Refining the upper limit of normal for the ascending aorta: In search of optimal criteria ‐‐ a large database study of normal individuals

Abstract

Objectives

The cutoff for dilated mid-ascending aorta (mAA) is controversial and has several definitions. The present study was carried out to determine the prevalence of mAA dilation based on published definitions and to identify the optimal cutoff.

Methods

Echocardiographic studies of patients >15 years of age performed at a large tertiary care center over 4 years, n = 49,330, were retrospectively evaluated. Leading-edge-to-leading-edge technique was used to measure the mAA in diastole. Several cutoff criteria were included. In addition, we defined normals in our database as those who, after 28 causes of dilated aorta were excluded, were normal both clinically and echocardiographically (n = 2334).

Results

The mean age was 64.2 ± 17.1 years, and 31.5% were men. The prevalence of dilated mAA based on absolute criteria with sex stratification varied between 17% and 23% and based on relative criteria (to age, body surface area, and sex) varied between 6% and 11%. It further decreased to 7.6% on the addition of narrow age stratification (10 year intervals) performed on normals in our database. The multivariate adjusted R² (for variation in mAA diameter) was 0.25 for age, decreasing to 0.12 for weight and 0.07 for sex and height.

Conclusions

The lowest prevalence of 7.6% probably represents the optimal cutoff for dilated mAA because it includes age, which explains most of the variation in mAA, in narrow (10 year) intervals only performed in our normals, which represents the largest sample size to date.

Keywords

Aneurysm echocardiography thoracic aorta

Introduction

Thoracic aortic aneurysm and dissection (TAAD) still involves significantly high mortality rates despite significant diagnostic and therapeutic advances. The incidence of TAAD ranges from 2.4 to 10.4 cases per 100,000 people, and it has been increasing over the past 33 years.¹ Overall mortality from ruptured thoracic aortic aneurysms is estimated to be up to 100%, with 59% of patients dying before reaching the hospital.² Mortality after elective repair of thoracic aortic aneurysm is about 4%, but it increases to 28.6% when the repair is performed emergently.³ Since emergent repair is associated with such a high mortality rate, emphasis in recent decades has been placed on early diagnosis, leading to placement of patients on preventive measures. These measures, aimed at slowing the progression of disease, are beta-blockers (animal and human studies),^4–7 angiotensin receptor blockers (animal and human studies),^7–9 and doxycycline as a matrix metalloproteinase inhibitor (animal and human studies).^7,10,11 The effectiveness of medical therapy in the general population, not limited to Marfan syndrome, is still under investigation as all of these studies are in syndromic (most frequently Marfan syndrome) patients^5,9 or show the association of abdominal aorta diameter with antihypertensives.¹²

Detecting a dilated thoracic aorta allows early medical and surgical interventions in high-risk patients. Thus, identifying the normal range of thoracic aortic measurement becomes imperative for screening and diagnosis. Many previous studies have attempted to define the reference range of aortic dimensions in healthy populations.^13–16 These studies suffered from a small sample size for the mid-ascending aorta (mAA) (Table 1) as well as lax criteria to define normal subjects. Some used clinical criteria for inclusion as a normal subject (Table 1),^15,17 whereas others used echocardiographic criteria in addition to clinical criteria for inclusion.^13,14,16 None of these studies excluded the 28 causes of TAAD in adults as outlined by the recent American Heart Association 2010 statement.¹⁸

Table 1.

Summary of studies defining normal dimensions of mid-ascending aorta in adults.

