Coronary calcium on electron beam tomography imaging as a surrogate marker of coronary artery disease

doi:10.1016/S0002-9149(01)01422-9

The American Journal of Cardiology

Volume 87, Issue 4, Supplement 1, 16 February 2001, Pages 27-34

https://doi.org/10.1016/S0002-9149(01)01422-9 Get rights and content

Abstract

Although currently recognized risk factors for coronary artery disease are helpful to predict the development of atherosclerosis, their ability to identify individual patients at risk of events is limited. Therefore, surrogate markers are being investigated to identify disease in its early phases in an attempt to decrease cardiovascular morbidity and mortality. Coronary artery calcification is a useful surrogate marker of coronary artery disease, and it can be visualized and measured noninvasively by means of electron beam tomography (EBT) imaging. Atherosclerosis starts to infiltrate the arterial intima layer much before luminal stenosis develops. Calcium is present in the large majority of mature atherosclerotic plaques, although, in rare cases, it may be absent. Recent research indicates that in selected patient subsets, coronary calcium may add incremental prognostic value to conventional risk factors for coronary artery disease and should therefore be used in association with such factors. EBT imaging for detection of arterial calcification is best employed in asymptomatic individuals at intermediate risk of coronary artery disease, symptomatic patients at low risk of coronary artery disease, and to track disease progression.

Section snippets

Coronary calcification

One such marker is coronary calcification, which often accompanies atherosclerosis (Figure 1). Although coronary calcification can be detected by means of spiral computed tomography, the scanners employing such technology are often too slow to obtain clear and motionless pictures of the heart. On the contrary, image acquisition proceeds very rapidly with the electron beam computed tomography (EBT) scanners.

EBT is currently the gold standard for calcium detection in the coronary arteries (see

Comparison of EBT with other investigative methods

The sensitivity of EBT compares well with other tools used to investigate the presence of atherosclerotic disease. One study comparing EBT and intravascular ultrasound (IVUS) in 56 patients found that EBT was positive in 97% of patients showing plaque with IVUS imaging.7 When IVUS showed soft plaque only, EBT demonstrated the presence of coronary calcium 47% of the time. Interestingly, 25% of the patients with no plaque on IVUS showed calcium on EBT imaging. This apparent paradox might be

Coronary calcification scoring methods

Coronary calcification is quantitated via a score calculated according to the Agatston’s method.9 The area of a calcified plaque is multiplied by a coefficient estimated on the basis of the peak density of the calcified lesion. For a density of 130–200 Hounsfiled Units (HU), the density coefficient is 1, for 201–300 HU it is 2, for 301–400 HU it is 3, and for ≥401 HU the density coefficient used is 4. The main limitation of this score is its limited reproducibility that renders it inadequate

Coronary calcification scores and the prediction of cardiovascular events

Coronary artery calcium appears to be a good predictor of cardiovascular events. Arad et al13 followed 1,172 patients for an average of 3.6 years. A total of 39 mixed coronary events (death, myocardial infarction, and revascularizations) were recorded during the follow-up period. Patients with events had a significantly greater calcium score at screening than patients without events (764 ± 935 vs 135 ± 432, p <0.0001). Furthermore, a calcium score >160 was associated with an odds ratio of

EBT, disease progression, and assessment of response to treatment

One of the most appealing applications of EBT imaging is the noninvasive follow-up of the progression of coronary artery disease. As mentioned earlier, initial studies on the interscan variability of the Agatston’s calcium score showed that this measurement had limited reproducibility and it was therefore considered unreliable for sequential studies.

In response to the need for a more reliable score, Callister et al10 recently introduced a new volumetric calcium score based on the principle of

Conclusion

In summary, coronary calcium is an excellent marker of underlying atherosclerotic disease that has accumulated in the context of the vascular wall. Calcium screening is best employed in asymptomatic subjects at intermediate risk of coronary artery disease to address the presence of atherosclerotic disease and to assess the risk of the individual patient. Because the majority of cardiovascular events happen in patients at intermediate risk, an effective risk stratification tool—such as EBT—can

Discussion

Jacques D. Barth, MD, PhD (Los Angeles, California):

EBT calcium screening has been surrounded by strong emotional feelings. Why do you think that is?

