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Coronary Artery Atherosclerosis Is Related to Reduced Regional Left Ventricular
Function in Individuals Without History of Clinical Cardiovascular Disease: The
Multiethnic Study of Atherosclerosis
Thor Edvardsen, Robert Detrano, Boaz D. Rosen, J. Jeffrey Carr, Kiang Liu, Shenghan Lai,
Steven Shea, Li Pan, David A. Bluemke and João A.C. Lima
Arterioscler Thromb Vasc Biol. 2006;26:206-211; originally published online November 3,
2005;
doi: 10.1161/01.ATV.0000194077.23234.ae
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Coronary Artery Atherosclerosis Is Related to Reduced
Regional Left Ventricular Function in Individuals Without
History of Clinical Cardiovascular Disease
The Multiethnic Study of Atherosclerosis
Thor Edvardsen, Robert Detrano, Boaz D. Rosen, J. Jeffrey Carr, Kiang Liu, Shenghan Lai,
Steven Shea, Li Pan, David A. Bluemke, João A.C. Lima
Objective—We investigated whether regional coronary calcium score by computed tomography is related to regional left
ventricular systolic function measured by MRI tagging in participants of the Multiethnic Study of Atherosclerosis.
Methods and Results—The Multiethnic Study of Atherosclerosis is a prospective observational study of men and women
without a history of previous heart disease from 4 ethnic groups. Calcium scores were measured separately for the left
anterior descendent (LAD), left circumflex (LCX), and right (RCA) coronary arteries. Left ventricular strain and strain
rate were determined by tagged MRI in the corresponding vascular territories of the coronary vessels in 509 participants.
Greater coronary calcification in the LAD, LCX, and right RCA coronary arteries were related to worse function in their
respective perfusion. Anterior wall strain rate was ⫺1.37⫾0.41 when LAD calcium was zero versus ⫺1.17⫾0.24 1/s
in the highest quartile of calcium score (P⬍0.001). Similar relationships were evident in the LCX and RCA regions.
Participants with 1- and 2-vessel coronary artery calcium had better myocardial function in the remote area compared
with the territory supplied by the diseased artery.
Conclusions—High-local calcium score is related to regional dysfunction in the corresponding coronary territory among
individuals without a history of previous heart disease. These results indicate a link between atherosclerosis and
subclinical regional left ventricular dysfunction. (Arterioscler Thromb Vasc Biol. 2006;26:206-211.)
Key Words: atherosclerosis 䡲 coronary circulation 䡲 calcification 䡲 MRI 䡲 myocardial function
L
eft ventricular dilatation and global dysfunction in patients
without signs or symptoms of heart failure have been
directly linked to the eventual development of symptomatic
congestive heart failure in clinical and epidemiologic studies.1,2
These structural and functional alterations of the left ventricle are
currently considered as subclinical manifestations of heart failure.3 In the United States and Europe, coronary artery disease is
the leading cause of left ventricular dysfunction and heart
failure.4 Moreover, because coronary atherosclerosis is the most
important primary etiologic factor underlying heart failure, it is
expected that myocardial dysfunction would begin as a regional
process, later progressing to global ventricular failure and
symptomatic congestive disease. However, the relationship between subclinical atherosclerosis and subclinical myocardial
dysfunction remains undefined.
MRI offers a unique opportunity to assess regional left ventricular function in a detailed and quantitative manner through myo-
cardial tagging.5,6 MRI tagging is an accurate and objective method
for assessing regional myocardial dysfunction.7,8 Similarly, coronary calcification measured by computed tomography (CT) is
considered to be a specific and quantifiable subclinical marker of
coronary atherosclerosis.9,10 CT also allows for separate assessments of coronary calcification in the 3 main coronary arterial trees
supplying the human left ventricle; namely, the left anterior descending (LAD), left circumflex (LCX), and right (RCA) coronary
arteries. Therefore, the main hypothesis of this study is that regional
coronary calcium scores are related to regional myocardial dysfunction defined by MRI tagging in the corresponding myocardial
territories of individuals without any history of clinical cardiac
disease. We investigated this hypothesis in the Multiethnic Study of
Atherosclerosis (MESA).
Methods
MESA is a prospective, population-based observational cohort study
of men and women free of a history or symptoms of clinical
Original received June 6, 2005; final version accepted October 24, 2005.
