Decreased arterial distensibility is an early manifestation of adverse structural and functional changes within the vessel wall. Its correlation with thoracic aortic calcium (TAC), a marker of atherosclerosis, has not been well demonstrated. We tested the hypothesis that decreasing aortic compliance and increasing arterial stiffness would be independently associated with increased TAC. We included 3,540 subjects (61 ± 10 years, 46% men) from the Multi-ethnic Study of Atherosclerosis who had undergone an aortic distensibility (AD) assessment using magnetic resonance imaging. TAC was calculated using a modified Agatston algorithm on noncontrast cardiac computed tomographic scans. Multivariate regression models were calculated for the presence of TAC. Overall, 861 subjects (24%) had detectable TAC. Lower AD was observed among those with versus without TAC (2.02 ± 1.34 vs 1.28 ± 0.74, p <0.0001). The prevalence of TAC increased significantly across decreasing quartiles of AD (7%, 17%, 31%, and 42%, p <0.0001). Using multivariate analysis, TAC was independently associated with AD after adjusting for age, gender, ethnicity, and other covariates. In conclusion, our analysis has demonstrated that increased arterial stiffness is associated with increased TAC, independent of ethnicity and other atherosclerotic risk factors.
A paucity of data is available on the association between atherosclerosis in the aorta and vessel distensibility. Aortic distensibility (AD) is an accurate measure of arterial stiffness and can evaluate regional stiffness through the aorta. In contrast, thoracic aortic calcium (TAC) has been shown to correlate with coronary artery disease. However, the association between TAC and AD and the effect of age, gender, and ethnicity on this association is not clear. Thus, the aim of the present analysis is to test the hypothesis that decreasing AD measured by magnetic resonance imaging (MRI) is independently associated with increased TAC on noncontrast computed tomographic (CT) scans.
Methods
The Multi-ethnic Study of Atherosclerosis (MESA) investigated the prevalence, correlates, and progression of subclinical cardiovascular disease in a population-based sample of 6,814 men and women aged 45 to 84 years who were free of known cardiovascular disease at baseline. The study objectives and design have been previously published. In brief, the present prospective cohort study included recruited subjects from 6 United States communities (Baltimore, Maryland; Chicago, Illinois; Forsyth County, North Carolina; Los Angeles County, California; Northern Manhattan, New York; and St. Paul, Minnesota). In the present analysis, we included 3,540 subjects (61 ± 10 years, 46% men) who had undergone a baseline AD assessment using MRI and TAC measurement. We used the baseline data from the MESA (2000 to 2002).
The medical history, and laboratory data for the present study were taken from the first examination of the MESA cohort (July 2000 to August 2002). Information about age, gender, ethnicity, and medical history were obtained by questionnaire. The use of antihypertensive and other medications was determined from clinical staff entry of the prescribed medications verified by the staff. Hypertension was defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or the use of medications prescribed for hypertension. The body mass index was calculated as the weight (in kilograms divided by the height in square meters. The total and high-density lipoprotein cholesterol levels were measured from blood samples obtained after a 12-hour fast. Low-density lipoprotein cholesterol was estimated using the Friedewald equation. In the first examination of the MESA, the participants reported the presence or absence of a family history of coronary heart disease.
All participants underwent CT scanning at the same time for evaluation of coronary calcium, after providing written informed consent. The image acquisition protocol has been previously described. In brief, CT scanning of the chest was performed with either an electrocardiographic-triggered (at 80% of the RR interval) electron beam CT scanner (Chicago, Los Angeles, and New York field centers: Imatron C-150, Imatron, San Francisco, California) or with prospectively electrocardiographic-triggered scan acquisition at 50% of the RR interval using a multidetector CT system that acquired 4 simultaneous, 2.5-mm slices for each cardiac cycle in a sequential or axial scan mode (Baltimore, Forsyth County, and St. Paul field centers: LightSpeed, General Electric, Piscataway, New Jersey, or Volume Zoom, Siemens, New York, New York). The image slices were obtained with the participant supine, with no couch angulation.
A minimum of 35 contiguous images with a 2.5- or 3-mm slice thickness was obtained, starting above the left main coronary artery to the bottom of both ventricles. Each scan was obtained within a single breath hold. A section thickness of 3 mm, field of view of 35 cm, and matrix of 512 × 512 were used to reconstruct the raw image data. The nominal section thickness was 3.0 mm for electron beam CT scanning and 2.5 mm for 4-detector row CT scanning. The spatial resolution is described by the smallest volume element, or voxel, for the protocol for each system: 1.15 mm 3 for 4-detector row CT scanning (0.68 × 0.68 × 2.50 mm) and 1.38 mm 3 for electron beam CT scanning (0.68 × 0.68 × 3.00 mm).
Ascending and descending TAC were measured from the lower edge of the pulmonary artery bifurcation to the cardiac apex (imaged on every study of coronary calcium) and were quantified using the same lesion definition as for coronary artery calcium. TAC included both ascending TAC and descending TAC on the portion of the aorta imaged by cardiac CT scanning. Any calcified focus seen extending into the aortic root wall was excluded from the aortic wall calcium. The absence of ascending and descending TAC was assigned a score of 0.
