Evidence for lower variability of coronary artery calcium mineral mass measurements by multi-detector computed tomography in a community-based cohort—Consequences for progression studies
Introduction
Coronary artery calcium (CAC) can be detected by electron beam computed tomography (CT) and multi-detector computed tomography (MDCT). While CAC measurements may be potentially helpful to identify asymptomatic individuals at increased risk for cardiovascular events [1], [2], [3], [4], it has been proposed that CT-based measurements of CAC may be valuable for predicting risks for coronary events or for monitoring the natural progression of coronary artery disease or the response to therapeutic interventions such as lipid-lowering therapy [5], [6], [7].
Three algorithms have been generally used to determine the amount of CAC. The Agatston score (AS) method was developed for electron beam CT, but it has been used with minor modifications for MDCT. The interscan reproducibility of the AS method is moderate, ranging from 15 to 21% [8], [9], [10], [11]. The volume score (VS) has improved reproducibility as compared with the AS (from 9 to 16%) [9], [11]. However, the VS is susceptible to partial volume artifacts and may not be adequate to compare CAC measurements obtained using different CT protocols (slice thickness, tube energy) and scanners [12].
A third algorithm, the calculation of mineral mass, provides an actual quantitative measurement of CAC and, as such, has been proposed to be a superior measurement method that could replace the AS or VS methods [11], [13], [14]. Mineral mass measurements require calculation of calcium concentration (CC) within calcified plaques based upon the calibration of the CT attenuation using a reference calcium hydroxyapatite phantom [15], [16]. Ex vivo studies on phantoms [17], [18] and excised arterial specimens [12] have demonstrated that calibrated mineral mass accurately measures the mineral content of calcified atherosclerotic plaques. Mineral mass measurements may allow for better correction for variation of CAC measurements due to individual scanner type, scan parameter (tube energy, image noise) and patient-dependent factors [12], [13], [15], [19], [20]. It is also possible that there is significantly reduced interscan variability of CAC measurements determined by the mineral mass method [11], [12].
One potential advantage of mineral mass would be for accurate quantification of plaque progression. CAC appears to consistently progress with increasing age [21], [22]. Electron beam CT studies have demonstrated that the relative natural progression over time is a function of the presence and amount of baseline CAC [6], [7], [23], [24]. In addition, some studies in small selected patient cohorts report a significantly slower progression of CAC measured by electron beam CT in subjects receiving lipid-lowering therapy as compared to untreated subjects (17–60% for VS) [5], [6], [25], [26]. An association between a reduction in low-density lipoprotein levels and a reduction of CAC progression in the treated groups has been suggested [5], [6], [7], [23]. However, other studies failed to demonstrate an association between changes in low-density lipoprotein and CAC progression or differences in CAC progression between treated and untreated subjects [7], [27]. It is possible that the discordant results of these studies were due to either patient selection or measurement variability of CAC. A CAC measurement with improved interscan reproducibility would facilitate research on CAC progression and the effect of therapeutic interventions.
The goal of this study was to determine the reproducibility of CAC measurements by mineral mass compared with modified AS and VS in a general community-based cohort, and to estimate the effect of improved reproducibility of CAC measurements on observational studies and randomized clinical trials on the progression of CAC.
Section snippets
Subjects
One hundred and sixty-two consecutive subjects (83 women, 79 men, mean age 55 ± 13 years) from the Framingham Heart Study Offspring and third-generation cohorts underwent two MDCT scans in immediate succession for the detection of CAC. The subjects were enrolled as part of an ongoing MDCT study of over 3000 Framingham Heart Study subjects. The study was approved by the institutional review board of Boston Medical Center and the Massachusetts General Hospital. All subjects provided written
Statistical analysis
We calculated the mean, standard deviation and median values of CAC per subject for modified AS, VS and mineral mass. To assess inter-, intraobserver and interscan reproducibility of CAC measurements we calculated the absolute and relative measurement differences. The coefficient of variation was calculated as follows:
Measurements of individual observers were pooled for analysis. Only data from subjects with CAC detected in both scans
Measurement variability
In the 162 subjects, CAC was detected in both scans in 69 (42%), and CAC was not detected in either scan in 72 (45%). In 21/162 subjects (13%) CAC was present in one but not in the other CT scan. In these subjects the modified AS was <20 in 20/21 subjects (mean modified AS 4.6 ± 1.9).
The mean ± S.D. (median) values for 69 subjects with CAC detected in both CT scans were 235.7 ± 466.0 (77.6) for modified AS, 196.9 ± 380.2 (62.0) mm3 for VS, and 47.2 ± 90.5 (13.0) mg for mineral mass.
As shown in Fig. 1,
Discussion
This study was drawn from a series of men and women from a general community-based cohort and demonstrated that the variability of CAC measurements using mineral mass is significantly smaller than using modified AS or VS. The magnitude of the variability of CAC measurements between two CT scans is predominantly a function of the amount of CAC, with greater variability at lower levels of CAC, regardless of the quantification method. Although, the mineral mass algorithm is associated with
Limitations
The relatively small sample size of our current study has some limitations. Larger studies will provide more reliable, clinically applicable estimates of differences in variability by strata of age and sex and validation of mineral mass for coronary heart disease risk prediction or CAC progression. However, our reported distribution of CAC in our small initial series is consistent with that of larger studies [22]. Our study was conducted using MDCT not electron beam CT, and our findings may not
References (35)
- et al.
Continuous probabilistic prediction of angiographically significant coronary artery disease using electron beam tomography
Circulation
(2002) - et al.
Probabilistic model for prediction of angiographically defined obstructive coronary artery disease using electron beam computed tomography calcium score strata
Circulation
(2000) - et al.
Prognostic value of coronary electron-beam computed tomography for coronary heart disease events in asymptomatic populations
Am J Cardiol
(2000) - et al.
Using the coronary artery calcium score to predict coronary heart disease events: a systematic review and meta-analysis
Arch Intern Med
(2004) - et al.
Influence of lipid-lowering therapy on the progression of coronary artery calcification: a prospective evaluation
Circulation
(2002) - et al.
Effect of HMG-CoA reductase inhibitors on coronary artery disease as assessed by electron-beam computed tomography
N Engl J Med
(1998) - et al.
Evaluation by electron beam tomography of changes in calcified coronary plaque in treated and untreated asymptomatic patients and relation to serum lipid levels
Am J Cardiol
(2003) - et al.
Variability of repeated coronary artery calcium measurements by electron beam tomography
Am J Cardiol
(2001) - et al.
Coronary artery disease: improved reproducibility of calcium scoring with an electron-beam CT volumetric method
Radiology
(1998) - et al.
Causes of interscan variability of coronary artery calcium measurements at electron-beam CT
Acad Radiol
(2002)
Coronary artery calcium: accuracy and reproducibility of measurements with multi-detector row CT—assessment of effects of different thresholds and quantification methods
Radiology
Coronary artery calcium: absolute quantification in nonenhanced and contrast-enhanced multi-detector row CT studies
Radiology
Ultra-low-dose coronary artery calcium screening using multislice CT with retrospective ECG gating
Eur Radiol
In vitro atherosclerotic plaque and calcium quantitation by intravascular ultrasound and electron-beam computed tomography
Am Heart J
Coronary calcium quantification using various calibration phantoms and scoring thresholds
Invest Radiol
Accurate coronary calcium phosphate mass measurements from electron beam computed tomograms
Am J Card Imaging
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