From the Division of Cardiology (T.E., B.D.R., L.P., J.A.C.L.), Department of Epidemiology (S.L.), and Department of Radiology (D.A.B.,J.A.C.L.),
Johns Hopkins University, Baltimore, MD; Division of Cardiology (R.D.), University of California Los Angeles School of Medicine, Torrance, CA;
Department of Radiology (J.J.C.), Wake Forest University School of Medicine, Winston-Salem, NC; Department of Preventive Medicine (K.L.), Feinberg
School of Medicine, Northwestern University, Chicago, IL; and Department of Medicine and Epidemiology (S.S.), Schools of Medicine and Public
Health, Columbia University, New York, NY.
Correspondence to Joao A.C. Lima, Johns Hopkins Hospital, Cardiology Division, 600 N Wolfe St/Blalock 524, Baltimore, MD 21287-0409. E-mail
[email protected]
© 2005 American Heart Association, Inc.
Arterioscler Thromb Vasc Biol. is available at http://www.atvbaha.org
DOI: 10.1161/01.ATV.0000194077.23234.ae
206
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Edvardsen et al
TABLE 1.
Exclusion Criteria for MESA
Age ⬍45 or ⬎84 years
High Calcium Score Is Related to LV Dysfunction
207
pant. The average calcium score was used in all of the analyses.9 The
presence of calcification was defined as an average calcium score ⬎0
(or ⬎0 on either scan).
Physician-diagnosed heart attack
Physician-diagnosed angina or taking nitroglycerin
Physician-diagnosed stroke or TIA
Physician-diagnosed heart failure
Current atrial fibrillation
Having undergone procedures related to cardiovascular disease
Active treatment for cancer
Pregnancy
Any serious medical condition that would prevent long-term participation
Weight ⬎300 pounds
Cognitive inability as judged by the interviewer
Living in a nursing home or on the waiting list for a nursing home
Plans to leave the community within 5 years
Language barrier (speaks other than English, Spanish, Cantonese, or
Mandarin)
Chest CT scan in the past year
cardiovascular disease at study enrollment. Study design and population characteristics have been described in greater detail elsewhere.11 Briefly, 6814 men and women from 4 different ethnic
groups (white, African-American, Hispanic, and Chinese), aged 45
to 85 years at baseline, were enrolled in MESA. The exclusion
criteria in MESA are listed in Table 1. Participants with known
clinical disease were not recruited, and eligibility was determined
from self-reported information. Of those, 509 participants underwent
both tagged MRI and CT scanning the same day at 6 different centers
(Wake Forest University, Winston-Salem, NC; Columbia University,
New York, NY; Johns Hopkins University, Baltimore, MD; University of Minnesota, MN; Northwestern University, Chicago, IL, and
University of California at Los Angeles, Torrance, CA) between July
2000 and September 2002. These individuals were included in the
regional function analyses.
All of the MESA participants gave informed consent for the study
protocol. The Institutional Review Boards in all of the MESA Field
Centers, MRI, and CT Reading Centers approved this protocol.
CT Protocol
All of the MESA participants underwent measurement of coronary
artery calcium score using either 4-detector row CT (MDCT) or
electron beam CT (EBCT) at the baseline examination. All of the
EBCT (University of California Los Angeles, Columbia University,
and Northwestern University) and MDCT scans were prospectively
triggered.
EBCT was performed on Imatron C-150 ultrafast scanners with a
100-ms exposure and 35-cm field view. For the sites that used
EBCT, parameters were: 130 kVp, 630 mA, scan time of 100 ms,
3-mm collimation, and sharp reconstruction filter. For EBCT scans,
prospective cardiac gating was used with scanner triggering at 80%
of the electrocardiographic RR interval.
MDCT was performed on either GE Light Speed or Siemens
Volume Zoom scanners with 330-ms and 361-ms exposure, respectively, and 35-cm field of view.12,13 Participants were scanned twice
in succession. At Wake Forest University, a GE Light Speed was
used with 120 kVp, 200 mA, 0.8-s scan, 4⫻2.5-mm collimation,
sequential axial scans, segmented reconstruction, and standard filter.
Johns Hopkins University and the University of Minnesota used
Siemens Volume Zoom at 140 kVp, 139 mA, 0.361-s scan,
4⫻2.5-mm collimation, sequential axial scans with prospective
cardiac gating, and standard filter reconstruction.
