)  <0.001  −0.36 (0.002)  <0.001  −0.36 (0.22)  <0.001  BMI, kg/m2  27.9 ± 4.6      0.71 (0.01)  <0.001  0.09 (2.25)  0.02  WC, cm  95.0 ± 11.7  0.71 (0.01)  <0.001      0.57 (4.68)  <0.001  WHR  0.91 ± 0.08  0.09 (2.25)  0.02  0.57 (4.68)  <0.001      Race-ethnicity   White (%)  85 (13.5)  Ref.  Ref.  Ref.   African Americans, n (%)  92 (14.6)  0.11 (0.69)  0.03  0.03 (1.75)  0.56  −0.04 (0.01)  0.42   Hispanics, n (%)  439 (69.8)  0.20 (0.54)  <0.001  0.06 (1.38)  0.27  0.006 (0.01)  0.92   Other, n (%)  13 (2.1)  −0.005 (1.37)  0.91  −0.05 (3.47)  0.29  −0.05 (0.02)  0.21  Hypertension, n (%)  484 (77.0)  −0.19 (0.004)  <0.001  0.19 (0.001)  <0.001  0.12 (0.20)  0.003  Anti-hypertensive medication, n (%)  441 (70.1)  0.18 (0.004)  <0.001  0.18 (0.002)  <0.001  0.11 (0.22)  0.005  Diabetes mellitus, n (%)  175 (27.8)  0.15 (0.004)  <0.001  0.16 (0.002)  <0.001  0.08 (0.23)  0.05  Hypercholesterolaemia, n (%)  408 (64.9)  0.09 (0.004)  0.02  0.05 (0.002)  0.214  0.04 (0.23)  0.35  Coronary artery disease, n (%)  33 (5.3)  0.07 (0.002)  0.09  0.15 (0.001)  <0.001  0.12 (0.11)  0.003  Smoking history, n (%)  332 (52.8)  −0.09 (0.004)  0.02  0.001 (0.002)  0.99  0.07 (0.24)  0.07    N = 629  BMI   WC   WHR       β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  Age (years)  70.6 ± 9.2  −0.14 (0.08)  0.001  0.01 (0.03)  0.72  0.07 (4.50)  0.09  Woman, n (%)  381 (60.6)  0.16 (0.004)  <0.001  −0.36 (0.002)  <0.001  −0.36 (0.22)  <0.001  BMI, kg/m2  27.9 ± 4.6      0.71 (0.01)  <0.001  0.09 (2.25)  0.02  WC, cm  95.0 ± 11.7  0.71 (0.01)  <0.001      0.57 (4.68)  <0.001  WHR  0.91 ± 0.08  0.09 (2.25)  0.02  0.57 (4.68)  <0.001      Race-ethnicity   White (%)  85 (13.5)  Ref.  Ref.  Ref.   African Americans, n (%)  92 (14.6)  0.11 (0.69)  0.03  0.03 (1.75)  0.56  −0.04 (0.01)  0.42   Hispanics, n (%)  439 (69.8)  0.20 (0.54)  <0.001  0.06 (1.38)  0.27  0.006 (0.01)  0.92   Other, n (%)  13 (2.1)  −0.005 (1.37)  0.91  −0.05 (3.47)  0.29  −0.05 (0.02)  0.21  Hypertension, n (%)  484 (77.0)  −0.19 (0.004)  <0.001  0.19 (0.001)  <0.001  0.12 (0.20)  0.003  Anti-hypertensive medication, n (%)  441 (70.1)  0.18 (0.004)  <0.001  0.18 (0.002)  <0.001  0.11 (0.22)  0.005  Diabetes mellitus, n (%)  175 (27.8)  0.15 (0.004)  <0.001  0.16 (0.002)  <0.001  0.08 (0.23)  0.05  Hypercholesterolaemia, n (%)  408 (64.9)  0.09 (0.004)  0.02  0.05 (0.002)  0.214  0.04 (0.23)  0.35  Coronary artery disease, n (%)  33 (5.3)  0.07 (0.002)  0.09  0.15 (0.001)  <0.001  0.12 (0.11)  0.003  Smoking history, n (%)  332 (52.8)  −0.09 (0.004)  0.02  0.001 (0.002)  0.99  0.07 (0.24)  0.07  BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; SE, standard error. Table 1 Demographics and clinical characteristics of the study population and univariate relationships with body size metrics   N = 629  BMI   WC   WHR       β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  Age (years)  70.6 ± 9.2  −0.14 (0.08)  0.001  0.01 (0.03)  0.72  0.07 (4.50)  0.09  Woman, n (%)  381 (60.6)  0.16 (0.004)  <0.001  −0.36 (0.002)  <0.001  −0.36 (0.22)  <0.001  BMI, kg/m2  27.9 ± 4.6      0.71 (0.01)  <0.001  0.09 (2.25)  0.02  WC, cm  95.0 ± 11.7  0.71 (0.01)  <0.001      0.57 (4.68)  <0.001  WHR  0.91 ± 0.08  0.09 (2.25)  0.02  0.57 (4.68)  <0.001      Race-ethnicity   White (%)  85 (13.5)  Ref.  Ref.  Ref.   African Americans, n (%)  92 (14.6)  0.11 (0.69)  0.03  0.03 (1.75)  0.56  −0.04 (0.01)  0.42   Hispanics, n (%)  439 (69.8)  0.20 (0.54)  <0.001  0.06 (1.38)  0.27  0.006 (0.01)  0.92   Other, n (%)  13 (2.1)  −0.005 (1.37)  0.91  −0.05 (3.47)  0.29  −0.05 (0.02)  0.21  Hypertension, n (%)  484 (77.0)  −0.19 (0.004)  <0.001  0.19 (0.001)  <0.001  0.12 (0.20)  0.003  Anti-hypertensive medication, n (%)  441 (70.1)  0.18 (0.004)  <0.001  0.18 (0.002)  <0.001  0.11 (0.22)  0.005  Diabetes mellitus, n (%)  175 (27.8)  0.15 (0.004)  <0.001  0.16 (0.002)  <0.001  0.08 (0.23)  0.05  Hypercholesterolaemia, n (%)  408 (64.9)  0.09 (0.004)  0.02  0.05 (0.002)  0.214  0.04 (0.23)  0.35  Coronary artery disease, n (%)  33 (5.3)  0.07 (0.002)  0.09  0.15 (0.001)  <0.001  0.12 (0.11)  0.003  Smoking history, n (%)  332 (52.8)  −0.09 (0.004)  0.02  0.001 (0.002)  0.99  0.07 (0.24)  0.07    N = 629  BMI   WC   WHR       β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  Age (years)  70.6 ± 9.2  −0.14 (0.08)  0.001  0.01 (0.03)  0.72  0.07 (4.50)  0.09  Woman, n (%)  381 (60.6)  0.16 (0.004)  <0.001  −0.36 (0.002)  <0.001  −0.36 (0.22)  <0.001  BMI, kg/m2  27.9 ± 4.6      0.71 (0.01)  <0.001  0.09 (2.25)  0.02  WC, cm  95.0 ± 11.7  0.71 (0.01)  <0.001      0.57 (4.68)  <0.001  WHR  0.91 ± 0.08  0.09 (2.25)  0.02  0.57 (4.68)  <0.001      Race-ethnicity   White (%)  85 (13.5)  Ref.  Ref.  Ref.   African Americans, n (%)  92 (14.6)  0.11 (0.69)  0.03  0.03 (1.75)  0.56  −0.04 (0.01)  0.42   Hispanics, n (%)  439 (69.8)  0.20 (0.54)  <0.001  0.06 (1.38)  0.27  0.006 (0.01)  0.92   Other, n (%)  13 (2.1)  −0.005 (1.37)  0.91  −0.05 (3.47)  0.29  −0.05 (0.02)  0.21  Hypertension, n (%)  484 (77.0)  −0.19 (0.004)  <0.001  0.19 (0.001)  <0.001  0.12 (0.20)  0.003  Anti-hypertensive medication, n (%)  441 (70.1)  0.18 (0.004)  <0.001  0.18 (0.002)  <0.001  0.11 (0.22)  0.005  Diabetes mellitus, n (%)  175 (27.8)  0.15 (0.004)  <0.001  0.16 (0.002)  <0.001  0.08 (0.23)  0.05  Hypercholesterolaemia, n (%)  408 (64.9)  0.09 (0.004)  0.02  0.05 (0.002)  0.214  0.04 (0.23)  0.35  Coronary artery disease, n (%)  33 (5.3)  0.07 (0.002)  0.09  0.15 (0.001)  <0.001  0.12 (0.11)  0.003  Smoking history, n (%)  332 (52.8)  −0.09 (0.004)  0.02  0.001 (0.002)  0.99  0.07 (0.24)  0.07  BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; SE, standard error. Higher BMI was associated with younger age, female sex, African American or Hispanic race/ethnicity, hypertension, anti-hypertensive medication, diabetes, hypercholesterolaemia, and no history of cigarette smoking (all P < 0.05). Neither WC nor WHR was associated with age, but both were associated with male sex, hypertension, hypertension medication, diabetes and coronary artery disease (all P < 0.05). Association of body size metrics with LA phasic volumes and reservoir function Echocardiographic characteristics of the study population and their association with BMI, WC, and WHR are shown in Table 2. BMI was significantly associated with higher LV ejection fraction, greater LV mass, lower e′, and higher E/e′ ratio (all P < 0.05). WC was not associated with LV ejection fraction and E/e′, but was significantly associated with greater LV mass and mass index, and lower e′ (all P < 0.05). WHR was not associated with E/e′, but was significantly associated with lower LV ejection fraction, with greater LV mass and mass index, and lower e′ (all P < 0.05). Table 2 Echocardiographic variables and univariate relationships with body size metrics   N = 629  BMI   WC   WHR       β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  LV ejection fraction (%)  64.4 ± 4.9  0.11 (0.04)  0.006  0.00003 (0.02)  0.999  −0.09 (2.37)  0.03  LV mass (gr)  179.9 ± 46.8  0.22 (0.40)  <0.001  0.35 (0.15)  <0.001  0.27 (22.0)  <0.001  LV mass index (gr/m2)  101.8 ± 23.9  0.02 (0.21)  0.57  0.19 (0.08)  0.003  0.19 (11.43)  <0.001  e’ (cm/s)  7.4 ± 1.7  −0.08 (0.02)  0.05  −0.13 (0.006)  0.001  −0.13 (0.83)  0.001  E/e’  10.2 ± 3.1  0.12 (0.03)  0.003  0.07 (0.01)  0.10  −0.01 (1.54)  0.78  LAVmax (mL)  47.7 ± 12.4  0.11 (0.11)  0.004  0.18 (0.04)  <0.001  0.09 (6.03)  0.02  LAVmin (mL)  23.6 ± 9.5  0.10 (0.08)  0.01  0.18 (0.03)  <0.001  0.11 (4.61)  0.007  LAEVI (mL/m2)  10.8 ± 3.6  −0.09 (0.03)  0.02  −0.13 (0.01)  0.002  −0.08 (1.78)  0.06  LAEF (%)  45.3 ± 11.4  −0.05  0.18  −0.10  0.01  −0.08  0.05  LAEI (%)  91.3 ± 42.0  −0.06 (0.36)  0.17  −0.10 (0.14)  0.01  −0.08 (20.43)  0.05    N = 629  BMI   WC   WHR       β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  LV ejection fraction (%)  64.4 ± 4.9  0.11 (0.04)  0.006  0.00003 (0.02)  0.999  −0.09 (2.37)  0.03  LV mass (gr)  179.9 ± 46.8  0.22 (0.40)  <0.001  0.35 (0.15)  <0.001  0.27 (22.0)  <0.001  LV mass index (gr/m2)  101.8 ± 23.9  0.02 (0.21)  0.57  0.19 (0.08)  0.003  0.19 (11.43)  <0.001  e’ (cm/s)  7.4 ± 1.7  −0.08 (0.02)  0.05  −0.13 (0.006)  0.001  −0.13 (0.83)  0.001  E/e’  10.2 ± 3.1  0.12 (0.03)  0.003  0.07 (0.01)  0.10  −0.01 (1.54)  0.78  LAVmax (mL)  47.7 ± 12.4  0.11 (0.11)  0.004  0.18 (0.04)  <0.001  0.09 (6.03)  0.02  LAVmin (mL)  23.6 ± 9.5  0.10 (0.08)  0.01  0.18 (0.03)  <0.001  0.11 (4.61)  0.007  LAEVI (mL/m2)  10.8 ± 3.6  −0.09 (0.03)  0.02  −0.13 (0.01)  0.002  −0.08 (1.78)  0.06  LAEF (%)  45.3 ± 11.4  −0.05  0.18  −0.10  0.01  −0.08  0.05  LAEI (%)  91.3 ± 42.0  −0.06 (0.36)  0.17  −0.10 (0.14)  0.01  −0.08 (20.43)  0.05  BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; SE, standard error; LV, left ventricular; LAVmax, LA maximum volume; LAV, LA