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Background and Aims: Calcific aortic valve disease is associated with increased thrombin formation, platelet activation, decreased fibrinolysis, and subclinical brain infarcts. We examined the long-term association of aortic valve calcification (AVC) with newly diagnosed dementia and incident stroke in the Multi-Ethnic Study of Atherosclerosis (MESA)., Methods: AVC was measured using non-contrast cardiac CT at Visit 1. We examined AVC as a continuous (log-transformed) and categorical variable (0, 1-99, 100-299, ≥300). Newly diagnosed dementia was adjudicated using International Classification of Disease codes. Stroke was adjudicated from medical records. We calculated absolute event rates (per 1000 person-years) and multivariable adjusted Cox proportional hazards ratios (HR)., Results: Overall, 6812 participants had AVC quantified with a mean age of 62.1 years old, 52.9 % were women, and the median 10-year estimated atherosclerotic cardiovascular disease (ASCVD) risk was 13.5 %. Participants with AVC >0 were older and less likely to be women compared to those with AVC=0. Over a median 16-year follow-up, there were 535 cases of dementia and 376 cases of stroke. The absolute risk of newly diagnosed dementia increased in a stepwise pattern with higher AVC scores, and stroke increased in a logarithmic pattern. In multivariable analyses, AVC was significantly associated with newly diagnosed dementia as a log-transformed continuous variable (HR 1.09; 95 % CI 1.04-1.14) and persons with AVC ≥300 had nearly a two-fold higher risk (HR 1.77; 95 % CI 1.14-2.76) compared to those with AVC=0. AVC was associated with an increased risk of stroke after adjustment for age, sex, and race/ethnicity, but not after adjustment for ASCVD risk factors., Conclusions: After multivariable adjustment, AVC >0 was significantly associated with an increased risk of newly diagnosed dementia, but not incident stroke. This suggests that AVC may be an important risk factor for the long-term risk of dementia beyond traditional ASCVD risk factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mitral annular calcification (MAC) may be a potential marker of biologic aging. However, the association of MAC with noncardiovascular measures, including bone mineral density (BMD), incident renal failure, dementia, and noncardiovascular mortality, is not well-studied in a multiracial cohort. We used data from 6,814 participants (mean age: 62.2 ± 10.2 years, 52.9% women) without cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis. MAC was assessed with noncontrast cardiac computed tomography at study baseline. Using multivariable-adjusted linear and logistic regression, we assessed the cross-sectional association of MAC with BMD and walking pace. Furthermore, using Cox proportional hazards, we evaluated the association of MAC with incident renal failure, dementia, and all-cause mortality. In addition, we assessed the association of MAC with cardiovascular and noncardiovascular mortality using competing risks regression. The prevalence of MAC was 9.5% and was higher in women (10.7%) than in men (8.0%). MAC was associated with low BMD (coefficient -0.04, 95% confidence interval [CI] -0.06 to -0.02), with significant interaction by gender (p-interaction = 0.035). MAC was, however, not associated with impaired walking pace (odds ratio 1.09, 95% CI 0.89 to 1.33). Compared with participants without MAC, those with MAC had an increased risk of incident renal failure, albeit nonsignificant (hazard ratio [HR] 1.18, 95% CI 0.95 to 1.45), and a significantly higher hazards of dementia (HR 1.36, 95% CI 1.10 to 1.70). In addition, participants with MAC had a substantially higher risk of all-cause (HR 1.47, 95% CI 1.29 to 1.69), cardiovascular (subdistribution HR 1.39, 95% CI 1.04 to 1.87), and noncardiovascular mortality (subdistribution HR 1.35, 95% CI 1.14 to 1.60) than those without MAC. MAC ≥100 versus <100 was significantly associated with reduced BMD, incident renal failure, dementia, all-cause, cardiovascular, and noncardiovascular mortality. In conclusion, MAC was associated with reduced BMD and dementia and all-cause, cardiovascular, and noncardiovascular mortality in this multiracial cohort. Thus, MAC may be a marker not only for atherosclerotic burden but also for other metabolic and inflammatory factors that increase the risk of noncardiovascular outcomes and death from other causes., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Aortic valve calcification (AVC), Lp(a) [lipoprotein(a)], and low-density lipoprotein cholesterol (LDL-C) are associated with severe aortic stenosis (AS). We aimed to determine which of these risk factors were most strongly associated with the risk of incident severe AS., Methods: A total of 6792 participants from the MESA study (Multi-Ethnic Study of Atherosclerosis) had computed tomography-quantified AVC, Lp(a), and LDL-C values at MESA visit 1 (2000-2002). We calculated the absolute event rate of incident adjudicated severe AS per 1000 person-years and performed multivariable adjusted Cox proportional hazards regression., Results: The mean age was 62 years old, and 47% were women. Over a median 16.7-year follow-up, the rate of incident severe AS increased exponentially with higher AVC, regardless of Lp(a) or LDL-C values. Participants with AVC=0 had a very low rate of severe AS even with elevated Lp(a) ≥50 mg/dL (<0.1/1000 person-years) or LDL-C ≥130 mg/dL (0.1/1000 person-years). AVC >0 was strongly associated with severe AS when Lp(a) <50 mg/dL hazard ratio (HR) of 33.8 (95% CI, 16.4-70.0) or ≥50 mg/dL HR of 61.5 (95% CI, 7.7-494.2) and when LDL-C <130 mg/dL HR of 31.1 (95% CI, 14.4-67.1) or ≥130 mg/dL HR of 50.2 (95% CI, 13.2-191.9)., Conclusions: AVC better identifies people at high risk for severe AS compared with Lp(a) or LDL-C, and people with AVC=0 have a very low long-term rate of severe AS regardless of Lp(a) or LDL-C level. These results suggest AVC should be the preferred prognostic risk marker to identify patients at high risk for severe AS, which may help inform participant selection for future trials testing novel strategies to prevent severe AS., Competing Interests: Disclosures None.