The results of the 2 scans were averaged. Calcium scores among
scanning centers and between participants were adjusted with a
standard calcium phantom scanned simultaneously with the partici-
MRI Protocol
Images were obtained using 1.5 T magnetic resonance scanners,
including Signa LX or CVi (GE Medical Systems) or Symphony or
Sonata (Siemens Medical Systems). Images were acquired using a
segmented k-space, ECG-gated fast spoiled gradient recalled echo
sequence pulse sequence. Torso phase array coils were used for
signal reception. One vertical long axis and 6 short axis cine images
were prescribed. After completing the standard protocol, 3 tagged
short axis slices were obtained. Striped tags were prescribed separately in 2 orthogonal orientations (0o and 90o) using spatial modulation of magnetization. Images were acquired at resting lung volume
during ⬇12-s to 18-s breath holds. Parameters for tagged MRI
images included field of view, 40 cm; slice thickness, 8 to 10 mm;
repetition time, 3.5 to 7.2 ms; echo time, 2.0 to 4.2 ms; flip angle,
12°; matrix size, 256⫻96 to 140; 4 to 9 phase encoding views per
segment; bandwidth range pf 24.9 to 62.5 kHz); temporal resolution
of 36.3⫾12.0 ms; and tag spacing of 7 mm.
Analysis
For each of the 509 subjects in whom both CT and tagged cardiac
MRI data were obtained, stroke volume and ejection fraction were
determined using standard commercially available software (MASS
4.2, MEDIS). Regional myocardial deformation can be calculated
from a tagged MRI study. Peak regional systolic strain in the
circumferential direction (Ecc) was used in the 509 consecutive
participants who enrolled in the tagged MRI study and were analyzed
by Harmonic Phase Imaging14 at the MRI Reading Center (Johns
Hopkins University). Ecc was determined in 6 left ventricular
segments (anterior, anterolateral, inferolateral, inferior, anteroseptal,
and inferoseptal) from the basal and mid-part of left ventricle and 4
segments (anterior, lateral, inferior, and septal) in the apical part. The
midwall layer in each segment was analyzed. The assignment of
segments to coronary arterial territories (LAD, LCX, and RCA) was
done in accordance with clinical recommendations.15 The apex was
excluded from the analyses because of great variability in myocardial
blood supply. Myocardial strain is a measure of regional deformation, whereas strain rate is the rate of deformation or velocity of
shortening. Thus, strain and strain rate provide complementary
information on segmental myocardial function.16 Strain rate was
determined as the first derivative of strain measurements (Ecc) at 2
consecutive time points.17 Peak systolic strain rate was derived from
the strain trace as shown in Figure 1. By definition, systolic strain
and strain rate are negative, because they indicate shortening.
Therefore, an increased negativity denotes better function. Individual
strain and strain rate reread variability was found to be 4% and 3%,
respectively, for all 3 of the arterial systems.
CT scans were evaluated blindly with respect to scan pairs and to
all of the clinical data using a computerized interactive scoring
system similar to that described by Yaghoubi et al.18 Calcium scores
were measured at the CT Reading Center (University of California
Los Angeles) using dedicated analysis software that incorporated
adjustment for image attenuation based on the calibration phantom.
The computer system used a minimum pixel attenuation of 131 HU
and a minimum lesion volume of 5 mm3 to calculate the calcium
score.12 Furthermore, calcium mass and volume were calculated for
each participant. Individual calcium scores for LAD, LCX, and RCA
were determined. Agreement with regard to the presence of coronary
calcification was high (␬-statistic, 0.90 to 0.93 between and within
readers), and the intraclass correlation coefficient for the calcium
score between readers was 0.99.12,13
Statistical Analysis
Values are presented as mean⫾SD. Participants were divided into 2
groups: those with positive (greater than 0) calcium scores and those
with zero calcium scores. Participants with positive calcium scores
were additionally subdivided into quartiles by regional calcium score
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208
Arterioscler Thromb Vasc Biol.
January 2006
TABLE 2. Demographic and Hemodynamic Data From
All Participants
Variable
Calcium
Score⫽0
(n⫽225)
Calcium
Score ⬎0
(n⫽284)
P Value
⬍0.001
Age, y
62⫾9
70⫾8
Women/men, n
113/112
176/108
0.067
Calcium scores
0⫾0
364⫾666
⬍0.001
Total calcium volume score
0⫾0
279⫾509
⬍0.001
90⫾162
⬍0.001
Total mass score
0⫾0
Systolic blood pressure, mm Hg
127⫾21
128⫾21
Diastolic blood pressure, mm Hg
74⫾11
71⫾10
0.005
Ejection fraction, %
68⫾7
68⫾8
0.452
Stroke volume, mL
LV end diastolic mass, g
Glucose, mmol/L
Creatinine, ␮mol/L
85⫾18
86⫾20
0.660
145⫾37
153⫾42
0.025
5.8⫾1.4
6.2⫾1.9
0.007
71.4⫾14.6
77.3⫾22.3
0.001
Diabetes, n
Cholesterol, mmol/L
0.673
23
55
5.1⫾0.9
5.0⫾0.9
⬍0.001
0.225
Mean⫾SD.
