Aortic valve calcium independently predicts coronary and cardiovascular events in a primary prevention population.

OBJECTIVES: This study sought to test whether aortic valve calcium (AVC) is independently associated with coronary and cardiovascular events in a primary-prevention population. BACKGROUND: Aortic sclerosis is associated with increased cardiovascular morbidity and mortality among the elderly, but the mechanisms underlying this association remain controversial. Also, it is unknown whether this association extends to younger individuals. METHODS: We performed a prospective analysis of 6,685 participants in MESA (Multi-Ethnic Study of Atherosclerosis). All subjects, ages 45 to 84 years and free of clinical cardiovascular disease at baseline, underwent computed tomography for AVC and coronary artery calcium scoring. The primary, pre-specified combined endpoint of cardiovascular events included myocardial infarctions, fatal and nonfatal strokes, resuscitated cardiac arrest, and cardiovascular death, whereas a secondary combined endpoint of coronary events excluded strokes. The association between AVC and clinical events was assessed using Cox proportional hazards regression with incremental adjustments for demographics, cardiovascular risk factors, inflammatory biomarkers, and subclinical coronary atherosclerosis. RESULTS: Over a median follow-up of 5.8 years (interquartile range: 5.6 to 5.9 years), adjusting for demographics and cardiovascular risk factors, subjects with AVC (n = 894, 13.4%) had higher risks of cardiovascular (hazard ratio [HR]: 1.50; 95% confidence interval [CI]: 1.10 to 2.03) and coronary (HR: 1.72; 95% CI: 1.19 to 2.49) events compared with those without AVC. Adjustments for inflammatory biomarkers did not alter these associations, but adjustment for coronary artery calcium substantially attenuated both cardiovascular (HR: 1.32; 95% CI: 0.98 to 1.78) and coronary (HR: 1.41; 95% CI: 0.98 to 2.02) event risk. AVC remained predictive of cardiovascular mortality even after full adjustment (HR: 2.51; 95% CI: 1.22 to 5.21). CONCLUSIONS: In this MESA cohort, free of clinical cardiovascular disease, AVC predicts cardiovascular and coronary event risk independent of traditional risk factors and inflammatory biomarkers, likely due to the strong correlation between AVC and subclinical atherosclerosis. The association of AVC with excess cardiovascular mortality beyond coronary atherosclerosis risk merits further investigation. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).

Relation of mitral annular calcium and coronary calcium (from the Multi-Ethnic Study of Atherosclerosis [MESA]).

Atherosclerosis is a complex diffuse disorder. The close correlation between coronary artery calcium (CAC) score on computed tomogram and extent and severity of coronary atherosclerosis is well established. It has been suggested that mitral annular calcification (MAC) may be a manifestation of generalized atherosclerosis. The MESA population included a population-based sample of 4 ethnic groups (12% Chinese, 38% white, 22% Hispanic, and 28% black) of 6,814 women and men 45 to 84 years of age. Computed tomographic scans were performed for all participants. The calcium score of each lesion was calculated by multiplying lesion area by a density factor derived from maximal Hounsfield units. A total calcium score was determined by summing individual lesion scores at each anatomic site. Relative risk regression was used to model the probability of MAC as a function of CAC >0 and CAC categories (0, 1 to 99, 100 to 399, and ≥400) with the referent group being CAC 0. The final study population consisted of 6,814 subjects (mean age 62 ± 10 years, 47% men). Overall 9% and 50% had detectable MAC and CAC, respectively. Of those with absent CAC, only 4% had MAC, whereas 9%, 19%, and 15% had MAC scores with increasing CAC scores of 1 to 99, 100 to 399, and ≥400, respectively (p<0.0001 for trend). After taking into account demographics and other risk factors, the prevalence ratio of MAC in those with mild CAC (1 to 99) was 2.13 (95% confidence interval 1.69 to 2.69) and increased to 7.57 (95% confidence interval 5.95 to 9.62) for CAC ≥400. Similar statistically significant increased risk of MAC was found when CAC was assessed as a continuous variable. In conclusion, we observed a strong association between MAC and increasing burden of CAC. This association weakened but persisted after adjustment for age, gender, and other traditional cardiovascular risk factors. These findings suggest that presence of MAC is an indicator of atherosclerotic burden rather than just a degenerative change of the mitral valve.

Thoracic aortic calcification and coronary heart disease events: the multi-ethnic study of atherosclerosis (MESA).

