Extracoronary Calcification Research Articles

On the association between circulating biomarkers and atherosclerotic calcification in a cohort of arterial disease participants

Background and aimsAtherosclerotic calcification is a powerful predictor of cardiovascular disease. This study aims to determine whether circulating levels of a local/systemic calcification inhibitor or a marker of bone formation correlate with measures of coronary or extracoronary calcification. Methods and resultsClinical computed tomography (CT) was performed on 64 arterial disease participants undergoing carotid and lower extremity endarterectomy. Coronary artery calcium (CAC) scores and volumes were acquired from the CT scans (n = 42). CAC scores and volumes were used to derive CAC density scores. Micro-CT was performed on excised carotid (n = 36) and lower extremity (n = 31) plaques to quantify the volume and volume fraction of extracoronary calcification. Circulating levels of dephospho-uncarboxylated Matrix Gla Protein (dp-ucMGP), fetuin-A, carboxylated and uncarboxylated osteocalcin (ucOC) were quantified using commercial immunoassays. Carotid participant CAC density scores were moderately negatively correlated with plasma dp-ucMGP (rs = −0.592, P = 0.008). A weak negative association was found between CAC scores and %ucOC for all participants (rs = −0.335, P = 0.040). Another weak negative correlation was observed between fetuin-A and the volume of calcification within excised carotid specimens (rs = −0.366, P = 0.031). Despite substantial differences in coronary and extracoronary calcium measurements, the levels of circulating biomarkers did not vary significantly between carotid and lower extremity subgroups. ConclusionCorrelations identified between circulating biomarkers and measures of coronary and extracoronary calcium were not consistent among participant subgroups. Further research is required to determine the association between circulating biomarkers, coronary and extracoronary calcium.

Abstract 15249: Association of Coronary Artery and Extra-coronary Calcification With Reduced Physical Function and Frailty in Older Adults: The Atherosclerosis Risk in Communities Study

Introduction: Coronary artery calcium (CAC) and extra-coronary calcification (ECC) have been associated with age-related phenotypes such as cognitive impairment. However, their relationship with poor physical function and frailty/pre-frailty in older adults is unclear. Hypothesis: CAC and ECC (aortic valve, aortic valve ring, mitral valve, ascending aorta, and descending aorta) are associated with poor physical function and frailty/pre-frailty. Methods: We defined poor physical function as a Short Physical Performance Battery (SPPB) score ≤9 and frailty/pre-frailty as the presence of at least one frailty criterion: weight loss, slow walking speed, exhaustion, low grip strength, and low physical activity. The number of vascular beds with any calcification (CAC and five ECC sites [0-6]) was calculated for a composite measure of calcification. Logistic regression was used to quantify cross-sectional associations with SPPB or frailty/pre-frailty among 1,564 ARIC participants aged 74-92 without prior CVD at visit 7 (2018-19). Results: The prevalence of low SPPB, frailty, and pre-frailty was 50%, 5%, and 56%, respectively. Highest (vs. lowest) quartile of aortic valve and mitral valve calcification was associated with low SPPB (OR 1.47 [1.15, 1.88] and 1.53 [1.19,1.97]) and frailty/pre-frailty (1.34 [1.05, 1.71] and 1.41 [1.10, 1.80]). Aortic valve ring calcification was associated with frailty/pre-frailty, and descending aorta calcification with low SPPB. The total number of calcified vascular beds demonstrated a dose-response relationship to both outcomes (Table), with 5-6 calcified vascular beds demonstrating ~2-fold higher odds. Conclusions: Cardiovascular calcification, especially aortic valve and mitral valve calcification, was robustly associated with higher risk of poor physical function and frailty/pre-frailty, suggesting the potential etiological link between cardiovascular calcification and functional decline at older age.

