(Circulation. 1995;92:1414-1421.)
© 1995 American Heart Association, Inc.
Articles |
Extracoronary Atherosclerotic Plaque at Multiple Sites and Total Coronary Calcification Deposit in Asymptomatic Men
Association With Coronary Risk Profile
From Centre de Médecine Préventive Cardiovasculaire, INSERM U 28, Hôpital Broussais, Paris, France.
Correspondence to Prof Alain Simon, Centre de Médecine Préventive Cardiovasculaire, Hôpital Broussais, 96 rue Didot, 75674 Paris Cedex 14, France.
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Abstract |
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Background Recent studies have suggested that knowledge of the extent of subclinical atherosclerosis may improve prognostic information in subjects at risk of cardiovascular disease. Therefore, we tested the value of extracoronary plaque detected with echography at multiple sites and that of total coronary calcification deposit evaluated with ultrafast computed tomography for predicting the risk of coronary events estimated on the basis of traditional risk factors.
Methods and Results We analyzed in 618 asymptomatic at-risk men the extent of extracoronary atherosclerosis, as assessed with ultrasound imaging of carotid, aortic, and femoral sites and coded as number of disease sites (none, one, two, or three) on the basis of the presence of plaque at each site, and the amount of total coronary calcification deposit, as evaluated with ultrafast computed tomography and coded as grade 0, 1, 2, or 3 on the basis of the determination of a total coronary calcium score. Concomitantly, age, systolic pressure, total and HDL cholesterol levels, current smoking, presence of diabetes, and presence of ECG left ventricular hypertrophy (ECG-LVH) were evaluated with the goal of estimating coronary risk with the use of the Framingham Study risk algorithm. The prevalence rates of at least one extracoronary disease site and coronary calcification (any grade) were high (72% and 63%). There was a strong association between the number of extracoronary disease sites and the grade of coronary calcification (P<.001). As the number of extracoronary disease sites increased, age, systolic pressure, smoking frequency, and number of risk factors increased (P<.001). As the grade of coronary calcification increased, age and systolic pressure increased (P<.001), as did the number of risk factors (P<.01). The estimated coronary risk increased with the number of extracoronary disease sites and the grade of coronary calcification (P<.001). The odds ratio of coronary risk between three and no extracoronary disease site was 2.37 (95% confidence interval [CI], 1.08 to 5.21), whereas that between grade 3 and grade 0 of coronary calcification was 1.79 (95% CI, 0.94 to 3.40).
Conclusions In an apparently healthy population, the extracoronary atherosclerotic burden as measured with multiple-site echography appears to be more powerful than the ultrafast computed tomography–detected coronary calcium burden in reflecting the multifactorial coronary risk profile. However, only men were included in the present study, and the present findings cannot be extrapolated to women.
Key Words: tomography • ultrasonics • risk factors • coronary disease • atherosclerosis
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Introduction |
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The estimation of cardiovascular risk in persons free of clinical disease traditionally is based on the evaluation of established risk factors, such as hypercholesterolemia, hypertension, cigarette smoking, or diabetes, which can be measured through simple office procedures and laboratory tests.1 2 Furthermore, it is the summation of multiple individual risk factors that best serves to identify subjects at high risk.2 Nevertheless, it remains hazardous for a physician to predict accurately which subject will develop disease on the basis of the single assessment of traditional risk factors.3 It is therefore important to improve the delineation of risk of cardiovascular disease, especially for individuals who have not had a clinical event. Because the initiation and progression of the extent of atherosclerosis are the primary determinants of clinical coronary artery disease and other atherosclerotic disease, the detection of subclinical atherosclerosis before the onset of complications might increase the ability to predict subsequent risk of complication.4 5 Our goal was to test this hypothesis by detecting subclinical lesions in extracoronary and coronary arteries among asymptomatic men with at least one major risk factor, such as hypertension, hypercholesterolemia, or current smoking. We used noninvasive techniques that provide high-resolution imaging of atherosclerotic plaque in peripheral arteries (B-mode echography) and of calcification in coronary arteries (ultrafast computed tomography).6 We evaluated the clinical usefulness of these noninvasive vascular tests by analyzing the extent of arterial lesions in relation to the estimated multifactorial risk of coronary events assessed according to the Framingham Study survey.7
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Methods |
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Study Subjects
Subjects were recruited from an ongoing risk-factor screening program conducted at worksites for employees of several companies within the Paris area by a group of occupational health physicians (Prévention Cardiovasculaire en Médecine du Travail [PCVMETRA]6 ). From June 1989 through January 1994, 11 721 subjects were screened, and 3600 consecutive subjects were referred to the hospital after giving consent because of the presence of risk factors. At the hospital, they underwent a complete examination that included a multifactorial evaluation of cardiovascular risk and detection of subclinical extracoronary and coronary arterial lesions. For each subject, the investigations were performed during 1 day of hospitalization. Requirements for inclusion in the present study were (1) male sex, (2) measurements available for evaluation of risk factors and arterial lesions, (3) presence of at least one risk factor, such as essential hypertension, primary hypercholesterolemia, or current smoking, and (4) freedom from cardiovascular disease, including stroke, transient ischemia, coronary heart disease, congestive heart failure, and intermittent claudication. In brief, the study involved only men who were symptom free and at risk of cardiovascular disease. Six hundred eighteen men between the ages of 30 and 70 years and with a body mass index of 26±3 (±SD) kg/m2 were included in the final study population.