minimum volume; LAEVI, LA total emptying volume index; LAEF, LA total emptying fraction; LAEI, LA expansion index. Table 2 Echocardiographic variables and univariate relationships with body size metrics   N = 629  BMI   WC   WHR       β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  LV ejection fraction (%)  64.4 ± 4.9  0.11 (0.04)  0.006  0.00003 (0.02)  0.999  −0.09 (2.37)  0.03  LV mass (gr)  179.9 ± 46.8  0.22 (0.40)  <0.001  0.35 (0.15)  <0.001  0.27 (22.0)  <0.001  LV mass index (gr/m2)  101.8 ± 23.9  0.02 (0.21)  0.57  0.19 (0.08)  0.003  0.19 (11.43)  <0.001  e’ (cm/s)  7.4 ± 1.7  −0.08 (0.02)  0.05  −0.13 (0.006)  0.001  −0.13 (0.83)  0.001  E/e’  10.2 ± 3.1  0.12 (0.03)  0.003  0.07 (0.01)  0.10  −0.01 (1.54)  0.78  LAVmax (mL)  47.7 ± 12.4  0.11 (0.11)  0.004  0.18 (0.04)  <0.001  0.09 (6.03)  0.02  LAVmin (mL)  23.6 ± 9.5  0.10 (0.08)  0.01  0.18 (0.03)  <0.001  0.11 (4.61)  0.007  LAEVI (mL/m2)  10.8 ± 3.6  −0.09 (0.03)  0.02  −0.13 (0.01)  0.002  −0.08 (1.78)  0.06  LAEF (%)  45.3 ± 11.4  −0.05  0.18  −0.10  0.01  −0.08  0.05  LAEI (%)  91.3 ± 42.0  −0.06 (0.36)  0.17  −0.10 (0.14)  0.01  −0.08 (20.43)  0.05    N = 629  BMI   WC   WHR       β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  LV ejection fraction (%)  64.4 ± 4.9  0.11 (0.04)  0.006  0.00003 (0.02)  0.999  −0.09 (2.37)  0.03  LV mass (gr)  179.9 ± 46.8  0.22 (0.40)  <0.001  0.35 (0.15)  <0.001  0.27 (22.0)  <0.001  LV mass index (gr/m2)  101.8 ± 23.9  0.02 (0.21)  0.57  0.19 (0.08)  0.003  0.19 (11.43)  <0.001  e’ (cm/s)  7.4 ± 1.7  −0.08 (0.02)  0.05  −0.13 (0.006)  0.001  −0.13 (0.83)  0.001  E/e’  10.2 ± 3.1  0.12 (0.03)  0.003  0.07 (0.01)  0.10  −0.01 (1.54)  0.78  LAVmax (mL)  47.7 ± 12.4  0.11 (0.11)  0.004  0.18 (0.04)  <0.001  0.09 (6.03)  0.02  LAVmin (mL)  23.6 ± 9.5  0.10 (0.08)  0.01  0.18 (0.03)  <0.001  0.11 (4.61)  0.007  LAEVI (mL/m2)  10.8 ± 3.6  −0.09 (0.03)  0.02  −0.13 (0.01)  0.002  −0.08 (1.78)  0.06  LAEF (%)  45.3 ± 11.4  −0.05  0.18  −0.10  0.01  −0.08  0.05  LAEI (%)  91.3 ± 42.0  −0.06 (0.36)  0.17  −0.10 (0.14)  0.01  −0.08 (20.43)  0.05  BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; SE, standard error; LV, left ventricular; LAVmax, LA maximum volume; LAV, LA minimum volume; LAEVI, LA total emptying volume index; LAEF, LA total emptying fraction; LAEI, LA expansion index. Figure 2 displays the unadjusted relationship between quintiles of body size metrics (BMI, WC, and WHR) and LA phasic volumes (LAVmax and LAVmin) with intergroup differences. There was a significant linear trend between the quintiles of WC and WHR with LAVmax (P = 0.004 and P = 0.04, respectively) and LAVmin (P = 0.006 and P = 0.001, respectively). On the other hand, quintiles of BMI did not show a significant linear trend with either LAVmax or LAVmin. Figure 3 displays the unadjusted relationship between quintiles of body size metrics (BMI, WC, and WHR) and LA reservoir function (LAEVI, LAEF, and LAEI) with intergroup differences. WC quintiles showed a significant linear trend with LAEVI (P = 0.02) with significant intergroup differences, whereas quintiles of BMI and WHR did not reveal a significant linear trend with LAEVI. Quintiles of all body size metrics (BMI, WC, and WHR) did not show a linear trend with LAEF and LAEI, however there were significant intergroup differences between the quintiles of WC and WHR, and LAEF and LAEI (both P < 0.05). BMI quintiles did not reveal any significant intergroup differences for LAEF and LAEI. Figure 2 View largeDownload slide Relationship between quintiles of body size metrics with left atrial phasic volumes. *P < 0.05 vs. Q1, ‡P < 0.05 vs. Q1 and Q2. BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; Q, quintile. Figure 2 View largeDownload slide Relationship between quintiles of body size metrics with left atrial phasic volumes. *P < 0.05 vs. Q1, ‡P < 0.05 vs. Q1 and Q2. BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; Q, quintile. Figure 3 View largeDownload slide Relationship between quintiles of body size metrics with left atrial reservoir function. *P < 0.05 vs. Q1, ‡P < 0.05 vs. Q1 and Q2. BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; Q, quintile. Figure 3 View largeDownload slide Relationship between quintiles of body size metrics with left atrial reservoir function. *P < 0.05 vs. Q1, ‡P < 0.05 vs. Q1 and Q2. BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; Q, quintile. Univariate associations of BMI, WC, and WHR with LA phasic volumes and reservoir function are shown in Table 2. Higher BMI was significantly associated with higher LA phasic volumes (LAVmax and LAVmin), and reduced LAEVI (all P < 0.05), but showed no association with LAEF and LAEI. Higher WC was significantly associated with higher LA phasic volumes (LAVmax and LAVmin), and reduced LA reservoir function (LAEVI, LAEF, and LAEI, all P < 0.05). Higher WHR was significantly associated with higher LA phasic volumes (LAVmax and LAVmin, both P < 0.05), but was not associated with LA reservoir function. When WC and BMI were entered into the same model, the association between LA phasic volumes, LA reservoir function and WC became stronger, whereas BMI lost its association with LA phasic volumes (Table 3). When WHR and BMI were entered into the same model, WHR remained significantly associated only with LAVmin, and BMI lost its association with LA volumes (also Table 3). In a multivariate model adjusted for potential confounders, higher WC remained significantly associated with higher LA phasic volumes (LAVmax, β = 0.10, P = 0.007 and LAVmin, β = 0.12, P = 0.002) and reduced reservoir function (LAEVI, β = −0.15, P = 0.001 and LAEI, β = −0.09, P = 0.027), whereas higher WHR remained only significantly associated with reduced LAEVI (β = −0.11, P = 0.012) (Table 4). Table 3 Adjusted relationships of general obesity and abdominal adiposity with left atrial volumes and reservoir function   BMIa   WCb   WHRb     β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  LAVmax (mL)  −0.03 (0.15)  0.63  0.20 (0.06)  <0.001  0.08 (6.02)  0.05  LAVmin (mL)  −0.05 (0.12)  0.36  0.20 (0.05)  <0.001  0.10 (4.61)  0.010  LAEVI (mL/m2)  −0.01 (0.04)  0.85  −0.11 (0.02)  0.04  −0.07 (1.78)  0.095  LAEF (%)  0.03 (0.14)  0.57  −0.12 (0.06)  0.03  −0.07 (5.56)  0.070  LAEI (%)  0.04 (0.51)  0.53  −0.13 (0.20)  0.02  −0.07 (20.51)  0.065    BMIa   WCb   WHRb     β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  LAVmax (mL)  −0.03 (0.15)  0.63  0.20 (0.06)  <0.001  0.08 (6.02)  0.05  LAVmin (mL)  −0.05 (0.12)  0.36  0.20 (0.05)  <0.001  0.10 (4.61)  0.010  LAEVI (mL/m2)  −0.01 (0.04)  0.85  −0.11 (0.02)  0.04  −0.07 (1.78)  0.095  LAEF (%)  0.03 (0.14)  0.57  −0.12 (0.06)  0.03  −0.07 (5.56)  0.070  LAEI (%)  0.04 (0.51)  0.53  −0.13 (0.20)  0.02  −0.07 (20.51)  0.065  BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; SE, standard error; LV, left ventricular; LAVmax, LA maximum volume; LAVmin, LA minimum volume; LAEVI, LA total emptying volume index; LAEF, LA total emptying fraction; LAEI, LA expansion index. a Adjusted for WC. b Adjusted for BMI. Table 3 Adjusted relationships of general obesity and abdominal adiposity with left atrial volumes and reservoir function   BMIa   WCb   WHRb     β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  LAVmax (mL)  −0.03 (0.15)  0.63  0.20 (0.06)  <0.001  0.08 (6.02)  0.05  LAVmin (mL)  −0.05 (0.12)  0.36  0.20 (0.05)  <0.001  0.10 (4.61)  0.010  LAEVI (mL/m2)  −0.01 (0.04)  0.85  −0.11 (0.02)  0.04  −0.07 (1.78)  0.095  LAEF (%)  0.03 (0.14)  0.57  −0.12 (0.06)  0.03  −0.07 (5.56)  0.070  LAEI (%)  0.04 (0.51)  0.53  −0.13 (0.20)  0.02  −0.07 (20.51)  0.065    BMIa   WCb   WHRb     β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  LAVmax (mL)  −0.03 (0.15)  0.63  0.20 (0.06)  <0.001  0.08 (6.02)  0.05  LAVmin (mL)  −0.05 (0.12)  0.36  0.20 (0.05)  <0.001  0.10 (4.61)  0.010  LAEVI (mL/m2)  −0.01 (0.04)  0.85  −0.11 (0.02)  0.04  −0.07 (1.78)  0.095  LAEF (%)  0.03 (0.14)  0.57  −0.12 (0.06)  0.03  −0.07 (5.56)  0.070  LAEI (%)  0.04 (0.51)  0.53  −0.13 (0.20)  0.02  −0.07 (20.51)  0.065  BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; SE, standard error; LV, left ventricular; LAVmax, LA maximum volume; LAVmin, LA minimum volume; LAEVI, LA total emptying volume index; LAEF, LA total emptying fraction; LAEI, LA expansion index. a Adjusted for WC. b Adjusted for BMI. Table 4 Association of abdominal adiposity measured by WC and WHR with left atrial volumes and reservoir function after multivariate adjustment   WCa   WHRa     β (SE)  P-value  β (SE)  P-value  LAVmax (mL)  0.10 (0.10)  0.008  −0.06 (6.10)  0.14  LAVmin (mL)  0.12 (0.08)  0.002  −0.03 (4.49)  0.55  LAEVI (mL/m2)  −0.15 (0.03)  <0.001  −0.11 (2.0)  0.012  LAEF (%)  −0.07 (0.10)  0.057  −0.04 (5.62)  0.34  LAEI (%)  −0.09 (0.36)  0.027  −0.03 (21.18)  0.44    