Progression of Valvular Calcification is Associated with 10-Year Change in Left Ventricular Structure and Incident Heart Failure: MESA

Heart failure (HF) is a leading cause of morbidity.1 It results from impairment in ventricular filling or relaxation and can be broadly classified as heart failure with preserved ejection fraction (HFpEF) or with reduced ejection fraction (HFrEF).2 Strategies for preventing HF are paramount. Prevalent coronary artery calcium and extracoronary calcification are associated with future coronary heart disease3-7 and HF8 events. Less is known about the impact of progression of valvular calcification (VC) (mitral annular [MAC] and aortic valve calcification [AVC]) on HF risk.

Effect of Progression of Valvular Calcification on Left Ventricular Structure and Frequency of Incident Heart Failure (from the Multiethnic Study of Atherosclerosis)

Heart failure (HF) is a leading cause of morbidity. Strategies for preventing HF are paramount. Prevalent extracoronary calcification is associated with HF risk but less is known about progression of mitral annular (MAC) and aortic valve calcification (AVC) and HF risk. Progression of valvular calcification (VC) [interval change of >0 units/yr] was assessed by 2 cardiac computed tomography scans over a median of 2.4 years. We used Cox regression to determine the risk of adjudicated HF and linear mixed effects models to determine 10-year change in left ventricular (LV) parameters measured by cardiac magnetic resonance imaging associated with VC progression. We studied 5,591 MESA participants free of baseline cardiovascular disease. Mean ± SD age was 62 ± 10 years; 53% women; 83% had no VC progression, 15% progressed at 1 site (AVC or MAC) and 3% at both sites. There were 251 incident HF over 15 years. After adjusting for cardiovascular risk factors, the hazard ratios (95% confidence interval) of HF associated with VC progression at 1 and 2 sites were 1.62 (1.21 to 2.17) and 1.88 (1.14 to 3.09), respectively, compared with no progression (p-for-trend <0.001). Hazard ratios were higher for HFpEF (2.52 [1.63 to 3.90] and 2.49 [1.19 to 5.25]) but nonsignificant for HFrEF. Both AVC (1.61 [1.19 to 2.19]) and MAC (1.50 [1.09 to 2.07]) progression were associated with HF. VC was associated with worsening of some LV parameters over 10 years. In conclusion, VC progression was associated with increased risk of HF and change in LV function. Interventions targeted at reducing VC progression may also impact HF risk, particularly HFpEF.

Abstract P435: Associations of Endogenous Sex Hormone Levels With the Prevalence and Progression of Valvular and Thoracic Aortic Calcification in the Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Sex hormone (SH) levels may contribute to sex differences in cardiovascular disease (CVD) risk among women and men. We previously found that high free testosterone (T) and low sex hormone binding globulin (SHBG) were associated with progression of coronary artery calcification in women. Extra-coronary calcification (ECC) predicts incident clinical CVD independent of traditional risk factors. We examined whether SH were also associated with ECC prevalence and progression among MESA participants free of clinical CVD at baseline. Methods: We studied 2883 postmenopausal women and 3164 men who had endogenous SH levels measured at baseline. ECC was measured by non-contrast cardiac CT at baseline and at a follow-up visit up to 5 years later. ECC included ascending and descending thoracic aortic calcification (ATAC, DTAC), mitral annular calcification (MAC) and aortic valve calcification (AVC). We used multivariable Poisson regression to evaluate associations with ECC prevalence and risk of developing ECC (Agatston scores &gt;0) and linear mixed effects models for ECC progression, per 1 SD increment in log (SH) level in women and men separately. Results: The mean (SD) age was 64 (9) years for women and 62 (10) years for men. In women, greater free T and lower SHBG were associated with MAC incidence in a demographic-adjusted model but were no longer statistically significant after adjustment for CVD risk factors ( Table ). In men, lower free T was associated with MAC prevalence, DTAC incidence and progression while greater SHBG was associated with MAC prevalence and DTAC progression in fully adjusted models. We did not find associations of SH with AVC or ATAC in either men or women. Conclusion: In this diverse cohort free of CVD, we found certain associations of SH with measures of ECC. In particular, free T was inversely associated with prevalent MAC and DTAC progression in men independent of CVD risk factors. SH may influence vascular calcification but further work is needed to understand the clinical implications of these findings.