Evaluation of Risk Factors
We evaluated risk factors that
were considered standard in the
Framingham Study.7 With subjects in the supine position
for at least 10 minutes after 14 hours of fasting, we measured serum
cholesterol levels with the use of enzymatic methods to
determine total and HDL cholesterol levels after the
precipitation of LDL and VLDL by phosphotungstic acid and magnesium
chloride.6 Subjects with diseases or factors causing
secondary hypercholesterolemia were excluded
from the study. Hypercholesterolemia was
defined as a total cholesterol level of 
6.2 mmol/L, the
use of lipid-lowering drug treatment, or both.8
Sixty-eight subjects were receiving lipid-lowering treatment; the type
of drug therapy was distributed as follows: fibrate derivative (40
subjects), HMG-CoA reductase inhibitor (23 subjects), and
association of fibrate or HMG-CoA reductase inhibitor with
bile acid sequestrant (5 subjects). Blood pressure was measured in the
arm with the subject in the supine position for at least 10 minutes and
was recorded as the average of at least three consecutive
measurements by standard sphygmomanometric procedure.6
Essential hypertension was established on the basis of appropriate
laboratory tests, and subjects with secondary hypertension were
excluded from the study. Hypertension was defined by systolic blood
pressure of 140 mm Hg, diastolic blood pressure of 90
mm Hg, the use of antihypertensive treatment, or a
combination.9 Eighty-five subjects were receiving
antihypertensive treatment, and the type of antihypertensive drug was
distributed as follows: diuretic (5 subjects), ß-blocker (19
subjects), angiotensin-converting enzyme
inhibitor (18 subjects), calcium channel blocker (10
subjects), and a combination of two or three of these drugs (33
subjects). Current smoking was carefully assessed by querying the
subject and was defined as regular smoking each day of the previous 3
months regardless of the amount smoked.6 Blood glucose
level was measured after the subject fasted for 14 hours, and diabetes
was defined as fasting blood glucose level of 1.40 g/L, the use of
antidiabetic drug treatment, or both.6 Left
ventricular hypertrophy (LVH) was measured with
ECG (ECG-LVH) and defined as present according to the criteria of
Sokolow and Lyon.10 The estimated multifactorial risk of
coronary events at 10 years was calculated for each subject by
entering into the equations of the Framingham Study risk model the
following variables7 : age, male sex coded as yes,
systolic blood pressure, total-to-HDL cholesterol ratio,
current smoking coded as present or absent, diabetes coded as
present or absent, and ECG-LVH coded as present or absent.
Measures of Vascular Lesions
Three arterial sites were
examined echographically
at the extracoronary level: carotid arteries on both sides,
abdominal aorta, and femoral arteries on both sides. We detected the
presence of plaque in each site by considering that plaque was
present when one or more plaques were found regardless of the
precise location and the number of plaques in the site investigated. We
classified the number of sites with the presence of plaque as follows:
no disease sites indicates no present plaque at the carotid,
aortic, and femoral sites; one disease site, presence of plaque at one
site, which may be carotid, aortic, or femoral; two disease sites,
presence of plaque at two sites, which may be carotid and aortic,
carotid and femoral, or aortic and femoral; and three disease sites,
presence of plaque at the three (carotid, aortic, and femoral) sites.
Investigations were performed with high-resolution B-mode echography
(Radius CG, General Electric, CGR France; Ultramark 4, Advanced
Technologies Laboratories) according to a procedure reported in detail
elsewhere.6 11 12 13 Briefly,
investigation of carotid
arteries was performed with a 7.5-MHz probe and included the common
carotid artery, carotid bifurcation, carotid bulb, and extracranial
internal carotid artery on both sides. The abdominal aorta was examined
with a 3.75-MHz probe placed just above the umbilicus and moved distal
along the left of the umbilical medial line. The investigation of the
femoral arteries was performed with a 7.5-MHz probe and included the
common femoral artery and superficial and profunda femoral arteries in
the upper thigh on both sides. In each vessel, plaque was defined as an
echogenic structure encroaching into the vessel lumen with a distinct
focal area of >50% of the intima-media thickness of the surrounding
walls.6 12
Coronary calcifications were
detected in epicardial
coronary arteries with ultrafast computed tomography (IMATRON)
according to a procedure previously described.6 Briefly,
20 contiguous slices (60 mm) were acquired caudal to the bifurcation of
the main pulmonary artery, triggered at 80% of the RR
interval, and analyzed automatically to determine the presence
and amount of calcium in each of the major coronary arteries:
the left trunk main artery, left circumflex artery, left anterior
descending coronary artery, and right coronary artery.