WCa   WHRa     β (SE)  P-value  β (SE)  P-value  LAVmax (mL)  0.10 (0.10)  0.008  −0.06 (6.10)  0.14  LAVmin (mL)  0.12 (0.08)  0.002  −0.03 (4.49)  0.55  LAEVI (mL/m2)  −0.15 (0.03)  <0.001  −0.11 (2.0)  0.012  LAEF (%)  −0.07 (0.10)  0.057  −0.04 (5.62)  0.34  LAEI (%)  −0.09 (0.36)  0.027  −0.03 (21.18)  0.44  WC, waist circumference; WHR, waist-to-hip ratio; SE, standard error; LV, left ventricular; LAVmax, LA maximum volume; LAVmin, LA minimum volume; LAEVI, LA total emptying volume index; LAEF, LA total emptying fraction; LAEI, LA expansion index. a Adjusted for age, gender, hypertension, hypertension medication, diabetes, coronary artery disease, left ventricular ejection fraction, left ventricular mass index [LV mass/body surface area (BSA)] and E/e’. Table 4 Association of abdominal adiposity measured by WC and WHR with left atrial volumes and reservoir function after multivariate adjustment   WCa   WHRa     β (SE)  P-value  β (SE)  P-value  LAVmax (mL)  0.10 (0.10)  0.008  −0.06 (6.10)  0.14  LAVmin (mL)  0.12 (0.08)  0.002  −0.03 (4.49)  0.55  LAEVI (mL/m2)  −0.15 (0.03)  <0.001  −0.11 (2.0)  0.012  LAEF (%)  −0.07 (0.10)  0.057  −0.04 (5.62)  0.34  LAEI (%)  −0.09 (0.36)  0.027  −0.03 (21.18)  0.44    WCa   WHRa     β (SE)  P-value  β (SE)  P-value  LAVmax (mL)  0.10 (0.10)  0.008  −0.06 (6.10)  0.14  LAVmin (mL)  0.12 (0.08)  0.002  −0.03 (4.49)  0.55  LAEVI (mL/m2)  −0.15 (0.03)  <0.001  −0.11 (2.0)  0.012  LAEF (%)  −0.07 (0.10)  0.057  −0.04 (5.62)  0.34  LAEI (%)  −0.09 (0.36)  0.027  −0.03 (21.18)  0.44  WC, waist circumference; WHR, waist-to-hip ratio; SE, standard error; LV, left ventricular; LAVmax, LA maximum volume; LAVmin, LA minimum volume; LAEVI, LA total emptying volume index; LAEF, LA total emptying fraction; LAEI, LA expansion index. a Adjusted for age, gender, hypertension, hypertension medication, diabetes, coronary artery disease, left ventricular ejection fraction, left ventricular mass index [LV mass/body surface area (BSA)] and E/e’. Discussion In this study, among indices of adiposity, only WC was independently associated with LA phasic volumes (LAVmax and LAVmin) and reservoir function (LAEVI and LAEI) in the elderly, whereas WHR remained only associated with LAEVI, and BMI showed no association with LA phasic volumes when simultaneously entered with WC into the model. This study was carried out in an elderly community based cohort with no history of AF and LV dysfunction, and no more than mild mitral regurgitation detected by echocardiography. WC therefore can be considered to be directly associated with reduced LA reservoir function and increased LA volumes. BMI is commonly used as a measure of obesity in clinical studies because of its ease of acquisition and well-documented association with cardiovascular events and mortality.16 However, the association of an increased BMI with mortality seems to be less pronounced in elderly than in younger populations, as in older people BMI is a poor measure of body fat.17,18 The measurement of weight does not differentiate between fat and fat-free mass, and fat-free mass (muscle) is progressively lost with increasing age.19 In a previous study, abdominal adiposity, but not BMI, was associated with a greater risk of death in adults aged over 75 years.20 The observations from the present and previous studies suggest that abdominal adiposity measures have the potential to show a different impact than BMI on cardiovascular risk, and perhaps add to the information provided by BMI alone. An increase in LA volume is associated with the development of atrial arrhythmias and is a predictor of cardiovascular events, especially in the elderly.4,21 In a cohort of 1160 elderly patients with cardiovascular disease referred for echocardiography, both LA volume index and LV diastolic dysfunction were independently predictive of cardiovascular events.22 Both obesity and aging have been identified as independent predictors of LA enlargement.1 Indeed, in the present study, although the values of the LA volumes were within the expected normal ranges, higher BMI was significantly associated with both higher LAVmax and LAVmin, and these associations were stronger for WC.23 When BMI and WC were simultaneously entered into the same model, the association between LA volumes and WC became stronger, whereas the association between BMI and LA volumes was lost. When body size metrics were divided into quintiles, WC and WHR revealed a significant linear trend for LAmax and LAVmin, whereas there was no trend observed between BMI, LAVmax, and LAVmin. Most of the previous studies that looked into the association of LA size and obesity were conducted in selected samples or in cohorts of significantly younger age, in which the increase in BMI is paralleled by an increase of both fat and fat-free mass. Also, the LA volumes were evaluated by 2D rather than 3D echocardiography. LA enlargement occurs in all three spatial dimensions, but not uniformly, with the medial-lateral LA expansion being less prominent than the longitudinal and anteroposterior expansion. Therefore, changes in LA volume during the cardiac cycle may not be accurately evaluated by 2D echocardiography, as the shape of the LA changes during the cycle. RT3D echocardiography, have made it possible to measure the change in LA volume throughout the cardiac cycle, and to assess the LA reservoir function. LA volume measurements by RT3D echocardiography correlate closely with those obtained on magnetic resonance imaging.24 It was recently shown that parameters derived from RT3D LA volume tend to be stronger predictors of paroxysmal atrial fibrillation than those obtained with 2D volume.25 LA function has been reported to be abnormal due mainly to increased LV filling pressure, which is a reflection of LV cavity stiffness, and is manifested in the form of increased LA volume, reduced reservoir and overall pump function.26–28 A reduced LA reservoir function is associated with hypertension, LV hypertrophy, LV diastolic dysfunction, and other cardiovascular risk factors, and therefore could be a surrogate marker of cardiovascular risk, including predisposal to atrial arrhythmias.4,29 In fact, the LA reservoir function has been demonstrated to be a better correlate of LV diastolic dysfunction and better predictor of incident atrial arrhythmias and new-onset AF than indexed LAVmax.4,30 Very limited data is available to date that evaluated the relationship between LA reservoir function and body size metrics. In a recent study, 164 untreated hypertensive subjects were separated into 3 groups (lean, overweight and obese) according to their BMI, and the LA reservoir function was evaluated by 2D echocardiography.31 LA reservoir function gradually decreased, from lean to obese hypertensive patients. The study population was considerably younger compared with our population, with a limited number of subjects in each group. We did not find any association between WHR and LA reservoir function in the univariate analysis, and BMI was only associated with LAEVI, whereas WC was significantly associated with all LA reservoir function parameters (LAEVI, LAEF and LAEI). After adjusting for potential confounders that could impact LA reservoir function, higher WC remained significantly associated with reduced LA reservoir function. Although WC and WHR are both used to measure abdominal adiposity, quintiles of WHR were less related to LA phasic volumes than of WC, and not related to LA reservoir function. This finding is in line with a previous study that compared BMI, WHR, and WC as predictors with all-cause mortality in the elderly, observing that the higher quintiles of WC, but not of BMI and WHR, were related to increased mortality.32 Another study found WC to be the best anthropometric measure for identifying individuals with cardiovascular risk factors.33 WC is easier to measure than WHR and it is associated with few measurement errors. WHR is more difficult to interpret, especially in the elderly, because it is the ratio of two complex variables, such as increased WHR may reflect both greater intraabdominal fat mass (higher WC) and/or reduced gluteofemoral muscle mass (lower hip circumference).34 To our knowledge, the present study is the first to assess the relationship between body size metrics and LA phasic volumes and reservoir function using RT3D echocardiography in a large, tri-ethnic, community-based cohort of elderly subjects. The current results from this study are consistent with our previous data on the relationship between abdominal adiposity and subclinical left ventricular dysfunction, which might also be implicated in the pathophysiology of LA dysfunction in the elderly.8 The strengths of our study include the large number of subjects studied, the minimal risk of selection bias (as the study sample