Download Arterial wall MRI characteristics are associated with elevated serum

JOURNAL OF MAGNETIC RESONANCE IMAGING 14:698 –704 (2001)
Original Research
Arterial Wall MRI Characteristics Are Associated
With Elevated Serum Markers of Inflammation
in Humans
Clifford R. Weiss, MD,1 Andrew E. Arai, MD,2 Minh N. Bui, MD,4
Kwabena O. Agyeman, MD,2 Myron A. Waclawiw, PhD,3 Robert S. Balaban, PhD,2
and Richard O. Cannon III, MD4*
Inflammation contributes to atherosclerosis, but assessment in humans is largely restricted to measurement of
markers in blood. We determined whether MRI properties of
large arteries were associated with markers of inflammation
in serum. Double inversion recovery, fast spin-echo images
of the common carotid arteries and infrarenal aorta were
obtained at 1.5 T both before and after gadolinium-DTPA (0.1
mmol/kg) in 52 subjects >40 years of age, 17 of whom had no
risk factors for atherosclerosis and thus served as controls.
Twenty-two study participants had increases in wall thickness (14), T2-weighted signal intensity (11), and/or contrast
enhancement values (7) that were >2 standard deviations
(SDs) from control group mean values. Ten subjects in this
group had evidence of focal plaques in the carotids (5) and/or
aorta (6). Compared with the remaining 30 subjects, these 22
had significantly higher levels of interleukin-6 (3.53 ⴞ 2.46
vs. 1.97 ⴞ 1.37 pg/mL, P ⴝ 0.004), C-reactive protein (0.56 ⴞ
0.98 vs. 0.30 ⴞ 0.52 mg/dL, P ⴝ 0.019), vascular cell adhesion molecule-1 (572 ⴞ 153 vs. 471 ⴞ 130 ng/mL, P ⴝ 0.012),
and intercellular adhesion molecule-1 (244 ⴞ 80 vs. 202 ⴞ 45
ng/mL, P ⴝ 0.015), and nonsignificant differences in levels of
E-selectin (46.1 ⴞ 18.9 vs. 42.3 ⴞ 11.3 ng/mL, P ⴝ 0.369).
Thus, MRI characteristics of the aorta and carotid arteries
were associated with elevated serum markers of inflammation, frequently in the absence of definite atheroma. MRI of
large arteries may provide a new approach to investigate the
contribution of inflammation to atherogenesis.
J. Magn. Reson. Imaging 2001;14:698 –704.
© 2001 Wiley-Liss, Inc.
Index terms: inflammation; magnetic resonance imaging;
atherosclerosis; cell adhesion molecules; hyperlipidemia
INFLAMMATION IS BELIEVED to contribute importantly to the development and clinical expression of
1
Johns Hopkins University School of Medicine, Baltimore, Maryland.
Laboratory of Caridac Energetics, National Heart, Lung, and Blood
Institute, National Institutes of Health, Bethesda, Maryland.
3
Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
4
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
*Address reprint requests to: R.O.C., National Institutes of Health,
Building 10, Room 7B-15, 10 Center Drive, MSC 1650, Bethesda, MD
20892-1650. E-mail: [email protected]
Received April 4, 2001; Accepted August 16, 2001.
2
© 2001 Wiley-Liss, Inc.
DOI 10.1002/jmri.10023
atherosclerosis (1–3), although evidence for this association in humans is derived largely from measures of
surrogate markers of inflammation. In this regard, risk
of future cardiovascular events has been found to correlate with serum markers of inflammation in large
groups of patients with known or suspected coronary
artery disease, as well as in apparently healthy subjects
(4 –9). However, the sensitivity and specificity for any
given serum level of a marker in defining the presence of
active vascular inflammation is unknown. In this regard, many proposed markers of vascular inflammation
may be elevated in chronic inflammatory conditions not
associated with atherosclerosis (10). Also unknown is
whether high levels of serum markers of inflammation
may be present due to vascular inflammation preceding
plaque development. Accordingly, techniques capable
of demonstrating active arterial inflammation might
identify individuals with significantly increased risk of
developing atherosclerosis or acute coronary syndromes, and could prove useful in targeting aggressive
therapies to reduce vascular inflammation.