The novel inflammatory marker GlycA and the prevalence and progression of valvular and thoracic aortic calcification: The Multi-Ethnic Study of Atherosclerosis

Background and aimsGlycA is a novel composite biomarker of systemic inflammation reflecting posttranslational glycosylation of acute phase reactants. GlycA has been associated with coronary artery calcium, cardiovascular disease (CVD) events and mortality. Vascular calcifications outside of the coronary arteries are risk markers of CVD and mortality. Whether GlycA is linked to extra-coronary calcifications (ECC) is not well established. MethodsWe studied 6462 MESA participants free of clinical CVD who had plasma GlycA measured at baseline. ECCs [calcification in aortic valve (AVC), mitral annulus (MAC), ascending and descending thoracic aorta (ATAC, DTAC)] were ascertained at baseline and follow-up visit (median 2.3-yrs later) by cardiac CT. Poisson regression models with robust variance estimation assessed associations of GlycA with prevalent and incident ECC. Linear mixed models assessed the cross-sectional and 2-year change in ECC. Models were adjusted for demographic and lifestyle factors. ResultsIn cross-sectional analysis, GlycA (per SD increment) was positively associated with prevalent AVC, ATAC and DTAC with adjusted prevalence ratios (95% CI) of 1.08 (1.01–1.14), 1.18 (1.03–1.34) and 1.10 (1.06–1.14), respectively. There was also a significant association between GlycA and baseline extent of both ATAC and DTAC. Longitudinally, GlycA was positively associated with incident MAC and DTAC, with adjusted incidence ratios of 1.18 (1.03–1.37) and 1.17 (1.07–1.28), respectively. GlycA was also associated with 2-year change in MAC and DTAC extent. ConclusionsIn this diverse cohort free from clinical CVD, we found GlycA was positively associated with prevalent and incident ECC measures, in particular for progression of MAC and DTAC.

The Relationship Between Extra-Coronary Calcification and Coronary Artery Lesion Characteristics

The Relationship Between Extra-Coronary Calcification and Coronary Artery Lesion Characteristics

Thoracic extra-coronary calcification for the prediction of stroke: The Multi-Ethnic Study of Atherosclerosis

Background and aimsAtherosclerosis is a systemic disease. We examined whether the cumulative burden of thoracic extra-coronary calcification (ECC) improves prediction of stroke, transient ischemic attack (TIA), and stroke mortality beyond traditional risk factors and coronary artery calcium (CAC). MethodsWe followed a total of 6805 participants (mean age 62.1 ± 10.2 years, 47.2% male) from the Multi-Ethnic Study of Atherosclerosis (MESA) over a median of 12.1 years. The presence or absence of calcification at 4 thoracic ECC sites (mitral valve annulus, aortic valve, aortic root, and thoracic aorta) was determined from baseline cardiac-gated non-contrast CT scans. A multisite thoracic ECC score, ranging 0–4, was calculated by summing the 4 individual sites, which were treated as binary variables. Multivariable Cox proportional hazards regression models, controlled for traditional risk factors and CAC, were used to estimate hazard ratios for ischemic (primary endpoint) and hemorrhagic stroke, total stroke, TIA, and stroke mortality with increasing thoracic ECC. ResultsWith an increasing number of thoracic ECC sites, there was a significant (p < 0.05) multivariable adjusted step-wise increase in the risk for ischemic stroke (n = 184), total stroke (n = 235), and TIA (n = 85), but not hemorrhagic stroke (n = 32) and stroke mortality (n = 42). Thoracic ECC increased the c-statistic and net reclassification index beyond traditional risk factors and CAC, but the results were not significant (p > 0.10). ConclusionsAlthough multisite thoracic ECC is independently associated with ischemic stroke, total stroke, and TIA, the incremental predictive value of thoracic ECC beyond traditional risk factors and CAC appears to be minimal.