The threshold for a calcific lesion was set at a computed tomographic
density of 130 Hounsfield units (HU) with an area of 1
mm2.14 The maximal density of each lesion was
classified as one of four classes as follows: 1, 130 to 199 HU; 2, 200
to 299 HU; 3, 300 to 399 HU; and 4, 400 HU.14 A lesion
score was calculated by multiplying the density number by the area of
the lesion in square millimeters. A total calcium score was defined as
the sum of lesion scores for all 20 slices. The amount of total
coronary calcification deposit was characterized in a
polychotomous way and coded as grade 0, 1, 2, or 3. Grade 0 (no
coronary calcification) corresponded to a total calcium score
of 0. The other three grades were determined by dividing subjects with
present coronary calcification into three groups on the
basis of the total calcium score expressed in semilogarithmic scale.
Grade 1 corresponds to a total calcium score of 1 to 9, grade 2
corresponds to a total calcium score of 10 to 99, and grade 3
corresponds to a total calcium score of 100.
Statistical Analysis
Quantitative variables were expressed as
mean±SD. ANOVA
with Dunnett's t test was used for comparing quantitative
variables between groups. 
2 test was used for
comparing qualitative variables between groups. Odds ratio with
95% confidence interval (CI) was calculated from two-sided
2 test. Logistic regression analyses were
performed between the number of extracoronary disease sites
and the grade of calcification deposit and between each of these two
polychotomous variables and risk factors.15
Statistical significance was considered to be P<.05. The
statistical analysis was carried out on a computer (Macintosh
Apple Computers) with the use of JMP (SAS) and
EXCEL (Microsoft) software.
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Results |
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Table 1
shows that in the study population, the
prevalence of risk factors was 76% for
hypercholesterolemia, 54% for hypertension,
39% for smoking, and 4% each for diabetes and ECG-LVH; moreover, 40%
of the population had one risk factor, 45% had two risk factors, and
15% had three or more risk factors.
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The distributions of arterial lesions within the study
population are given in Tables 2 through
4. One hundred seventy
subjects (28% of the population) had no extracoronary
disease site (Table 2), and 228 subjects (37% of the
population) had
no coronary calcification deposit (Table 3). Table
4 shows that
96 subjects (16% of the population) had no extracoronary
disease site and no coronary calcification deposit, whereas 32
subjects (5% of the population) had three extracoronary
disease sites and grade 3 coronary calcification deposit. Table
4 also shows that in the group with no extracoronary
disease site, the number of subjects with no coronary
calcification deposit (96 subjects) was 12-fold greater than the number
of subjects with grade 3 calcification deposit (8 subjects);
conversely, in the group with three extracoronary disease
sites, the number of subjects with grade 3 calcification deposit (32
subjects) was almost fourfold greater than the number of subjects with
no calcification deposit (9 subjects). A logistic regression
analysis showed that the number of extracoronary
disease sites was associated with the grade of coronary
calcification deposit even after controlling for age
(P<.001).
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Tables 2
and 3 show the risk factor
associations for the number of
extracoronary disease sites and grade of coronary
calcification deposit. As the number of extracoronary
disease sites increased, there was a significant increase in age,
systolic pressure, frequency of smoking, and number of risk factors
(P<.001) but nonsignificant changes in total-to-HDL
cholesterol ratio, frequency of diabetes, and frequency of
ECG-LVH (Table 2). Compared with the group with no
extracoronary disease site, age was higher in groups with
three disease sites, two disease sites, or one disease site
(P<.001); systolic pressure was higher in groups with three
disease sites (P<.001), two disease sites
(P<.001), or one disease site (P<.05); smoking
frequency was higher in groups with three disease sites
(P<.001) or two disease sites (P<.001); and the
number of risk factors was higher in groups with three disease sites
(P<.001), two disease sites (P<.001), or one
disease site (P<.01) (Table 2). A logistic
regression
analysis showed that the number of extracoronary
disease sites was independently associated with age, systolic pressure,
total-to-HDL cholesterol ratio, and smoking frequency
(P<.001) (Table 5). As the grade of
coronary calcification deposit increased, there was a
significant increase in age and systolic pressure (P<.001)
and in the number of risk factors (P<.01) but
nonsignificant changes in total-to-HDL cholesterol ratio,
frequency of smoking, frequency of diabetes, and frequency of ECG-LVH
(Table 3). Compared with the group with no coronary
calcification deposit, age was higher in groups with grade 3
(P<.001), grade 2 (P<.001), or grade 1
(P<.01) calcification deposit; systolic pressure was higher
in groups with grade 3 (P<.001), grade 2
(P<.01), or grade 1 (P<.01) calcification
deposit; and the number of risk factors was higher in the group with
grade 3 calcification deposit (P<.01) (Table 3). A
logistic
regression analysis showed that the grade of coronary
calcification deposit was independently associated with age
(P<.001), systolic pressure (P<.01), and
total-to-HDL cholesterol ratio (P<.01) (Table 5).