Prior magnetic resonance imaging (MRI) studies of
human atherosclerosis have largely focused on plaque
morphology and composition, which may be important
in determining the risk of plaque rupture (11–15). However, MRI may also permit noninvasive demonstration
of inflammation within the vessel wall, as suggested by
experimental and clinical studies. Thus, MRI of sheep
iliac arteries following implantation of Dacron-covered
stents showed both increased T2-weighted signal intensity and contrast enhancement of the arterial wall adjacent to the stent (16). At necropsy, vascular segments
surrounding the prosthesis were found to be infiltrated
with inflammatory cells, including macrophages, lymphocytes, granulocytes, and foreign body giant cells.
Polyester-covered iliac artery stent implantation in 14
patients produced similar MRI findings in 11, while
none of 20 patients who received conventional metallic
stents or underwent balloon angioplasty of the iliac
artery had these findings (17). MRI studies of intracranial vertebral and carotid arterial walls demonstrated
contrast enhancement that correlated with age, and
was hypothesized to be due to neovascularization associated with atherosclerotic plaques (18). Recently, pa-
698
Detection of Arterial Inflammation by MRI
tients with clinically active Takayasu arteritis were reported to have aortic wall thickening with gadolinium
contrast enhancement by MRI, associated with elevated
levels of C-reactive protein (19).
The purpose of this study was to determine whether
MRI could identify features compatible with active inflammation in large arteries of middle-aged and older
subjects, especially those with clinically established
atherosclerosis or its risk factors. We hypothesized that
arterial inflammation would cause increases in wall
thickness, T2-weighted signal intensity, and/or arterial
wall gadolinium contrast enhancement because of enhanced endothelial permeability with increased tissue
water, cellular infiltration, and vasovasorum dilatation
or neovascularization. Due to technical limitations in
high-resolution coronary artery MRI, we chose to image
large arteries commonly affected by atherosclerosis: the
carotid arteries and the infrarenal aorta. Serum markers of inflammation were obtained to determine associations with the MRI characteristics of arterial walls that
we considered to be potentially indicative of arterial wall
inflammation.
METHODS
Study Population
Fifty-two subjects ⱖ40 years of age (average age 56
years, range 40 –79 years) were included in the primary
analysis of the study, representing a continuous series
of subjects who completed the required MRI procedure.
There were three predefined groups: 1) 10 men and
seven women with no modifiable risk factors for atherosclerosis (all with LDL cholesterol ⱕ130 mg/dL, blood
pressure ⬍140/90 mm Hg, fasting blood glucose ⬍120
mg/dL, and no smoking within the past 2 years) who
served as controls for the determination of normal MRI
parameters (mean value ⫾ 2 SD); 2) 13 men and five
women with hypercholesterolemia (LDL cholesterol ⱖ
160 mg/dL), who had received no medications, hormone therapies, or antioxidant vitamins for at least 2
months prior to the study; and 3) 15 men and two
women with angiographically defined coronary atherosclerosis (⬎70% luminal narrowing of at least one coronary artery at the time of diagnostic cardiac catheterization) with stable cardiac symptoms on appropriate
medical management, including aspirin (16) and lipidlowering therapy (10). An additional group of 17 young
adults between 25 and 30 years of age were studied for
comparison with the older “control group” to assess the
possibility of age-dependence of MRI features and serum markers of inflammation. No participant had
known carotid disease, abdominal aortic aneurysm,
systemic inflammatory disorder, or any contraindication to MRI. This protocol was approved by the Institutional Review Board of the National Heart, Lung, and
Blood Institute, and all participants gave written informed consent.
Laboratory Assays
After an overnight fast except for water, blood was obtained from the antecubital vein. Serum aliquots were
coded by a research nurse to blind laboratory personnel
699
as to subject identity, and were frozen at –70°C until
processed as one batch for the following markers of
inflammation: interleukin-6 (IL-6), E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell
adhesion molecule-1 (VCAM-1) by enzyme-linked immunoassays (R&D Systems, Minneapolis, MN); and Creactive protein (CRP) by two-site chemiluminescent
enzyme immunometric assay with a sensitivity of 0.01
mg/dL (Immulite, DPC, Los Angeles, CA).