Figure 1. Representative strain rate (top) and strain (bottom)
profiles from 1 MESA participant with positive calcium score in
the LAD territory. This example is demonstrating a typical strain
rate pattern with E and A waves and is from the anterior midwall
segment at mid-left ventricular level.
levels to test a possible threshold effect. ANOVA methods with
Bonferroni corrections were used to test possible differences among
the groups. A paired t test was used to compare left ventricle (LV)
function (strain and strain rate) in the calcified and noncalcified
regions in patients with 1- and 2-vessel coronary calcium. Proportions were compared with the use of ␹2 tests. The log normal–
transformed calcium scores were used for regression analyses that
are based on the assumption of normality. Multiple linear regression
was used to study the relationship between global [ejection factor
(EF)] and regional LV function (strain and strain rate) and logtransformed total and regional calcium scores (SPSS v 12.0).
Variables that might influence on the regional myocardial function
were entered into the regression model including age, gender, race,
systolic blood pressure, left ventricular end diastolic mass index,
heart rate, and diabetes. All of the reported P values are 2-sided with
the ␣ level set at 0.05.
Results
The study population consisted of 136 white, 85 AfricanAmerican, 222 Hispanic, and 66 Chinese subjects. The 509
individuals studied had a mean total coronary calcium score
of 529⫾203 U. The results in this study did not differ
significantly when using calcium volume or mass scores. The
Hispanic participants were younger than the white and
Chinese groups (63.5⫾9.6 versus 68.6⫾8.7 years, P⬍0.001,
and 69.4⫾8.0 years, P⬍0.001, respectively).
Global Measures of Coronary Calcium and Left
Ventricular Function
Demographic data from the subset of MESA participants who
had the MRI tagging study are shown in Table 2. Calcium
scores greater than zero were found in 284 (56%) partici-
pants, were more common in men than in women (61%
versus 49%; P⬍0.01), and were associated with greater age
(70⫾8 versus 62⫾9 years; P⬍0.001) when compared with
participants with zero scores.
Participants with positive calcium scores had similar EF
and stroke volume as those with zero calcium scores. EF was
similar in participants with 1- and 2-vessel coronary calcification (68⫾7% versus 68⫾9%; P⫽0.88).
Coronary Calcification and Regional Left
Ventricular Function
Positive calcium scores were present in the LAD, LCX, and
RCA coronary arteries in 257 (50%), 163 (32%), and 156
(31%), respectively. Eighteen percent of subjects had detectable calcium in 1 artery, 17% in 2 arteries, and 19% in all 3
major coronary arteries. We did not find ethnicity-related
differences regarding the distribution of coronary calcium in
the separate arterial trees.
The group with calcium score above zero showed reduced
regional myocardial function compared with the group with
zero calcium score. The differences between the 2 groups at
the basal LV level were moderate. Importantly, the most
apical levels showed decreased strain and strain rate in each
myocardial segment with calcium score above zero. The
differences were ⫺1.5⫾0.4 versus ⫺1.3⫾0.4 (P⬍0.01) in
the LAD area, ⫺1.5⫾0.5 versus ⫺1.4⫾0.4 (P⬍0.01) in the
LCX area, and ⫺1.4⫾0.5 versus ⫺1.2⫾0.4 in the RCA area.
The regional LV function in the calcified territory was
impaired compared with regional LV function in the noncalcified territory in participants with 1-vessel coronary calcium
(⫺1.5⫾0.4 versus ⫺1.3⫾0.3 L/s; P⬍0.01). The same pattern
was found for strain measurements and in participants with
2-vessel calcification (Table 3).