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Figs 1 and 2 provide comparisons of the
estimated coronary risk according to the number of
extracoronary disease sites and the grade of
coronary calcification deposit. As the number of
extracoronary disease sites increased, the coronary
risk increased significantly (P<.001) and was greater in
groups with three, two, or one disease site (P<.001) than
in the group with no disease site (Fig 1, left). The odds ratio
of
coronary risk between the group with three disease sites and
the group with no disease site was 2.37 (95% CI, 1.08 to 5.21). When
the analysis of coronary risk was performed in four
age-matched (mean age, 50±7 years) subgroups of 52 subjects with no,
one, two, or three extracoronary disease sites (Fig 1,
right), the risk increased significantly (P<.001) as the
number of disease sites increased, and the risk was greater in
subgroups with three disease sites (P<.001) or two disease
sites (P<.01) than in the subgroup with no disease site. As
the grade of coronary calcification deposit increased, the
coronary risk increased significantly (P<.001) and
was greater in groups with grade 3 (P<.001), grade 2
(P<.001), or grade 1 (P<.05) calcification
deposit than in the group with no calcification deposit (Fig 2,
left).
The odds ratio of coronary risk between the group with grade 3
coronary calcification deposit and the group with no
calcification was 1.79 (95% CI, 0.94 to 3.40). When the
analysis of coronary risk was performed in four
age-matched (mean age, 50±7 years) subgroups of 76 subjects with grade
0, 1, 2, or 3 coronary calcification deposit (Fig 2, right),
the risk increased significantly (P<.001) as the grade of
calcification deposit increased, and the risk was greater in the
subgroup with grade 3 calcification deposit (P<.001) than
in the subgroup with no calcification.
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P<.01, 
P<.001.
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Table 6 provides a comparison of subjects with no
extracoronary plaque and no coronary calcification
with subjects with three extracoronary disease sites and
grade 3 coronary calcification deposit. In the latter, age and
systolic pressure were higher (P<.001), smoking frequency
was higher (P<.05), and the number of risk factors was
higher (P<.001) than in subjects with no
extracoronary or coronary lesion, and the increase
in systolic pressure and in the number of risk factors remained
significant after adjustment for age (P<.001) (Table
6).
The estimated coronary risk was greater in subjects with three
extracoronary disease sites and grade 3 coronary
calcification than in those with no extracoronary or
coronary lesion (P<.001), and the difference
remained significant after adjustment for age (P<.001)
(Table 6).
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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The results of the present study indicate that the extent of subclinical lesion in extracoronary arteries (plaque) as well as in coronary arteries (calcification) is associated with an increased estimated risk of coronary events and therefore may reflect the aggregate effects of multiple established risk factors over time.