Study	n	Male (%)	Age (y)	Overall (cm)	Absolute values		Indexed values
Study	n	Male (%)	Age (y)	Overall (cm)	Men (cm)	Women (cm)	Men (cm)	Women (cm)
Roman et al¹³	135	50.4	>15	N/A	3.0 ± 0.3	2.7 ± 0.4	1.5 ± 0.2	1.6 ± 0.3
Vriz et al¹⁵	422	67.3	16–29	N/A	2.4 ± 0.6	2.3 ± 0.4	1.27 ± 0.30	1.34 ± 0.17
			30–39	N/A	2.7 ± 0.3	2.4 ± 0.4	1.35 ± 0.17	1.47 ± 0.17
			40–49	N/A	2.8 ± 0.3	2.6 ± 0.3	1.46 ± 0.16	1.56 ± 0.21
			50–59	N/A	3.1 ± 0.4	2.7 ± 0.3	1.57 ± 0.19	1.63 ± 0.2
			>60	N/A	3.3 ± 0.4	3.0 ± 0.3	1.69 ± 0.22	1.81 ± 0.21
Saura et al¹⁶	704	44.0	19–78	N/A	2.99 ± 0.38	2.73 ± 0.34	1.7 ± 0.22	1.67 ± 0.22
Campens et al¹⁹	849	46.6	1–85	2.7 ± 0.55	N/A	N/A	N/A	N/A
	133	60.2	<15 years	N/A	1.89 ± 2.9	1.78 ± 3.2	N/A	N/A
	716	44.1	>15 years	N/A	3.00 ± 4.3	2.77 ± 3.9	N/A	N/A
Present study
Overall	2334	31.5	>15	2.77 ± 0.31	2.92 ± 0.40	2.70 ± 0.36	1.41 ± 0.22	1.48 ± 0.23
By age group	827	34.8	15–29	2.55 ± 0.31	2.66 ± 0.32	2.19 ± 0.29	1.33 ± 0.19	1.45 ± 0.19
	492	27.9	30–39	2.73 ± 0.34	2.92 ± 0.31	2.66 ± 0.32	1.38 ± 0.22	1.44 ± 0.21
	452	29.0	40–49	2.85 ± 0.35	3.02 ± 0.33	2.77 ± 0.33	1.42 ± 0.20	1.50 ± 0.22
	352	33.2	50–59	3.04 ± 0.37	3.25 ± 0.33	2.94 ± 0.35	1.53 ± 0.19	1.58 ± 0.24
	211	29.4	60 and older	3.06 ± 0.36	3.28 ± 0.34	2.96 ± 0.32	1.60 ± 0.21	1.65 ± 0.24

The data are presented (in columns 1–5) with respect to upper limits of normal, which was defined as 2 standard deviations (SD) above mean. This is not the usual way of data presentation, which is mean ± SD. However, the upper limit of normal is the clinically relevant number, as well as relevant to the central theme of this paper. The standard format data are available upon request.

The studies by Devereux et al.¹⁴ and Vasan et al.¹⁷ were not included in this table as they only looked at sinus of Valsalva whereas our study was focused on mid-ascending aorta diameter.

In view of these limitations, this study was carried out to determine the normal dimension of the ascending thoracic aorta in a large population using much stricter clinical and echocardiographic criteria for defining normalcy.

Methods

This study was approved by the Aurora St Luke’s Medical Center Institutional Review Board, Milwaukee, WI, USA (13-37E). The requirement for informed consent was waived.

Study population

This study included all patients older than 15 years of age who had undergone echocardiography since November 2011 in our health care system based in Milwaukee, Wis., and for whom aortic measurements were available. We further queried the ICD-9-based electronic medical record database for 28 risk factors of dilated aorta as described in the 2010 American Heart Association guidelines.¹⁸

Echocardiographic evaluation

The protocol at Aurora Health Care dictates that mAA diameter be measured in the parasternal long-axis view in a plane perpendicular to that of the long axis of the aorta, at end-diastole, and using the leading-edge-to-leading-edge technique as described in the recent guidelines²⁰ by the American Society of Echocardiography (Figure 1). Right parasternal images or images in an interspace higher, closer to the sternum were obtained only if the standard transthoracic window failed to reveal the mAA. For patients who were defined as normals echocardiographically and clinically, if their ascending aorta diameter was missing from the report (n = 50) then their echocardiograms were viewed by KAA and remeasured.

Figure 1.