MRI of the Carotid Arteries and Aorta
MRI was performed on a 1.5T General Electric CV/i
scanner (Waukesha, WI) using a high-resolution, black
blood, ECG-gated, double inversion recovery, fast spin
echo pulse sequence (20). Common carotid arteries and
the infrarenal aorta were imaged in this protocol because of the predilection for atherosclerosis, and because the laminar nature of the blood flow in these
regions minimizes intraluminal signal associated with
eddy currents in the vessel. Imaging of the carotid arteries was performed using a dual 3-inch surface coil
phased array with a 16 –18-cm field of view (FOV)
(256 ⫻ 256 matrix) and 2-mm slices. The average number of pixels per carotid ROI was 14 ⫾ 7 (range 8 –72),
with pixel dimensions of 0.63 ⫻ 0.63 mm, and an acquisition time of 32 heartbeats. Imaging of the aorta
was performed using a four-element cardiac phased
array coil with a 24-cm FOV (256 ⫻ 128 matrix) and
4-mm slices. The average number of pixels per aortic
ROI was 13 ⫾ 6 (range 4 –35), with pixel dimensions of
0.94 ⫻ 1.88 mm, and an acquisition time of 16 heartbeats. All imaging was ECG-gated (32 echos every other
heartbeat). Fat saturation was used on all images analyzed quantitatively. Carotid imaging was performed
5–10 minutes after contrast (gadolinium DTPA 0.1
mmol/kg I.V.), and aortic imaging occurred 10 –25 minutes after contrast. Proton density-weighted images
(baseline) with echo time (TE) ⫽ 5 msec were compared
with T2-weighted images (TE ⫽ 60 msec) (Fig. 1), and
gadolinium contrast-enhanced images (TE ⫽ 5 msec)
(Fig. 2). The same prescan values were used within a
subject to minimize signal intensity changes from scan
to scan as well as pre- and postcontrast. Further, interscan variability was minimized by immobilization of
the patient’s head within a cradle apparatus, and by
securing surface coils to the neck with a clamp device
and to the abdomen with Velcro straps. The inversion
time was empirically adjusted to minimize the blood
pool signal.
Data Analysis
Two representative imaging planes were chosen for
analysis from each vessel out of the five to seven planes
acquired. If focal wall thickening was seen, such a slice
was preferentially selected. Otherwise, vessels with optimal contrast from the surrounding tissue were used
to facilitate generating regions of interest (ROIs). The
inner and outer borders of the vessel wall were drawn
on the baseline scan with the assistance of a semiautomated edge detection tool. ROIs were copied onto images from different acquisitions at the same location
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Weiss et al.
Figure 1. a and b: Baseline and T2-weighted images of a normal-appearing left carotid artery based on (a) the proton
density-weighted scan. b: The T2-weighted image has a 48% decrease in signal intensity from the baseline image. c and d: A
normal-appearing right carotid artery based on the (c) proton density-weighted scan. d: The T2-weighted image shows a 32%
decrease in signal intensity from the baseline image. The window and level are the same for each patient.
and modified, if needed, to account for minor registration differences. Once defined, the wall was divided into
eight equal segments which were analyzed for 1) wall
thickness, measured from the baseline series (TE ⫽ 5
msec with fat saturation); 2) T2-weighted signal intensity, measured as percent change in signal intensity
between the baseline and the TE ⫽ 60 msec series; and
3) postcontrast signal enhancement, measured as percent change in signal intensity between the baseline
and the TE ⫽ 5 msec postcontrast series. MRI studies
were analyzed by an experienced reader who was
blinded to the diagnoses of study participants and the
results of serum assays.
Interobserver variability of the fundamental measurements was performed on 20 carotid arteries and 10
aortas using computer-assisted image analysis, as described in the Methods section. Thus, with eight sectors
per vessel, 20 arteries, three image acquisitions methods per vessel, two different wall thickness methods, an
area measurement, and signal intensity measurements, a total of 2880 measurements were compared
between two observers unaware of the results obtained
by the other. The correlation between two observers’
measurements of carotid wall thickness was y ⫽
0.93x ⫹ 0.00, r ⫽ 0.88. In the comparison studies, the
average carotid wall thickness was 1.71 ⫾ 0.49 mm.
Bland-Altman analysis showed a small bias in absolute
wall thickness determination. The difference in wall
thickness between the two observers averaged 0.25 ⫾
0.28 mm, which represents approximately one-third of
a pixel and about 15% of the arterial wall thickness. The
coefficient of variation between the two observers’ measurement of wall thickness was 14%.
The average carotid arterial wall signal intensity in a
sector was 949 ⫾ 328 (arbitrary units (AU)) on baseline
studies (TE ⫽ 5 msec), 572 ⫾ 232 AU on T2-weighted
images, and 1086 ⫾ 375 AU on postcontrast images.
The difference in signal intensity measurements between the two observers averaged 52 ⫾ 54 AU for TE ⫽
5 msec images, 50 ⫾ 55 AU for T2-weighted images, and
50 ⫾ 50 AU on postcontrast images. This translates to
coefficients of variation of 5%, 8%, and 4% for baseline,
T2-weighted, and postcontrast images, respectively.