By searching systematically for the presence of B-mode–echography detected plaque at three extracoronary sites (carotid and femoral arteries and abdominal aorta), we found that as the number of extracoronary disease sites increased (a disease site being characterized by the presence of at least one plaque), age, systolic pressure, and frequency of smoking increased significantly. On average, age increased 10 years, systolic pressure increased 12 mm Hg, and smoking frequency increased 23% in subjects with three disease sites compared with subjects who were free of extracoronary plaque. A logistic regression analysis showed that age, systolic pressure, and smoking were independently associated with the number of disease sites; moreover, multivariate analysis showed that the total-to-HDL cholesterol ratio was associated with the number of disease sites, whereas in univariate analysis this parameter increased insignificantly as the number of disease sites increased. In contrast, no association existed between the number of extracoronary disease sites and diabetes or ECG-LVH, possibly because of the low prevalence (4%) of these risk factors in the study population. We also noted that as the number of extracoronary disease sites increased, the number of risk factors increased, as did the estimated risk of coronary events, even after adjustment for age. This finding is in agreement with previous prospective studies establishing that atherosclerosis in the carotid arteries16 or in the lower limb arteries17 increases the subsequent incidence of coronary events. Therefore, the estimation of the atherosclerotic burden of an individual by measurement of peripheral atherosclerosis at multiple sites with the use of B-mode echography may be a method of increasing the ability to predict coronary events.18 The atherosclerotic process that results in coronary artery disease is a generalized process that may involve the entire vasculature, especially multiple peripheral vessels.19
Nevertheless, the direct measurement of coronary atherosclerosis appears to be a more rational approach than measurement of peripheral atherosclerosis for identifying subjects at risk of coronary artery disease. The clinical value of detection of subclinical coronary artery disease is supported by the well-known observation that nonobstructive lesions may be a cause of a catastrophic event.20 21 22 No simple, noninvasive technique for measuring coronary atherosclerosis has been available, except radiographic detection of coronary calcification.23 Such lesions have been shown to be sensitive markers of coronary atherosclerosis because, unlike peripheral arterial calcification, they are seen only in the presence of atherosclerotic plaque.24 In the present study, we detected coronary calcification with the use of ultrafast computed tomography according to a previous procedure.6 Because the extent of extracoronary atherosclerosis was defined as a polychotomous variable (no, one, two, or three disease sites), we did likewise for the amount of coronary calcification deposit, which was coded as grade 0, 1, 2, or 3. We found that as the grade of coronary calcification deposit increased, age and systolic pressure increased. On average, age increased 8 years and systolic pressure increased 10 mm Hg in subjects with grade 3 coronary calcification deposit compared with those without calcification. A logistic regression analysis showed that age and systolic pressure were independently associated with the grade of calcification deposit. In multivariate analysis, total-to-HDL cholesterol ratio was also associated with the grade of calcification deposit, whereas in univariate analysis this parameter did not increase significantly as the grade of calcification deposit increased. Smoking was not associated with the grade of coronary calcification deposit, a finding that was different from the association found between smoking and extracoronary plaques. Furthermore, presence of diabetes or ECG-LVH was not associated with coronary calcification. This lack of association, which also existed with extracoronary plaque, may be due to the low prevalence of these two risk factors. Last, we found that as the grade of coronary calcification deposit increased, the number of risk factors increased, as did estimated coronary risk, even after adjustment for age. This finding is supported by a recent prospective study that showed that the presence of coronary calcification detected with the use of cinefluoroscopy incurs an increased risk of coronary heart disease in asymptomatic high-risk subjects.25
Although total coronary calcification deposit is a direct marker of the extent of atherosclerotic disease in coronary arteries, in the present study it appeared unexpectedly as a weaker indicator of coronary risk profile than the extent of peripheral atherosclerosis at multiple sites. The odds ratio of coronary risk between grade 3 and grade 0 calcification deposits was lower than that between three extracoronary disease sites and no extracoronary disease site. Nevertheless, in the present study, we compared the results of the imaging studies with the estimated risk based on the Framingham Study data and not with the presence of angiographic coronary artery disease or subsequent coronary event rate. Therefore, it is not possible to state that coronary ultrafast computed tomography is less efficient than ultrasound imaging of the three vessel sites in identifying coronary artery disease or "hard" coronary event rate. The lesser ability of total coronary calcification deposit to reflect the coronary risk profile may be due to the fact that arterial calcification is a less-subtle marker of atherosis than arterial plaque as detected with the use of B-mode echography in peripheral arteries. Atherosclerotic plaque in coronary vessels as well in extracoronary vessels is not invariably associated with calcium.26 27 Therefore, it is likely that subjects with a total absence of coronary calcification (grade 0) may have early noncalcified atherosclerotic coronary lesions. However, the possible false-negative results of ultrafast computed tomography–detected calcification with regard to early coronary atherosclerosis did not confound the strong association observed in the present study between the number of extracoronary disease sites and the grade of coronary calcification. This association agrees with that previously reported in the literature between angiographically detected coronary atherosclerosis and the extent of B-mode echography–detected carotid atherosclerosis.18 The lesser ability of total coronary calcification deposit than the extent of extracoronary atherosclerosis to reflect coronary risk profile may also be due to different risk factor associations for the two types of vascular lesions. Although associations with age, systolic pressure, and total-to-HDL cholesterol ratio were similar for total coronary calcification deposit and for the number of extracoronary disease sites, associations with smoking were different. The influence of smoking on peripheral atherosclerosis and on its extent to multiple sites has been shown in previous studies.6 12 13 In contrast, the association between smoking and coronary calcification has been poorly documented. An association between previous smoking and coronary calcification has been reported in studies based on autopsy results.28 29 It is possible that coronary calcification, which reflects a more advanced lesion than uncalcified plaque, is influenced by the cumulative long-term effect of smoking rather than by current consumption of tobacco. Finally, to test whether the extent of subclinical lesions in both extracoronary and coronary arteries could better reflect the coronary risk profile, we compared the subgroup of subjects with three extracoronary disease sites and grade 3 coronary calcification deposit with the subgroup of subjects who were free of extracoronary plaque and coronary calcification. We found that the former group had significant increases in age, systolic pressure, frequency of smoking, number of risk factors, and estimated risk of coronary events compared with the latter. Nevertheless, the coronary risk of the subjects with three extracoronary disease sites and grade 3 coronary calcification deposit was similar to the risk of the subjects with three extracoronary disease sites without considering the grade of coronary calcification. This observation indicates that the assessment of generalized extracoronary and coronary lesions added nothing to the ability of the single measure of the extent of peripheral atherosclerosis at multiple sites to reflect the risk of coronary events.