Extra-coronary calcification (aortic valve calcification, mitral annular calcification, aortic valve ring calcification and thoracic aortic calcification) in HIV seropositive and seronegative men: Multicenter AIDS Cohort Study

IntroductionPrevious studies have demonstrated an association between HIV infection and coronary artery disease (CAD); little is known about potential associations between HIV infection and extra-coronary calcification (ECC). MethodsWe analyzed 621 HIV infected (HIV+) and 384 HIV uninfected (HIV−) men from the Multicenter AIDS Cohort Study who underwent non-contrast computed tomography (CT) from 2010-2013. Agatston scores were calculated for mitral annular calcification (MAC), aortic valve calcification (AVC), aortic valve ring calcification (AVRC), and thoracic aortic calcification (TAC). The associations between HIV infection and the presence of each type of ECC (score > 0) were evaluated by multivariable logistic regression. We also evaluated the association of ECC with inflammatory biomarker levels and coronary plaque morphology. ResultsAmong HIV+ and HIV− men, the age-standardized prevalences were 15% for TAC (HIV+ 14%/HIV− 16%), 10% for AVC (HIV+ 11%/HIV− 8%), 24% for AVRC (HIV+ 23% HIV− 24%), and 5% for MAC (HIV+ 7%/HIV− 3%). After adjustment, HIV+ men had 3-fold greater odds of MAC compared to HIV− men (OR = 3.2, 95% CI: 1.5–6.7), and almost twice the odds of AVC (1.8, 1.1–2.9). HIV serostatus was not associated with TAC or AVRC. AVRC was associated with higher Il-6 and sCD163 levels. TAC was associated with higher ICAM-1, TNF-α RII, and Il-6 levels. AVC and AVRC calcification were associated with presence of non-calcified plaque in HIV+ but not HIV− men. ConclusionHIV infection is an independent predictor of MAC and AVC. Whether these calcifications predict mortality in HIV+ patients deserves further investigation.

An Update on the Utility of Coronary Artery Calcium Scoring for Coronary Heart Disease and Cardiovascular Disease Risk Prediction.

Estimating cardiovascular disease (CVD) risk is necessary for determining the potential net benefit of primary prevention pharmacotherapy. Risk estimation relying exclusively on traditional CVD risk factors may misclassify risk, resulting in both undertreatment and overtreatment. Coronary artery calcium (CAC) scoring personalizes risk prediction through direct visualization of calcified coronary atherosclerotic plaques and provides improved accuracy for coronary heart disease (CHD) or CVD risk estimation. In this review, we discuss the most recent studies on CAC, which unlike historical studies, focus sharply on clinical application. We describe the MESA CHD risk calculator, a recently developed CAC-based 10-year CHD risk estimator, which can help guide preventive therapy allocation by better identifying both high- and low-risk individuals. In closing, we discuss calcium density, regional distribution of CAC, and extra-coronary calcification, which represent the future of CAC and CVD risk assessment research and may lead to further improvements in risk prediction.

Extracoronary Thoracic and Coronary Artery Calcifications on Chest CT for Lung Cancer Screening: Association with Established Cardiovascular Risk Factors - The “CT-Risk” Trial

