Decreased arterial compliance is an early manifestation of adverse structural and functional changes within the vessel wall. Its correlation with left ventricular (LV) area on computed tomography, a marker of LV remodeling, has not been well demonstrated. The aim of this study was to test the hypothesis that decreasing aortic compliance and increasing arterial stiffness are independently associated with increased LV area. The study population consisted of 3,540 patients (mean age 61 ± 10 years, 46% men) from the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent aortic distensibility (AD) assessment on magnetic resonance imaging and LV area measurement on computed tomography (adjusted to body surface area). Multivariate logistic regression was performed to assess the association between body surface area–normalized LV area >75th percentile and AD after adjusting for baseline clinical, historical, and imaging covariates. Mean LV area index was 2,153 cm 2 , and mean AD was 1.84 × 10 3 mm Hg −1 . Subjects in the lowest AD quartile were older, with higher prevalence rates of hypertension, diabetes, and hypercholesterolemia (p <0.05 for all comparisons). Using multivariate linear regression adjusting for demographics, traditional risk factors, coronary artery calcium, and C-reactive protein, each SD decrease was associated with an 18-cm 2 increase in LV area. In addition, decreasing AD quartiles were independently associated with increasing LV area index, defined as >75th percentile. In conclusion, in this multiethnic cohort, reduced AD was associated with increased LV area. Longitudinal studies are needed to determine if decreased distensibility precedes and directly influences increased LV area.
Decreased arterial compliance is an early manifestation of adverse structural and functional changes within the vessel wall. The use of different imaging techniques optimized for the assessment of vascular elasticity and quantification of luminal and vessel wall parameters allows a comprehensive and detailed view of the vascular system. The distensibility coefficient (a measure of compliance) has been validated in large study populations and has been used to predict adverse cardiovascular outcomes. Several studies have also documented the prognostic importance of arterial stiffness in various populations as an independent predictor of cardiovascular morbidity and all-cause mortality. Increased left ventricular (LV) mass is also well established as an independent predictor of cardiovascular morbidity and mortality. Recently, LV area has been shown to be an accurate and highly reproducible surrogate of LV mass and volumes. It is easily obtained on gated chest computed tomography (CT). Although the correlation between LV mass and aortic distensibility (AD) has been well demonstrated, the correlation between LV area on CT and AD has not been studied. Thus, we tested the hypothesis that decreasing aortic compliance and increasing arterial stiffness are independently associated with increased LV area.
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 free of known cardiovascular disease at baseline. The study objectives and design have been published. In brief, this prospective cohort study includes 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 this analysis, we included all subjects who underwent baseline AD assessment on magnetic resonance imaging (MRI) as well as LV area on noncontrast CT. We used baseline data from MESA (2000 to 2002). A total of 3,540 subjects (mean age 61 ± 10 years, 46% men) had LV area and AD on MRI measured and formed the study cohort. Institutional review board approval was obtained at all MESA sites, and written informed consent obtained from all participants.
Medical histories, anthropometric measurements, 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, family history of coronary heart disease, and medical history were obtained using questionnaires. Current smokers were defined as having smoked a cigarette in the past 30 days. Diabetes mellitus was defined as fasting glucose ≥126 mg/dl or use of hypoglycemic medications. Blood pressure was measured 3 times at rest in the seated position, and the average of the second and third readings was recorded. Hypertension was defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or use of medications prescribed for hypertension. Body mass index was calculated as weight in kilograms divided by the square of height in meters. Total and high-density lipoprotein cholesterol were measured from blood samples obtained after a 12-hour fast. Low-density lipoprotein cholesterol was estimated using the Friedewald equation. Estimated glomerular filtration rate was calculated using the creatinine-based 4-variable Modification of Diet in Renal Disease (MDRD) equation.