Paolo Raggi, MD (New Orleans, Louisiana):

I think there are several reasons. First, the field has received very negative publicity from an abusive use of advertisement in the mass media. This has damaged the scientific validity of the “calcium message” in the eyes of physicians not completely familiar with its meaning. Also, most physicians think of

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Cited by (51)

The epidemiology of subclavian artery calcification
2011, Journal of Vascular Surgery
Citation Excerpt :
Numerous studies have examined the prevalence of coronary artery calcification in the general population.10-13 The presence of coronary calcification is a marker for subclinical atherosclerosis, and the degree of calcification may provide important prognostic information, even in asymptomatic individuals.14 Comparatively fewer studies have examined the prevalence and predictive value of peripheral vascular calcification.
The purpose of the present study was to determine the prevalence and risk factor associations for subclavian artery calcification.
Arterial calcification is a marker of atherosclerosis, and its presence portends an adverse prognostic risk. The prevalence and associated risk factors for aortic arch, carotid, renal, and coronary calcification have been well described. Fewer data are available for subclavian artery calcification.
Electron-beam computed tomography was used to evaluate the extent of vascular calcification in multiple arterial beds in 1387 consecutive individuals who presented for preventive medicine services at a university-affiliated disease prevention center. Laboratory values for blood pressure, lipids, anthropomorphic data, and self-reported medical history were obtained.
Subclavian artery calcification was present in 439 of 1387 individuals (31.7%). Those with subclavian artery calcification were significantly older, had a smaller body mass index, and were more likely to also have calcification of nonsubclavian vascular beds. When adjusted for cardiovascular disease risk factors, the presence of subclavian artery calcification was significantly associated with age (prevalence ratio [PR], 1.04; P < .001), hypertension (PR, 1.20; P = .01), history of smoking (PR, 1.21; P = .01), and calcification in nonsubclavian vascular beds (PR, 1.58; P = .01). Subclavian artery calcification was also associated with an increased pulse pressure (β-coefficient = 2.2, P = .008).
Subclavian artery calcification is relatively common and is significantly associated with age, smoking, hypertension, and nonsubclavian vascular calcification. There may be a relationship between vascular stiffness, as manifested by a widened pulse pressure, and the presence of subclavian artery calcification.
Incidence of focal myocardial <sup>18</sup>F-FDG uptake and correlation with coronary calcifications by PET/CT
2011, Revista Espanola de Medicina Nuclear
Evaluar la incidencia de focos miocárdicos de captación de ¹⁸F-FDG y su correlación con calcificaciones en territorios coronarios.
Se analizaron retrospectivamente 130 pacientes en los que se realizó una PET/TC con indicación oncológica. De ellos a 65 se les había realizado también un estudio de perfusión miocárdica por posible enfermedad coronaria (grupo 1). Los hallazgos se compararon con un grupo de la misma serie (n = 65; grupo 2). Dos observadores independientes identificaron los focos miocárdicos de captación de ¹⁸F-FDG y su correspondencia con las calcificaciones en territorios coronarios.
Grupo 1: en 18/65 estudios (28%) se detectó un foco miocárdico de captación de ¹⁸F-FDG (en 5/18 de ellos 2; total: 23 focos). En 43/65 estudios (66%) existían calcificaciones coronarias.
Grupo 2: en 6/65 estudios (9%) se detectó un foco miocárdico de captación de ¹⁸F-FDG (en 1/6 de ellos 2; total: 7 focos). En 17/65 estudios (26%) existían calcificaciones coronarias.
Análisis comparativo: la presencia de focos miocárdicos de captación de ¹⁸F-FDG y la calcificación de los vasos coronarios es más frecuente en el grupo 1 (p < 0,01).
No ha existido correlación entre la presencia de calcificaciones coronarias y la existencia de focos miocárdicos de captación de ¹⁸F-FDG en ninguno de los grupos (grupo 1: p = 0,7; grupo 2: p = 0,163).
La PET/TC, en una única exploración, evidencia la frecuencia de focos miocárdicos de captación de ¹⁸F-FDG y calcificaciones coronarias. Dicha incidencia es mayor en los pacientes con posible enfermedad coronaria. En ambos grupos estos hallazgos fueron independientes.
To evaluate the incidence of ¹⁸F-FDG focal uptake in the myocardium as well as its correlation with coronary vessel calcifications.