To investigate the correlation between prevalence and degree of coronary artery calcification (CAC) and extracoronary calcifications (ECCs), scored quantitatively according to Agatston and semiquantitatively by visual analysis, in chest computed tomography (CT) studies obtained for lung cancer screening in asymptomatic subjects and in patients with known coronary heart disease (CHD), and to compare the association of ECC and CAC to established cardiovascular risk factors. Prospective study on 501 males (67 ± 8 years) with a history of working dust exposure who underwent nongated low-dose chest CT for lung cancer screening. Of these, 63 (12.6%) had a history of CHD, the remaining 438 subjects (87.4%) were clinically asymptomatic and without a history of CHD. On the day of the CT study, subjects underwent a thorough clinical examination including blood tests and completed a standardized questionnaire to establish a complete medical history. ECC and CAC scores were quantified according to Agatston and, in addition, by visual rating of calcium load of individual vessel territories on a five-point scale from "absent" to "extensive." Results were correlated with the respective subjects' cardiovascular risk factors and with the presence or absence of CHD. ECC scores correlated significantly with CAC scores (two-sided Spearman 0.515; P < .001). ECC scores were associated significantly (P < .001) with cardiovascular risk factors (smoking history, hypertension, diabetes, and hypercholesterolemia) and with subjects' Framingham/prospective cardiovascular münster study scores, whereas CAC scores were associated only with the presence of hypercholesterolemia. CAC scores were strongly associated with CHD than ECC scores (area under the curve, 0.88 vs. 0.66 at receiver operating characteristic analysis). Visual scoring of ECC/CAC load correlated closely with the respective Agatston values (P < .001) and revealed the same association (or lack thereof) with cardiovascular risk factors/CHD. In nongated low-dose CT for lung cancer screening, CAC and ECC load can be accurately established by visual analysis. ECC and CAC scores correlate closely, but not perfectly. There is a strong association between established cardiovascular risk factors and ECC load, but not CAC load, providing further evidence that ECC scoring may complement CAC scoring for broader risk assessment, for example, regarding prediction of extracoronary vascular events.

Multisite extracoronary calcification indicates increased risk of coronary heart disease and all-cause mortality: The Multi-Ethnic Study of Atherosclerosis

BackgroundCardiovascular calcification outside of the coronary tree, known as extracoronary calcification (ECC), is highly prevalent, often occurs concurrently in multiple sites, and yet its prognostic value is unclear. ObjectiveTo determine whether multisite ECC is associated with coronary heart disease (CHD) events, CHD mortality, and all-cause mortality. MethodsWe evaluated 5903 participants from the Multi-Ethnic Study of Atherosclerosis without diabetes who underwent CT imaging for calcification of the aortic valve, aortic root, mitral valve, and thoracic aorta. Participants were followed for 10.3 years. Multivariable adjusted hazard ratios estimated risk of outcomes for increasing numbers of ECC sites (0, 1, 2, 3, and 4), and receiver operator characteristic analysis assessed model discrimination. ResultsPrevalence of any ECC was 45%; median age was 62 years. Compared with those without ECC, those with ECC in 4 sites had increased hazards of 4.5, 7.1 and 2.3 for CHD events, CHD mortality, and all-cause mortality, respectively, independent of traditional risk factors (TRF; all P ≤ .05), and had ≥2-fold increased hazards for outcomes independent of coronary artery calcification (CAC). Each additional site of ECC was positively associated with each outcome in a graded fashion. When added to TRF, ECC significantly increased the area under the receiver operator characteristic curve for all outcomes and modestly increased the area under the curve for mortality beyond TRF + CAC (0.799 to 0.802; P = .03). ConclusionIncreasing multisite ECC has a graded association with higher CHD and mortality risk, contributing information beyond TRF. Multisite ECC incidentally identified on imaging can be used to improve individualized risk prediction.

The association between extracoronary calcification and coronary artery disease in patients with type 2 diabetes mellitus

Cardiovascular complications are the major cause of diabetes-associated morbidity and mortality. However, not all patients with diabetes are at increased risk for cardiovascular disease (CVD). Coronary artery calcification was found to be a powerful predictor of coronary artery disease (CAD). The presence of extracoronary cardiac calcification as a useful predictor of CAD is not yet established, especially in type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the relation between extracoronary calcification and extent of CAD in a group of T2DM patients who were scheduled for computed tomographic coronary angiography (CTCA). We prospectively studied 380 patients (151 had T2DM) under the age of 60 years who were scheduled for CTCA because of suspected CAD. Severity of CAD was assessed by Gensini score. Coronary artery calcium score (CACS) as well as calcium score in the aortic valve, mitral annulus, ascending aorta, and descending aorta were measured by a 256-row multidetector computed tomography scanner with dedicated software for calcium calculation. Patients with known CAD were excluded. Diabetic and nondiabetic patients had comparable age and gender distribution. However, the diabetic group had higher Gensini score, CACS, and extracoronary calcium score (ECCS). Logistic regression analyses identified male gender and ECCS as significant predictors for the presence of CAD in diabetic patients. Age, smoking, and ECCS were the significant predictors of CAD in nondiabetic patients. Type 2 diabetic patients had increased coronary and extracoronary calcification. ECCS was found to be a significant predictor of CAD in diabetic and nondiabetic patients only when CACS was not taken into account.