was derived from a community-cohort study that employed random participant selection), the fact that a wide range of cardiovascular risk profiles were present in our study population, and the confirmation of our findings after adjustment for pertinent confounders. Moreover, we used state-of-the art technique, RT3D echocardiography, which has been demonstrated to be more accurate than 2 D assessment by comparison with non-echocardiographic gold standards, and has shown better reproducibility.24 However, our study has limitations. Since the study population included subjects > 50 years of age, our results may not fully apply to younger subjects. Also, the high cardiovascular risk profile of the study participants might preclude the generalization of our findings to populations with lower cardiovascular risk. The cross-sectional design of the analysis allowed us to describe associations between abdominal adiposity metrics and LA phasic volumes and reservoir function, but not to draw conclusions regarding cause–effect relationships. The coefficients of determination of the adjusted multiple regression analysis were low, which indicate that there may be nonlinear relationship as well as some biological variability in atrial dimensions not explained entirely by demographic and anthropometric variables. Finally, although we used clinically accepted metrics of body size (BMI, WC, and WHR), in the elderly population body fat estimation has difficulties using conventional anthropometric indices for both genders.35 The assessment of fat mass and fat-free mass, which is helpful to better understand the relationships between body size and body composition, was not performed in our study. In conclusion, in this community cohort of prevalently elderly subjects, only WC among indices of body size was associated with greater LA phasic volumes and reduced LA reservoir function, independent of other confounders. The simple measurement of WC may improve the cardiovascular risk stratification in the elderly. Conflict of interest: None declared. Acknowledgements The authors wish to thank Janet De Rosa, MPH (project manager), Rafi Cabral, MD, Michele Alegre, RDCS, and Palma Gervasi-Franklin (collection and management of the data). 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Association of body size metrics with left atrial phasic volumes and reservoir function in the elderly

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Abstract

Abstract Aims General obesity, defined by increased body mass index (BMI), is associated with left atrial (LA) enlargement, a marker of cardiovascular risk in the general population. The association between abdominal adiposity, defined by increased waist circumference (WC) or waist-to-hip ratio (WHR), and LA phasic volumes and reservoir function is not well known. The aim of this study was to evaluate the association between different body size metrics and LA phasic volumes and reservoir function in the elderly. Methods and results Participants from the CABL (Cardiovascular Abnormalities and Brain Lesions) study underwent measurement of BMI, WC, and WHR. The LA maximum (LAVmax) and minimum (LAVmin) volumes, and LA reservoir function, measured as total emptying volume index (LAEVI), total emptying fraction (LAEF), and expansion index (LAEI), were assessed by real-time 3D echocardiography. The study population included 629 participants (mean age 71 ± 9 years, 61% women). Mean BMI was 27.9 ± 4.6 kg/m2, WC was 95.0 ± 11.7 cm, WHR was 0.91 ± 0.08. After adjusting for multiple potential confounders (demographics, cardiovascular risk factors, left ventricular mass index, and diastolic function), higher WC was significantly associated with higher LA phasic volumes (LAVmax, β = 0.10, P = 0.007 and LAVmin, β = 0.12, P = 0.002) and reduced reservoir function (LAEVI, β = −0.15, P = 0.001 and LAEI, β = −0.09, P = 0.027). WHR was significantly associated only with reduced reservoir function (LAEVI, β = −0.11, P = 0.012), whereas BMI was not associated with either LA phasic volumes or reservoir function. Conclusion In the elderly, WC may have more impact on LA phasic volumes and reservoir function, and therefore risk for cardiovascular events, than WHR and BMI. left atrial volume , reservoir function , three-dimensional echocardiography , obesity , abdominal adiposity Introduction Analysis of population-based studies suggests that obesity is the main risk factor for left atrial (LA) enlargement during aging.1 Increased LA size is associated with higher mortality and cardiovascular events.2 The strength of the association between LA remodelling and cardiovascular risk in various clinical studies is influenced by the characteristics of the studied population, and the method used to evaluate LA enlargement. Among different measures of LA size, LA volume has shown the strongest association with adverse outcomes.3 Growing evidence suggests that the analysis of LA volume in different phases of the cardiac cycle (LA phasic volumes) may provide additional, clinically relevant information regarding LA remodelling and dysfunction.4 The introduction of real-time 3D (RT3D) echocardiography has made it possible to measure the change in LA volume throughout the cardiac cycle, and to assess the LA reservoir function which have been identified as important predictors of atrial fibrillation (AF) occurrence, and of its recurrence after catheter ablation, in overweight/obese patients.5 Body mass index (BMI) has been identified as an independent predictor of LA size in adults.1 Recent studies have shown that measures of abdominal adiposity such as waist circumference (WC) and waist-to-hip ratio (WHR), which take into account body fat distribution, may be more important for prognosis than general obesity measured by BMI.6 WC is strongly associated with cardiovascular risk factors and metabolic abnormalities, and is a strong predictor of incident cardiovascular events, especially in the elderly.7 Previously, we looked at the association of general and abdominal adiposity with subclinical left ventricular (LV) systolic dysfunction in the elderly.8 Abdominal adiposity was independently associated with subclinical LV systolic dysfunction in all BMI categories (normal, overweight, or obese), whereas BMI was not associated with LV dysfunction. More recently, another study found that abdominal adiposity is associated with several measures of impaired LV systolic and diastolic functions, independent of BMI, and even in non-obese individuals.9 Most studies that looked into the relationship between obesity and LA enlargement used BMI as an indicator of obesity. One recent study found and association between LA dilatation and visceral adiposity in the general population, however it is not known whether, and to what extent, parameters of LA volume and function are associated with abdominal adiposity in the elderly population.10 The aim of this study was to investigate the relationships of LA phasic volumes and reservoir function measured by RT3D echocardiography with the presence of general obesity, quantified by BMI, and abdominal adiposity, quantified by WC and WHR. Methods Study population The study population was derived from the CABL (Cardiac Abnormalities and Brain Lesion) Study, a community-based epidemiological study whose primary aim was to investigate the possible cardiac predictors of silent brain disease in the community. The CABL study based its recruitment on the NOMAS (Northern Manhattan Study), a population-based prospective study that enrolled 3298 participants from the community living in northern Manhattan between 1993 and 2001. The study design and recruitment details of NOMAS have been described previously.11 Participants were invited to participate in an MRI sub-study beginning in 2003 and were eligible for the MRI cohort if they: (i) were at least 55 years of age; (ii) had no contraindications to MRI; and (iii) did not have a prior diagnosis of stroke. From September 2005 to July 2010, NOMAS MRI participants who voluntarily agreed to undergo a more extensive cardiovascular evaluation were included in the CABL study. The 1004 CABL participants underwent transthoracic echocardiography, and 854 had complete datasets for RT3D, 148 of whom were excluded because of suboptimal image quality for LA volume measurements. Subjects with a history of AF, LV ejection fraction < 50% and more than mild mitral regurgitation were also excluded from the study, leading to a final study sample of 629 participants. Written informed consent was obtained from all study participants. The study was approved by the institutional review boards of Columbia University Medical Center and of the University of Miami. Risk factors and body size assessment Cardiovascular risk factors were ascertained through direct examination and interview