Variations in measurement of aortic dimension by technique. In echocardiography, measurement of aortic dimension is done via two acceptable methods, that is, inner-wall-to-inner-wall as well as leading-edge-to-leading-edge. In non-contrast computed tomography/magnetic resonance imaging, it is done outer-wall-to-outer-wall, and in contrast computed tomography/magnetic resonance imaging, it is done inner-wall-to-inner-wall. In echocardiography, the wall blooms, making the inner-wall-to-inner-wall diameter smaller, and on contrast computed tomography, the contrast blooms, making the inner-wall-to-inner-wall diameter larger than what it is in reality. In addition, the aortic wall thickness is 2 mm, which can add up to 4 mm variation in measurement even within echocardiography depending on the method used.

Definition of normal

We used clinical and echocardiographic criteria based on the 2010 American Heart Association guidelines¹⁸ to exclude any subjects with the presence of risk factors for dilated aorta. The clinical and echocardiographic criteria are described in the following sections.

Clinical criteria

All patients with any of 28 risk factors present were excluded from our study (Supplementary Figure S1). These risk factors included hypertrophic obstructive cardiomyopathy, diabetes, hypertension, tobacco use, heart failure, Marfan syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome, ischemic cardiomyopathy, bicuspid aortic valve, aortic valve stenosis or regurgitation, Turner syndrome, pheochromocytoma, cocaine use, coarctation of the aorta, history of valve replacement, syphilis, Takayasu arteritis, giant cell arteritis, Behcet’s syndrome, polycystic kidney disease, and corticosteroid immunosuppression, among others. The reader is referred to the American Heart Association document for details.¹⁸ During the echocardiographic visit, all patients had their blood pressure measured in the left arm, while sitting, prior to the study. All those with a blood pressure >140/90 mm HG or a clinical diagnosis of hypertension were classified as hypertensives.

Echocardiographic criteria

Patients whose echocardiograms demonstrated abnormal findings also were excluded. These abnormal findings included known thoracic aortic aneurysm, previously repaired thoracic aortic dissection, coarctation of the aorta, aortic regurgitation (any degree of regurgitation), aortic stenosis (any degree of stenosis), bicuspid aortic valve, mitral regurgitation (moderate or worse), mitral stenosis (moderate or worse), diastolic dysfunction (any grade), regional wall motion abnormality, akinesis or hypokinesis, systolic dysfunction (left ventricular ejection fraction <50%), left ventricular hypertrophy (mild or worse), pulmonary hypertension (moderate or worse), a severely enlarged left atrium, atrial septal defect or ventricular septal defect (repaired or unrepaired), and technically difficult studies.

Application of different cutoffs to overall population

In order to compare the impact of different criteria on the prevalence of dilated mAA, these and previous criteria were applied to the entire study population. If the upper limit of the mAA was not described in a study, then +2 standard deviations (SD) was used as the upper limit of normal.

Statistical analysis

Univariate analysis was done; aortic diameters were presented as mean ± SD, and prevalence was presented as a percentage of the overall population. To evaluate the strength of association between dilated mAA and the determinants age, sex, height, weight, and blood pressure, we performed bivariate linear regression followed by multivariate linear regression. The strength of association was defined by the slope (β) of association. Because the units of these parameters were very different, standardized β were used, making variables with markedly different ranges and units evaluable.

In order to evaluate the impact of individual parameters such as age, sex, weight, and blood pressure on mAA diameters, we utilized the adjusted R², which is generated by multiple linear regression equations. For example, an R² of 0.26 for age would mean that 26% of the variation in mAA diameter in normal subjects can be explained by age.

All analysis was carried out using JMP version 12 (SAS, Cary, NC).

Results

We identified 49,307 adults (age >15 years) who had undergone echocardiography at our tertiary care center. The mean age of our study population was 64.2 ± 17.1 and 23,445 (47.6%) were men. The mean height of our study population was 169.1 ± 10.9 cm, mean body surface area (BSA) was 2.01 ± 0.31 m², and mean body mass index was 30.6 ± 7.7 kg/m². Within the study population, 82.1% of participants were white, 12% black, 4.8% Hispanic, 1.2% Asian, and 0.1% other races.