The association of self-reported BMI at age 20, at age 40, the highest BMI within the past 3 years, and current BMI with current mid-life cardiovascular risk factors and coronary artery calcium (CAC) was evaluated among 1148 South Asian American participants (mean age 57 years) in the MASALA study. A 1 kg/m 2 higher BMI at age 20 was associated with higher odds of hypertension (aOR 1.07, 95% CI 1.03-1.12), pre-diabetes/diabetes (aOR 1.05 [1.01-1.09]), and prevalent CAC (aOR 1.06 [1.02-1.11]) in mid-life. Associations were similar for all BMI measures. Weight across young adulthood is associated with mid-life cardiovascular health in South Asian American adults., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nilay Shah reports financial support was provided by National Heart Lung and Blood Institute. Alka Kanaya reports financial support was provided by National Heart Lung and Blood Institute. Alka Kanaya reports financial support was provided by National Center for Advancing Translational Sciences., (Copyright © 2023 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Aims: Anecdotal reports have suggested increased soft tissue calcification in individuals with long-term exposures to high blood glucose. The association of costal cartilage calcification (CCC), a reliably quantifiable marker obtainable from non-contrast cardiac computed tomography (CT) with cumulative fasting blood glucose (FBG) exposure, is unknown. In this study, we aimed to determine the association between quantified CCC and cumulative glucose exposure using non-contrast coronary artery calcium (CAC) scoring computed tomography (CT) images in the Multi-Ethnic Study of Atherosclerosis (MESA)., Methods: The volume of bilateral CCC was quantified in high-density pixels (threshold of Hounsfield Unit>180) using the CAC scoring CT images acquired in the 5 th MESA exam. Prior long-term cumulative exposure to FBG was calculated by area under the FBG-time curve over ten years before the time of the CT exam., Results: A total of 2,305 participants (mean age: 69, female/male: 1.3) were included in this study. The median CCC volume was lower in females than males (1158 mm 3 [IQR: 1751] vs. 3054 mm 3 [3851], p<0.001). In cross-sectional analysis, quantified CCC was associated with FBG (9% increase per SD) and HbA1c (7% increase per SD) at the CT exam only in female participants after adjustment for age, race, BMI, and glomerular filtration rate. Only in female participants, quantified CCC was also associated with prior cumulative FBG (3% increase per decile change). In the subgroup of females with zero CAC scores, the adjusted CCC was still associated with FBG (13% increase per SD) at the time of CT exam and with prior cumulative FBG exposure (4% increase per decile change) before the CT exam., Conclusions: The CCC, a reliably quantified marker in non-contrast cardiac CT, is associated with 10-year cumulative FBG exposure only in female participants, even those with zero CAC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AS declared a shared affiliation with one of the authors, CW, to the handling editor at time of review., (Copyright © 2021 Shabani, Pishgar, Akhtarkhavari, Quinaglia, Budoff, Bluemke, Barr, Post, Wu, Arbab-Zadeh, Sidhaye, Lima and Demehri.)

The early stages of aortic valve calcification (AVC) and coronary artery calcification (CAC) include shared ASCVD risk factors, yet there is considerable heterogeneity between the burden of AVC, and CAC. We sought to identify the markers associated with limited CAC among persons with significant AVC. There were 325 participants from the Multi-Ethnic Study of Atherosclerosis without clinical ASCVD and with AVC ≥100 Agatston units (AU) at Visit 1. Multivariable-adjusted prevalence ratios for limited CAC (0 to 99 AU) were calculated using modified Poisson regression. Participants had a mean age of 72.1 years, median AVC score of 209, and 34% were women. A total of 133 (41%) participants had CAC <100, of whom 46/133 had CAC = 0. Younger age (PR = 1.40, 95% CI: 1.22 to 1.62, per 10-years), female gender (PR = 1.68, 95% CI: 1.28 to 2.20), and low 10-year ASCVD risk (PR = 2.30, 95% CI: 1.85 to 2.85) were most strongly associated with limited CAC. Neither a normal lipoprotein(a) nor normal measures of inflammation were significantly associated with limited CAC. Lower serum phosphate (PR = 1.15, 95% CI: 1.01 to 1.31; per 0.5 mg/dl lower) and calcium-phosphate product (PR = 1.16, 95% CI: 1.02 to 1.34; per SD lower) were associated with an approximately 15% higher prevalence of limited CAC. In conclusion, more than 40% of persons with significant AVC had CAC. Beyond traditional risk factors, lower serum phosphate, and lower calcium-phosphate product were associated with a higher prevalence of limited CAC., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Lipoprotein (a) [Lp(a)] is a risk factor for coronary heart disease and calcific aortic valve disease. We determined the relationships of Lp(a) with prevalence and progression of coronary artery calcification (CAC), mitral annular calcification (MAC), and thoracic aortic calcification (TAC) in a multi-ethnic cohort of middle to older-aged adults., Methods: This analysis included 6705 Multi-Ethnic Study of Atherosclerosis participants. Lp(a) was measured with a turbidimetric immunoassay. CAC, MAC, and TAC were assessed by cardiac computed tomography both at baseline and once during follow-up., Results: In adjusted relative risk regression cross-sectional analysis, a Lp(a) level ≥50 ​mg/dL was associated with a 22% higher prevalence of MAC (relative risk (RR) ​= ​1.22, 95% confidence interval (CI) 1.00, 1.49). No significant associations were observed for prevalent CAC or TAC. In adjusted prospective analyses, participants with Lp(a) ≥50 ​mg/dL were at significantly higher risk for rapid CAC progression (median follow-up ​= ​8.9 years), defined as ≥100 units/year, compared to those with lower Lp(a) levels (RR ​= ​1.67, 95% CI ​= ​1.23, 2.27). The association between higher Lp(a) levels and incident CHD was no longer significant after adjusting for CAC progression. No significant associations were observed for MAC or TAC progression (median follow-up ​= ​2.6 years)., Conclusions: Higher Lp(a) levels are associated with more rapid CAC progression. Additional study is needed to better understand how this relationship can further improve the ability of Lp(a) to enhance cardiovascular disease risk prediction., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Aortic stenosis (AS) is common and increasing in prevalence as the population ages. Using computed tomography (CT) to quantify aortic valve calcification (AVC) it has been reported that men have greater degrees of calcification than women among subjects with severe AS. These data, however, were derived in largely Caucasian populations and have not been verified in non-Caucasian subjects. This retrospective study identified 137 patients with severe AS who underwent valve replacement and had CT scans within 6 months prior to surgery. AVC scores were compared between men and women, both in the entire sample and in racial subgroups. 52% of subjects were male and 62.8% were non-Caucasian. Mean AVC score for the entire cohort was 3062.08±2097.87 with a range of 428-13,089. Gender differences in aortic valve calcification were found to be statistically significant with an average AVC score of 3646±2422 in men and 2433±1453 in women (p=0.001). On multivariate analysis, gender remained significantly associated with AVC score both in the entire sample (p=0.014) and in the non-Caucasian subgroup (p=0.008). Mean AVA was significantly greater in males than females but this difference disappeared when AVA was indexed to BSA (p=0.719). AVA was not different between racial groups (p=0.369). In this research we observed that among subjects with severe AS men have higher AVC scores than women regardless of racial background. This is consistent with previous studies in predominantly Caucasian populations.