The contrast enhancement measurements for carotid
arteries correlated well between observers (y ⫽ 0.99x ⫹
0.01, r ⫽ 0.81) and there was no systematic bias between observers on Bland-Altman analysis. For contrast enhancement that averaged 0.17 ⫾ 0.11, the average difference in contrast enhancement between
observers was 0.01 ⫾ 0.08. T2-weighted measurements
also correlated well between observers (y ⫽ 1.14x –
0.08, r ⫽ 0.93) and there was no systematic bias between observers on Bland-Altman analysis. For T2weighted measurements that averaged 0.39 ⫾ 0.07, the
average difference in contrast enhancement between
observers was 0.02 ⫾ 0.03. Aortic measurements
showed similar trends.
Detection of Arterial Inflammation by MRI
701
Figure 2. a: A normal-appearing right carotid artery. Compared with (a) the baseline proton density-weighted image, (b) infusion
of gadolinium contrast increased signal intensity by 15%. c: A left carotid artery with focal plaque. Gadolinium caused a 32%
increase in signal intensity not only in the plaque (arrows), but also in (d) the adjacent arterial wall. Postcontrast enhancement
of the veins (anterior to the carotid artery) was seen in subjects from all groups, and may represent an artifact of low velocity
blood flow (25). We have seen similar venous effects in normal volunteers after contrast, which were eliminated by repositioning
the surface coil off the surface of the neck. Since the black blood contrast is accomplished by a combination of flow, inversion
recovery timing, and the fast spin echo readout, the low pressure and lower flow of veins may be more susceptible to the effects
of light pressure on the neck surface than the arteries. The window and level before and after contrast are the same for each
patient.
For each parameter measured on each subject, an
average value for each vessel and the most abnormal
segment value were determined for each of the three
MRI features. Subjects who had a value greater than 2
SDs from the control group mean directionally anticipated for inflammation (increased wall thickness, increased T2-weighted signal intensity (lower percent
change in signal intensity from baseline), and postcontrast signal enhancement (greater percent change in
signal intensity from baseline)) for at least one parameter were designated as having an MRI study compatible with inflammation. Based on these criteria, study
participants were then divided into two groups: those
with an abnormal MRI study, and those with entirely
normal MRI studies. Levels of serum markers of inflammation in these two groups were compared using the
two-tailed, unpaired t-test for normally distributed
data, and the nonparametric Mann-Whitney test for
non-normal data. P ⬍ 0.05 was accepted as indicating
statistical significance.
RESULTS
MRI data for carotid artery and aorta wall thickness,
T2-weighted signal intensity, and postcontrast signal
intensity for the 17 subjects ⱖ40 years of age who had
no risk factors for atherosclerosis and served as controls are provided in Table 1. Of the total cohort of 52
subjects ⱖ40 years of age, 22 subjects had values for
these imaging characteristics of the carotid arteries
and/or aorta that were greater than two SDs from the
control group mean in the direction compatible with
inflammation: 14 had increased wall thickness (of
Table 1
MRI Data for Control Group ⱖ40 Years of Age
Thickness (mm)
Average
Maximum
T2-weighted signal intensity
(percent below baseline)
Average
Maximum
Post-contrast signal intensity
(percent above baseline)
Average
Maximum
Data ⫽ mean ⫾ SD.
Carotid arteries
Infrarenal aorta
1.5 ⫾ 0.2
1.8 ⫾ 0.3
2.4 ⫾ 0.4
2.9 ⫾ 0.7
42 ⫾ 6
10 ⫾ 17
30 ⫾ 10
3 ⫾ 23
13 ⫾ 12
56 ⫾ 29
19 ⫾ 14
68 ⫾ 41
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Weiss et al.
Figure 3. Bar graphs show levels of serum markers of inflammation in 22 subjects with abnormal MRI compared with 30
subjects with normal MRI vascular studies. IL-6 ⫽ interleukin-6, CRP ⫽ C-reactive protein, ICAM-1 ⫽ intercellular adhesion
molecule-1, and VCAM-1 ⫽ vascular cell adhesion molecule-1. Data ⫽ mean ⫾ SEM.
whom seven also had increased T2-weighted signal intensity and two had increased postcontrast signal intensity) and eight had normal wall thickness, but increased T2-weighted signal intensity (3), increased
postcontrast signal intensity (4), or a combination of
these findings (1). Seven subjects had abnormal carotid
MRI studies with normal aorta MRI studies, 10 had
abnormal aorta but normal carotid MRI studies, and
five had abnormal MRI studies of both the carotids and
the aorta. Ten subjects had evidence of focal plaque in
the carotids (5) and/or aorta (6). Of these 22 subjects
with abnormal MRI studies, 13 had coronary artery
disease, five had hypercholesterolemia, and four were
from the healthy control group. Conversely, 30 subjects, including four patients with coronary artery disease, 13 hypercholesterolemic subjects, and 13 healthy
controls, had values for these imaging characteristics
that fell within 2 SDs of the control group means for all
parameters measured.