Application of exclusion criteria

As depicted in Supplementary Figure S1, application of clinical exclusion criteria removed 40,239 patients. Subsequent review of echocardiographic reports led to removal of an additional 6734 patients, leaving a final population of 2334 normal subjects.

Characteristics of final study population

Supplementary Table S1 shows the baseline characteristics of our study population compared with the overall population. Out of the 2334 normal subjects, 735 (31.5%) were men. Normal subjects were significantly younger (37.5 ± 14.9 years vs. 64.2 ± 17.1 years) and had lower weight (79.5 ± 20.7 kg vs. 87.7 ± 24.4 kg), BSA (1.92 ± 0.27 m² vs. 2.01 ± 0.3 m²), and body mass index (27.8 ± 6.7 kg/m² vs. 30.6 ± 7.7 kg/m²) than the overall population, with a p value <0.0001. Mean height was similar between the two groups (168.9 ± 10.1 cm vs. 169.1 ± 10.9 cm; p = .72).

Definition of normal aortic dimensions

The upper limits of normal mAA diameter and sinus of Valsalva (SV) are reported in Table 2. The results are depicted in absolute values and in “relative” values, relative to BSA and stratified by age and sex, defined by more than two SD above the mean among normal subjects. The absolute upper limits of normal mAA were 3.72 cm in men and 3.42 cm in women. The BSA-indexed mAA cutoff values were 1.86 cm in men and 1.94 cm in women. The absolute upper limits of normal SV were 2.84 cm in men and 2.52 cm in women. The BSA-indexed SV cutoff values were 1.81 cm in men and 1.82 cm in women. Absolute mAA and SV dimensions were greater in men across all age groups as opposed to women. Women had greater BSA-indexed aortic dimensions in all age groups. Mid-ascending aorta dimensions significantly increased with advancing age, and this was less prominent in SV measurements.

Table 2.

Upper limits of normal SV and mAA diameter based on age, sex, and body surface area.

Age group (y)	Absolute SV cm (n)		Indexed SV cm/m² (n)		Absolute mAA cm (n)		Indexed MAA cm/m² (n)
Age group (y)	Male	Female	Male	Female	Male	Female	Male	Female
>15 (overall)	2.84 (212)	2.52 (451)	1.81 (212)	1.82 (451)	3.7 (735)	3.4 (1599)	1.85 (735)	2.0 (1599)
15–29	3.05 (110)	2.70 (316)	1.78 (110)	1.87 (316)	3.3 (288)	3.07 (539)	1.73 (288)	1.79 (539)
30–39	3.21 (118)	2.74 (313)	1.86 (118)	1.88 (313)	3.54 (137)	3.30 (355)	1.82 (137)	1.86 (355)
40–49	3.37 (92)	2.85 (244)	1.99 (92)	2.00 (244)	3.68 (131)	3.44 (321)	1.82 (131)	1.94 (321)
50–59	3.22 (35)	2.90 (109)	1.92 (35)	1.99 (109)	3.91 (117)	3.64 (235)	1.90 (117)	2.06 (235)
60–69	3.22 (17)	2.97 (29)	1.91 (17)	2.17 (29)	3.90 (62)	3.62 (149)	1.93 (62)	2.07 (149)

The upper limit of normal diameters is expressed in 2 standard deviations (SD) above mean.

mAA, mid-ascending aorta; SV, sinus of Valsalva.

Prevalence of dilated aorta after application of new definition

The overall prevalence of dilated mAA was 23.2% (n = 11,444) when absolute cutoff values were utilized. Of these subjects, 5676 were men and 5768 were women. When BSA-indexed cutoff values were employed, the overall prevalence of dilated mAA decreased to 15.4% (n = 7571), with 3997 men and 3574 women.

Bivariate determinants of aortic dimensions

In our normal population, age had the highest standardized β (0.50, p < .0001), followed by weight (0.35, p < .0001), sex (0.27, p < .0001), and height (0.26, p < .0001). BSA had a much stronger association with mAA diameter than body mass index, with a higher standardized β (0.375 vs. 0.247, p < .0001) and higher adjusted R² as well (0.140 vs. 0.061). Age had the highest R² (0.260, p < .0001), followed by weight (0.12, p < .0001), sex (0.069, p < .0001), and height (0.065, p < .0001). Twenty-six percent of mAA diameter variation is explained by age. If age increases by 10 years, mAA diameter increases by 0.13 cm.