Aldosterone is a steroid hormone regulating fluid and electrolyte homeostasis and is known to increase the risk of atherosclerosis. In this study, we examined the associations of serum aldosterone concentrations with subclinical atherosclerosis and all-cause mortality. This study included 948 adults aged 46 to 88 years from the MESA (Multi-Ethnic Study of Atherosclerosis) with measurements of serum aldosterone and plasma renin activity and not taking antihypertensive medications. Coronary calcification was longitudinally assessed using Agatston coronary artery calcium score from computed tomography scans. All-cause mortality was ascertained from the medical record. The average age (SD) was 62.3 (9.4) years and 53% were male. Among 700 subjects who had follow-up coronary artery calcium score (median follow-up of 6.4 years), higher aldosterone levels (per 100 pg/mL) were associated with higher coronary artery calcium (relative ratio, 1.17 [95% CI, 1.04-1.32]), with the association being stronger in individuals with suppressed plasma renin activity (≤0.5 μg/L/hr). Systolic or diastolic blood pressure mediated around 45% of the total effect of aldosterone on coronary artery calcium. Over a median follow-up of 12.5 years (120 deaths identified among 948 subjects), aldosterone was associated with the increased risk of all-cause mortality when plasma renin activity was suppressed; hazard ratio per 100 pg/mL, 1.70 (95% CI, 1.10-2.63). In this study, we found that higher aldosterone levels were associated with the increased risk of subclinical coronary atherosclerosis and all-cause mortality particularly when renin was suppressed. Our findings indicate the importance of aldosterone levels (even within the reference range) with respect to the cardiovascular system and overall health.

Objective: Ultraviolet (UV) radiation is considered to be an important environmental factor in the clinical course of children with juvenile dermatomyositis (DM). We aimed to evaluate the association between UV radiation and severe disease outcomes in juvenile DM., Methods: This is a cross-sectional study of patients with juvenile DM enrolled in the US multicenter Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry from 2010 to 2015. The mean UV index (UVI) in the calendar month prior to symptom onset in each subject's zip code was calculated from daily satellite solar noon measurements. Multivariable logistic regression was used to model the relationship between the mean UVI and calcinosis as well as other outcomes of severe disease. Covariates included sex, race, age, time to diagnosis, disease duration, and latitude., Results: In a multivariable model, there was no association between the mean UVI and calcinosis. African American race was associated with a 3-fold greater odds of calcinosis. However, there was a significant statistical interaction between race and mean UVI. Accounting for this interaction, the odds of calcinosis markedly decreased in African American subjects and steadily increased in non-African American subjects over a range of increasing the mean UVI. Higher mean UVI was associated with decreased odds of using biologics or nonmethotrexate disease-modifying antirheumatic drugs and skin ulceration., Conclusion: We described a novel association between UV radiation, calcinosis, and race in a large cohort of patients with juvenile DM. This study furthers our knowledge of the role of UV radiation in the clinical course of juvenile DM and highlights the complex interplay between genes and environment in the clinical phenotypes and development of calcinosis in children with juvenile DM., (© 2019, American College of Rheumatology.)

Background and Aims: Aortic valve calcification (AVC) may be associated with atherogenic processes arising from endothelial dysfunction (ED). Limited data is available about the relationship between ED, defined by flow mediated dilation (FMD%) and biomarkers, and the prevalence and progression of AVC in a multiethnic population., Methods: A sample of 3475 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA), with both initial and repeat CT scans at a mean of 2.65 ± 0.84 years and FMD% and serologic markers of ED [ C-reactive protein (CRP), Von Willebrand factor (vWF), Plasminogen Activator Inhibitor (PAI), fibrinogen, Interleukin 6 (IL6), E-selectin and ICAM-1 (Intercellular Adhesion Molecule 1)], were analyzed. Multivariate modeling evaluated the association between ED and the prevalent AVC and AVC progression., Results: The median levels of FMD% was lower and vWF%, fibrinogen, IL6 and ICAM-1 were significantly higher in the AVC prevalence group versus no AVC prevalence (all p < 0.001). In the fully adjusted model for established risk factors, decreasing FMD% or increasing biomarkers was not independently associated with AVC prevalence [OR FMD% 1.028 (0.786, 1.346), CRP 0.981 (0.825, 1.168), vWF 1.132 (0.559, 2.292), PAI 1.124 (0.960, 1.316), fibrinogen 1.116 (0.424, 2.940), IL6 1.065 (0.779, 1.456), E-selectin 0.876 (0.479, 1.602) and ICAM-1 1.766 (0.834, 3.743)]. In the AVC progression group, FMD%, vWF%, fibrinogen and IL6 were significantly different (p < 0.05). After adjusting for cardiac risk factors, AVC progression was not independently associated with decreasing FMD% or increasing biomarkers [OR FMD% 1.105 (0.835, 1.463), CRP 1.014 (0.849, 1.210), vWF% 1.132 (0.559, 2.292), PAI 1.124 (0.960, 1.316), fibrinogen 0.909 (0.338, 2.443), IL6 1.061 (0.772, 1.459), E-selectin 0.794 (0.426, 1.480) and ICAM-1 0.998 (0.476, 2.092)]., Conclusions: Endothelial dysfunction by FMD% and biomarkers is not significantly associated with the prevalence or progression of aortic valve calcification after adjustment for cardiac risk factors., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Data are limited on whether valvular calcification is associated with aortic wall stiffness. We tested whether aortic valve calcification (AVC) and/or mitral valve calcification (MVC) is inversely associated with aortic distensibility (AD). Cross-sectional study conducted in a subset of the Multi-Ethnic Study of Atherosclerosis (MESA) included 3676 MESA participants aged 44 to 84 years with AD measured with magnetic resonance imaging and with AVC and MVC measured with noncontrast cardiac computed tomography scans. Both AVC and MVC were divided into 3 categories: zero, < median values (low), and ≥ median values (high) for patients with nonzero values. Overall, 88% (n = 3256) and 92% (n = 3365) of participants had zero AVC and MVC, while 6% (n = 211) and 4% (n = 156) had low, and 6% (n = 209) and 4% (n = 155) had high values of AVC and MVC, respectively. The AVC was independently associated with AD after adjusting for age, gender, and ethnicity ( P = .035). No association was noted between AVC groups and AD after adjustment for all covariates or MVC groups and AD in any model.