BACKGROUND: The presence and extent of coronary artery calcium (CAC) is an independent predictor of coronary heart disease (CHD) morbidity and mortality. Few studies have evaluated interactions or independent incremental risk for coronary and thoracic aortic calcification (TAC). The independent predictive value of TAC for CHD events is not well-established. METHODS: This study used risk factor and computed tomography scan data from 6807 participants in the multi-ethnic study of atherosclerosis (MESA). Using the same images for each participant, TAC and CAC were each computed using the Agatston method. The study subjects were free of incident CHD at entry into the study. RESULTS: The mean age of the study population (n=6807) was 62±10 years (47% males). At baseline, the prevalence of TAC and CAC was 28% (1904/6809) and 50% (3393/6809), respectively. Over 4.5±0.9 years, a total of 232 participants (3.41%) had CHD events, of which 132 (1.94%) had a hard event (myocardial infarction, resuscitated cardiac arrest, or CHD death). There was a significant interaction between gender and TAC for CHD events (p<0.05). Specifically, in women, the risk of all CHD event was nearly 3-fold greater among those with any TAC (hazard ratio: 3.04, 95% CI: 1.60-5.76). After further adjustment for increasing CAC score, this risk was attenuated but remained robust (HR: 2.15, 95% CI: 1.10-4.17). Conversely, there was no significant association between TAC and incident CHD in men. In women, the likelihood ratio chi square statistics indicate that the addition of TAC contributed significantly to predicting incident CHD event above that provided by traditional risk factors alone (chi square=12.44, p=0.0004) as well as risk factors+CAC scores (chi square=5.33, p=0.02). On the other hand, addition of TAC only contributed in the prediction of hard CHD events to traditional risk factors (chi-square=4.33, p=0.04) in women, without contributing to the model containing both risk factors and CAC scores (chi square=1.55, p=0.21). CONCLUSION: Our study indicates that TAC is a significant predictor of future coronary events only in women, independent of CAC. On studies obtained for either cardiac or lung applications, determination of TAC may provide modest supplementary prognostic information in women with no extra cost or radiation.

Stages of systemic hypertension and blood pressure as correlates of computed tomography-assessed aortic valve calcium (from the Multi-Ethnic Study of Atherosclerosis).

Hypertension has been identified as a risk factor for aortic valve calcium (AVC) but the magnitude of the risk relation with hypertension severity or whether age affects the strength of this risk association has not been studied. The relation of hypertension severity, as defined by Joint National Committee 7 (JNC-7) hypertension stages or blood pressure (BP), to computed tomographically assessed AVC prevalence and severity was examined in 4,274 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) without treated hypertension. Analyses were stratified by age < 65 or ≥ 65 years, were adjusted for common cardiovascular risk factors, and excluded those on antihypertensive medications. In age-stratified adjusted analyses, stage I/II hypertension was associated with prevalent AVC in those <65 but not in those ≥ 65 years of age (odds ratio [OR] 2.31, 95% confidence interval [CI] 1.35 to 3.94, vs 1.33, 0.96 to 1.85, p for interaction = 0.041). Similarly, systolic BP and pulse pressure were more strongly associated with prevalent AVC in those <65 than in those ≥ 65 years of age (OR 1.21, 95% CI 1.08 to 1.35, vs 1.07, 1.01 to 1.14, per 10-mm Hg increase in systolic BP, p for interaction = 0.006; and OR 1.41, 95% CI 1.21 to 1.64, vs 1.14, 1.05 to 1.23, per 10-mm Hg increase in pulse pressure). No associations were found between hypertension stage or BP and AVC severity. In conclusion, stage I/II hypertension and higher systolic BP and pulse pressure were associated with prevalent AVC. These risk associations were strongest in participants < 65 years of age.