Multivariate determinants of aortic dimensions

The pattern remained in the multivariate linear regression model, with age (0.499, p < .0001) having the highest adjusted standardized β, followed by weight (0.202, p < .0001), sex (0.150, p < .0001), and height (0.116, p < .0001). There was no meaningful difference in the adjusted R² for the multivariate models, including age, sex, and height and weight versus age, sex, and BSA (39% vs. 38.9%), indicating that height and weight is replaceable by BSA. Removal of sex increased R² to 0.36 from 0.39. Removal of age reduced R² from 0.39 to 0.14, indicating that age plays the biggest role.

Prevalence of dilated mid-ascending aorta by other definitions and their comparison with our criteria

The upper limits of normal aorta from other studies were generated from the data provided within the published manuscripts, as they all provided means and standard deviations for their populations; we used the upper 95% CI as the cutoff for normal. The prevalence of dilated mAA measured by the present study was higher than the prevalence measured in prior studies, including those by Saura et al.,¹⁶ Lang et al.,²¹ and Campens et al.¹⁹ (23.2% vs. 20.2% vs. 17.3% vs. 14%, respectively) (Figure 2(a)). The prevalence found by Roman et al.¹³ was similar to the prevalence in our study (23.3% vs. 23.2%). The prevalence of dilated mAA was higher based on these criteria without age stratification and meaningfully dropped to 7.6% when criteria stratified by age group were used (Figures 2(b) and (c)). This was lower than the prevalence calculated using the age-stratified definition described by Vriz et al.¹⁵ (10.5% vs. 7.6%). The prevalence measured by the present study using the definition indexed by age, sex, and BSA was higher than the prevalence measured using definitions by Campens et al. and Vriz et al. using similar stratification (Figure 2(d)).

Figure 2.

Graphic representation of prevalence of dilated mid-ascending aorta (mAA) with increasingly sophisticated criteria used. (a) Prevalence of dilated mAA using sex-based cutoffs. (b) Prevalence of dilated mAA using age- and sex-based cutoffs. (c) Prevalence of dilated mAA using sex- and body surface area-based cutoffs. (d) Prevalence of dilated mAA using age-, sex-, and body surface area-based cutoffs.

Association of blood pressure with aortic dimensions

Both systolic and diastolic blood pressure were positively but weakly correlated with mAA and SV diameters, with a stronger correlation with the mAA than SV. A 10 mmHg increase in systolic blood pressure was associated with a 0.3 mm increase in mAA diameter and 0.1 mm increase in SV diameter (β = 0.003, p < .001 vs. β = 0.001, p < .001). A 10 mmHg increase in diastolic blood pressure was associated with a 0.5 mm increase in mAA diameter (β = 0.005, p < .001) and 0.2 mm increase in SV diameter (β = 0.002, p < .001). Heart rate had a negative correlation with mAA (β = −0.001, p = .0254) and SV diameters (β = −0.002, p = .001). Mean arterial pressure was weakly but positively associated with both mAA (β = 0.005, p < .0001) and SV diameters (β = 0.002, p < .0001).

Discussion

The present study represents the largest dataset of mAA diameters in a normal population. It also represents the strictest definition of abnormal aorta compared to all prior studies.^13,15,16 These data suggest lower cutoff points for dilated aorta in the general population, as well as when stratified by age and sex. The prevalence varies markedly depending on the criteria used and decreases from as much as 23% to 7.6% if age, sex, and BSA adjustment is used. Because age and weight had the strongest impact on mAA diameter, definitions that incorporate age and weight (or BSA) should be preferred over others that predominantly use sex or height stratification.