A total of 130 patients who underwent an oncological PET/CT study were reviewed retrospectively. Sixty-five had undergone a myocardial perfusion study because of clinical suspicion of coronary artery disease (group 1). There were no significant differences in age and gender regarding another group of the same series (n = 65; group 2). Focal myocardial ¹⁸F-FDG uptake and the presence of coronary vessel calcifications were identified by 2 independent observers.
Group 1: in 18 out of 65 patients (28%) focal myocardial ¹⁸F-FDG uptake was identified (5 had 2 foci; total: 23 foci). In 43 out of 65 studies (66%), calcification was identified in the coronary vessels.
Group 2: in 6 out of 65 patients (9%) focal myocardial ¹⁸F-FDG uptake was identified (1 had 2 foci; total: 7 foci). In 17 out of 65 studies (26%), calcification was identified in the coronary vessels.
Comparative analysis: focal myocardial ¹⁸F-FDG uptake and coronary vessel calcifications were more frequent in the group 1 patients (p < 0.01).
There was no correlation between the presence of coronary vessel calcifications and focal myocardial ¹⁸F-FDG uptake in individual patients in both groups (group 1: p = 0.7; group 2: p = 0.163).
PET/CT allows simultaneous assessment of focal myocardial ¹⁸F-FDG uptake and myocardial vessel calcifications. Patients with clinical suspicion of coronary artery disease have a higher incidence of focal myocardial ¹⁸F-FDG uptake and coronary calcifications. However, ¹⁸F-FDG focal uptake is often observed in sites remote from those with calcification.
Measurement of carotid artery intima-media thickness in dyslipidemic patients increases the power of traditional risk factors to predict cardiovascular events
2007, Atherosclerosis
Citation Excerpt :
Conventional risk factor assessment predicts only 60–65% of cardiac risk, and cardiac events occur in many individuals who have no established risk factors for atherosclerosis [1–3]. It has been suggested [4–7] that the combination of markers of sub-clinical atherosclerosis with algorithms for risk assessment may increase the predictability of future vascular events. Carotid artery IMT measurement is widely available but is generally used in large-scale clinical studies of treatment effects [8,9].
A longitudinal observational study investigated whether the measurement, in clinical practice, of carotid maximum intima-media thickness (Max-IMT) could be combined with the Framingham risk score (FRS) to improve the predictability of cardiovascular events in dyslipidemic patients who are at low or intermediate risk.
Max-IMT was measured by ultrasound in 1969 patients attending a lipid clinic. The “best threshold values” (BTVs) above which we considered the Max-IMT to be abnormally high were calculated for our dyslipdemic population for each 10-year age interval in men and women. Two hundred and forty-two patients (age 54 ± 10 years; 43.8% women) with an FRS <20%, i.e. at low or intermediate risk, were monitored for more than 5 years. Twenty-four of these patients suffered a cardiovascular event within 5.1 ± 2.3 years. Both FRS and Max-IMT proved to be independent outcome predictors (p < 0.04, both), with a hazard ratio (HR) of 6.7 (95% CI 1.43, 31.04; p = 0.015) in patients in whom FRS was 10–20% and Max-IMT was above the BTV (60th percentile of Max-IMT distribution for men or 80th for women). In Kaplan–Meier analysis, the Max-IMT significantly improved the predictive value of the FRS (χ² = 8.13, p = 0.04). Patients with FRS 10–20% (currently considered intermediate-risk) and also elevated Max-IMT values came into the same high-risk category as patients with FRS 20–30%.
The combination of FRS with Max-IMT measurement can be used in routine clinical practice to greatly enhance the predictability of cardiovascular events in the large number of patients who fall into the intermediate-risk category, which currently does not call for aggressive preventive measures.
Changing patterns of abnormal vascular wall F-18 fluorodeoxyglucose uptake on follow-up PET/CT studies
2006, Journal of Nuclear Cardiology
Fluorine 18 fluorodeoxyglucose (FDG) uptake may be increased in atherosclerotic plaques in asymptomatic patients. Repeat positron emission tomography (PET)/computed tomography (CT) studies were assessed for changes in patterns of FDG uptake and CT calcifications.
Fifty consecutive cancer patients (mean age, 68 ± 8 years) had repeat PET/CT studies 8 to 26 months apart. PET, CT, and PET/CT images were retrospectively evaluated for vascular wall abnormalities and for interval changes in the thoracic and abdominal aortas, as well as in carotid and iliac arteries, classified as PET+/CT+, PET+/CT−, and PET−/CT+. There were 485 abnormal sites in the first study and 495 in the second. CT calcifications were found in 46 patients (92%) in the first study and in 47 (94%) in the second. Vascular wall FDG uptake was found in both studies in 37 patients (74%). The pattern changed in 57 of 119 PET+ sites (48%) in the second study compared with 15 of 366 PET− sites (4%) (P < .0001). In the second study new PET+ sites were observed in 36 of 111 sites (32%) versus new PET−/CT+ sites in 19 of 384 sites (5%) (P < .0001).
