Background
Currently available echocardiographic reference values are derived mainly from North American and European population studies, and no echocardiographic reference values are available for the Chinese population. The aim of this study was to establish normal values of echocardiographic measurements of the cardiac chambers and great arteries in a nationwide, population-based cohort of healthy Han Chinese adults.
Methods
A total of 1,586 healthy Han Chinese volunteers aged 18 to 79 years were screened at 43 collaborating laboratories throughout China. Standard M-mode and two-dimensional echocardiography was performed to obtain measurements of the cardiac chambers and great arteries. The impacts of gender and age on all echocardiographic measurements were analyzed.
Results
A total of 1,394 qualified healthy subjects (mean age, 47.3 ± 16.0 years; 678 men) were ultimately enrolled. Except for left ventricular ejection fraction, values of cardiac chamber and great arterial dimensions were significantly higher in men than in women. Most measurements of the atrial and great arterial dimensions, left ventricular wall thickness, and left ventricular mass increased with age in both men and women.
Conclusions
Normal reference values of cardiac dimensional parameters were established for the first time in a nationwide, population-based cohort of healthy Han Chinese adults. Because most of these parameters were found to vary with gender and age, reference values stratified for gender and age should be used in clinical practice.
Quantitative measurements of cardiac chamber dimensions and function are crucial to disease severity estimation and therapeutic effect assessment, and a widely accepted set of normal reference values of echocardiographic measurements is indispensable for distinguishing normality from abnormality. Recent studies have demonstrated that ethnicity-related differences exist in cardiac dimensions. However, currently available echocardiographic reference values are derived mainly from North American and European population studies with wide heterogeneity of inclusion and exclusion criteria, and no nationwide echocardiographic reference values are available for the healthy Chinese population. Therefore, it is highly warranted to establish race-specific echocardiographic reference values for the Chinese population to facilitate a quick and proper judgment in daily clinical practice. From January 2012 to December 2012, the Echocardiography Working Group of the Chinese Society of Ultrasound in Medicine designed, organized, and conducted a prospective, nationwide, multicenter study, Echocardiographic Measurements in Normal Chinese Adults (EMINCA), with the purpose of establishing normal reference values of cardiac chamber and great arterial dimensions (Part 1) as well as Doppler parameters (Part 2) and to identify the impacts of gender and age on these echocardiographic parameters in a large population of healthy Han Chinese adults over a wide range of ages. Here we report the results of EMINCA Part 1.
Methods
Study Population
The EMINCA study was initially designed to enroll a total of 1,320 healthy Han Chinese volunteers aged 18 to 79 years, who were divided into six age groups: 18 to 29, 30 to 39, 40 to 49, 50 to 59, 60 to 69, and 70 to 79 years ( n = 220 in each group, 50% men). All participating echocardiographic laboratories were to be from the tertiary hospitals of all provinces and municipalities throughout China except Taiwan and should be accredited by the Chinese Society of Ultrasound in Medicine. The healthy volunteers were recruited mainly from hospital staff members, health examination centers, and adjacent communities. The inclusion criteria required that all volunteers be aged 18 to 79 years, have Han nationality, have normal blood pressure (systolic blood pressure [SBP] < 140 mm Hg, diastolic blood pressure [DBP] < 90 mm Hg), have normal results on physical examination and electrocardiography, and have no history of cardiovascular diseases. The exclusion criteria were coronary artery disease, structural heart disease, heart failure, hypertension, stroke, hyperlipidemia (serum total cholesterol ≥ 5.72 mmol/L or triglyceride ≥ 1.70 mmol/L), diabetes mellitus (fasting blood glucose > 7.0 mmol/L), and any other endocrine diseases, acute or chronic respiratory diseases, anemia, connective tissue disease, abnormal liver function (serum alanine aminotransferase or aspartate aminotransferase > 2.0 times the upper limit of normal), abnormal renal function (serum creatinine > 2 mg/dL), obesity (body mass index ≥ 28.0 kg/m 2 ), abnormal results on electrocardiography, valvular stenosis, more than mild valvular regurgitation, or wall motion abnormalities on echocardiographic recordings. Professional athletes, pregnant or lactating women, subjects addicted to alcohol, and subjects with inadequate echocardiographic images were also excluded. Body surface area (BSA) was calculated using the formula of Du Bois and Du Bois.