by trained research assistants. Hypertension was defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, or use of antihypertensive medication. Diabetes mellitus was defined as fasting blood glucose ≥126 mg/dL or use of diabetes medications. Hypercholesterolemia was defined as total serum cholesterol >240 mg/dL, or use of lipid-lowering treatment. Cigarette smoking, either at the time of the interview or in the past, was recorded. Coronary artery disease was defined as history of myocardial infarction, coronary artery bypass grafting, or percutaneous coronary intervention. The race–ethnicity classification was based on self-identification, and modelled after the US Census. Height and weight were measured using a standard scale. The BMI was calculated as weight (kg) divided by height (m) squared. Waist and hip circumferences were measured using flexible measuring tape with participants standing and relaxed without outer garments. The WC was measured at the level of the umbilicus, and hip circumference was measured at the level of the greater trochanters. Echocardiography Transthoracic echocardiography was performed using a commercially available system (iE 33; Philips, Andover, MA, USA) by a trained, registered cardiac sonographer according to a standardized protocol. The LV dimensions were measured from a parasternal long-axis view according to the recommendations of the American Society of Echocardiography,12 and LV mass was calculated with a validated method13 and indexed by body surface area. LV ejection fraction was calculated using the biplane modified Simpson’s rule. In addition, LV diastolic function was assessed from the apical four-chamber view by means of the peak early velocity (E) of the transmitral flow and the early diastolic velocity (e′) of the mitral annulus (average of septal and lateral site) by pulsed-wave tissue-Doppler, as described previously.14 The ratio E/e′ was calculated as an indicator LV diastolic function and filling pressure. LA phasic volume measurements were performed by RT3D echocardiography. A full volume loop was acquired from an apical window using an X3-1 matrix array transducer over four cardiac cycles. Measurements of 3D LA volumes were performed offline using commercially available software (QLAB Advanced Quantification software, V.8.1, Philips). A detailed description of the technique has been reported previously.15 Briefly, five anatomical landmarks (septal, lateral, anterior and inferior mitral annulus, and posterior wall of the LA) were manually identified by the operator, semi-automated border detection was performed by the software, and LA borders were tracked throughout the entire cardiac cycle (Figure 1). Manual correction on all possible 3D planes was performed by the reader in case of inaccurate endocardial automated detection. The parameters of LA size and function included in our analyses were: Figure 1 View largeDownload slide Left atrial phasic volumes by real-time 3D echocardiography. Arrows indicate LAVmax and LAVmin. Figure 1 View largeDownload slide Left atrial phasic volumes by real-time 3D echocardiography. Arrows indicate LAVmax and LAVmin. LA minimum volume (LAVmin): LA end-diastolic volume at the first frame after mitral valve closure. LA maximum volume (LAVmax): LA end-systolic volume right before mitral valve opening. LA total emptying volume index (LAEVI): LAVmax − LAVmin/body surface area. LA total emptying fraction (LAEF): 100 × (LAVmax − LAVmin)/LAVmax. LA expansion index (LAEI): 100 ×  (LAVmax − LAVmin)/LAVmin. Statistics Data are presented as mean ± standard deviation for continuous variables and as percentage for categorical variables. BMI, WC, and WHR were categorized in quintiles of the observed distribution, and one-way analysis of variance was used to compare the differences between mean values of LA volumes (LAVmax and LAVmin) and LA reservoir function (LAEVI, LAEF, and LAEI) across the groups. Linear regression analysis was used to assess the association of parameters of LA volume and LA reservoir function with body size measures, and unstandardized (B) and standardized (β) parameter estimates and standard errors (SE) were reported. Linear regression models were used to determine whether BMI, WC or WHR were associated with LA volumes and LA reservoir function when simultaneously entered into the same model (BMI with WC, and WHR with BMI). Covariates adjusted in multivariate models were selected based on their univariate association with body size metrics at significance level P < 0.1. For all statistical analyses, a two-tailed P < 0.05 was considered significant. Statistical analyses were performed using IBM SPSS Statistics software version 22 (IBM Corp., Armonk, NY, USA). Reproducibility of LA volumes Reproducibility of LA volume measurements was assessed in 15 randomly selected subjects. LAVmin and LAVmax were remeasured by the original reader (CR) and by a second reader experienced in 3D echocardiography (AT) in a blinded fashion. Intra-observer ICC intra-class correlation coefficients were 0.96 for LAVmin [95% confidence intervals (CI): 0.88–0.99] and 0.94 for LAVmax (95% CI: 0.85–0.98). The mean difference between two measurements was 0.23 ± 3.17 ml for LAVmin (P = 0.78) and 0.74 ± 4.05 mL for LAVmax (P = 0.49). Inter-observer ICC intra-class correlation coefficients were 0.94 for LAVmin (95% CI: 0.85–0.98) and 0.95 for LAVmax (95% CI: 0.86–0.98). The mean difference between two measurements was 0.78 ± 4.02 mL for LAVmin (P = 0.46) and 0.92 ± 4.53 mL for LAVmax (P = 0.45). Results Clinical characteristics Demographics and clinical characteristics of study participants and associations with BMI, WC, and WHR are reported in Table 1. The study population consisted of 629 participants (mean age 70.6 ± 9.2 years, 60.6% women). Mean BMI was 27.9 ± 4.6 kg/m2, mean WC was 95.0 ± 11.7 cm, and mean WHR was 0.91 ± 0.08. BMI showed a good correlation with WC (β = 0.71, P < 0.001), whereas its correlation with WHR was weaker although statistically significant (β = 0.09, P = 0.02). Table 1 Demographics and clinical characteristics of the study population and univariate relationships with body size metrics   N = 629  BMI   WC   WHR       β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  Age (years)  70.6 ± 9.2  −0.14 (0.08)  0.001  0.01 (0.03)  0.72  0.07 (4.50)  0.09  Woman, n (%)  381 (60.6)  0.16 (0.004)  <0.001  −0.36 (0.002)  <0.001  −0.36 (0.22)  <0.001  BMI, kg/m2  27.9 ± 4.6      0.71 (0.01)  <0.001  0.09 (2.25)  0.02  WC, cm  95.0 ± 11.7  0.71 (0.01)  <0.001      0.57 (4.68)  <0.001  WHR  0.91 ± 0.08  0.09 (2.25)  0.02  0.57 (4.68)  <0.001      Race-ethnicity   White (%)  85 (13.5)  Ref.  Ref.  Ref.   African Americans, n (%)  92 (14.6)  0.11 (0.69)  0.03  0.03 (1.75)  0.56  −0.04 (0.01)  0.42   Hispanics, n (%)  439 (69.8)  0.20 (0.54)  <0.001  0.06 (1.38)  0.27  0.006 (0.01)  0.92   Other, n (%)  13 (2.1)  −0.005 (1.37)  0.91  −0.05 (3.47)  0.29  −0.05 (0.02)  0.21  Hypertension, n (%)  484 (77.0)  −0.19 (0.004)  <0.001  0.19 (0.001)  <0.001  0.12 (0.20)  0.003  Anti-hypertensive medication, n (%)  441 (70.1)  0.18 (0.004)  <0.001  0.18 (0.002)  <0.001  0.11 (0.22)  0.005  Diabetes mellitus, n (%)  175 (27.8)  0.15 (0.004)  <0.001  0.16 (0.002)  <0.001  0.08 (0.23)  0.05  Hypercholesterolaemia, n (%)  408 (64.9)  0.09 (0.004)  0.02  0.05 (0.002)  0.214  0.04 (0.23)  0.35  Coronary artery disease, n (%)  33 (5.3)  0.07 (0.002)  0.09  0.15 (0.001)  <0.001  0.12 (0.11)  0.003  Smoking history, n (%)  332 (52.8)  −0.09 (0.004)  0.02  0.001 (0.002)  0.99  0.07 (0.24)  0.07    N = 629  BMI   WC   WHR       β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  Age (years)  70.6 ± 9.2  −0.14 (0.08)  0.001  0.01 (0.03)  0.72  0.07 (4.50)  0.09  Woman, n (%)  381 (60.6)  0.16 (0.004)  <0.001  −0.36 (0.002)  <0.001  −0.36 (0.22)  <0.001  BMI, kg/m2  27.9 ± 4.6      0.71 (0.01)  <0.001  0.09 (2.25)  0.02  WC, cm  95.0 ± 11.7  0.71 (0.01)  <0.001      0.57 (4.68)  <0.001  WHR  0.91 ± 0.08  0.09 (2.25)  0.02  0.57 (4.68)  <0.001      Race-ethnicity   White (%)  85 (13.5)  Ref.  Ref.  Ref.   