The landmark study by Roman et al.¹³ had a much smaller sample size (135 vs. 2334) than the present study. Their definition of normality included unaffected family members of patients with mitral prolapse and Marfan syndrome, which is much weaker than ours because we excluded patients with 28 causes of dilated aorta based on clinical chart review (ICD-9) and echocardiographic reports. Studies subsequent to the Roman et al.¹³ study demonstrated that women had decreased aortic dimension compared with men across the ages.¹⁴ In addition, only three age groups were used: <20, 20–39, and >40 years of age. Since age is the strongest determinant of mAA diameter, smaller intervals are preferable. This could be achieved in our study owing to a larger sample size. Similar to our study, the study carried out by Vriz et al.¹⁵ stratified the results by 15 year age intervals, while previous studies, including Roman et al.¹³ and Saura et al.,¹⁶ categorized their study populations as less than or more than 40 years and 50 years of age, respectively. In addition, subjects aged 15–25 were not included in the study by Saura et al.,¹⁶ which is a limitation not faced by our data. The narrower age interval in our study is able to accommodate the age-specific increment of aortic dimensions, with Vriz et al.¹⁵ being the only other study to accomplish this goal. The present study minimized selection bias by including patients across different races, while some of the prior studies only included Caucasian patients.

A recent major study by Campens et al.¹⁹ included a large sample of 849 subjects to determine reference values for SV and mAA diameter in all age categories. The inclusion criterion for this study was all echocardiograms performed in the echocardiography lab at Ghent University. Only those patients who had bicuspid aortic valves, significant valvular disease, or connective tissue disorders like Marfan syndrome were excluded. All other causes of dilated aorta, including hypertension, were not excluded. While this important study is clearly inferior to the current study in terms of sample size, racial diversity (100% white vs. 82% white), and exclusion criteria (3 vs. 28), it brings forth a similar message of a much lower prevalence of dilated mAA when sophisticated criteria utilizing not only age but sex and BSA as well are employed.

Because age has a significant impact on mAA diameter (β = 0.50; p < .0001), the definitions that included 15- or 10-years age intervals should be preferred over those with larger age intervals. The present study compared the absolute cutoff values of normal mAA with the values stratified by age groups. In the present study, age groups were divided into 15–29 years old, 30–39 years old, 40–49 years old, 50–59 years old, and older than 59 years, with numbers of normal subjects decreasing with advancing age. Our age-based definition of dilated mAA had the second lowest prevalence (7.6%) of dilated mAA in the entire population (n = 49,330), second only to Vriz et al.’s¹⁵ definition (6.0%), and much lower than 10.9%, which is based on an absolute cutoff with sex stratification as compared with 23.2% prevalence using a definition without age stratification. Similarly, the prevalence of mAA dilation with BSA indexed dropped from 10.9% without age stratification to 7.7% with age stratification.

When BSA-indexed criteria were used to define dilated mAA, the prevalence was highest by our definition and decreased with definitions given by Roman et al.,¹³ Lang et al.,²¹ and Saura et al.¹⁶ (10.9% vs. 9.4% vs. 9.4% vs. 6.2%, respectively). Our data suggest the use of age stratification over sex stratification to define dilated mAA. BSA was the second most meaningful determinant of mAA; therefore, BSA should be the second factor taken into consideration when choosing a definition of dilated mAA. Age and sex are non-modifiable risk factors, whereas weight is modifiable, indicating the importance of weight control, which is the single most important modifiable risk factor. Blood pressure was the least important modifiable risk factor for mAA dilation in normal subjects.

Our data pose the clinical and epidemiological question of whether we should use criteria that would render 23% (approximately one in four) of people as abnormal or criteria that would declare only 7.6% (approximately one in 14) of people to have an abnormally dilated aorta. While our data would favor the definition with lower prevalence, based on cross-sectional data of β and R², a better way may be to employ prognostic data such as aneurysm rupture and death in future studies.