The study protocol was approved by the ethical committees of all collaborating hospitals, and written informed consent was obtained from all volunteers participating in this study. The EMINCA study was registered as ChiCTR-OCS-12002119 at the Chinese Clinical Trial Registry ( http://www.chictr.org ) , an authorized registry organization of the International Clinical Trial Registry Platform of the World Health Organization.
Echocardiographic Image Acquisition
In an attempt to standardize echocardiographic image acquisitions and measurements, one or two experienced sonographers from each of the participating laboratories received intensive training at one of the two core laboratories (Shandong University Qilu Hospital and Sichuan Provincial People’s Hospital) to get acquainted with the study protocol and to derive standard images and measurements.
Commercially available ultrasound equipment, the Philips iE33 (Philips Ultrasound, Bothell, WA) or the GE Vivid E9 (GE Vingmed Ultrasound AS, Horten, Norway), was used for this study. Standard M-mode and two-dimensional echocardiography were performed in all subjects according to American Society of Echocardiography (ASE) guidelines. After the technical parameters were adjusted to obtain optimal images, all subjects were connected to an electrocardiograph and examined in the left lateral decubitus position to obtain the parasternal and apical cross-sectional views or in the supine position to obtain the subcostal and suprasternal cross-sectional views. To minimize the impact of respiratory motion on echocardiographic parameters, images were acquired during breath holding at the end of expiration. To avoid left atrial (LA) and right atrial (RA) or left ventricular (LV) or right ventricular (RV) foreshortening in the apical views, great care was taken to angulate the transducer to separately image the maximal LA and RA or LV and RV chambers. The frame rate was set at ≥50 sec −1 for two-dimensional echocardiographic recordings. At least five cardiac cycles were recorded from each view on optical disks in digital Digital Imaging and Communications in Medicine format for online and offline analyses.
Echocardiographic Image Analysis
Image analyses were initially performed at each participating center laboratory. All echocardiographic measurements were made over three cardiac cycles, and the mean values were calculated. The demographic and echocardiographic data were reported on spreadsheets which, together with the optical disks, were sent to one of the two core laboratories at which two experienced echocardiographers (G.-H.Y., from Shandong University Qilu Hospital, and Y.D. from Sichuan Provincial People’s Hospital) evaluated the image quality and measurement accuracy and then made remeasurements of all echocardiographic parameters. Measurements from the core laboratories were used for final statistical analysis.
All echocardiographic measurements were made at ventricular end-diastole or end-systole. Ventricular end-diastole was defined as the frame following the atrioventricular valve closure or the frame in which the ventricular dimension was the largest, and ventricular end-systole was defined as the frame preceding the atrioventricular valve opening or the frame in which the ventricular dimension was the smallest. For the measurement of aortic and pulmonary arterial diameters, the peak of the R wave on the simultaneously recorded electrocardiogram was used to define end-diastole. The aortic dimensions were measured at end-diastole using the leading edge–to–leading edge convention, whereas other cardiac chamber dimensions and ventricular wall thickness were measured using the black-white interface.
Quantification of the Left Atrium and Left Ventricle
LA size was measured at ventricular end-systole when the LA chamber was the largest during the cardiac cycle. The anteroposterior dimension of the left atrium (LA-ap) was obtained from the parasternal long-axis view and measured distal to the aortic sinus and perpendicular to the aortic posterior wall. From the apical four-chamber view, the long-axis length of the left atrium was determined as the distance between the midpoint of the mitral annular plane and the superior wall of the left atrium, which was not necessarily perpendicular to the mitral annular plane. The transverse dimension of the left atrium was measured as the distance from the midpoint of the interatrial septum to the lateral wall, which should be perpendicular to LA long-axis length. LA area was traced from the apical four-chamber view with the LA appendage and confluences of the pulmonary veins being excluded. LA volume (LAV) was measured using the biplane Simpson’s rule in the apical four- and two-chamber views.