There were, however, several study limitations, including potential section bias, the use of imperfect technologies for measuring extent of atherosclerotic disease, and the use of the Framingham Study calculation risk algorithm for estimating risk of coronary events. The results of this study should not be applied to screening of the general population because the subjects who underwent vascular evaluations were a selected population in whom the prevalence of hypercholesterolemia and hypertension was greater than in the general population.30 Furthermore, the present study involved only men, and therefore the results cannot be extrapolated to women. The technologies used for measuring subclinical lesions had some limitations. B-mode echography at multiple sites allowed us to characterize the extent of peripheral atherosclerosis in a polychotomous manner. Its reproducibility for detecting the presence or the absence of plaque at each arterial site investigated is excellent.6 12 In a previous study, we found from 94% to 100% agreement at the three arterial sites between the original echographic assessment and reassessment 6 hours later.12 The time to perform the ultrasound imaging of the three vessel sites is approximately 60 minutes per subject,12 and the cost of the examination in France is the equivalent of approximately US $100.00. Nevertheless, this semiqualitative assessment of peripheral atherosclerosis does not impart to the present study the ability to focus on factors that are associated with earlier pathogenic processes, but the ability of B-mode imaging of carotid and femoral arteries to provide measures of submillimeter changes in intima-media thickness should allow this in the near future.31 32 Likewise, the ultrafast computed tomographic detection of coronary calcification visualizes advanced calcium-rich atherosclerotic plaque but may overlook noncalcified lesions26 27 and therefore does not allow an analysis of the risk factor associations with early coronary atherosclerosis.33 A 97% agreement has been found regarding the presence or absence of calcification when the same scan was reviewed by two independent observers.27 Total calcium score quantification showed lesser reproducibility since the interobserver agreement was found at 80% or 86% for the same scan.14 27 Furthermore, the reproducibility between two different ultrafast computed tomographic scans appears to be even less since 77% agreement in the total calcium score was found between a first scan and a second scan repeated later in the same day.34 The total procedure for performing the ultrafast computed tomographic scan of the coronary arteries lasted an average of 10 minutes14 and cost the equivalent of approximately US $160.00. Last, the model based on the data from the Framingham Study, the most documented follow-up of cardiovascular risk factors, was shown to overestimate coronary heart disease incidence35 36 when applied to populations with low cardiovascular morbidity, such as the French population.37 Nevertheless, it was suggested that the basal coronary morbidity might be lower in such a population, whereas the additional risk due to the levels of risk factors included in the model might be unchanged.38 Therefore, the Framingham Study model may be used in comparing risks of different subgroups within the same population, even a population at low risk, because the basal coronary morbidity, which represents the constant term of the Framingham Study equation, has very little influence on such a comparison. Another limitation of the study is that risk factors such as a lack of physical exercise, obesity, and heredity have not been addressed. It is of note that the level of physical activity that is an important modifiable coronary risk factor has not been investigated in the present study. In addition, the measurements of this factor as well as of obesity, heredity, and newer risk factors are not required for calculating coronary risk according to the Framingham Study.7
Finally, because the present study assessed the coronary risk according to the Framingham Study and not the subsequent coronary event rate, further prospective studies are needed to evaluate and compare definitively the efficacy of peripheral multiple-site echography and ultrafast computed tomography in predicting coronary events.
In conclusion, results of the present study indicate that in apparently healthy asymptomatic men at risk of cardiovascular disease, B-mode echography at multiple extracoronary sites appears to be more capable than ultrafast computed tomography detection of coronary calcification deposit of reflecting the estimated coronary risk profile. This could be of clinical value for identifying individuals who are candidates for fairly aggressive preventive treatment and special follow-up.5
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Acknowledgments |
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This work was supported by grants from the Institut National de la Santé et de la Recherche Médicale and from the PCVMETRA Group. We thank Banque Nationale de Paris; L'Oréal, Paris; Matra SA; Procter and Gamble France; and Peugeot SA for sponsoring the PCVMETRA Group. We gratefully acknowledge collaborations with the PCVMETRA Group (chairman, P. Segond) for screening the population at worksites; M.C. Plainfossé and A. Hernigou, Department of Radiology, Broussais Hospital, for performing the ultrafast computed tomographic scanning; and N. Moatti, Department of Biology, Broussais Hospital, for measuring blood parameters. We also acknowledge the assistance of Dr J.L. Mégnien and several medical students, including Drs S. Jeannin, M. Lemariey, and N. Denarie, in patient evaluation and data collection; the assistance of Drs J. Gariepy, A. Malek, and A. Linhart in ultrasound examinations; and the assistance of I. d'Argentré in ultrafast computed tomographic data entry and manuscript preparation.