Relationships of mitral annular calcification to cardiovascular risk factors: the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Mitral annular calcification (MAC) is a fibrous, degenerative calcification of the mitral valve. The relationship between MAC and cardiovascular disease (CVD) risk factors is not well defined. Thus, we performed a cross-sectional study to determine which CVD risk factors are independently associated with MAC in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: MESA includes 6814 women and men ages 45-84 years old without apparent CVD in 4 ethnic groups (12% Chinese, 38% Caucasian, 22% Hispanic, and 28% African American). MAC was defined by presence of calcium in the mitral annulus by cardiac computed tomography at enrollment. Multivariable logistic regression was used to evaluate relationships between MAC and CVD risk factors. RESULTS: The overall prevalence of MAC was 9%. The prevalence of MAC was highest in Caucasians (12%), followed by Hispanics (10%), African Americans (7%) and was lowest in Chinese (5%). Characteristics associated with MAC included age (p<0.01), female gender (p<0.01), increased body mass index (BMI) (p=0.03), and former smoking status (p<0.008). The MAC group had a higher prevalence of hypertension, diabetes mellitus (DM), and family history of heart attack (all p<0.001). After adjusting for all variables, age, female gender, diabetes mellitus, and increased BMI remained strongly associated with MAC. CONCLUSIONS: Age, female gender, DM, and increased BMI were significantly associated with MAC. Prevalence of MAC was strongly associated with female gender and increasing age in all ethnicities.

Thoracic aortic distensibility and thoracic aortic calcium (from the Multi-Ethnic Study of Atherosclerosis [MESA]).

Decreased arterial distensibility is an early manifestation of adverse structural and functional changes within the vessel wall. Its correlation with thoracic aortic calcium (TAC), a marker of atherosclerosis, has not been well demonstrated. We tested the hypothesis that decreasing aortic compliance and increasing arterial stiffness would be independently associated with increased TAC. We included 3,540 subjects (61 +/- 10 years, 46% men) from the Multi-ethnic Study of Atherosclerosis who had undergone an aortic distensibility (AD) assessment using magnetic resonance imaging. TAC was calculated using a modified Agatston algorithm on noncontrast cardiac computed tomographic scans. Multivariate regression models were calculated for the presence of TAC. Overall, 861 subjects (24%) had detectable TAC. Lower AD was observed among those with versus without TAC (2.02 +/- 1.34 vs 1.28 +/- 0.74, p <0.0001). The prevalence of TAC increased significantly across decreasing quartiles of AD (7%, 17%, 31%, and 42%, p <0.0001). Using multivariate analysis, TAC was independently associated with AD after adjusting for age, gender, ethnicity, and other covariates. In conclusion, our analysis has demonstrated that increased arterial stiffness is associated with increased TAC, independent of ethnicity and other atherosclerotic risk factors.

Prevalence and prognostic significance of renal artery calcification in patients with diabetes and proteinuria.

BACKGROUND AND OBJECTIVES: Vascular calcification is common and severe in chronic kidney disease. Because the consequences of calcification may differ by vascular beds, we sought to test the hypothesis that patients who have diabetes with proteinuria and have significant renal artery calcification (RAC) have a higher risk for progression to ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using electron-beam computed tomography, RAC was computed as the sum of Agatston scores at each of the two renal ostia and renal arteries. Time-to-event analysis was conducted to compare the risk in individuals with or without significant RAC (total score >10). RESULTS: Of 172 patients with type 2 diabetes and overt proteinuria studied (estimated GFR 56 ± 25 ml/min per 1.73 m(2)), significant RAC was present in 31%. In 33 ± 21 months, 41 progressed to ESRD and 65 reached a composite outcome (ESRD or death). Serum phosphorus was a significant predictor of progression to ESRD but was replaced by the significant RAC in multivariate models that included the latter. Individuals with significant RAC had a higher risk for reaching the composite outcome. In contrast, there was no association between coronary artery calcification scores and progression to ESRD. CONCLUSIONS: Significant RAC was an independent predictor of progression to ESRD as well as reaching the composite outcome. Understanding the pathogenesis of RAC would allow determination of whether this risk is potentially modifiable.

Coronary artery calcification and mortality in diabetic patients with proteinuria.

Vascular calcification is one of the mechanisms mediating the higher mortality risk associated with the hyperphosphatemia of chronic kidney disease. Though common, and often severe in non-dialyzed proteinuric diabetics, there are no studies on the prognostic significance of coronary artery calcification in early stage type 2 diabetic nephropathy. Here we determine this significance in 225 proteinuric diabetic patients (mean age 57 years, mean estimated glomerular filtration rate (eGFR) 52 ml/min per 1.73 m(2) and a median urine protein-creatinine ratio of 2.7). Coronary artery calcification, measured by electron beam computed tomography, was diagnosed in 86% of the patients, the severity of which correlated with older age, male gender, and white ethnicity. However, no association was found between eGFR, serum calcium, phosphorus, parathyroid hormone, or 25-hydroxy vitamin D. Over an average follow-up of 39 months, 54 patients died. A graded relationship between the severity of calcification and all-cause mortality was consistently demonstrated on both univariate and multivariate analyses. Patients in the highest quartile of calcification score had a 2.5-fold higher risk for death. Our results show the severity of coronary artery calcification early in the course of chronic kidney disease is an independent predictor of all-cause mortality. Additional studies need to determine whether altering the natural history of coronary artery calcification in early chronic kidney disease prolongs survival.