The relationship of insulin resistance and extracoronary calcification in the multi-ethnic study of atherosclerosis

ObjectiveWe hypothesized that insulin resistance, measured by the homeostasis model assessment of insulin resistance (HOMA), is independently associated with prevalent and incident extra-coronary calcification (ECC). MethodsWe studied calcium scores of the aortic valve calcification (AVC), mitral valve calcification (MVC), thoracic aorta calcification (TAC) and aortic valve root calcification (AVR) in 6104 MESA participants not on diabetes medication who had baseline cardiac CT scans; 5312 had follow-up scans (mean 2.4 years). Relative-risk regression modeled prevalent and incident ECC adjusted for baseline demographics (model 1), and additionally for CVD risk factors (model 2). ResultsIn model 1, prevalence and incidence risk-ratios for the highest versus lowest quartile of HOMA were 20–30% higher in all ECC locations (p-value for trend ≤0.05 for all but incident-AVC). In model 2, all associations were attenuated, primarily by adjustment for metabolic syndrome components. ConclusionsHOMA has a positive and graded association with ECC, but not independently of cardiovascular risk factors—particularly metabolic syndrome components.

Ethnic differences between extra-coronary measures on cardiac computed tomography: Multi-ethnic study of atherosclerosis (MESA)

Background Emerging evidence indicates that calcifications in valvular and thoracic aorta are manifestations of generalized atherosclerosis. Assessing the presence and extent of extra-coronary atherosclerosis may further improve prognostic information in subjects who are at risk for cardiovascular disease. The aim of the study is to determine the relative prevalence and quantity of extra-coronary calcifications across ethnic groups in a multi-ethnic population based cohort of asymptomatic individuals. Methods and results The ethnic differences associated with aortic valve calcification (AVC), mitral valve calcification (MVC), aortic valve root calcification (AVRC) and thoracic aortic wall calcification (TAC) were assessed in 6814 asymptomatic individuals in the multi-ethnic study of atherosclerosis (MESA) study. The overall prevalence of AVC, MVC, AVRC and TAC was 13, 10, 34 and 28%, respectively). As far as the valvular calcifications (AVC, MVC, AVRC) are concerned, the highest prevalence was observed in the Whites, followed by Hispanics and African-Americans with the lowest levels of calcification among the Chinese (all p < 0.001). On the other hand, the Chinese along with Whites had the highest prevalence of TAC ( p < 0.001). After adjustment for traditional CVD risk factors and coronary artery calcification, the relative risk of AVC compared with Whites was 0.72 in Blacks (95% CI 0.59–0.90), 1.03 in Hispanics (95% CI 0.82–1.28) and 0.56 in Chinese (95% CI 0.40–0.80). Similar associations were observed for the presence of MVC and AVRC. However, as compared to Whites, the relative risk for presence of TAC was not significantly lower among Hispanics (RR: 0.83, 95% CI: 0.68–1.01) and Chinese Americans (RR: 1.24, 95% CI: 0.95–0.1.62); however Blacks had a significantly lower risk of TAC (RR: 0.50, 95% CI: 0.41–0.60), respectively. Conclusions Racial differences exist in the prevalence of extra-coronary calcification in a large multi-ethnic population of asymptomatic individuals, thus underscoring the need for developing population specific nomograms to identify overall atherosclerotic burden in a more accurate manner in different ethnic groups. Further studies are needed to assess prognostic potential of each of these new measures of extra-coronary calcification in predicting subsequent cardiovascular events, independently and incrementally above known cardiovascular risk factors and the amount of calcified coronary plaque.