Received January 25, 1995; revision received March 21, 1995; accepted March 26, 1995.
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References |
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|
TopAbstractIntroductionMethods Results Discussion References |
|---|
1. Kannel WB, McGee D, Gordon T. A general cardiovascular risk profile: the Framingham Study. Am J Cardiol. 1976;38:46-96. [Medline] [Order article via Infotrieve]
2.
Laskey WR. Assessment of
cardiovascular risk: a return to basics.
Ann Intern Med. 1993;118:149-150.
3. American Heart Association. Coronary Risk Handbook: Estimating Risk of Coronary Heart Disease in Daily Practice. New York, NY: American Heart Association; 1973.
4. Kuller LH. AHA Symposium/Epidemiology Meeting on Atherosclerosis: discussion: why measure atherosclerosis? Circulation. 1993;87(suppl II):II-34-II-37.
5. Simon A, Levenson J. Could the identification of subclinical atherosclerosis offer an alternative to the mass drug treatment of hypercholesterolemia? Atherosclerosis. 1994;105:245-249. [Medline] [Order article via Infotrieve]
6.
Megnien JL, Sene V, Jeannin S, Hernigou A,
Plainfossé MC, Merli I, Atger V, Moatti N, Levenson J, Simon A,
and the PCVMETRA Group. Coronary calcification and its
relation to extracoronary atherosclerosis
in asymptomatic
hypercholesterolemic men.
Circulation. 1992;85:1799-1807.
7.
Anderson KM, Wilson PWF, Odell PM, Kannel WB.
An updated coronary risk profile: a statement for health
professionals. Circulation. 1991;83:356-362.
8.
The Expert Panel. Report of the National
Cholesterol Education Program Expert Panel on Detection,
Evaluation, and Treatment of High Blood Cholesterol in
Adults. Arch Intern Med. 1988;148:36-69.
9. WHO/ISH Guidelines Subcommittee. 1993 Guidelines for the Management of Mild Hypertension: memorandum from a WHO/ISH meeting. High Blood Pressure. 1993;2:169-186.
10. Sokolow M, Lyon TP. The ventricular complex in left ventricular hypertrophy as obtained by unipolar precordial and limb leads. Am Heart J. 1949;37:161-168. [Medline] [Order article via Infotrieve]
11. Giral P, Filitti V, Levenson J, Pithois-Merli I, Plainfossé MC, Mainardi C, Gold A, Simon A, PCVMETRA Group. Relation of risk factors for cardiovascular disease to early atherosclerosis detected by ultrasonography in middle-aged normotensive hypercholesterolemic men. Atherosclerosis. 1990;85:151-159. [Medline] [Order article via Infotrieve]
12.
Giral P, Filitti V, Levenson J, Pithois-Merli I,
Plainfossé MC, Mainardi C, Simon A. Risk factors and early
extracoronary atherosclerotic plaques detected by three
site ultrasound imaging in hypercholesterolemic
men. Arch Intern Med. 1991;151:950-956.
13.
Cambillau M, Simon A, Amar J, Giral P, Atger V, Segond
P, Levenson J, Merli I, Mégnien JL, Plainfossé MC, Moatti
N, and the PCVMETRA Group. Serum Lp(a) as a discriminant marker
of early atherosclerotic plaque at three extraconary sites in
hypercholesterolemic men.
Arterioscler Thromb. 1992;12:1346-1352.
14. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990;15:827-832. [Abstract]
15. McGullagh P. Regression models for ordinal data. J R Stat Soc (B). 1980;42:109-142.
16.
Salonen JT, Salonen R. Ultrasonographically
assessed carotid morphology and the risk of coronary heart
disease. Arterioscler Thromb. 1991;11:1245-1249.
17. Criqui MH, Langer RD, Fronek A, Feigelson HS, Klauber MR, McCann TJ, Browner D. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med. 1992;326:381-386. [Abstract]
18.
Wofford JL, Kahl FR, Howard GR, McKinney WM, Toole JF,
Crouse JR III. Relation of extracranial carotid artery
atherosclerosis as measured by B-mode ultrasound to the
extent of coronary atherosclerosis.
Arterioscler Thromb. 1991;11:1786-1794.
19. Epstein FH. Risk factors for peripheral and cerebral atherosclerosis: similarities and differences with coronary atherosclerosis. In: Ventura A, Crepaldi G, Senin U, eds. Extracoronary Atherosclerosis, monograph on atherosclerosis, vol 14. Basel, Switzerland: Karger; 1986:1-5.