Changes in vascular FDG activity and CT calcifications can be assessed by repeat PET/CT. FDG-avid foci may represent a dynamic process, transient inflammation, whereas CT calcifications may indicate stable atherosclerosis. These preliminary results support the need for further research.
Arterial stiffness index as a screening test for cardiovascular risk: A comparative study between coronary artery calcification determined by electron beam tomography and arterial stiffness index determined by a VitalVision device in asymptomatic subjects
2005, European Journal of Internal Medicine
Arterial stiffness has recently been proposed as a powerful independent predictor of cardiovascular disease. However, the influence of arterial stiffening on the interaction between the heart and large vessels and atherosclerosis is not well defined. The arterial stiffness index (ASI) has recently been determined with a new device (VitalVision) that calculates ASI in the upper arm using computerized oscillometry. Coronary artery calcification (CAC) is a useful surrogate marker of coronary artery disease detected non-invasively by electron beam tomography (EBT). We investigated the correlation between ASI and CAC in a group of patients.
CAC and ASI measurements were determined with EBT and a VitalVision device, respectively, on the same day in 97 asymptomatic patients. Patients with calcium scores above 0 were classified as CAC+ and those with calcium scores equal to 0 were classified as CAC−. The ASI index was divided into three groups – mild, moderate, and high – according to the H-value, provided by the VitalVision device.
In patients below 51 years of age, no correlation between the ASI and CAC was found. In patients over 50 years of age, a moderate positive and significant correlation was found between the CAC score and ASI measurements (r = 0.40, p = 0.001).
The presence of a correlation between the CAC and ASI in patients over 50 shows that the ASI can be used to investigate atherosclerotic risk.
Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis
2005, Kidney International
Effects of sevelamer and calcium on coronary artery calcification in patients to new hemodialysis.
Hemodialysis patients are at increased risk for progressive coronary artery calcification; however, the development and progression of this disease process in patients new to hemodialysis is unknown.
One hundred and twenty-nine patients new to hemodialysis were randomized to receive calcium containing phosphate binders or the noncalcium phosphate binder sevelamer hydrochloride. Subjects underwent electron beam computed tomography scanning (EBCT) at entry into the study and again at 6, 12, and 18 months.
One hundred and nine patients underwent baseline and at least one additional assessment of coronary calcification. At baseline, 37% of sevelamer treated and 31% of calcium treated patients had no evidence of coronary calcification. No subject with a zero coronary artery calcium score (CACS) at baseline progressed to a CACS >30 over 18 months. Subjects with a CACS > 30 at baseline showed progressive increases in CACS in both treatment arms (P < 0.05 for each time point in both groups). Subjects treated with calcium containing phosphate binders showed more rapid and more severe increases in CACS when compared with those receiving sevelamer hydrochloride (P = 0.056 at 12 months, P = 0.01 at 18 months).
New hemodialysis patients with no evidence of coronary calcification showed little evidence of disease development over 18 months independent of phosphate binder therapy. However, subjects with evidence of at least mild coronary calcification had significant progression at 6, 12, and 18 months. Use of calcium containing phosphate binders resulted in more rapid progression of coronary calcification than did use of sevelamer hydrochloride.

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Coronary calcium on electron beam tomography imaging as a surrogate marker of coronary artery disease

Abstract

Section snippets

Coronary calcification

Comparison of EBT with other investigative methods

Coronary calcification scoring methods

Coronary calcification scores and the prediction of cardiovascular events

EBT, disease progression, and assessment of response to treatment

Conclusion

Discussion

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Mayo Clin Proc

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

Coronary plaque disruption

Circulation

The pathophysiology of acute coronary syndromes

Heart

The sequence of cell and matrix changes in atherosclerotic lesions of coronary arteries in the first forty years of life

Eur Heart J