Incidence and progression of aortic valve calcium in the Multi-ethnic Study of Atherosclerosis (MESA).

Aortic valve calcium (AVC) is common among older adults and shares epidemiologic and histopathologic similarities to atherosclerosis. However, prospective studies have failed to identify meaningful risk associations with incident ("new") AVC or its progression. In the present study, AVC was quantified from serial computed tomographic images from 5,880 participants (aged 45 to 84 years) in the Multi-Ethnic Study of Atherosclerosis, using the Agatston method. Multivariate backward selection modeling was used to identify the risk factors for incident AVC and AVC progression. During a mean follow-up of 2.4 +/- 0.9 years, 210 subjects (4.1%) developed incident AVC. The incidence rate (mean 1.7%/year) increased significantly with age (p <0.001). The risk factors for incident AVC included age, male gender, body mass index, current smoking, and the use of lipid-lowering and antihypertensive medications. Among those with AVC at baseline, the median rate of AVC progression was 2 Agatston units/year (interquartile range -21 to 37). The baseline Agatston score was a strong, independent predictor of progression, especially among those with high calcium scores at baseline. In conclusion, in this ethnically diverse, preclinical cohort, the rate of incident AVC increased significantly with age. The incident AVC risk was associated with several traditional cardiovascular risk factors, specifically age, male gender, body mass index, current smoking, and the use of both antihypertensive and lipid-lowering medications. AVC progression risk was associated with male gender and the baseline Agatston score. Additional research is needed to determine whether age- and stage-specific mechanisms underlie the risk of AVC progression.

Relationship of aortic valve calcification with coronary artery calcium severity: the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Aortic valve calcification (AVC) and atherosclerosis share causative and pathologic features. OBJECTIVE: We evaluated the relationship between AVC and coronary artery calcium (CAC) severity in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: Men and women aged 45-84 years (n=6809; mean age, 62 years) were studied. The presence and burden of AVC and CAC were determined by noncontrast cardiac computed tomography. Relative risk regression was used to model the probability of AVC as a function of CAC > 0 as well as CAC categories (0, 1-99, 100-399, and > or = 400) with the reference group being CAC=0. RESULTS: The prevalence of AVC and CAC was 13% and 50%, respectively. Among those without CAC, the prevalence of AVC was 5% and increased across levels of CAC severity such that 14%, 25%, and 38% had AVC with increasing CAC scores of 1-99, 100-399, and > or = 400, respectively (P for trend<0.0001). After controlling for patient demographic factors and cardiovascular risk factors, the prevalence ratio of AVC among those with mild CAC (1-99) was 1.83 (95% CI, 1.45-2.31) and increased to 3.36 (95% CI, 2.56-4.42) for CAC > or = 400. Similar statistically significant increased risk of AVC was found when CAC was assessed as a continuous variable. CONCLUSION: Our study shows that AVC is independently associated with increasing severity of CAC.