Interventricular septal end-diastolic thickness (IVSd) and interventricular septal end-systolic thickness (IVSs), LV posterior wall end-diastolic thickness (LVPWd) and LV posterior wall end-systolic thickness (LVPWs), and LV end-diastolic diameter (LVEDD) and LV end-systolic diameter were measured from the parasternal long-axis view at the level of the mitral valve leaflet tips ( Figure 1 A). In cases in which the endocardial or epicardial borders were difficult to define, M-mode echocardiography was used to measure IVSd, IVSs, LVPWd, and LVPWs. The diameter of the LV outflow tract was determined at a level 1 cm proximal to the aortic valve annulus at ventricular end-systole in the long-axis view. LV end-diastolic volume (LVEDV) and LV end-systolic volume and LV ejection fraction (LVEF) were measured using the biplane Simpson’s rule in the apical four- and two-chamber views. And LV mass (LVM) was calculated by the following formula :
LVM ( g ) = 0.8 × { 1.04 [ ( IVSd + LVEDD + LVPWd ) 3 − ( LVEDD ) 3 ] } + 0.6
Quantification of Right Atrium and Right Ventricle
From the apical four-chamber view, the RA long-axis dimension (RA-l) and RA transverse dimension (RA-t) were gauged at end-systole, while the RV long-axis, middle, and basal dimensions were measured at end-diastole. RA-l was determined as the distance between the midpoint of the tricuspid annulus plane to the superior wall of the right atrium, whereas RA-t was measured as the distance from the midpoint of interatrial septum to the lateral wall, which should be perpendicular to RA-l. At end-diastole, the RV anterior wall thickness and anteroposterior dimension were determined from the parasternal long-axis view, and the RV free wall thickness was assessed from the subcostal view at the level of the tricuspid valve chordae tendineae. The systolic diameter of the RV outflow tract was measured at a level 2 cm proximal to the pulmonary valve annulus from the parasternal short-axis view.
Quantification of Great Arteries
The parasternal long-axis view was recorded to visualize the aortic root and proximal ascending aorta. Diameters of the aortic annulus, aortic sinus, and proximal ascending aorta at a level 2 cm above the sinotubular junction were individually measured at end-diastole ( Figure 1 B). Similarly, at end-diastole, from the parasternal aortic short-axis view, diameters of the pulmonary valve annulus, main pulmonary artery at a level 1 cm distal to the pulmonary valve annulus, left pulmonary artery, and right pulmonary artery at a level 1 cm distal to the bifurcation were obtained. Measurement of the diameters of the aortic arch and descending aorta were made at end-diastole from the suprasternal aortic arch long-axis view.
Interobserver and Intraobserver Variability
To test the reproducibility of measurements, four key parameters, including LA-ap, LAV, LVEDD, and LVEDV, were remeasured in 50 randomly selected subjects from the two core laboratories. Interobserver variability was assessed between the two core laboratories (by G.-H.Y., from Shandong University Qilu Hospital, and Y.D., from Sichuan Provincial People’s Hospital) and intraobserver variability was assessed by G.-H.Y., from Shandong University Qilu Hospital. The method of Bland-Altman plots was used to analyze interobserver and intraobserver variability, and interclass correlation coefficients were calculated.
Statistical Analysis
SPSS version 16.0 (SPSS, Inc, Chicago, IL) was used for data analysis. Data were stratified by gender and age and are expressed as the mean ± SD. Independent-samples t tests were used to compare the mean values between men and women and between subjects aged 18 to 29 years and other age groups. Analysis of variance was applied to compare values among age groups stratified by gender. Online MedCalc software was used to perform Bland-Altman analysis. Two-tailed P values < .05 were considered statistically significant.
Results
Study Population
We initially screened 1,586 subjects, and a total of 1,394 healthy volunteers who met the inclusion and exclusion criteria were ultimately enrolled from 43 collaborating laboratories. There were 678 men aged 47.1 ± 16.2 years and 716 women aged 47.5 ± 15.8 years. Demographic data and a total of 34 echocardiographic parameters were obtained from these subjects.