Comparison with other modalities for aortic measurement

Mechanistically, unlike echocardiography, computed tomography (CT) and non-contrast magnetic resonance imaging (MRI) provide a multiplanar evaluation of the aorta with the ability to visualize the entire aorta. CT requires outer-wall-to-outer-wall diameter measurement in non-contrast studies and inner-wall-to-inner-wall diameter measurement in contrast-based studies. Because the wall is usually about 2 mm thick, the measurement by echocardiography and CT can differ by up to 4 mm, even in the same patient (Figure 1). Even with inner-wall-to-inner-wall diameter measurement on CT, contrast blooming artifact can cause the measurement to be larger than actual size.

Epidemiologically, on contrast CT the mean ascending aorta diameters were 3.60 cm and 3.35 cm in men and women (n = 1442 normal subjects), respectively, compared with 2.92 cm and 2.7 cm in our study, which is a 6.8 mm greater value in men and 6.5 mm in women on CT than in our study.²² This may be the result of the blooming artifact seen with contrast CT or differences in the populations.

Similarly, on MRI the mean ascending aorta diameters were 3.33 cm in men and 3.05 cm in women (n = 3573 normal subjects),²³ compared with 2.92 cm in men and 2.70 cm in women in our study, indicating a 4.1 mm greater value in men and a 3.5 mm greater value in women on echocardiographic examination. MRI has inferior spatial and contrast resolution compared with CT. MRI measurement of the aorta is done based on inner-wall-to-inner-wall measurement, whether with or without contrast. All these issues would suggest MRI correlation with echocardiography may be less valuable than CT correlation with echocardiography. This issue has not been addressed in the literature yet.

The statistically significant but weak correlation of systolic blood pressure, diastolic blood pressure, and mean arterial pressure with mAA and SV is in consonance with prior studies²⁴ that suggest that the main effect of hypertension is on the abdominal aorta and that ascending aortopathy is more of an inherited disease than an acquired illness. In addition, the stronger relationship of blood pressure with mAA than with SV also is in line with these prior studies, suggesting that the mAA is more affected by blood pressure than the SV.²⁴

Limitations and strengths

The present study suffers from a retrospective study design and its inherent limitations. The echocardiograms were performed as part of clinical care; therefore, they may not reach the excellence ensured in research echocardiograms. However, the studies were done in Intersocietal Commission for the Accreditation of Echocardiography Laboratories (ICAEL)-certified echocardiographic laboratories, which ensure a minimum standard of performance set by ICAEL.

In many patients, the dilation in the ascending aorta is located in the middle-upper part of the tubular segment of the ascending aorta. To correctly visualize distal ascending aorta diameter, non-standard parasternal long-axis windows with an upper interspace and medial transducer position is recommended, or right parasternal window imaging is recommended, neither of which were used in this study. These additional maneuvers are undertaken by our sonographers only if they fail to demonstrate the ascending aorta from standard windows. This is a measurement limitation of this study.

The biggest strength of the current study is its sample size, which was larger than all prior studies. The second strength is its stricter criteria for normalcy. This study used ICD-9 codes as well as echocardiographic abnormalities to exclude 28 risk factors of dilated aorta as defined by 2010 American Heart Association guidelines.¹⁸ After exclusion, the present study still had more participants than in all three prior studies combined.

Conclusion

Based on our criteria, the prevalence of dilated mAA is higher than the prevalence found in previous studies. Early identification of individuals at risk may lead to reduced mortality from aortic aneurysms and dissections.

Supplemental Material

Supplemental Material - Refining the upper limit of normal for the ascending aorta: In search of optimal criteria a large database study of normal individuals

Supplemental Material for Refining the upper limit of normal for the ascending aorta: In search of optimal criteria a large database study of normal individuals by Ji A Yoon, Mirza M Ahmad, Muhammad N Syed, Mirza N Ahmad, Sharmeen F Hussaini, Mustafa N Muhammad, Syed Haris A Pir, Bijoy K Khandheria, AJ Tajik and Khawaja A Ammar in Vascular

Footnotes

Acknowledgements

The authors thank Jennifer Pfaff and Sarah Kennedy for editorial preparation of the manuscript and Brian Miller and Brian Schurrer for help with the figures.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

A. Jamil Tajik

Khawaja Afzal Ammar

Supplemental Material

Supplemental material for this article is available online.

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