Relationship between common carotid intima-media thickness and thoracic aortic calcification: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Mean maximum carotid intima-media thickness (CIMT) is associated with both coronary artery disease and cerebral thromboembolism. Thoracic aortic calcification (TAC) detected by computed tomography (CT) is also highly associated with vascular disease and cardiovascular risk. No previous study has examined the relationship between CIMT and TAC in a large patient cohort. We performed a cross-sectional study to determine whether, at baseline, there is a relationship between CIMT and CT-determined TAC score. METHODS: In the Multi-Ethnic Study of Atherosclerosis, the study cohort included a population based sample of four ethnic groups (Chinese, White, Hispanic and African-American) of 6814 women and men ages 45-84 years. After exclusion of 198 persons due to incomplete information, we compared results of 6616 participants with both CIMT and TAC. TAC was measured from the lower edge of the pulmonary artery bifurcation to the cardiac apex. CIMT at the common carotid artery site was represented as the mean maximal CIMT of the right and left near and far walls, respectively. Multivariable relative risk regression analysis was used to evaluate relationships between TAC and CIMT. RESULTS: The prevalence of TAC was 28% (n=1846) and the mean maximum (+SD) CIMT was 0.87+/-0.19mm. A higher prevalence of TAC was noted across increasing CIMT quartiles (1st: 12%, 2nd: 21%, 3rd: 30%, 4th: 49%, p<0.0001). One standard deviation increase in CIMT was associated with a 16% higher likelihood for presence of TAC after adjusting for demographics and cardiovascular disease (CVD) risk factors (95% CI: 1.12-1.26). In addition, individuals with CIMT in the highest quartile, as compared to those with CIMT in the first quartile, had a 76% higher likelihood for presence of TAC (prevalence ratio [PR]: 1.76, 95% CI: 1.37-2.26). In race-ethnic stratified analyses, similar associations were seen in all groups. Among those with TAC>0, a higher CIMT was significantly associated with continuous TAC scores (log transformed) in the overall population as well as among all ethnic-racial groups. CONCLUSIONS: Our study demonstrates that TAC is associated with increasing severity of carotid atherosclerotic burden as measured by CIMT. The combined utility of these two noninvasive measures of subclinical atherosclerosis for CVD risk assessment needs to be determined in future studies.

Relationship of carotid distensibility and thoracic aorta calcification: multi-ethnic study of atherosclerosis.

Stiffening of the central elastic arteries is one of the earliest detectable manifestations of adverse change within the vessel wall. Although an association between carotid artery stiffness and adverse events has been demonstrated, little is known about the relationship between stiffness and atherosclerosis. Even less is known about the impact of age, sex, and race on this association. To elucidate this question, we used baseline data from the Multi-Ethnic Study of Atherosclerosis (2000-2002). Carotid artery distensibility coefficient was calculated after visualization of the instantaneous waveform of the common carotid diameter using a high-resolution B-mode ultrasound. Thoracic aorta calcification was identified using noncontrast cardiac computed tomography. We found a strong association between decreasing distensibility coefficient (increasing carotid stiffness) and increasing thoracic aorta calcification, as well as a graded increase in the thoracic aorta calcification score (P<0.001). After controlling for age, sex, race, and traditional and emerging cardiovascular risk factors, individuals in the stiffest quartile had a prevalence ratio of 1.52 (95% CI: 1.15 to 2.00) for thoracic aorta calcification compared with the least stiff quartile. In exploratory analysis, carotid stiffness was more highly correlated with calcification of the aorta than calcification of the coronary arteries (rho=0.32 versus 0.22; P<0.001 for comparison). In conclusion, there is a strong independent association between carotid stiffness and thoracic aorta calcification. Carotid stiffness is more highly correlated with calcification of the aorta, a central elastic artery, than calcification of the coronary arteries. The prognostic significance of these findings requires longitudinal follow-up of the Multi-Ethnic Study of Atherosclerosis cohort.

Ethnic-specific risks for atherosclerotic calcification of the thoracic and abdominal aorta (from the Multi-Ethnic Study of Atherosclerosis).

The aims of this study were to (1) determine the association between ethnicity and thoracic aortic calcium (TAC) and abdominal aortic calcium (AAC) and (2) investigate associations between cardiovascular disease (CVD) risk factors and TAC and AAC. Participants were 1,957 men and women enrolled in the Multi-Ethnic Study of Atherosclerosis who had computed tomographic scans of the chest and abdomen. These scans were obtained at the same clinic visit and calcium scores were computed using the Agatston method. Regression analyses were conducted using relative risk regression. Mean age was 65 years and 50% were women. Forty percent were white, 26% Hispanic, 21% African-American, and 13% Chinese. Whites had the highest prevalence of AAC (80%), which was significantly higher than Hispanics (68%, p <0.001), African-Americans (63%, p <0.001), and Chinese (74%, p = 0.029). Similarly, whites had the highest prevalence of TAC (42%), which was significantly higher than in Hispanics (30%, p <0.01) and African-Americans (27%, p <0.001) but was not significantly different from that in Chinese (38%). Compared to whites and after adjustment for age, gender, body mass index, hypertension, diabetes, dyslipidemia, smoking, and family history of CVD, Hispanics and African-Americans, but not Chinese-Americans, had a significantly lower risk for the presence of any AAC or any TAC. In these models, diabetes, smoking, and dyslipidemia had stronger associations with AAC, whereas hypertension was stronger for TAC. In conclusion, compared to whites, African-Americans and Hispanics, but not Chinese, have evidence of less atherosclerosis in the thoracic and abdominal aortas, which does not appear to be accounted for by traditional CVD risk factors.