African Americans, n (%)  92 (14.6)  0.11 (0.69)  0.03  0.03 (1.75)  0.56  −0.04 (0.01)  0.42   Hispanics, n (%)  439 (69.8)  0.20 (0.54)  <0.001  0.06 (1.38)  0.27  0.006 (0.01)  0.92   Other, n (%)  13 (2.1)  −0.005 (1.37)  0.91  −0.05 (3.47)  0.29  −0.05 (0.02)  0.21  Hypertension, n (%)  484 (77.0)  −0.19 (0.004)  <0.001  0.19 (0.001)  <0.001  0.12 (0.20)  0.003  Anti-hypertensive medication, n (%)  441 (70.1)  0.18 (0.004)  <0.001  0.18 (0.002)  <0.001  0.11 (0.22)  0.005  Diabetes mellitus, n (%)  175 (27.8)  0.15 (0.004)  <0.001  0.16 (0.002)  <0.001  0.08 (0.23)  0.05  Hypercholesterolaemia, n (%)  408 (64.9)  0.09 (0.004)  0.02  0.05 (0.002)  0.214  0.04 (0.23)  0.35  Coronary artery disease, n (%)  33 (5.3)  0.07 (0.002)  0.09  0.15 (0.001)  <0.001  0.12 (0.11)  0.003  Smoking history, n (%)  332 (52.8)  −0.09 (0.004)  0.02  0.001 (0.002)  0.99  0.07 (0.24)  0.07  BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; SE, standard error. Table 1 Demographics and clinical characteristics of the study population and univariate relationships with body size metrics   N = 629  BMI   WC   WHR       β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  Age (years)  70.6 ± 9.2  −0.14 (0.08)  0.001  0.01 (0.03)  0.72  0.07 (4.50)  0.09  Woman, n (%)  381 (60.6)  0.16 (0.004)  <0.001  −0.36 (0.002)  <0.001  −0.36 (0.22)  <0.001  BMI, kg/m2  27.9 ± 4.6      0.71 (0.01)  <0.001  0.09 (2.25)  0.02  WC, cm  95.0 ± 11.7  0.71 (0.01)  <0.001      0.57 (4.68)  <0.001  WHR  0.91 ± 0.08  0.09 (2.25)  0.02  0.57 (4.68)  <0.001      Race-ethnicity   White (%)  85 (13.5)  Ref.  Ref.  Ref.   African Americans, n (%)  92 (14.6)  0.11 (0.69)  0.03  0.03 (1.75)  0.56  −0.04 (0.01)  0.42   Hispanics, n (%)  439 (69.8)  0.20 (0.54)  <0.001  0.06 (1.38)  0.27  0.006 (0.01)  0.92   Other, n (%)  13 (2.1)  −0.005 (1.37)  0.91  −0.05 (3.47)  0.29  −0.05 (0.02)  0.21  Hypertension, n (%)  484 (77.0)  −0.19 (0.004)  <0.001  0.19 (0.001)  <0.001  0.12 (0.20)  0.003  Anti-hypertensive medication, n (%)  441 (70.1)  0.18 (0.004)  <0.001  0.18 (0.002)  <0.001  0.11 (0.22)  0.005  Diabetes mellitus, n (%)  175 (27.8)  0.15 (0.004)  <0.001  0.16 (0.002)  <0.001  0.08 (0.23)  0.05  Hypercholesterolaemia, n (%)  408 (64.9)  0.09 (0.004)  0.02  0.05 (0.002)  0.214  0.04 (0.23)  0.35  Coronary artery disease, n (%)  33 (5.3)  0.07 (0.002)  0.09  0.15 (0.001)  <0.001  0.12 (0.11)  0.003  Smoking history, n (%)  332 (52.8)  −0.09 (0.004)  0.02  0.001 (0.002)  0.99  0.07 (0.24)  0.07    N = 629  BMI   WC   WHR       β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  Age (years)  70.6 ± 9.2  −0.14 (0.08)  0.001  0.01 (0.03)  0.72  0.07 (4.50)  0.09  Woman, n (%)  381 (60.6)  0.16 (0.004)  <0.001  −0.36 (0.002)  <0.001  −0.36 (0.22)  <0.001  BMI, kg/m2  27.9 ± 4.6      0.71 (0.01)  <0.001  0.09 (2.25)  0.02  WC, cm  95.0 ± 11.7  0.71 (0.01)  <0.001      0.57 (4.68)  <0.001  WHR  0.91 ± 0.08  0.09 (2.25)  0.02  0.57 (4.68)  <0.001      Race-ethnicity   White (%)  85 (13.5)  Ref.  Ref.  Ref.   African Americans, n (%)  92 (14.6)  0.11 (0.69)  0.03  0.03 (1.75)  0.56  −0.04 (0.01)  0.42   Hispanics, n (%)  439 (69.8)  0.20 (0.54)  <0.001  0.06 (1.38)  0.27  0.006 (0.01)  0.92   Other, n (%)  13 (2.1)  −0.005 (1.37)  0.91  −0.05 (3.47)  0.29  −0.05 (0.02)  0.21  Hypertension, n (%)  484 (77.0)  −0.19 (0.004)  <0.001  0.19 (0.001)  <0.001  0.12 (0.20)  0.003  Anti-hypertensive medication, n (%)  441 (70.1)  0.18 (0.004)  <0.001  0.18 (0.002)  <0.001  0.11 (0.22)  0.005  Diabetes mellitus, n (%)  175 (27.8)  0.15 (0.004)  <0.001  0.16 (0.002)  <0.001  0.08 (0.23)  0.05  Hypercholesterolaemia, n (%)  408 (64.9)  0.09 (0.004)  0.02  0.05 (0.002)  0.214  0.04 (0.23)  0.35  Coronary artery disease, n (%)  33 (5.3)  0.07 (0.002)  0.09  0.15 (0.001)  <0.001  0.12 (0.11)  0.003  Smoking history, n (%)  332 (52.8)  −0.09 (0.004)  0.02  0.001 (0.002)  0.99  0.07 (0.24)  0.07  BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; SE, standard error. Higher BMI was associated with younger age, female sex, African American or Hispanic race/ethnicity, hypertension, anti-hypertensive medication, diabetes, hypercholesterolaemia, and no history of cigarette smoking (all P < 0.05). Neither WC nor WHR was associated with age, but both were associated with male sex, hypertension, hypertension medication, diabetes and coronary artery disease (all P < 0.05). Association of body size metrics with LA phasic volumes and reservoir function Echocardiographic characteristics of the study population and their association with BMI, WC, and WHR are shown in Table 2. BMI was significantly associated with higher LV ejection fraction, greater LV mass, lower e′, and higher E/e′ ratio (all P < 0.05). WC was not associated with LV ejection fraction and E/e′, but was significantly associated with greater LV mass and mass index, and lower e′ (all P < 0.05). WHR was not associated with E/e′, but was significantly associated with lower LV ejection fraction, with greater LV mass and mass index, and lower e′ (all P < 0.05). Table 2 Echocardiographic variables and univariate relationships with body size metrics   N = 629  BMI   WC   WHR       β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  LV ejection fraction (%)  64.4 ± 4.9  0.11 (0.04)  0.006  0.00003 (0.02)  0.999  −0.09 (2.37)  0.03  LV mass (gr)  179.9 ± 46.8  0.22 (0.40)  <0.001  0.35 (0.15)  <0.001  0.27 (22.0)  <0.001  LV mass index (gr/m2)  101.8 ± 23.9  0.02 (0.21)  0.57  0.19 (0.08)  0.003  0.19 (11.43)  <0.001  e’ (cm/s)  7.4 ± 1.7  −0.08 (0.02)  0.05  −0.13 (0.006)  0.001  −0.13 (0.83)  0.001  E/e’  10.2 ± 3.1  0.12 (0.03)  0.003  0.07 (0.01)  0.10  −0.01 (1.54)  0.78  LAVmax (mL)  47.7 ± 12.4  0.11 (0.11)  0.004  0.18 (0.04)  <0.001  0.09 (6.03)  0.02  LAVmin (mL)  23.6 ± 9.5  0.10 (0.08)  0.01  0.18 (0.03)  <0.001  0.11 (4.61)  0.007  LAEVI (mL/m2)  10.8 ± 3.6  −0.09 (0.03)  0.02  −0.13 (0.01)  0.002  −0.08 (1.78)  0.06  LAEF (%)  45.3 ± 11.4  −0.05  0.18  −0.10  0.01  −0.08  0.05  LAEI (%)  91.3 ± 42.0  −0.06 (0.36)  0.17  −0.10 (0.14)  0.01  −0.08 (20.43)  0.05    N = 629  BMI   WC   WHR       β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  LV ejection fraction (%)  64.4 ± 4.9  0.11 (0.04)  0.006  0.00003 (0.02)  0.999  −0.09 (2.37)  0.03  LV mass (gr)  179.9 ± 46.8  0.22 (0.40)  <0.001  0.35 (0.15)  <0.001  0.27 (22.0)  <0.001  LV mass index (gr/m2)  101.8 ± 23.9  0.02 (0.21)  0.57  0.19 (0.08)  0.003  0.19 (11.43)  <0.001  e’ (cm/s)  7.4 ± 1.7  −0.08 (0.02)  0.05  −0.13 (0.006)  0.001  −0.13 (0.83)  0.001  E/e’  10.2 ± 3.1  0.12 (0.03)  0.003  0.07 (0.01)  0.10  −0.01 (1.54)  0.78  LAVmax (mL)  47.7 ± 12.4  0.11 (0.11)  0.004  0.18 (0.04)  <0.001  0.09 (6.03)  0.02  LAVmin (mL)  23.6 ± 9.5  0.10 (0.08)  0.01  0.18 (0.03)  <0.001  0.11 (4.61)  0.007  LAEVI (mL/m2)  10.8 ± 3.6  −0.09 (0.03)  0.02  −0.13 (0.01)  0.002  −0.08 (1.78)  0.06  LAEF (%)  45.3 ± 11.4  −0.05  0.18  −0.10  0.01  −0.08  0.05  LAEI (%)  91.3 ± 42.0  −0.06 (0.36)  0.17  −0.10 (0.14)  0.01  −0.08 (20.43)  0.05  BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; SE, standard error; LV, left ventricular; LAVmax, LA maximum volume; LAV, LA minimum volume; LAEVI, LA total emptying volume index; LAEF, LA total emptying fraction; LAEI, LA expansion index. Table 2 Echocardiographic variables and univariate relationships with body size metrics   N = 629  BMI   WC   WHR       β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  LV ejection fraction (%)  64.4 ± 4.9  0.11 (0.04)  0.006  0.00003 (0.02)  0.999  −0.09 (2.37)  0.03  LV mass (gr)  179.9 ± 46.8  0.22 (0.40)  <0.001  0.35 (0.15)  <0.001  0.27 (22.0)  <0.001  LV mass index (gr/m2)  101.8 ± 23.9  0.02 (0.21)  0.57  0.19 (0.08)  0.003  0.19 (11.43)  <0.001  e’ (cm/s)  7.4 ± 1.7  −0.08 (0.02)  0.05  −0.13 (0.006)  0.001  −0.13 (0.83)  0.001  E/e’  10.2 ± 3.1  0.12 (0.03)  0.003  0.07 (0.01)  0.10  −0.01 (1.54)  0.78  LAVmax (mL)  47.7 ± 12.4  0.11 (0.11)  0.004  0.18 (0.04)  <0.001  0.09 (6.03)  0.02  LAVmin (mL)  23.6 ± 9.5  0.10 (0.08)  0.01  0.18 (0.03)  <0.001  0.11 (4.61)  0.007  LAEVI (mL/m2)  10.8 ± 3.6  −0.09 (0.03)  0.02  −0.13 (0.01)  0.002  −0.08 (1.78)  0.06  LAEF (%)  45.3 ± 11.4  −0.05  0.18  −0.10  0.01  −0.08  0.05  LAEI (%)  91.3 ± 42.0  −0.06 (0.36)  0.17  −0.10 (0.14)  0.01  −0.08 (20.43)  0.05    N = 629  BMI   WC   WHR       β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  LV ejection fraction (%)  64.4 ± 4.9  0.11 (0.04)  0.006  0.00003 (0.02)  0.999  −0.09 (2.37)  0.03  LV mass (gr)  179.9 ± 46.8  0.22 (0.40)  <0.001  0.35 (0.15)  <0.001  0.27 (22.0)  <0.001  LV mass index (gr/m2)  101.8 ± 23.9  0.02 (0.21)  0.57  0.19 (0.08)  0.003  0.19 (11.43)  <0.001  e’ (cm/s)  7.4 ± 1.7  −0.08 (0.02)  0.05  −0.13 (0.006)  0.001  −0.13 (0.83)  0.001  E/e’  10.2 ± 3.1  0.12 (0.03)  0.003  0.07 (0.01)  0.10  −0.01 (1.54)  0.78  LAVmax (mL)  47.7 ± 12.4  0.11 (0.11)  0.004  0.18 (0.04)  <0.001  0.09 (6.03)  0.02  LAVmin (mL)  23.6 ± 9.5  0.10 (0.08)  0.01  0.18 (0.03)  <0.001  0.11 (4.61)  0.007  LAEVI (mL/m2)  10.8 ± 3.6  −0.09 (0.03)  0.02  −0.13 (0.01)  0.002  −0.08 (1.78)  0.06  LAEF (%)  45.3 ± 11.4  −0.05  0.18  −0.10  0.01  −0.08  0.05  LAEI (%)  91.3 ± 42.0  −0.06 (0.36)  0.17  −0.10 (0.14)  0.01  −0.08 (20.43)  0.05  BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; SE, standard error; LV, left ventricular; LAVmax, LA maximum volume; LAV, LA minimum volume; LAEVI, LA total emptying volume index; LAEF, LA total emptying fraction; LAEI, LA expansion index. Figure 2 displays the unadjusted relationship between quintiles of body size metrics (BMI, WC, and WHR) and LA phasic