Moreover, when participants with positive calcium scores
are subdivided according to the degree of coronary calcification, those in the higher quartiles have additional reductions
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Edvardsen et al
High Calcium Score Is Related to LV Dysfunction
209
TABLE 3. Myocardial Function in Regions With and Without Coronary Calcium in
Patients With 1 and 2 Vessel Calcification
Variable
Strain rate, 1/s
Strain, %
One Vessel Coronary Calcification
Two Vessel Coronary Calcification
Region With
Calcium ⬎0
Regions With
Calcium ⬎0
Regions Without
Calcium
⫺1.3⫾0.3*
⫺1.5⫾0.4
⫺1.3⫾0.3
⫺16.4⫾3.7*
⫺17.7⫾3.0
⫺17.2⫾2.6
Region Without
Calcium
⫺1.4⫾0.4†
⫺17.1⫾3.7
*P⬍0.01; †P⬍0.05.
in regional function as compared with those in the lower
quartiles (Figure 2). These differences in myocardial function
were even more pronounced when comparing participants in the
highest coronary calcification quartile with those with zero
calcium scores: LAD territory ⫺1.37⫾0.41 versus ⫺1.17⫾0.24
L/s (P⬍0.001), LCX ⫺1.54⫾0.53 versus ⫺1.09⫾0.45 L/s
(P⬍0.001), and RCA ⫺1.37⫾0.44 versus ⫺1.09⫾0.24 L/s
(P⬍0.001), respectively.
The relationship between regional calcium score and regional myocardial function was also demonstrated by multiple linear regressions. After adjustment for age, gender, race,
systolic blood pressure, left ventricular end diastolic mass
index, heart rate, and diabetes, the most important variable
predictive of regional dysfunction indexed as reduced strain
rate in all of the coronary territories was the respective
coronary calcium score (Table 4).
Discussion
To our knowledge, this is the first study showing a direct
relationship between local coronary atherosclerosis and regional left ventricular dysfunction in a population of individuals without a history of heart disease. We found that
coronary calcium scores were associated with reduced function in the corresponding myocardial perfusion territories of
MESA participants. These relationships indicate that subclinical myocardial damage induced by atherosclerosis may
occur earlier than previously suspected.
Prior clinical and epidemiologic studies on the natural
history of heart failure have focused on global indices of left
ventricular dilatation and dysfunction to examine the transition from subclinical to symptomatic disease.1,2 Those studies
demonstrated that the progression can be delayed by therapy
but is fundamentally irreversible.19,20 The pathophysiology of
the processes that precede global enlargement and dysfunction have been investigated mainly in patients who develop
congestive heart failure as a consequence of clinically documented myocardial infarction.21,22 In those patients, regional
myocardial damage resulting from either a single large infarct
or from cumulative damage caused by multiple small infarcts
triggers a series of structural alterations and compensatory
mechanisms, which ultimately lead to left ventricular dilatation, eccentric hypertrophy, and remodeling.23 However, as
many as half of the first coronary events have been reported
to be clinically silent.24 Additionally, chronic coronary artery
disease may lead to congestive heart failure in the absence of
discrete episodes of myocardial infarction, through pathways
that may or may not be similar to those documented in
patients who have a clinical history of myocardial infarction.25 Our findings support the theory that chronic myocardial injury is directly related to the degree of upstream
coronary atherosclerosis in individuals free of cardiovascular
disease. This mechanism may underlie the dysfunctional
process that is often seen in patients with coronary artery
disease but no history of discrete previous myocardial
infarction.
Global Left Ventricular Function
Coronary calcium score measured by fast CT has been
demonstrated to correlate strongly with histological measurements of calcified plaque, total plaque burden, as well as
prevalence of coronary stenoses by coronary angiography.10,26 However, increased calcium score was not associated with declines in ejection fraction or stroke volume in this
study. Whereas decreased global left ventricular function may
Figure 2. Participants with positive calcium score in the LAD, LCX, and RCA arterial trees divided into quartiles by level of calcium
score. Participants with a higher regional calcium score demonstrate lower regional myocardial function by strain rates in the different
myocardial segments. Values given are mean strain rates, and black bars indicate SD.
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210
Arterioscler Thromb Vasc Biol.