20. Epstein S, Quyymi A, Bonow R. Sudden cardiac death without warning: possible mechanisms and implications for screening asymptomatic populations. N Engl J Med. 1989;321:320-324. [Medline] [Order article via Infotrieve]
21. Little WC, Downes TR, Applegate RJ. The underlying coronary lesion in myocardial infarction: implications for coronary angiography. Clin Cardiol. 1991;14:868-874. [Medline] [Order article via Infotrieve]
22.
Little WC, Constantinescu M, Applegate RJ, Kutcher MA,
Burrows MT, Kahl FR, Santamore WP. Can coronary
angiography predict the site of a subsequent myocardial infarction in
patients with mild-to-moderate coronary artery disease?
Circulation. 1988;78:1157-1166.
23. Schwartz RS. Coronary artery calcification and prognosis: same song, second verse? J Am Coll Cardiol. 1994;24:359-361. [Medline] [Order article via Infotrieve]
24. Ultrafast CT for coronary calcification. Lancet. 1991;337:1449-1450.
25. Detrano RC, Wong ND, Tang W, French WJ, Georgiou D, Young E, Brezden OS, Doherty TE, Narahara KA, Brundage BH. Prognostic significance of cardiac cinefluoroscopy for coronary calcific deposits in asymptomatic high risk subjects. J Am Coll Cardiol. 1994;24:354-358. [Abstract]
26. Loecker TH, Schwartz RS, Cotta CW, Hickman JR Jr. Fluoroscopic coronary artery calcification and associated coronary disease in asymptomatic young men. J Am Coll Cardiol. 1992;19:1167-1172. [Abstract]
27.
Fallavollita JA, Brody AS, Bunnell IL, Kumar K, Canty
JM. Fast computed tomography dectection of coronary
calcification in the diagnosis of coronary artery
disease. Circulation. 1994;89:285-290.
28. Fuchs U, Caffier P, Schulz HG, Wieniecki P. Arterial calcification in diabetics. Virchows Arch A Pathol Anat Histopathol. 1985;407:431-439. [Medline] [Order article via Infotrieve]
29. Strong JP, Richard ML. Cigarette study and atherosclerosis in autopsied men. Atherosclerosis. 1976;23:451-459. [Medline] [Order article via Infotrieve]
30. Simon A, Segond P, Giard AM, Demure B, Gitel R, Levenson J, et le Groupe PCV METRA. Dépistage précoce de l'athérosclérose silencieuse et dépistage des facteurs de risque cardiovasculaire. Presse Med. 1993;22:1033-1038.
31.
Gariepy J, Massonneau M, Levenson J, Heudes D, Simon A,
and the Groupe de Prévention Cardiovasculaire en Médecine
du Travail. Evidence for in vivo carotid and femoral wall
thickening in human hypertension.
Hypertension. 1993;22:111-118.
32.
Persson J, Formgren J, Berglund G.
Ultrasound-determined intima-media thickness and
atherosclerosis: direct and indirect
validation. Arterioscler Thromb. 1994;14:261-264.
33. Wong ND, Kouwabunpat D, Vo AN, Detrano RC, Eisenberg H, Goel M, Tobis JM. Coronary calcium and atherosclerosis by ultrafast computed tomography in asymptomatic men and women: relation to age and risk factors. Am Heart J. 1994;127:422-430. [Medline] [Order article via Infotrieve]
34. Plainfossé MC, Boudeville JC, Séné V, Hernigou A, Challandre P, Simon A. Dépistage et signification des calcifications coronaires. J Radiol. 1994;75:693-699. [Medline] [Order article via Infotrieve]
35. Gordon T, Gardia-Palmieri MR, Kagan A, Kannel WB, Schiffman J. Differences in CHD in Framingham, Honolulu and Puerto Rico. J Chronic Dis. 1974;27:329-344. [Medline] [Order article via Infotrieve]
36.
Kozarevic D, Pirc B, Racic Z, Dawber TR, Gordon T,
Zukel WJ. The Yugoslavia Cardiovascular Disease
Study 2: factors in the incidence of coronary heart
disease. Am J Epidemiol. 1976;104:133-140.
37. Ducimetière P, Richard JL, Cambien F, Rakotovao R, Claude JR. Coronary heart disease in middle-aged Frenchmen: comparisons between Paris Prospective Study, Seven Countries Study, and Pooling Project. Lancet. 1980;1:1346-1350. [Medline] [Order article via Infotrieve]
38. Kinlay S, O'Connel D, Evans D, Francis L. The validity of estimating heart disease reduction from a Framingham logistic equation. J Clin Epidemiol. 1992;45:553-560. [Medline] [Order article via Infotrieve]
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