volumes (LAVmax and LAVmin) with intergroup differences. There was a significant linear trend between the quintiles of WC and WHR with LAVmax (P = 0.004 and P = 0.04, respectively) and LAVmin (P = 0.006 and P = 0.001, respectively). On the other hand, quintiles of BMI did not show a significant linear trend with either LAVmax or LAVmin. Figure 3 displays the unadjusted relationship between quintiles of body size metrics (BMI, WC, and WHR) and LA reservoir function (LAEVI, LAEF, and LAEI) with intergroup differences. WC quintiles showed a significant linear trend with LAEVI (P = 0.02) with significant intergroup differences, whereas quintiles of BMI and WHR did not reveal a significant linear trend with LAEVI. Quintiles of all body size metrics (BMI, WC, and WHR) did not show a linear trend with LAEF and LAEI, however there were significant intergroup differences between the quintiles of WC and WHR, and LAEF and LAEI (both P < 0.05). BMI quintiles did not reveal any significant intergroup differences for LAEF and LAEI. Figure 2 View largeDownload slide Relationship between quintiles of body size metrics with left atrial phasic volumes. *P < 0.05 vs. Q1, ‡P < 0.05 vs. Q1 and Q2. BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; Q, quintile. Figure 2 View largeDownload slide Relationship between quintiles of body size metrics with left atrial phasic volumes. *P < 0.05 vs. Q1, ‡P < 0.05 vs. Q1 and Q2. BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; Q, quintile. Figure 3 View largeDownload slide Relationship between quintiles of body size metrics with left atrial reservoir function. *P < 0.05 vs. Q1, ‡P < 0.05 vs. Q1 and Q2. BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; Q, quintile. Figure 3 View largeDownload slide Relationship between quintiles of body size metrics with left atrial reservoir function. *P < 0.05 vs. Q1, ‡P < 0.05 vs. Q1 and Q2. BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; Q, quintile. Univariate associations of BMI, WC, and WHR with LA phasic volumes and reservoir function are shown in Table 2. Higher BMI was significantly associated with higher LA phasic volumes (LAVmax and LAVmin), and reduced LAEVI (all P < 0.05), but showed no association with LAEF and LAEI. Higher WC was significantly associated with higher LA phasic volumes (LAVmax and LAVmin), and reduced LA reservoir function (LAEVI, LAEF, and LAEI, all P < 0.05). Higher WHR was significantly associated with higher LA phasic volumes (LAVmax and LAVmin, both P < 0.05), but was not associated with LA reservoir function. When WC and BMI were entered into the same model, the association between LA phasic volumes, LA reservoir function and WC became stronger, whereas BMI lost its association with LA phasic volumes (Table 3). When WHR and BMI were entered into the same model, WHR remained significantly associated only with LAVmin, and BMI lost its association with LA volumes (also Table 3). In a multivariate model adjusted for potential confounders, higher WC remained significantly associated with higher LA phasic volumes (LAVmax, β = 0.10, P = 0.007 and LAVmin, β = 0.12, P = 0.002) and reduced reservoir function (LAEVI, β = −0.15, P = 0.001 and LAEI, β = −0.09, P = 0.027), whereas higher WHR remained only significantly associated with reduced LAEVI (β = −0.11, P = 0.012) (Table 4). Table 3 Adjusted relationships of general obesity and abdominal adiposity with left atrial volumes and reservoir function   BMIa   WCb   WHRb     β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  LAVmax (mL)  −0.03 (0.15)  0.63  0.20 (0.06)  <0.001  0.08 (6.02)  0.05  LAVmin (mL)  −0.05 (0.12)  0.36  0.20 (0.05)  <0.001  0.10 (4.61)  0.010  LAEVI (mL/m2)  −0.01 (0.04)  0.85  −0.11 (0.02)  0.04  −0.07 (1.78)  0.095  LAEF (%)  0.03 (0.14)  0.57  −0.12 (0.06)  0.03  −0.07 (5.56)  0.070  LAEI (%)  0.04 (0.51)  0.53  −0.13 (0.20)  0.02  −0.07 (20.51)  0.065    BMIa   WCb   WHRb     β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  LAVmax (mL)  −0.03 (0.15)  0.63  0.20 (0.06)  <0.001  0.08 (6.02)  0.05  LAVmin (mL)  −0.05 (0.12)  0.36  0.20 (0.05)  <0.001  0.10 (4.61)  0.010  LAEVI (mL/m2)  −0.01 (0.04)  0.85  −0.11 (0.02)  0.04  −0.07 (1.78)  0.095  LAEF (%)  0.03 (0.14)  0.57  −0.12 (0.06)  0.03  −0.07 (5.56)  0.070  LAEI (%)  0.04 (0.51)  0.53  −0.13 (0.20)  0.02  −0.07 (20.51)  0.065  BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; SE, standard error; LV, left ventricular; LAVmax, LA maximum volume; LAVmin, LA minimum volume; LAEVI, LA total emptying volume index; LAEF, LA total emptying fraction; LAEI, LA expansion index. a Adjusted for WC. b Adjusted for BMI. Table 3 Adjusted relationships of general obesity and abdominal adiposity with left atrial volumes and reservoir function   BMIa   WCb   WHRb     β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  LAVmax (mL)  −0.03 (0.15)  0.63  0.20 (0.06)  <0.001  0.08 (6.02)  0.05  LAVmin (mL)  −0.05 (0.12)  0.36  0.20 (0.05)  <0.001  0.10 (4.61)  0.010  LAEVI (mL/m2)  −0.01 (0.04)  0.85  −0.11 (0.02)  0.04  −0.07 (1.78)  0.095  LAEF (%)  0.03 (0.14)  0.57  −0.12 (0.06)  0.03  −0.07 (5.56)  0.070  LAEI (%)  0.04 (0.51)  0.53  −0.13 (0.20)  0.02  −0.07 (20.51)  0.065    BMIa   WCb   WHRb     β (SE)  P-value  β (SE)  P-value  β (SE)  P-value  LAVmax (mL)  −0.03 (0.15)  0.63  0.20 (0.06)  <0.001  0.08 (6.02)  0.05  LAVmin (mL)  −0.05 (0.12)  0.36  0.20 (0.05)  <0.001  0.10 (4.61)  0.010  LAEVI (mL/m2)  −0.01 (0.04)  0.85  −0.11 (0.02)  0.04  −0.07 (1.78)  0.095  LAEF (%)  0.03 (0.14)  0.57  −0.12 (0.06)  0.03  −0.07 (5.56)  0.070  LAEI (%)  0.04 (0.51)  0.53  −0.13 (0.20)  0.02  −0.07 (20.51)  0.065  BMI, body mass index; WC, waist circumference; WHR, waist-to-hip ratio; SE, standard error; LV, left ventricular; LAVmax, LA maximum volume; LAVmin, LA minimum volume; LAEVI, LA total emptying volume index; LAEF, LA total emptying fraction; LAEI, LA expansion index. a Adjusted for WC. b Adjusted for BMI. Table 4 Association of abdominal adiposity measured by WC and WHR with left atrial volumes and reservoir function after multivariate adjustment   WCa   WHRa     β (SE)  P-value  β (SE)  P-value  LAVmax (mL)  0.10 (0.10)  0.008  −0.06 (6.10)  0.14  LAVmin (mL)  0.12 (0.08)  0.002  −0.03 (4.49)  0.55  LAEVI (mL/m2)  −0.15 (0.03)  <0.001  −0.11 (2.0)  0.012  LAEF (%)  −0.07 (0.10)  0.057  −0.04 (5.62)  0.34  LAEI (%)  −0.09 (0.36)  0.027  −0.03 (21.18)  0.44    WCa   WHRa     β (SE)  P-value  β (SE)  P-value  LAVmax (mL)  0.10 (0.10)  0.008  −0.06 (6.10)  0.14  LAVmin (mL)  0.12 (0.08)  0.002  −0.03 (4.49)  0.55  LAEVI (mL/m2)  −0.15 (0.03)  <0.001  −0.11 (2.0)  0.012  LAEF (%)  −0.07 (0.10)  0.057  −0.04 (5.62)  0.34  LAEI (%)  −0.09 (0.36)  0.027  −0.03 (21.18)  0.44  WC, waist circumference; WHR, waist-to-hip ratio; SE, standard error; LV, left ventricular; LAVmax, LA maximum volume; LAVmin, LA minimum volume; LAEVI, LA total emptying volume index; LAEF, LA total emptying fraction; LAEI, LA expansion index. a Adjusted for age, gender, hypertension, hypertension medication, diabetes, coronary artery disease, left ventricular ejection fraction, left ventricular mass index [LV mass/body surface area (BSA)] and E/e’. Table 4 Association of abdominal adiposity measured by WC and WHR with left atrial volumes and reservoir function after multivariate adjustment   WCa   WHRa     β (SE)  P-value  β (SE)  P-value  LAVmax (mL)  0.10 (0.10)  0.008  −0.06 (6.10)  0.14  LAVmin (mL)  0.12 (0.08)  0.002  −0.03 (4.49)  0.55  LAEVI (mL/m2)  −0.15 (0.03)  <0.001  −0.11 (2.0)  0.012  LAEF (%)  −0.07 (0.10)  0.057  −0.04 (5.62)  0.34  LAEI (%)  −0.09 (0.36)  0.027  −0.03 (21.18)  0.44    WCa   WHRa     β (SE)  P-value  β (SE)  P-value  LAVmax (mL)  0.10 (0.10)  0.008  −0.06 (6.10)  0.14  LAVmin (mL)  0.12 (0.08)  0.002  −0.03 (4.49)  0.55  LAEVI (mL/m2)  −0.15 (0.03)  <0.001  −0.11 (2.0)  0.012  LAEF (%)  −0.07 (0.10)  0.057  −0.04 (5.62)  0.34  LAEI (%)  −0.09 (0.36)  0.027  −0.03 (21.18)  0.44  WC, waist circumference; WHR, waist-to-hip ratio; SE, standard error; LV, left ventricular; LAVmax, LA maximum volume; LAVmin, LA minimum volume; LAEVI, LA total emptying volume index; LAEF, LA total emptying fraction; LAEI, LA expansion index. a Adjusted for age, gender, hypertension, hypertension medication, diabetes, coronary artery disease, left ventricular ejection fraction, left ventricular mass index [LV mass/body surface area (BSA)] and E/e’. Discussion In this study, among indices of adiposity, only WC was independently associated with LA phasic volumes (LAVmax and LAVmin) and reservoir function (LAEVI and LAEI) in the elderly, whereas WHR remained only associated with LAEVI, and BMI showed no association with LA phasic volumes when simultaneously entered with WC into the model. This study was carried out in an elderly community based cohort with no history of AF and LV dysfunction, and