The coronary calcium score of each lesion was calculated by multiplying the lesion area by a density factor derived from the maximum Hounsfield units (HU) within this area, as described by Agatston et al. The density factor was assigned in the following manner: 1 for lesions for which the maximum density was 130 to 199 HU, 2 for lesions with 200 to 299 HU, 3 for lesions with 300 to 399 HU, and 4 for lesions with ≥400 HU. A total calcium score (for both Agatston and volume) was determined by summing the individual lesion scores at each anatomic site. The volume of calcium was also measured (in cubic millimeters) as the volumetric score.
Gradient-echocardiographic phase-contrast cine MRI with electrocardiographic gating was performed to evaluate the distensibility of the aorta. Images of the ascending and descending aorta were obtained in the transverse plane at the level of the right pulmonary artery perpendicular to the vessel lumen. The imaging parameters were as follows: repetition time 10ms, echo time 1.9 ms, field of view 34 cm, slice thickness 8 mm, matrix size 256 × 224, 2 signal averages, temporal resolution 20 ms, velocity encoding gradient 150 cm/s, and receiver bandwidth ±32 kHz.
To determine the AD, the minimum and maximum cross-sectional areas of the ascending aorta vessel were determined using an automated contour routine and the software FLOW (Medis Medical Imaging Systems, Raleigh, North Carolina). AD was calculated as described by Gambleet al, where Δ D is the change in systolic/diastolic diameter, Δ P is the pulse pressure, D s is the systolic diameter, and D is the average aortic diameter.
Distensibility coefficient: Δ D Δ P D S × 1000
The blood pressure was measured immediately before and after the MRI aortic measurements, with the patient in the supine position on the MRI scanner gantry. The average systolic and diastolic values were then used to calculate the pulse pressure. The MRI reader was unaware of all variables of the study subjects, except for their identification numbers.
Statistical analyses were performed using the Statistical Package for Social Sciences, version 17.0 (SPSS, Chicago, Illinois) and Statistical Analysis Systems, version 9.1 (SAS Institute, Cary, North Carolina). Categorical data are presented as the percentage frequencies and compared between groups using the chi-square test or Fisher’s exact test. Continuous variables are presented as the mean ± SD and compared using Student’s t test. Non-normally distributed variables are presented as the median and twenty-fifth to seventy-fifth interquartile range and were compared using nonparametric testing. Multivariate modeling was performed using linear and logistic regression analysis. The primary analysis was to assess the association between TAC and AD (as a continuous variable and as a categorical variable) after adjusting for the baseline clinical, historical, and imaging covariates. The fourth quartile (most distensible) was used as the reference group for subsequent analysis. For all multivariate modeling, the threshold for variable entry into models was p <0.05, and the threshold for variable removal was p >0.10. The selection of variables for entry consideration was determined by univariate analysis. We also adjusted for known coronary artery disease risk factors. Model 1 included age, gender, and ethnicity. Model 2 was adjusted for age, gender, ethnicity, body mass index, hypertension, diabetes mellitus, cigarette smoking, family history of heart attack, low-density lipoprotein cholesterol levels, and the use of cholesterol-lowering medications. Model 3 included all the variables in model 2 plus the log-transformed coronary artery calcium + 1 and log-transformed C-reactive protein. A 2-sided p value <0.05 was considered significant.
Results
A total of 3,540 subjects were included in the present analysis. The mean difference between CT and MRI scanning was 26 days. TAC was detected in 861 participants (24%). Table 1 lists the baseline characteristics of the study cohort according to the presence of TAC. Participants with TAC were older and had a greater prevalence of hypertension, diabetes, and hypercholesterolemia (p <0.05 for all comparisons). In addition, participants with TAC had a lower glomerular filtration rate and greater high-sensitivity C-reactive protein levels ( Table 1 ). As expected, participants with TAC had higher levels of mean coronary artery calcium (61 ± 226 vs 305 ± 565, p <0.001). The mean AD was 1.84 ± 1.26 mm Hg −1 × 10 −3 , and lower AD was seen among those with TAC compared to those without TAC ( Figure 1 ).
| Variable | TAC | p Value | |
|---|---|---|---|
| Absent (n = 2,679) | Present (n = 861) | ||
| Age (years) | 56 (51–64) | 70 (65–76) | <0.0001 |
| Women | 1,243 (46%) | 374 (43%) | 0.13 |
| Ethnicity | <0.0001 | ||
| White | 1,040 (39%) | 444 (52%) | |
| Chinese | 303 (11%) | 95 (11%) | |
| Black | 838 (31%) | 217 (25%) | |
| Hispanic | 498 (19%) | 105 (12%) | |
| Body mass index (kg/m 2 ) | 27 (24–30) | 27 (24–30) | 0.33 |
| Hypertension | 928 (35%) | 541 (63%) | <0.0001 |
| Hypertensive medications | 789 (30%) | 455 (53%) | <0.0001 |
| Diabetes mellitus | 180 (7%) | 102 (12%) | <0.0001 |
| Smoker | 355 (13%) | 106 (12%) | 0.06 |
| Hypercholesterolemia | 325 (12%) | 213 (25%) | <0.0001 |
| Cholesterol-lowering medication | 325 (12%) | 213 (25%) | <0.0001 |
| Coronary calcium score | 0 (0–19.5) | 65 (2–332) | <0.0001 |
| High-sensitivity | 3.51 ± 5.32 | 2.0 (0.9–4.4) | 0.0017 |
| C-reactive protein | |||
| Aortic distensibility | 2 ± 1.3 | 1.3 ± 0.7 | <0.0001 |
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