Demographic Features
As shown in Table 1 , the mean values of height, weight, body mass index, BSA, SBP, and DBP were significantly higher in men than in women in the whole population ( P < .001), whereas no significant differences in age and heart rate were found between men and women ( P > .05). There was no significant difference in heart rate among the six age groups in both genders ( P > .05), though compared with subjects aged 18 to 29 years, heart rates were lower in those aged 50 to 59 and 70 to 79 years in men and in those aged 40 to 49 years in women ( P < .05). Height, weight, body mass index, BSA, SBP, and DBP were all significantly different among the six age groups ( P < .01). The highest value of height was in subjects aged 30 to 39 years in men and in those aged 18 to 23 years in women. The highest values of weight and BSA were in subjects aged 30 to 39 years in men and in those aged 40 to 49 years in women. The highest values of SBP and DBP were in subjects aged 70 to 79 years in men and in those aged 60 to 69 years in women.
| Parameter | Men | Women | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Total ( n = 678) | 18–29 y ( n = 128) | 30–39 y ( n = 118) | 40–49 y ( n = 138) | 50–59 y ( n = 106) | 60–69 y ( n = 105) | 70–79 y ( n = 83) | P | Total ( n = 716) | 18–29 y ( n = 116) | 30–39 y ( n = 139) | 40–49 y ( n = 135) | 50–59 y ( n = 141) | 60–69 y ( n = 97) | 70–79 y ( n = 88) | P | |
| Age (y) | 47.1 ± 16.2 | 25.1 ± 2.4 | 34.5 ± 2.8 † | 44.5 ± 3.1 † | 54.5 ± 3.0 † | 63.4 ± 2.9 † | 73.5 ± 2.7 † | <.001 | 47.5 ± 15.8 | 24.6 ± 2.7 | 35.0 ± 2.9 † | 44.6 ± 3.0 † | 54.4 ± 2.8 † | 63.4 ± 3.1 † | 73.2 ± 2.8 † | <.001 |
| Height (cm) | 171 ± 6 | 173 ± 6 | 173 ± 6 | 172 ± 5 | 170 ± 5 † | 170 ± 6 † | 169 ± 7 † | <.001 | 160 ± 5 ‡ | 162 ± 5 | 161 ± 5 | 160 ± 5 ∗ | 159 ± 5 † | 158 ± 6 † | 157 ± 6 † | <.001 |
| Weight (kg) | 67.6 ± 7.9 | 67.0 ± 7.7 | 69.7 ± 7.8 † | 69.5 ± 7.1 † | 67.2 ± 8.1 | 67.0 ± 7.6 | 63.8 ± 8.0 † | <.001 | 56.1 ± 6.6 ‡ | 54.0 ± 5.6 | 56.0 ± 6.2 ∗ | 57.7 ± 6.8 † | 56.8 ± 6.5 † | 56.4 ± 7.1 † | 54.9 ± 7.2 | <.001 |
| BMI (kg/m 2 ) | 23.0 ± 2.1 | 22.3 ± 2.1 | 23.2 ± 2.0 † | 23.5 ± 1.9 † | 23.3 ± 2.2 † | 23.2 ± 2.0 † | 22.4 ± 2.0 | <.001 | 22.0 ± 2.3 ‡ | 20.6 ± 1.9 | 21.5 ± 2.2 † | 22.5 ± 2.2 † | 22.4 ± 2.2 † | 22.6 ± 1.9 † | 22.3 ± 2.4 † | <.001 |
| BSA (m 2 ) | 1.82 ± 0.13 | 1.83 ± 0.12 | 1.86 ± 0.10 ∗ | 1.85 ± 0.11 | 1.80 ± 0.13 | 1.80 ± 0.13 | 1.75 ± 0.10 † | <.001 | 1.60 ± 0.11 ‡ | 1.59 ± 0.09 | 1.61 ± 0.10 | 1.62 ± 0.11 † | 1.60 ± 0.10 | 1.59 ± 0.12 | 1.56 ± 0.12 | <.001 |
| SBP (mm Hg) | 121 ± 9 | 118 ± 9 | 119 ± 9 | 119 ± 8 | 122 ± 9 † | 123 ± 10 † | 126 ± 9 † | <.001 | 116 ± 11 ‡ | 111 ± 11 | 112 ± 10 | 116 ± 10 † | 117 ± 11 † | 122 ± 9 † | 122 ± 11 † | <.001 |
| DBP (mm Hg) | 77 ± 7 | 75 ± 6 | 76 ± 6 | 77 ± 7 | 78 ± 7 ∗ | 77 ± 6 ∗ | 78 ± 8 † | <.001 | 74 ± 8 ‡ | 72 ± 7 | 72 ± 8 | 75 ± 8 † | 75 ± 7 † | 77 ± 8 † | 74 ± 8 ∗ | <.001 |
| HR (beats/min) | 72.2 ± 8.5 | 73.6 ± 8.6 | 72.6 ± 8.5 | 72.6 ± 8.7 | 70.1 ± 8.7 ∗ | 72.2 ± 8.2 | 70.6 ± 7.8 ∗ | >.05 | 72.9 ± 8.1 | 73.7 ± 7.7 | 73.3 ± 7.7 | 71.5 ± 7.5 ∗ | 71.8 ± 8.5 | 72.9 ± 9.0 | 75.1 ± 7.7 | >.05 |
Measurements of Left Atrium and Left Ventricle
As listed in Table 2 , the LA measurements, including LA-ap, LA long-axis length, LA transverse dimension, LA area, and LAV, were all significantly higher in men than in women in the whole population ( P < .001). They all increased with age in both genders ( P < .05–.001). The highest values of LA parameters were in subjects aged 70 to 79 years in both men and women.