Aged garlic extract supplemented with B vitamins, folic acid and L-arginine retards the progression of subclinical atherosclerosis: a randomized clinical trial.

OBJECTIVES: Previous studies demonstrated that aged garlic extract reduces multiple cardiovascular risk factors. This study was designed to assess whether aged garlic extract therapy with supplements (AGE+S) favorably affects inflammatory and oxidation biomarkers, vascular function and progression of atherosclerosis as compared to placebo. METHODS: In this placebo-controlled, double-blind, randomized trial (conducted 2005-2007), 65 intermediate risk patients (age 60+/-9 years, 79% male) were treated with a placebo capsule or a capsule containing aged garlic extract (250 mg) plus Vitamin B12 (100 microg), folic acid (300 microg), Vitamin B6 (12.5 mg) and l-arginine (100 mg) given daily for a 1 year. All patients underwent coronary artery calcium scanning (CAC), temperature rebound (TR) as an index of vascular reactivity using Digital Thermal Monitoring (DTM), and measurement of lipid profile, autoantibodies to malondialdehyde (MDA)-LDL, apoB-immune complexes, oxidized phospholipids (OxPL) on apolipoprotein B-100 (OxPL/apoB), lipoprotein (a) [Lp (a)], C-reactive protein (CRP), homocysteine were measured at baseline and 12 months. CAC progression was defined as an increase in CAC>15% per year and an increase in TR above baseline was considered a favorable response. RESULTS: At 1 year, CAC progression was significantly lower and TR significantly higher in the AGE+S compared to the placebo group after adjustment of cardiovascular risk factors (p<0.05). Total cholesterol, LDL-C, homocysteine, IgG and IgM autoantibodies to MDA-LDL and apoB-immune complexes were decreased, whereas HDL, OxPL/apoB, and Lp (a) were significantly increased in AGE+S to placebo. CONCLUSION: AGE+S is associated with a favorable improvement in oxidative biomarkers, vascular function, and reduced progression of atherosclerosis.

Relationship of thoracic aortic calcium to coronary calcium and its progression (from the Multi-Ethnic Study of Atherosclerosis [MESA]).

Thoracic aortic calcium (TAC) has been associated with a higher prevalence of coronary arterial calcium (CAC). The purpose of this study was to assess the relations between TAC and incident CAC and CAC progression in a cohort from the Multi-Ethnic Study of Atherosclerosis (MESA). MESA is a prospective cohort study of 6,814 participants free of clinical cardiovascular disease at entry who underwent noncontrast cardiac computed tomographic scanning at baseline examination and at a 2-year follow-up assessment. The independent associations between TAC and incident CAC in those without CAC at baseline and between TAC and CAC progression in those with CAC at baseline were investigated. The final study population consisted of 5,755 subjects (84%; mean age 62 +/- 10 years, 48% men) who had follow-up CAC scores an average of 2.4 years later. Incident CAC was significantly higher in those with TAC compared with those without TAC at baseline (11 per 100 patient-years vs 6 per 100 patient-years). Similarly, TAC was associated with a higher CAC change (p <0.0001) in those with some CAC at baseline. In analysis adjusted for demographics and follow-up duration, TAC was associated with incident CAC (relative risk 1.72, p <0.0001) as well as with a greater CAC change (first quartile: relative risk 2.89, 95% confidence interval -3.16 to 8.95; fourth quartile: relative risk 24.21, 95% confidence interval 18.25 to 30.18). In conclusion, TAC is associated with the incidence and progression of CAC. The detection of TAC may improve risk stratification efforts. Future clinical outcomes studies are needed to support such an approach.

Comparison of coronary artery calcium scores between electron beam computed tomography and 64-multidetector computed tomographic scanner.