Effect of Scanner Type on The Reproducibility of Extracoronary Measures of Calcification: The Multi-Ethnic Study of Atherosclerosis

Cardiac computed tomography (CT) has been used extensively to measure coronary artery calcification. However, extracoronary calcifications, such as aortic valve calcification (AVC), may have independent clinical significance as well. The ability to track calcification is dependent on the reproducibility of the original measurement, and the variability of extracoronary calcification measurements still is unknown. Accurate quantification of calcification of the aortic valve, mitral annulus (MAC), and thoracic aortic (TAC) may be possible by using cardiac CT. A total of 1,729 randomly chosen participants (ages 45-84, 53% female, 28% African-American, 36% Caucasian, 11% Chinese, 25% Hispanic) of the Multi-Ethnic Study of Atherosclerosis underwent dual scanning by electron beam CT (EBT) or multidetector CT (MDCT) to assess coronary and extra-coronary calcifications. Two calcium measurement methods--Agatston score (AS) and volume score (VS)--were measured for each scan. Concordance for calcium positivity was assessed among all scans. Mean absolute and relative differences between calcium measures on scans 1 and 2, excluding cases for which both scans had a measure of zero, was modeled by using linear regression to compare variability between scanner types. A repeated measures analysis of variance test was used to compare variability across calcium measures, with mean percentage absolute difference as the outcome measure. Concordances for the presence of calcium between duplicate scans were high and similar for both EBT and MDCT. Concordance was high for all three extracoronary measures, with a kappa statistic of kappa = 0.94-0.96. For all three extracoronary sites, Bland-Altman plots demonstrated excellent agreement, with almost all measures falling within the boundaries of the 95% confidence limits of reproducibility. AVC interscan variability was approximately 8% for both AS and VS, with improved variability for EBT as compared with MDCT. Mitral annular calcification demonstrated slightly lower variability than AVC for both scanner types (approximately 6%), with no significant differences between MDCT and EBT. Of the three extracoronary sites, TAC had the highest variability (10%), with MDCT variability slightly lower than EBT variability (9.3 vs. 10.2%, respectively, P = NS). Agatson and volume scores for each of the three extracoronary sites were similar. Overall rescan measurement variabilities for extracoronary calcification are low and should not be an impediment to the use of this test for studying progression of extracoronary calcification over time.

Reproducibility of CT Measurements of Aortic Valve Calcification, Mitral Annulus Calcification, and Aortic Wall Calcification in the Multi-Ethnic Study of Atherosclerosis

Extracoronary calcifications may have clinical significance. The error in extracoronary calcification measurements is still unknown. Accurate quantification of calcifications of the aortic valve (AVC), mitral annulus (MAC), and aortic wall (AWC) may be possible by using cardiac computed tomography (CT). We sought to establish the interscan, interobserver, and intraobserver reproducibility of these measures in all cardiac CT scans in the Multi-Ethnic Study of Atherosclerosis. We measured extracoronary calcifications in 100 randomly selected participants to assess interobserver, interscan, and intraobserver variability. Two scans were available for analysis in 99 of these participants, and we quantified thoracic aorta and valvular calcifications. Mean interscan variability of AVC was 9.7% +/- 11.4% and 8% +/- 10.3% for Agatston and volume scores, with variability of the median at 6.4% and 5.5%, respectively (P > .05). MAC inter-reader variability was 8.2% and 8.9%, with interscan variability of 28% and 33% and intrareader variability of 4% and 4.1%, respectively. For AWC, inter-reader variability was 3%-7.1%, interscan variability was 17%-18%, and intrareader variability was 0.4%-1.4%. AVC, MAC, and AWC measurements are sufficiently reproducible to allow serial investigations over a time suitable for clinical studies.