January 2006
TABLE 4. Predictors of Regional Myocardial Function in Participants in the LAD
(nⴝ229), LCX (nⴝ163), and RCA (nⴝ144) Territories, Respectively
LAD
Predictors
Correlation
Coefficient
LCX
P Value
Correlation
Coefficient
RCA
P Value
Correlation
Coefficient
P Value
RCAC
0.247
⬍0.001
0.333
⬍0.001
0.310
Age
0.148
0.027
0.094
0.238
0.119
0.163
⫺0.091
0.211
⫺0.255
0.005
⫺0.027
0.773
0.144
0.024
0.174
0.027
0.122
0.152
LVEDM
0.282
⬍0.001
0.210
0.019
0.278
0.003
SBP
0.004
0.946
0.048
0.540
⫺0.026
0.755
Heart rate
0.078
0.206
0.014
0.851
0.158
0.055
Diabetes
0.006
0.927
0.039
0.614
⫺0.094
0.242
Gender
Race
⬍0.001
The perfusion areas are divided according to standard perfusion territories as described in the
Methods. RCAC indicates regional coronary calcium score (log-transformed calcium score units);
LVEDM, left ventricular end diastolic mass; SBP, systolic blood pressure. Mean⫾SD.
or may not lead to symptoms of cardiac failure, entry criteria
to MESA precluded a history of symptomatic cardiac disease.
This exclusion criterion may have limited our ability to detect
a relationship between total calcium score and global left
ventricular function in MESA. Alternatively, a compensatory
increase of contractility in territories unaffected by atherosclerosis may have contributed to the masking of a relationship between total calcium score and LV ejection fraction in
this population.
Regional Left Ventricular Function
MRI is well suited for the determination of detailed regional
left ventricular function through myocardial tagging.5 Myocardial systolic deformation can be accurately quantified by
measurements of myocardial strain and strain rate.16 The
present study reports that coronary atherosclerosis is associated with depressed regional left ventricular function (Figure
2). Potential mechanisms linking local arterial calcification
and atherosclerosis to regional ventricular dysfunction include small vessel microembolization, as well as chronic
ischemia caused by stenotic atherosclerotic plaques, endothelial dysfunction, or both.
Coronary atherosclerosis can be detected in its subclinical
stages by cardiac CT.10,27,28 Relationships between the
amount of local coronary calcification and the percentage of
coronary luminal narrowing have been demonstrated.24,26
Moreover, a recent study by He et al29 showed a positive
relationship between stress myocardial perfusion tomography
and calcium score. The authors concluded that coronary
calcium score could identify a high-risk group of asymptomatic subjects who had clinically important ischemia. Our
study indicates that calcium score measured by cardiac CT
(MDCT and EBCT) may identify individuals at an increased
risk of developing local left ventricular dysfunction.
Methodological Considerations
The cross-sectional nature of the data reported in this study
should be kept in mind when interpreting its results. Moreover, the selection and enrollment of the MESA population
was not random, and, therefore, the prevalence of the various
risk factors may not exactly reflect the overall population.
The history of previous clinical cardiovascular disease was
self-reported in MESA. We cannot, therefore, completely
exclude that a few number of participants might have experienced overt cardiovascular disease.
Direct comparisons of the 2 different CT methods (MDCT
versus EBCT) used in this study have been found satisfactory.12,30 Only midwall circumferential strain and strain rate
measures were assessed. In our opinion, the midwall strains
and strain rates would best represent the regional function of
the whole segment in an epidemiologic study of this magnitude. Subendocardial and subepicardial measurements result
in more noisy data than midwall analysis.
Finally, this is the first study that correlates calcium scores
from separate arterial trees with regional function in the
corresponding myocardial territory. We recognize that there
is great individual anatomic variability in the coronary
arterial territories. Therefore, we have assigned the LV
segments to coronary arterial territories in accordance with
accepted clinical recommendations.15 The greatest variability
in myocardial blood supply is found in the apical segment,
and this segment was, thus, excluded from the analyses.
Clinical inferences should await confirmation from longitudinal studies.
In summary, coronary artery calcification is related to
regional left ventricular dysfunction in the corresponding
perfusion territory among individuals with no history of heart
disease. These results indicate a link between subclinical
atherosclerosis and subclinical regional left ventricular dysfunction that could represent an early step in the continuum of
events relating coronary artery disease to congestive heart
failure.
Acknowledgments
This study was supported by the National Heart, Lung, and Blood
Institute grant (RO1-HL66075-01) and the MESA study contracts
(NO1-HC-9808, NO1-HC-95168, and NO1-HC-95169). J.A.C.L. is
also supported by the Reynolds Foundation and T.E. by the UngerVetlesen Medical Fund, Jersey and Caroline Museaeus Heart Foundation, Norway. We thank the other investigators, the staff, and the
participants of the MESA study for their valuable contributions. A
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Edvardsen et al
full list of participating MESA investigators and institutions can be
found at http://www.mesa-nhlbi.org.
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