Rationale: Pantothenate kinase-associated neurodegeneration (PKAN) represents an autosomal recessive hereditary disease. In this report, a PANK2 gene mutation in a Chinese child was identified, as well as detections of PKAN among his family members. Our findings exposed a world-wide novel compound heterozygous mutation., Patient Concerns: We described a 6-year-old male patient with PKAN, exhibiting involuntary movement for a period of 1.5 years, as well as feeding difficulties for 2 weeks., Diagnosis: Due to brain computed tomography and magnetic resonance imaging results, and patient behavior, the attending physician suspected a hereditary effect., Interventions: The patient sample underwent high-throughput sequencing. Subsequently, his parents and sister were screened for the mutations identified in the patient genome., Outcomes: High-throughput sequencing revealed a novel complex heterozygous mutation of the PANK2 gene, which was detected in the second and fourth exons, c.A650G, and c.T1341G, respectively, resulting in amino acid alterations (p.D217G and p.D447E, respectively). The child's father was confirmed to possess a heterozygous c.A650G mutation, while his mother was heterozygous for the c.T1341G mutation., Lessons: The key finding of the study encompassed the detection of a novel PANK2 gene mutation in a child of Chinese ethnicity with PKAN. The PANK2 gene c.A650G, as well as c.T1341G, mutations may be potential mutation hotspots in children with PKAN in Mainland China.

Background: Long-term exposure to high ambient air pollution has been associated with coronary artery calcium (CAC), a marker of cardiovascular disease (CVD). Calcifications of left-sided heart valves are also markers of CVD risk. We investigated whether air pollution was associated with valvular calcification and its progression., Methods: We studied 6253 MESA participants aged 45-84 years who underwent two cardiac CT scans 2.5 years apart to quantify aortic valve calcium (AVC) and mitral annular calcium (MAC). CAC was included for the same timeframe for comparison with AVC/MAC. Ambient particulate matter <2.5 μm (PM 2.5 ) and oxides of nitrogen (NO x ) concentrations were predicted from residence-specific spatio-temporal models., Results: The mean age (SD) of the study sample was 62 (10) years, 39% were white, 27% black, 22% Hispanic, and 12% Chinese. The prevalence of AVC and MAC at baseline were 13% and 9% respectively, compared to 50% prevalence of CAC. The adjusted prevalence ratios of AVC and MAC for each 5 μg/m 3 higher PM 2.5 was 1.19 (95% CI 0.87, 1.62) and 1.20 (0.81, 1.77) respectively, and for CAC was 1.14 (1.01, 1.27). Over 2.5 years, the mean change in Agatston units/year for each 5 μg/m 3 higher PM 2.5 concentration was 0.29 (-5.05, 5.63) for AVC and 4.38 (-9.13, 17.88) for MAC, compared to 8.66 (0.61, 16.71) for CAC. We found no significant associations of NOx with AVC and MAC., Conclusion: Our findings suggest a trend towards increased 2.5-year progression of MAC with exposure to outdoor PM 2.5 , although this association could not be confirmed. Additional well-powered studies with longer periods of follow-up are needed to further study associations of air pollution with valvular calcium., Trial Registration: Although MESA is not a clinical trial, this cohort is registered at ClinicalTrials.gov Identifier: NCT00005487; Date of registration May 25, 2000.