All participants underwent CT at the same time for evaluation of coronary calcification in exam 1. The image acquisition protocol has been described. In summary, CT of the chest in the supine position was performed either with an electrocardiographically triggered (at 80% of the RR interval) electron-beam computed tomographic scanner or with prospectively electrocardiographically triggered scan acquisition at 50% of the RR interval with a multidetector computed tomographic system that acquired 4 simultaneous 2.5-mm slices for each cardiac cycle in sequential or axial scan mode. A minimum of 35 contiguous images with 2.5- or 3-mm slice thickness were obtained, starting above the left main coronary artery to the bottom of both ventricles. Each scan was obtained in a single breath hold. A field of view of 35 cm and a matrix size of 512 × 512 were used to reconstruct raw image data. The nominal section thickness was 3.0 mm for electron-beam CT and 2.5 mm for 4–detector row CT. 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 (0.68 × 0.68 × 2.50 mm) and 1.38 mm 3 for electron-beam CT (0.68 × 0.68 × 3.00 mm).
LV area was determined using a single midslice area at the level containing the coronary sinus slice or the first level below the left atrium during mid-diastole. In the core lab, the LV traces were done around region bounded by the outer border, the anterior interventricular groove (where the left anterior descending coronary artery resides), and the left posterior interventricular groove. This area included LV mass and LV intracavitary volume, as well as part of the interventricular septum. The LV area calculated was adjusted to body surface area (BSA) in all participants. Ascending and descending thoracic aortic calcium was measured in the aorta from the lower edge of the pulmonary artery bifurcation to the cardiac apex (imaged on every study of coronary calcium). Coronary calcium was traced in all 3 coronary arteries. The coronary calcium score as well as the thoracic aortic calcium score were calculated using the method of Agatston.
In MESA, gradient-echo phase-contrast cine MRI with electrocardiographic gating was performed to evaluate the distensibility of the descending aorta. Images of the descending aorta were obtained in the transverse plane at the level of the right pulmonary artery perpendicular to the vessel lumen. To determine AD, the minimum and maximum cross-sectional areas of the ascending aorta were determined using an automated contour routine using the software FLOW (MEDIS Medical Imaging Systems). AD was calculated using the following equation : AD = ΔD/ΔPD s × 1,000, where ΔPD is the difference between systolic and diastolic measurements of blood pressure, and ΔD is the difference between maximum and minimal cross-sectional aortic diameters. Blood pressure was measured immediately before and after the MRI aortic measurements, while the patient was in the supine position on the MRI scanner gantry; the average systolic and diastolic values were then used to calculate pulse pressure. The MRI reader was blinded to all variables of the study subjects.
Categorical data were compared between groups using chi-square tests and are presented as percentage frequencies. Continuous variables were compared using Student’s t tests and are presented as mean ± SD. Variables not normally distributed were compared using nonparametric Kruskal-Wallis tests and are presented as medians and interquartile ranges. Multivariate linear regression analysis was used to determine the association between BSA-normalized LV and AD after adjusting for baseline clinical, historical, and imaging covariates. The primary analysis was to assess the association between BSA-normalized LV area >75th percentile and AD after adjusting for baseline clinical, historical and imaging covariates by multivariate logistic regression. 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, using forward selection conditional logistic regression. Care was taken to avoid model overfitting by maintaining an outcome: covariate ratio ≥20:1. In addition to LV area, model 1 included age, gender, and ethnicity. Model 2 adjusted for age, gender, ethnicity, hypertension, diabetes, cigarette smoking, family history of coronary artery disease, low-density lipoprotein cholesterol level, and cholesterol-lowering medication. Model 3 included all variables in model 2 plus log-transformed coronary artery calcium + 1 and log-transformed C-reactive protein. Statistical analyses were performed using SPSS version 17.0 (SPSS, Inc., Chicago, Illinois) and SAS version 9.1 (SAS Institute Inc., Cary, North Carolina).