OBJECTIVE: Because almost all data currently available with coronary calcium scanning are from electron beam tomography (EBT), we assessed whether scores obtained with 64-multidetector computed tomography (CT; MDCT) are similar. We evaluated the interscan variation in coronary artery calcium (CAC), Agatston score (AS), and volume score (VS) between EBT and 64-MDCT (VCT; GE, Milwaukee, Wis). MATERIALS AND METHODS: One hundred two patients (mean age, 61.1 years; 27 women) underwent dual CAC scanning with both EBT and 64-MDCT. The AS and VS were measured with the Aquarius workstation (TeraRecon, Inc, San Mateo, Calif). The correlation coefficient, Bland-Altman analysis, interscanner variation, and agreement in AS and VS scores between EBT and 64-MDCT were computed. RESULTS: Interscan agreement for presence of CAC was 99%. Median values were 286 and 268 mm for AS and 243 and 213 mm for VS with EBT and 64-MDCT, respectively (P > 0.05). There was significant linear relationship between scores from the 2 scanners (R = 0.98 in AS and R = 0.99 in VS; P < 0.001). The interscanner variability between EBT and 64-MDCT was 20.9% and 17.6% in AS and VS, respectively (P = NS). Bland-Altman analysis demonstrated a mean difference in scores of 8.3% for AS and 7.8% by VS. When compared with EBT, there were larger and more prevalent motion artifacts (P < 0.001) and larger mean Hounsfield units using 64-MDCT (P < 0.001). CONCLUSIONS: At CAC scanning, 64-MDCT and EBT were comparable in AS and VS. The interscan variability between scanners is similar to interscan variability of 2 calcium scores done on the same equipment. However, heart rate control was achieved for this study for calcium scores. Whether these results are repeatable without heart rate control needs to be further assessed.

Relationship of metabolic syndrome with incident aortic valve calcium and aortic valve calcium progression: the Multi-Ethnic Study of Atherosclerosis (MESA).

OBJECTIVE: Metabolic syndrome (MetS) has been associated with increased prevalence of aortic valve calcium (AVC) and with increased progression of aortic stenosis. The purpose of this study was to determine whether MetS is associated with increased risks for the development of new ("incident") AVC or for progression of established AVC as assessed by CT. RESEARCH DESIGN AND METHODS: The relationships of MetS or its components as well as of diabetes to risks for incident AVC or AVC progression were studied among participants with CT scans performed at baseline and at either year 2 or year 3 examinations in the Multi-Ethnic Study of Atherosclerosis (MESA). RESULTS: Of 5,723 MESA participants meeting criteria for inclusion, 1,674 had MetS by Adult Treatment Panel III criteria, whereas 761 had diabetes. Among the 5,123 participants without baseline AVC, risks for incident AVC, adjusted for time between scans, age, sex, race/ethnicity, LDL cholesterol, lipid-lowering medications, and smoking, were increased significantly for MetS (odds ratio [OR] 1.67 [95% CI 1.21-2.31]) or diabetes (2.06 [1.39-3.06]). In addition, there was an increase in incident AVC risk with increasing number of MetS components. Similar results were found using the International Diabetes Federation MetS criteria. Among the 600 participants (10.5%) with baseline AVC, neither MetS nor diabetes was associated with AVC progression. CONCLUSIONS: In the MESA cohort, MetS was associated with a significant increase in incident ("new") AVC, raising the possibility that MetS may be a potential therapeutic target to prevent AVC development.

Relationship between coronary artery and descending thoracic aortic calcification as detected by computed tomography: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Cardiac computed tomography (CT) is a well-established tool for the detection of cardiovascular calcium. Coronary artery calcification (CAC) is highly sensitive for the detection of coronary artery disease (CAD) as well as predictive of future cardiovascular (CV) events. Descending thoracic aortic calcification (DTAC) is common in the elderly and its presence is also associated with increased risk of CV events. Previous studies demonstrate that DTAC is associated with obstructive CAD and coronary risk factors. However, no prior studies have examined the association of CAC and DTAC as detected by cardiac CT in a large population-based cohort. METHODS: In the Multi-Ethnic Study of Atherosclerosis, the study population included a population-based sample of four ethnic groups (Chinese, White, Hispanic and African-American) of 6814 women and men ages 45-84 years old. Participants underwent non-enhanced cardiac CT and both CAC and DTAC were quantified. DTAC was measured from the lower edge of the pulmonary artery bifurcation to the cardiac apex. Multivariable relative risk regression was used to evaluate relationships between CAC, DTAC and measured cardiovascular risk factors. RESULTS: Overall 3030 (44%) did not demonstrate any detectable CAC or DTAC. A total of 1930 (28%) had only CAC, 386 (6%) had isolated DTAC, and 1464 (22%) participants were found to have both CAC and DTAC. CAC had a higher prevalence than DTAC in men (58% vs. 45%). Participants with DTAC were older than those with CAC (mean age was 71 and 66 years old, respectively). Participants with DTAC had increased risk for the presence of CAC independent of cardiovascular risk factors (prevalence ratio [PR]: 1.17, 95% CI: 1.07-1.28). Severity of DTAC was a stronger predictor of the presence of CAC in women as compared to men (PR: 1.04, 95% CI: 1.02-1.06, and PR: 0.99, 95% CI: 0.98-1.01, respectively). CONCLUSIONS: DTAC was found to be a strong predictor of CAC independent of CV risk factors. Ongoing follow-up of this cohort will evaluate whether DTAC is an independent marker of risk for CV events.