The 22 subjects with abnormal MRI studies had significantly higher levels of IL-6, CRP VCAM-1, and
ICAM-1, and nonsignificantly higher levels of E-selectin, compared with the 30 subjects whose MRI values
fell within 2 SDs of the control group means (Fig. 3). For
IL-6, CRP, VCAM-1, and ICAM-1, the 14 subjects with
increased wall thickness alone had significantly higher
levels of these markers compared with the 30 subjects
with normal MRI studies. The eight subjects with normal wall thickness but increased T2-weighted and/or
postcontrast signal intensities tended to have intermediate values (Fig. 4).
The abnormal MRI group was older than the normal
MRI group (58.6 ⫾ 11.0; range 41–76 years vs. 53.2 ⫾
8.1; range 41–79 years, P ⫽ 0.048). There was no dif-
ference in sex distribution between the abnormal MRI
(18 men, four women) vs. the normal MRI group (22
men, eight women; P ⫽ 0.51 by Fisher’s Exact test).
There were no significant differences between these two
groups for the following lipid levels: total cholesterol
(198 ⫾ 40 vs. 212 ⫾ 53 mg/dL), LDL cholesterol (126 ⫾
35 vs. 137 ⫾ 46 mg/dL), HDL cholesterol (44 ⫾ 10 vs.
51 ⫾ 24 mg/dL), and triglycerides (174 ⫾ 160 vs. 153 ⫾
76 mg/dL) (all P ⬎ 0.20).
Compared with the 17 control subjects ⱖ40 years of
age, the 17 young adults 25–30 years of age had significantly thinner carotid arteries and aortas (Table 2). The
carotids showed significantly greater reduction in T2weighted signal intensity from the baseline proton density-weighted scans, and the aorta showed significantly
less increase in signal intensity following gadolinium
contrast infusion. The 17 young adults also had lower
levels of many of the markers of inflammation measured in this study: IL-6 (1.58 ⫾ 0.69 vs. 2.19 ⫾ 1.20
pg/mL, P ⫽ 0.082), CRP (0.17 ⫾ 0.10 vs. 0.41 ⫾ 0.70
mg/dL, P ⫽ 0.309), E-selectin (33.4 ⫾ 10 vs. 41.2 ⫾
12.0 ng/mL, P ⫽ 0.055), ICAM-1 (168 ⫾ 38 vs. 203 ⫾ 53
ng/mL, P ⫽ 0.033), VCAM-1 (480 ⫾ 137 vs. 499 ⫾ 115
ng/mL, P ⫽ 0.670).
DISCUSSION
Histologic studies in humans provide strong evidence
that not only is inflammation present in atherosclerotic
disease, but it may also be a powerful measure of the
degree of activity of the atherosclerotic process due to
its association with plaque rupture and acute coronary
syndromes (1–3). However, vascular inflammation may
contribute importantly to atherogenesis prior to the de-
Detection of Arterial Inflammation by MRI
703
Figure 4. Bar graphs show levels of serum markers of inflammation in 14 subjects with increased wall thickness (1WT), eight
subjects with normal wall thickness but increased postcontrast signal intensity and/or T2-weighted (1Gd/T2), and 30 subjects
with normal MRI studies. Data ⫽ mean ⫾ SEM. One-way analysis of variance was performed on each data set, with post-hoc
significance identified above the bars. Abbreviations are the same as for Fig. 3.