We assessed the relationships among adult height, coronary artery calcium (CAC) score, incident atherosclerotic cardiovascular disease (ASCVD) events, and atrial fibrillation (AFib) in a multiethnic cohort. We used race/ethnicity-specific height (dichotomized by median value and in quartiles) as the predictor variable within the 4 racial/ethnic groups in the Multi-Ethnic Study of Atherosclerosis (n = 6,814). After a mean of 10.2 years of follow-up (2000-2012), 556 ASCVD events (8.2%) and 539 AFib events (7.9%) occurred. Adult height was not associated with prevalent CAC score (ln(CAC + 1) or categories). Tall stature (i.e., race/ethnicity-specific height ≥median) had a significant but opposite association with future ASCVD and AFib (hazard ratios were 0.72 (95% confidence interval: 0.56, 0.92) and 1.38 (95% confidence interval: 1.07, 1.79), respectively). We observed a gradient-response but opposite association between quartiles of race/ethnicity-specific height and ASCVD/AFib events in our multivariable models. A formal test of interaction between race/ethnicity-specific height and sex was not significant in the ASCVD model (P = 0.78) but was significant in the AFib model (P = 0.03). Tall stature was associated (in a gradient-response fashion) with reduced risk of ASCVD events and increased risk of AFib. Adult height may signal interactions between genetic and environmental factors and may provide risk information independent of current traditional risk factors and CAC score., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Serum 25-hydroxyvitamin D [25(OH)D] concentration has been identified as a possible modifiable risk factor for cardiovascular disease (CVD). We hypothesized that serum 25(OH)D concentration would be associated with calcifications of the left-sided heart valves, which are markers of CVD risk. Aortic valve calcium (AVC) and mitral annular calcium (MAC) were quantified from cardiac computed tomography scans performed on 5,530 Multi-Ethnic Study of Atherosclerosis participants at the baseline examination (2000 to 2002) and at a follow-up visit at either Examination 2 (2002 to 2004) or Examination 3 (2004 to 2005). 25(OH)D was measured from serum samples collected at the baseline examination. Using relative risk regression, we evaluated the multivariable-adjusted risk of prevalent and incident AVC and MAC in this ethnically diverse population free of clinical CVD at baseline. The mean age of participants was 62 ± 10 years; 53% were women, 40% white, 26% black, 21% Hispanic, and 12% Chinese. Prevalent AVC and MAC were observed in 12% and 9% of study sample, respectively. There were no significant associations between 25(OH)D and prevalent AVC or MAC. Over a mean follow-up of 2.5 years, 4% developed incident AVC and 5% developed incident MAC. After adjusting for demographic variables, each 10 ng/ml higher serum 25(OH)D was associated with a 15% (relative risk 0.85, 95% confidence interval 0.74 to 0.98) lower risk of incident MAC but not AVC. However, this association was no longer significant after adjusting for lifestyle and CVD risk factors. Results suggest a possible link between serum 25(OH)D and the risk for incident MAC, but future studies with longer follow-up are needed to further test this association., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Progression of coronary artery calcium (CAC) is associated with increased risk of coronary heart disease (CHD) and is reported to be greater in whites than blacks, Hispanics, and Chinese in the US. Our objective was to compare progression of CAC between Japanese Americans and whites., Methods: Population-based sample of 303 Japanese American men and 310 white men aged 40-49years, free of clinical cardiovascular disease at baseline, were examined for CAC at baseline (2004-2007) and follow-up (2008-2013). Progression of CAC was defined as change in coronary calcium scores (CCS) in participants with baseline CCS>0 and incident CAC in participants with baseline CCS=0. Multiple linear regression and relative risk regression were used to compare change in CCS scores and incident CAC between the two races, respectively., Results: Japanese American men had significantly greater annual change in CCS than white men (median [interquartile range]: 11.3 Agatston units [1.4, 24.9] vs 2.5 [-0.22, 14.5]) in the unadjusted analyses. After adjusting for cardiovascular risk factors and follow-up time, change in CCS (beta±CI) and incidence rate ratio of CAC was similar in Japanese American men and white men: -0.12 (-0.34, 0.15) and (0.87 [95% CI: 0.20, 3.9]), respectively., Conclusions: In contrast to previously reported greater progression of CAC in whites than other races, we found a similar progression of CAC in Japanese American men as white men. Our study identifies Japanese American men as a target group for prevention of CHD. Large prospective studies are warranted to confirm these findings., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Calcinosis is a frequent complication of systemic sclerosis (SSc) that is usually located in extremities but may occur across the board. The aim of our study was to identify and quantify the distribution of calcinosis in a cohort of Mexican patients with SSc and its association with clinical features and autoantibodies. A cohort of patients with SSc (2013 ACR/EULAR criteria), classified in diffuse cutaneous (dcSSc) and limited cutaneous (lcSSc) (Le Roy criteria), was studied. For their analysis, patients were allocated into those with and without calcinosis (clinical and/or radiological). The evaluation included the modified Rodnan scale for skin and Medsger disease severity scale (DSS). Calcium, phosphorus, vitamin D, and parathyroid hormone (PTH) and antinuclear antibodies and extractable nuclear antigens were determined in serum. A total of 109 patients were included, 41 (37 %) with and 68 (63 %) without calcinosis. Calcinosis was more frequent in patients with dcSSc (55 vs 27 %). In total, we identified 354 sites with calcinosis and mean per patient of 12.0 ± 9.1; the most common sites affected were the hands (83 %), proximal upper extremity (27 %), and proximal lower extremity (22 %). Patients with calcinosis had a higher score of Rodnan scale, Mesdger DSS, and frequency of anti-nucleolar and anti-Scl-70 antibodies compared to those without calcinosis. Abnormal PTH elevation was found in 35 % of patients with calcinosis and 23 % without it. The prevalence of calcinosis is high in Mexican patients with SSc, especially in diffuse variety, and is associated with increased severity of disease.

To our knowledge, no study has investigated the association of long-term exposure to traffic pollution with markers of atherosclerosis in 4 vascular beds simultaneously in an all-African-American cohort. Among participants in the Jackson Heart Study (Jackson, Mississippi; baseline mean age = 55.5 (standard deviation, 12.7) years), we used linear regression to estimate percent differences in carotid intima-media thickness (CIMT) at baseline (2004) and used modified Poisson regression (robust error variance) to estimate prevalence ratios for peripheral artery disease (PAD), coronary artery calcification (CAC), and abdominal aortic calcification (AAC) at the first follow-up visit (2005-2008) for persons living less than 150 m (versus more than 300 m) from major roadways, adjusting for confounders. Living less than 150 m from such roadways was associated with a significant 6.67% (95% confidence interval: 1.28, 12.35) increase in CIMT (4,800 participants). PAD prevalence among persons living less than 150 m from a major roadway was 1.17 (95% confidence interval: 0.73, 1.86) times that of persons living more than 300 m away (4,443 participants), but this result was not statistically significant. There was no association for CAC or AAC. The association with CIMT was stronger in participants with a cardiovascular disease history than in those without one (P = 0.04). We observed an association in the carotid vascular beds but not the coronary, abdominal, or peripheral vascular beds. Our results highlight the need to consider residential proximity to roadways as a potential cardiovascular disease risk factor for blacks.