Results
A total of 3,540 subjects were included in this analysis. The mean interval between CT and MRI was 26 days. Participants were divided into 4 AD quartiles ( Table 1 ). With decreasing AD quartile (increasing aortic stiffness), participants were older and more likely to be male and black. Decreasing AD was associated with an increase in the prevalence of traditional atherosclerotic risk factors, including hypertension, diabetes, hypercholesterolemia, decreasing renal function, and 10-year Framingham risk score (p <0.0001; Table 1 ) and a higher prevalence of patients with thoracic and coronary aortic calcium. LV area increased significantly across decreasing quartiles of AD (p <0.0001). The subjects with least distensible aortas had the highest prevalence of BSA-normalized LV area in the highest quartile ( Figure 1 ).
| Variable | AD (×10 3 mm Hg −1 ) | p Value | |||
|---|---|---|---|---|---|
| ≥2.33 (n = 885) | 1.57–2.32 (n = 885) | 1.05–1.56 (n = 885) | ≤1.04 (n = 885) | ||
| Age (yrs) | 54 ± 7 | 58 ± 9 | 63 ± 9 | 69 ± 10 | <0.0001 |
| Women | 412 (47%) | 445 (50%) | 387 (44%) | 373 (42%) | 0.003 |
| White | 364 (41%) | 386 (44%) | 370 (42%) | 364 (41%) | <0.001 |
| Chinese | 129 (15%) | 98 (11%) | 93 (11%) | 78 (9%) | |
| Black | 203 (23%) | 244 (28%) | 295 (33%) | 313 (35%) | |
| Hispanic | 189 (21%) | 157 (18%) | 127 (14%) | 130 (15%) | |
| Antihypertension | 183 (20%) | 309 (35%) | 424 (48%) | 553 (62%) | <0.0001 |
| Hypertension medications | 181 (20%) | 263 (30%) | 356 (40%) | 444 (50%) | <0.0001 |
| Diabetes mellitus | 46 (5%) | 48 (5%) | 81 (9%) | 107 (12%) | <0.0001 |
| Smokers (former) | 288 (32%) | 295 (33%) | 330 (37%) | 337 (38%) | 0.06 |
| Smokers (current) | 111 (13%) | 130 (15%) | 114 (13%) | 106 (12%) | 0.60 |
| Cholesterol-lowering medication | 109 (12%) | 108 (12%) | 147 (17%) | 174 (20%) | <0.0001 |
| High-sensitivity C-reactive protein (mg/L) | 2.1 (0.9–4.4) | 1.8 (0.8–4.2) | 1.8 (0.8–4.1) | 1.7 (0.7–4.0) | 0.013 |
| Presence of TAC | 64 (7%) | 148 (17%) | 273 (31%) | 376 (42%) | <0.0001 |
| CAC = 0 | 512 (58%) | 471 (53%) | 373 (42%) | 276 (31%) | <0.0001 |
| BMI (kg/m 2 ) | 27.6 ± 4.8 | 27.6 ± 4.9 | 28.1 ± 5.2 | 27.9 ± 4.9 | 0.51 |
| Systolic blood pressure (mm Hg) | 113 ± 16 | 123 ± 19 | 129 ± 20 | 136 ± 23 | <0.0001 |
| Diastolic blood pressure (mm Hg) | 69 ± 11 | 72 ± 10 | 72 ± 11 | 74 ± 11 | <0.0001 |
| LDL (mg/dl) | 118 ± 31 | 117 ± 30 | 117 ± 30 | 116 ± 30 | 0.38 |
| HDL (mg/dl) | 51 ± 15 | 51 ± 15 | 53 ± 16 | 53 ± 15 | 0.024 |
| Triglycerides (mg/dl) | 110 (77–160) | 73 (51–105) | 75 (56–107) | 107 (75–157) | 0.21 |
| Estimated glomerular filtration rate (ml/min/1.73 m 2 ) | 84 ± 15 | 83 ± 17 | 81 ± 17 | 78 ± 11 | <0.0001 |
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