velopment of established plaque. Using MRI features we
hypothesized to be consistent with inflammatory processes in the vessel wall, we were able to stratify the
study population into two groups, with the abnormal
vascular MRI group having higher levels of serum
markers of inflammation than the group with normal
MRI studies. Intriguingly, abnormal MRI studies were
frequently not associated with MRI detection of actual
atherosclerotic plaque in the vessels imaged, and were
found in four of 17 control subjects. These findings
suggest that arterial inflammation may precede development of plaque, and that this process may occur in
subjects without conventional risk factors for atherosclerosis. In this regard, epidemiological studies suggest that only approximately one-half the excess risk of
atherosclerotic events, such as myocardial infarction,
Table 2
MRI Data for Young Adults 25–30 Years of Age
Wall thickness
Average
Maximum
T2-weighted signal intensity
(percent below baseline)
Average
Maximum
Post-contrast signal intensity
(percent above baseline)
Average
Maximum
Carotid arteries
Infrarenal aorta
1.2 ⫾ 0.1**
1.6 ⫾ 0.2**
2.2 ⫾ 0.3
2.5 ⫾ 0.4*
47 ⫾ 6*
12 ⫾ 16
34 ⫾ 8
11 ⫾ 20
13 ⫾ 14
71 ⫾ 48
7 ⫾ 17*
59 ⫾ 32
Data ⫽ mean ⫾ SD. *P ⬍ .05, **P ⬍ 0.01 vs. control group ⱖ40
years of age (Table 1).
in apparently healthy populations is accountable by
conventional risk factors, including hypercholesterolemia (21). Accordingly, alternative risk factors for atherosclerosis, such as serum markers of inflammation
(6 –9), are under investigation as potentially sensitive
markers of atherosclerosis risk. Of note, the majority of
patients with established coronary artery disease had
MRI evidence of arterial inflammation despite the use of
medications (aspirin and lipid-lowering therapies) associated with reduced risk of future cardiovascular
events (22).
Our studies extend the observations of Rohde et al.
(23), who reported significant correlations between
ICAM-1 and VCAM-1 levels, and carotid intimal-medial
thickness measured by 2D ultrasound. Our study suggests that MRI provides a more complete tissue characterization of the vessel wall which may permit the
identification of inflammation, even in the absence of
increased wall thickness. In this regard, eight of 22
subjects with abnormal MRI scans had increased T2weighted signal intensity and/or gadolinium contrast
enhancement in the absence of increased wall thickness, and had levels of several markers of inflammation
intermediate to those of the 14 subjects with increased
wall thickness and the 30 subjects with normal MRI
studies. This observation raises the possibility that T2weighted and contrast-enhanced properties of MRI may
identify arterial inflammation at an earlier stage than is
manifested by increased thickness of the arterial wall.
Limitations of Study
An important limitation of this study is the absence of
tissue from carotid arteries or aortae of our subjects for
704
histological demonstration of the presence or absence
of inflammation. Wasserman et al. (24) recently reported that gadolinium enhancement of carotid arteries
by MRI was associated with fibrocellular tissue in atherosclerotic plaque during subsequent microscopic
analysis following endarterectomy. Correlational studies of MRI and histopathology in animal models of atherosclerosis may be useful in further validating the capability of MRI to identify active vascular inflammation.
A second limitation of our study is that differences in
MRI characteristics and in levels of serum markers of
inflammation between the normal and abnormal vascular MRI groups could have resulted in part from differences in age, although the range of ages was the
same for the two groups. Due to the importance of age
as a determinant of atherosclerosis risk, any method
that detects pathophysiological features of atherosclerosis (i.e., inflammation) is expected to have an association with age. Of interest, the mean IL-6 value for the
abnormal MRI group in our study falls in the highest
quartile of IL-6 values in the Physicians’ Health Study,
using the same commercial assay, in whom a greater
than twofold risk of future myocardial infarction was
reported compared with men whose IL-6 values fell
within the lowest quartile (9). In this regard, MRI characteristics of large arteries may convey prognostic significance, although comparison of this testing with
more easily performed serum markers of inflammation
will require a much larger series of subjects followed
prospectively for development of cardiovascular events.
We conclude that MRI characteristics of vascular inflammation in large vessels are associated with increases in serum markers of inflammation. This occurred even in healthy middle-aged and older subjects
without modifiable risk factors for atherosclerosis, and
frequently in the absence of adjacent plaque. Accordingly, MRI of large arteries may provide a new approach
to investigate the contribution of inflammation to
atherogenesis.
ACKNOWLEDGMENTS
We thank Samuel Hou, M.S., Arnon Blum, M.D., Gyorgy Csako, M.D., William H. Schenke, B.A., Londa
Hathaway, R.N., Karen Bove-Bettis, M.R.T, and Bruce
Wasserman, M.D., for their invaluable assistance in the
conduct of this study, and Judith Taylor for typing the
manuscript. Clifford R. Weiss was a Fellow in the Clinical Research Training Program of the National Institutes of Health.
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