| Parameter | Men | Women | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Total ( n = 678) | 18–29 y ( n = 128) | 30–39 y ( n = 118) | 40–49 y ( n = 138) | 50–59 y ( n = 106) | 60–69 y ( n = 105) | 70–79 y ( n = 83) | P | Total ( n = 716) | 18–29 y ( n = 116) | 30–39 y ( n = 139) | 40–49 y ( n = 135) | 50–59 y ( n = 141) | 60–69 y ( n = 97) | 70–79 y ( n = 88) | P | |
| LA-ap (mm) | 31.1 ± 3.9 | 29.3 ± 3.8 | 30.5 ± 3.4 ∗ | 31.5 ± 3.7 † | 31.5 ± 4.0 † | 31.9 ± 3.7 † | 32.9 ± 3.8 † | <.001 | 29.4 ± 3.8 ‡ | 27.7 ± 3.4 | 28.0 ± 3.4 | 29.7 ± 3.9 † | 29.6 ± 3.5 † | 30.9 ± 3.8 † | 31.3 ± 3.7 † | <.001 |
| LA-l (mm) | 46.8 ± 5.9 | 44.8 ± 5.9 | 45.9 ± 5.7 | 46.0 ± 5.6 | 47.9 ± 5.6 † | 48.1 ± 5.4 † | 49.4 ± 6.3 † | <.001 | 45.1 ± 5.8 ‡ | 42.9 ± 5.6 | 43.9 ± 5.5 | 45.2 ± 6.0 † | 45.6 ± 5.2 † | 47.0 ± 5.2 † | 47.1 ± 6.2 † | <.001 |
| LA-t (mm) | 35.7 ± 4.6 | 35.0 ± 4.6 | 35.8 ± 5.0 | 35.5 ± 4.4 | 35.9 ± 4.4 | 35.4 ± 4.7 | 37.2 ± 4.4 † | <.05 | 34.6 ± 4.3 ‡ | 34.1 ± 4.1 | 33.3 ± 4.0 | 35.3 ± 4.5 ∗ | 34.5 ± 4.4 | 34.7 ± 4.3 | 35.9 ± 4.2 † | <.001 |
| LAA (cm 2 ) | 14.7 ± 3.2 | 14.0 ± 2.9 | 14.3 ± 3.0 | 14.1 ± 2.7 | 15.3 ± 3.4 † | 15.2 ± 3.4 † | 16.4 ± 3.3 † | <.001 | 13.9 ± 2.8 ‡ | 12.9 ± 2.5 | 13.0 ± 2.7 | 13.9 ± 2.8 † | 14.3 ± 2.9 † | 14.7 ± 2.6 † | 15.2 ± 3.1 † | <.001 |
| LAV (mL) | 38.0 ± 11.6 | 36.3 ± 10.9 | 36.4 ± 10.6 | 36.5 ± 9.3 | 38.8 ± 12.9 | 39.4 ± 13.4 | 42.4 ± 11.7 † | <.01 | 34.8 ± 10.7 ‡ | 31.1 ± 9.3 | 31.9 ± 10.8 | 35.3 ± 9.7 † | 35.6 ± 10.3 † | 37.3 ± 10.2 † | 39.0 ± 12.2 † | <.001 |
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