Context: Relative to European Americans, calcified atherosclerotic plaque (CP) is less prevalent and severe in African-Americans (AAs)., Objective: Predictors of progression of CP in the aorta, carotid, and coronary arteries were examined in AAs over a mean 5.3 ± 1.4-year interval., Design: This is the African American-Diabetes Heart Study., Setting: A type 2 diabetes (T2D)-affected cohort was included., Participants: A total of 300 unrelated AAs with T2D; 50% female, mean age 55 ± 9 years, baseline hemoglobin A1c 8.1 ± 1.8% was included., Main Outcome Measures: Glycemic control, renal parameters, vitamin D, and computed tomography-derived measures of adiposity, vascular CP, and volumetric bone mineral density (vBMD) in lumbar and thoracic vertebrae were obtained at baseline and follow-up., Results: CP increased in incidence and quantity/mass in all three vascular beds over the 5-year study (P < .0001). Lower baseline lumbar and thoracic vBMD were associated with progression of abdominal aorta CP (P < .008), but not progression of carotid or coronary artery CP. Lower baseline estimated glomerular filtration rate was associated with progression of carotid artery CP (P = .0004), and higher baseline pericardial adipose volume was associated with progression of coronary artery (P = .001) and aorta (P = .0006) CP independent of body mass index. There was a trend for an inverse relationship between change in thoracic vBMD and change in aortic CP (P = .05)., Conclusions: In this longitudinal study, lower baseline thoracic and lumbar vBMD and estimated glomerular filtration rate and higher pericardial adipose volumes were associated with increases in CP in AAs with T2D. Changes in these variables and baseline levels and/or changes in glycemic control, albuminuria, and vitamin D were not significantly associated with progression of CP.

Objectives: Racial differences in susceptibility and progression of pancreatitis have been reported in epidemiologic studies using administrative or retrospective data. There has been little study, however, on the clinical profile, causes, and outcome of chronic pancreatitis (CP) in black patients., Methods: We analyzed data on black patients with CP prospectively enrolled in the multicenter North American Pancreatitis Studies from 26 US centers during the years 2000-2014. CP was defined by definitive evidence on imaging studies or histology. Information on demographics, etiology, risk factors, disease phenotype, treatment, and perceived effectiveness was obtained from responses to detailed questionnaires completed by both patients and physicians., Results: Of the 1,159 patients enrolled, 248 (21%) were black. When compared with whites, blacks were significantly more likely to be male (60.9 vs. 53%), ever (88.2 vs. 71.8%), or current smokers (64.2 vs. 45.9%), or have a physician-defined alcohol etiology (77 vs. 41.9%). There was no overall difference in the duration of CP although for alcoholic CP, blacks had a longer duration of disease (8.6 vs. 6.97 years; P=0.02). Blacks were also significantly more likely to have advanced changes on pancreatic morphology (calcifications (63.3 vs. 55.2%), atrophy (43.2 vs. 34.6%), pancreatic ductal stricture or dilatation (72.6 vs. 65.5%) or common bile duct stricture (18.6 vs. 8.2%)) and function (endocrine insufficiency 39.9 vs. 30.2%). Moreover, the prevalence of any (94.7 vs. 83%), constant (62.6 vs. 51%), and severe (78.4 vs. 65.8%) pain and disability (35.1 vs. 21.4%) were significantly higher in blacks. Observed differences were in part related to variances in etiology and duration of disease. No differences in medical or endoscopic treatments were seen between races although prior cholecystectomy (31.1 vs. 19%) was more common in white patients., Conclusions: Differences were observed between blacks and whites in the underlying cause, morphologic expression, and pain characteristics of CP, which in part are explained by the underlying risk factor(s) with alcohol and tobacco being much more frequent in black patients as well as disease duration.

Background: Long-term exposure to fine particulate matter less than 2.5 μm in diameter (PM2.5) and traffic-related air pollutant concentrations are associated with cardiovascular risk. The disease process underlying these associations remains uncertain. We aim to assess association between long-term exposure to ambient air pollution and progression of coronary artery calcium and common carotid artery intima-media thickness., Methods: In this prospective 10-year cohort study, we repeatedly measured coronary artery calcium by CT in 6795 participants aged 45-84 years enrolled in the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) in six metropolitan areas in the USA. Repeated scans were done for nearly all participants between 2002 and 2005, for a subset of participants between 2005 and 2007, and for half of all participants between 2010 and 2012. Common carotid artery intima-media thickness was measured by ultrasound in all participants at baseline and in 2010-12 for 3459 participants. Residence-specific spatio-temporal pollution concentration models, incorporating community-specific measurements, agency monitoring data, and geographical predictors, estimated concentrations of PM2.5 and nitrogen oxides (NOX) between 1999 and 2012. The primary aim was to examine the association between both progression of coronary artery calcium and mean carotid artery intima-media thickness and long-term exposure to ambient air pollutant concentrations (PM2.5, NOX, and black carbon) between examinations and within the six metropolitan areas, adjusting for baseline age, sex, ethnicity, socioeconomic characteristics, cardiovascular risk factors, site, and CT scanner technology., Findings: In this population, coronary calcium increased on average by 24 Agatston units per year (SD 58), and intima-media thickness by 12 μm per year (10), before adjusting for risk factors or air pollutant exposures. Participant-specific pollutant concentrations averaged over the years 2000-10 ranged from 9.2-22.6 μg PM2.5/m(3) and 7.2-139.2 parts per billion (ppb) NOX. For each 5 μg PM2.5/m(3) increase, coronary calcium progressed by 4.1 Agatston units per year (95% CI 1.4-6.8) and for each 40 ppb NOX coronary calcium progressed by 4.8 Agatston units per year (0.9-8.7). Pollutant exposures were not associated with intima-media thickness change. The estimate for the effect of a 5 μg/m(3) higher long-term exposure to PM2.5 in intima-media thickness was -0.9 μm per year (95% CI -3.0 to 1.3). For 40 ppb higher NOX, the estimate was 0.2 μm per year (-1.9 to 2.4)., Interpretation: Increased concentrations of PM2.5 and traffic-related air pollution within metropolitan areas, in ranges commonly encountered worldwide, are associated with progression in coronary calcification, consistent with acceleration of atherosclerosis. This study supports the case for global efforts of pollution reduction in prevention of cardiovascular diseases., Funding: US Environmental Protection Agency and US National Institutes of Health., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: Lipoprotein(a) [Lp(a)] is a risk factor for calcific aortic valve disease (CAVD) but has not been evaluated across multiple races/ethnicities. This study aimed to determine whether Lp(a) cutoff values used in clinical laboratories to assess risk of cardiovascular disease identify subclinical CAVD and its severity and whether significant relations are observed across race/ethnicity., Approach and Results: Lp(a) concentrations were measured using a turbidimetric immunoassay, and subclinical CAVD was measured by quantifying aortic valve calcification (AVC) through computed tomographic scanning in 4678 participants of the Multi-Ethnic Study of Atherosclerosis. Relative risk and ordered logistic regression analysis determined cross-sectional associations of Lp(a) with AVC and its severity, respectively. The conventional 30 mg/dL Lp(a) clinical cutoff was associated with AVC in white (relative risk: 1.56; confidence interval: 1.24-1.96) and was borderline significant (P=0.059) in black study participants (relative risk: 1.55; confidence interval: 0.98-2.44). Whites with levels ≥50 mg/dL also showed higher prevalence of AVC (relative risk: 1.72; confidence interval: 1.36-2.17) than those below this level. Significant associations were observed between Lp(a) and degree of AVC in both white and black individuals. The presence of existing coronary artery calcification did not affect these associations of Lp(a) and CAVD. There were no significant findings in Hispanics or Chinese., Conclusions: Lp(a) cutoff values that are currently used to assess cardiovascular risk seem to be applicable to CAVD, but our results suggest race/ethnicity may be important in cutoff selection. Further studies are warranted to determine whether race/ethnicity influences Lp(a) and risk of CAVD incidence and its progression., (© 2016 American Heart Association, Inc.)