no more than mild mitral regurgitation detected by echocardiography. WC therefore can be considered to be directly associated with reduced LA reservoir function and increased LA volumes. BMI is commonly used as a measure of obesity in clinical studies because of its ease of acquisition and well-documented association with cardiovascular events and mortality.16 However, the association of an increased BMI with mortality seems to be less pronounced in elderly than in younger populations, as in older people BMI is a poor measure of body fat.17,18 The measurement of weight does not differentiate between fat and fat-free mass, and fat-free mass (muscle) is progressively lost with increasing age.19 In a previous study, abdominal adiposity, but not BMI, was associated with a greater risk of death in adults aged over 75 years.20 The observations from the present and previous studies suggest that abdominal adiposity measures have the potential to show a different impact than BMI on cardiovascular risk, and perhaps add to the information provided by BMI alone. An increase in LA volume is associated with the development of atrial arrhythmias and is a predictor of cardiovascular events, especially in the elderly.4,21 In a cohort of 1160 elderly patients with cardiovascular disease referred for echocardiography, both LA volume index and LV diastolic dysfunction were independently predictive of cardiovascular events.22 Both obesity and aging have been identified as independent predictors of LA enlargement.1 Indeed, in the present study, although the values of the LA volumes were within the expected normal ranges, higher BMI was significantly associated with both higher LAVmax and LAVmin, and these associations were stronger for WC.23 When BMI and WC were simultaneously entered into the same model, the association between LA volumes and WC became stronger, whereas the association between BMI and LA volumes was lost. When body size metrics were divided into quintiles, WC and WHR revealed a significant linear trend for LAmax and LAVmin, whereas there was no trend observed between BMI, LAVmax, and LAVmin. Most of the previous studies that looked into the association of LA size and obesity were conducted in selected samples or in cohorts of significantly younger age, in which the increase in BMI is paralleled by an increase of both fat and fat-free mass. Also, the LA volumes were evaluated by 2D rather than 3D echocardiography. LA enlargement occurs in all three spatial dimensions, but not uniformly, with the medial-lateral LA expansion being less prominent than the longitudinal and anteroposterior expansion. Therefore, changes in LA volume during the cardiac cycle may not be accurately evaluated by 2D echocardiography, as the shape of the LA changes during the cycle. RT3D echocardiography, have made it possible to measure the change in LA volume throughout the cardiac cycle, and to assess the LA reservoir function. LA volume measurements by RT3D echocardiography correlate closely with those obtained on magnetic resonance imaging.24 It was recently shown that parameters derived from RT3D LA volume tend to be stronger predictors of paroxysmal atrial fibrillation than those obtained with 2D volume.25 LA function has been reported to be abnormal due mainly to increased LV filling pressure, which is a reflection of LV cavity stiffness, and is manifested in the form of increased LA volume, reduced reservoir and overall pump function.26–28 A reduced LA reservoir function is associated with hypertension, LV hypertrophy, LV diastolic dysfunction, and other cardiovascular risk factors, and therefore could be a surrogate marker of cardiovascular risk, including predisposal to atrial arrhythmias.4,29 In fact, the LA reservoir function has been demonstrated to be a better correlate of LV diastolic dysfunction and better predictor of incident atrial arrhythmias and new-onset AF than indexed LAVmax.4,30 Very limited data is available to date that evaluated the relationship between LA reservoir function and body size metrics. In a recent study, 164 untreated hypertensive subjects were separated into 3 groups (lean, overweight and obese) according to their BMI, and the LA reservoir function was evaluated by 2D echocardiography.31 LA reservoir function gradually decreased, from lean to obese hypertensive patients. The study population was considerably younger compared with our population, with a limited number of subjects in each group. We did not find any association between WHR and LA reservoir function in the univariate analysis, and BMI was only associated with LAEVI, whereas WC was significantly associated with all LA reservoir function parameters (LAEVI, LAEF and LAEI). After adjusting for potential confounders that could impact LA reservoir function, higher WC remained significantly associated with reduced LA reservoir function. Although WC and WHR are both used to measure abdominal adiposity, quintiles of WHR were less related to LA phasic volumes than of WC, and not related to LA reservoir function. This finding is in line with a previous study that compared BMI, WHR, and WC as predictors with all-cause mortality in the elderly, observing that the higher quintiles of WC, but not of BMI and WHR, were related to increased mortality.32 Another study found WC to be the best anthropometric measure for identifying individuals with cardiovascular risk factors.33 WC is easier to measure than WHR and it is associated with few measurement errors. WHR is more difficult to interpret, especially in the elderly, because it is the ratio of two complex variables, such as increased WHR may reflect both greater intraabdominal fat mass (higher WC) and/or reduced gluteofemoral muscle mass (lower hip circumference).34 To our knowledge, the present study is the first to assess the relationship between body size metrics and LA phasic volumes and reservoir function using RT3D echocardiography in a large, tri-ethnic, community-based cohort of elderly subjects. The current results from this study are consistent with our previous data on the relationship between abdominal adiposity and subclinical left ventricular dysfunction, which might also be implicated in the pathophysiology of LA dysfunction in the elderly.8 The strengths of our study include the large number of subjects studied, the minimal risk of selection bias (as the study sample was derived from a community-cohort study that employed random participant selection), the fact that a wide range of cardiovascular risk profiles were present in our study population, and the confirmation of our findings after adjustment for pertinent confounders. Moreover, we used state-of-the art technique, RT3D echocardiography, which has been demonstrated to be more accurate than 2 D assessment by comparison with non-echocardiographic gold standards, and has shown better reproducibility.24 However, our study has limitations. Since the study population included subjects > 50 years of age, our results may not fully apply to younger subjects. Also, the high cardiovascular risk profile of the study participants might preclude the generalization of our findings to populations with lower cardiovascular risk. The cross-sectional design of the analysis allowed us to describe associations between abdominal adiposity metrics and LA phasic volumes and reservoir function, but not to draw conclusions regarding cause–effect relationships. The coefficients of determination of the adjusted multiple regression analysis were low, which indicate that there may be nonlinear relationship as well as some biological variability in atrial dimensions not explained entirely by demographic and anthropometric variables. Finally, although we used clinically accepted metrics of body size (BMI, WC, and WHR), in the elderly population body fat estimation has difficulties using conventional anthropometric indices for both genders.35 The assessment of fat mass and fat-free mass, which is helpful to better understand the relationships between body size and body composition, was not performed in our study. In conclusion, in this community cohort of prevalently elderly subjects, only WC among indices of body size was associated with greater LA phasic volumes and reduced LA reservoir function, independent of other confounders. The simple measurement of WC may improve the cardiovascular risk stratification in the elderly. Conflict of interest: None declared. Acknowledgements The authors wish to thank Janet De Rosa, MPH (project manager), Rafi Cabral, MD, Michele Alegre, RDCS, and Palma Gervasi-Franklin (collection and management of the data). 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European Heart Journal – Cardiovascular ImagingOxford University Press

Published: Oct 20, 2017

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