Comparison of left ventricular size by computed tomography with magnetic resonance imaging measures of left ventricle mass and volumes: the multi-ethnic study of atherosclerosis.

BACKGROUND: A non-contrast-enhanced cardiac computed tomography (NCE-CCT) scan for assessing coronary artery calcification (CAC) is being increasingly used for assessing underlying burden of atherosclerosis. Although many studies document the potential value of measuring CAC, little is known about the other measures such as left ventricular (LV) geometry that can be obtained from the same scan data. OBJECTIVES: We sought to evaluate the accuracy of noncontrast CT-derived LV size (LVS; sum of LV volume and mass) compared with magnetic resonance imaging (MRI)-derived measures as the clinical reference standard. METHODS: Participants (n = 5004) in the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent cardiac MRI studies from August 2000 to September 2002 were included. CT-derived LVS was defined as the sum of LV mass and LV intracavitary volume. The calculated LVS was taken from a measurement of a single slice from noncontrast images. Multivariate analysis adjusting for demographics was used to identify predictors of the relation between CT LVS and MRI LVS, and Bland-Altman analysis was performed comparing MRI-derived measures with CT-derived measure of LVS. RESULTS: The mean CT LVS was 187.8 +/- 56.8 mL (range, 33.6-486.4 mL). The correlation was 0.73 (P = 0.01) for MRI-derived LV volume and 0.74 (P = 0.01) for MRI-derived LV mass. The correlation between CT LVS and MRI-derived LV end-diastolic total volume (mass + volume) was 0.79. CONCLUSION: A single NCE-CT scan used to detect and quantify coronary calcification can also estimate LVS with reasonable accuracy compared with MRI. This provides a new method to study ventricular size in epidemiologic studies and potentially provide additional information for clinical screening of cardiac risk.

Soluble intercellular adhesion molecule-1 (sICAM-1) and aortic valve calcification in the multi-ethnic study of atherosclerosis (MESA).

BACKGROUND AND AIM OF THE STUDY: Previous studies have reported associations between individual inflammatory biomarkers and aortic valve disease, but none has examined associations with, baseline prevalence or severity of aortic valve calcium (AVC), as measured with cardiac computed tomography (CT). The study aim was to determine whether specific inflammatory markers were associated with AVC in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. METHODS: The associations of inflammatory biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, D-dimer, soluble intercellular adhesion molecule-1 (sICAM-1), heat shock protein 60 (Hsp60), soluble tumor necrosis factor receptor-1 (sTNF-R1), soluble tissue factor (sTF), soluble E-selectin and matrix metalloproteinases-3 and -9 (MMP-3 and -9) with baseline AVC prevalence and severity were examined. RESULTS: After adjusting for age, gender, race and cardiovascular risk factors (smoking, hypertension, diabetes, total cholesterol, HDL, serum creatinine, body mass index and lipid-lowering therapy), the point prevalence ratios (95% confidence interval) for prevalent AVC were 1.20 (1.04,1.39) for sICAM-1,1.13 (1.03, 1.24) for IL-6, and 1.11 (1.02, 1.21) for D-dimer. No other associations were statistically significant. When CRP, sICAM-1, IL-6 and D-dimer were modeled together, only sICAM-1 remained associated with increased AVC prevalence (1.18 (1.02, 1.38)). Only sICAM-1 was associated with increased AVC severity (relative difference (95% CI): 1.18 (1.00, 1.39)). CONCLUSION: In this large, multi-ethnic, asymptomatic cohort, sICAM-1- a marker of endothelial perturbation - was the only biomarker associated with both an increased prevalence and severity of AVC.