Objective: Accelerated atherosclerosis is a major cause of morbidity and death in SLE. The purpose of this study was to determine whether the prevalence and extent of coronary artery calcium (CAC) is higher in female SLE patients compared with a non-SLE sample from the Multi-Ethnic Study of Atherosclerosis (MESA)., Methods: CAC was measured in 80 female SLE patients and 241 female MESA controls from the Baltimore Field Centre, ages 45-64 years, without evidence of clinical cardiovascular disease. Binary regression was used to estimate the ratio of CAC prevalence in SLE vs MESA controls, controlling for demographic and cardiovascular risk factors. To compare the groups with respect to the quantity of CAC among those with non-zero Agatston scores, we used linear models in which the outcome was a log-transformed Agatston score., Results: The prevalence of CAC was substantially higher in SLE. The differences were most pronounced and statistically significant in those aged 45-54 years (58% vs 20%, P < 0.0001), but were still observed among those aged 55-65 years (57% vs 36%, P = 0.069). After controlling for age, ethnicity, education, income, diabetes mellitus, hypertension, hyperlipidaemia, high-density lipoprotein levels, smoking, education and BMI, SLE patients still had a significantly higher prevalence of CAC than controls. Among those with CAC, the mean log Agatston score did not differ significantly between SLE and MESA participants., Conclusion: Women with SLE have a higher prevalence of CAC than comparable women without SLE, even after adjusting for traditional cardiovascular risk factors, especially among those aged 45-54 years., (Published by Oxford University Press 2015. This work is written by US Government employees and is in the public domain in the US.)

Background: Several studies have demonstrated the tremendous potential of using coronary artery calcium (CAC) in addition to traditional risk factors for coronary heart disease (CHD) risk prediction. However, to date, no risk score incorporating CAC has been developed., Objectives: The goal of this study was to derive and validate a novel risk score to estimate 10-year CHD risk using CAC and traditional risk factors., Methods: Algorithm development was conducted in the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective community-based cohort study of 6,814 participants age 45 to 84 years, who were free of clinical heart disease at baseline and followed for 10 years. MESA is sex balanced and included 39% non-Hispanic whites, 12% Chinese Americans, 28% African Americans, and 22% Hispanic Americans. External validation was conducted in the HNR (Heinz Nixdorf Recall Study) and the DHS (Dallas Heart Study)., Results: Inclusion of CAC in the MESA risk score offered significant improvements in risk prediction (C-statistic 0.80 vs. 0.75; p < 0.0001). External validation in both the HNR and DHS studies provided evidence of very good discrimination and calibration. Harrell's C-statistic was 0.779 in HNR and 0.816 in DHS. Additionally, the difference in estimated 10-year risk between events and nonevents was approximately 8% to 9%, indicating excellent discrimination. Mean calibration, or calibration-in-the-large, was excellent for both studies, with average predicted 10-year risk within one-half of a percent of the observed event rate., Conclusions: An accurate estimate of 10-year CHD risk can be obtained using traditional risk factors and CAC. The MESA risk score, which is available online on the MESA web site for easy use, can be used to aid clinicians when communicating risk to patients and when determining risk-based treatment strategies., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Colorectal adenoma and coronary atherosclerosis have similar risk factors. The aim of this study was to investigate the association between colorectal adenoma and coronary artery calcification (CAC), which is used as a surrogate marker for coronary atherosclerosis., Methods: This is a cross-sectional study of 398 Koreans (290 males, mean age of 56.8 ± 8.1 years) who underwent CAC scoring by multi-slice computed tomography and colonoscopy on the same day as the screening examination. The CAC scores were divided into the following three categories according to severity: absent (CAC score = 0), mild (0 < CAC score ≤ 100), and moderate-to-severe CAC (CAC score > 100)., Results: Colorectal adenoma was detected in 149 (37.4%) subjects and was significantly associated with a CAC score of >0 (OR = 1.66, 95% CI = 1.05-2.64, P = 0.032), including both mild (OR = 1.80, 95% CI = 1.06-3.03, P = 0.029) and moderate-to-severe CAC (OR = 1.95, 95% CI = 1.05-3.63, P = 0.035), in multivariate analysis after adjusting for age, gender and other risk factors. The proportion of subjects with colorectal adenoma and advanced adenoma progressively increased with increasing CAC score (colorectal adenoma 28.9%-54.1%, P for trend < 0.001; advanced adenoma 7.0%-16.4%, P for trend = 0.026)., Conclusion: Colorectal adenoma is related to coronary artery calcification independent of traditional risk factors for asymptomatic Koreans. The prevalence of advanced adenoma is more common in individuals with severe coronary atherosclerosis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: In this study, we aimed to evaluate whether nonalcoholic fatty liver disease (NAFLD) was associated with the presence and morphology of coronary atherosclerotic plaques shown by multidetector computed tomography (MDCT) in asymptomatic subjects without a history of cardiovascular disease., Materials and Methods: We retrospectively enrolled 772 consecutive South Korean individuals who had undergone both dualsource 64-slice MDCT coronary angiography and hepatic ultrasonography during general routine health evaluations. The MDCT studies were assessed for the presence, morphology (calcified, mixed, and non-calcified), and severity of coronary plaques., Results: Coronary atherosclerotic plaques were detected in 316 subjects (40.9%) by MDCT, and NAFLD was found in 346 subjects (44.8%) by hepatic ultrasonography. Subjects with NAFLD had higher prevalences of all types of atherosclerotic plaque and non-calcified, mixed, and calcified plaques than the subjects without NAFLD. However, the prevalence of significant stenosis did not differ between groups. After adjusting for age, smoking status, diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome, NAFLD remained a significant predictor for all types of coronary atherosclerotic plaque [odds ratio (OR): 1.48; 95% confidence interval (CI): 1.05-2.08; p=0.025] in binary logistic analysis, as well as for calcified plaques (OR: 1.70; 95% CI: 1.07-2.70; p=0.025) in multinomial regression analysis., Conclusion: Our study demonstrated that NAFLD was significantly associated with the presence and the calcified morphology of coronary atherosclerotic plaques detected by MDCT. Further prospective clinical studies are needed to clarify the exact physiopathologic role of NAFLD in coronary atherosclerosis.

Objectives: To determine the association of HIV, immunologic, and inflammatory factors on coronary artery calcium (CAC), a marker of subclinical atherosclerosis., Methods: Cross-sectional study comparing baseline data of males from Hawaii Aging with HIV - Cardiovascular Study (HAHCS) with the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. The cohorts were pooled to determine effects of HIV on CAC and explore immunologic and inflammatory factors that may explain development of CAC in HIV. Multivariable regression models compared CAC prevalence in HAHCS with MESA adjusting for coronary heart disease (CHD) risk profiles., Results: We studied 100 men from HAHCS and 2733 men from MESA. Positive CAC was seen in 58% HAHCS participants and 57% MESA participants. Mean CAC was 260.8 in HAHCS and 306.5 in MESA. Using relative risk (RR) regression, HAHCS participants had a greater risk (RR = 1.20, P < 0.05) of having positive CAC than MESA when adjusting for age, smoking status, diabetes, antihypertensive therapy, BMI, systolic blood pressure, total cholesterol, and HDL cholesterol. Among participants with positive CAC, HIV infection was not associated with larger amounts of CAC. Among HAHCS participants, current HIV viral load, CD4, length of HIV, interleukin 6 (IL-6), fibrinogen, C-reactive protein (CRP), and D-dimer were not associated with the presence or amount of CAC., Discussion: HIV was independently associated with a positive CAC in men with increased likelihood occurring between 45 and 50 years of age. Current HIV viral load, CD4 count, length of HIV, and inflammatory markers were unrelated to either presence or amount of CAC.

Objective: Valvular calcification occurs via ongoing endothelial injury associated with inflammation. IL-10 is an anti-inflammatory cytokine and 75% of the variation in IL-10 production is genetically determined. However, the relationship between genetic polymorphisms of IL-10 and valvular calcification has not been studied. The objective of this study was to investigate the association between valvular calcification and IL-10 genetic polymorphisms in the Han, Uygur and Kazak populations in China., Patients and Methods: All of the participants were selected from subjects participating in the Cardiovascular Risk Survey (CRS) study. The single nucleotide polymorphisms (SNPs) rs1800871 and rs1800872 of the IL-10 gene were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Three independent case-control studies involving the Han population, the Uygur population and the Kazak population were used in the analysis., Results: For the Han and Kazak populations, rs1800871 was found to be associated with valvular calcification in the recessive model, and the difference remained statistically significant following multivariate adjustment (p<0.001, p=0.031, respectively). For the Han, Uygur and Kazak populations, rs1800872 was found to be associated with valvular calcification in the dominant model, and the difference remained statistically significant following multivariate adjustment (p<0.001, p=0.009, and p=0.023,respectively)., Conclusion: Both rs1800871 and rs1800872 of the IL-10 gene are associated with valvular calcification in the Han and Kazak populations in China. Rs1800872 is also associated with valvular calcification in the Uygur population.

Background: The prognostic value of coronary artery calcium (CAC) or carotid intima-media thickness (CIMT) among asymptomatic adults with a family history (FH) of premature coronary heart disease is unclear., Methods and Results: Multiethnic Study of Atherosclerosis enrolled 6814 adults without known atherosclerotic cardiovascular disease (ASCVD). Hard ASCVD events were ascertained over a median follow-up of 10.2 years. We estimated adjusted-hazard ratios for CAC and CIMT categories using Cox regression, both within and across FH status groups. Improvement in discrimination with CAC or CIMT added to variables from the ASCVD pooled cohort equation was also evaluated using receiver-operating characteristic curve and likelihood ratio analysis. Of 6125 individuals (62±10 years; 47% men) who reported information on FH, 1262 (21%) had an FH of premature coronary heart disease. Among these, 104 hard ASCVD events occurred. Crude incidence rates (per 1000 person-years) for hard ASCVD were 4.4 for CAC, 0 (n=574; 46% of the sample); 8.8 for CAC, 1 to 99 (n=368); 14.9 for CAC, 100 to 399 (n=178); and 20.8 for CAC, ≥400 (n=142). Relative to CAC=0, adjusted hard ASCVD hazard ratios for each CAC category among persons with an FH were 1.64 (95% confidence interval, 0.94-2.87), 2.45 (1.31-4.58), and 2.80 (1.44-5.43), respectively. However, there was no increased adjusted hazard for hard ASCVD in high versus low CIMT categories. In participants with an FH of premature coronary heart disease, CAC improved discrimination of hard ASCVD events (P<0.001). However, CIMT did not discriminate ASCVD (P=0.70)., Conclusions: Nearly half of individuals reporting FH have zero CAC and may receive less net benefit from aspirin or statin therapy. Among persons with an FH, CAC is a robust marker of absolute and relative risk of ASCVD, whereas CIMT is not., (© 2015 American Heart Association, Inc.)

Although a coronary artery calcium (CAC) score of 0 is associated with a very low 10-year risk for cardiac events, this risk is nonzero. Subjects with a family history of coronary heart disease (CHD) has been associated with more subclinical atherosclerosis than subjects without a family history of CHD. The purpose of this study was to assess the significance of a family history for CHD in subjects with a CAC score of 0. The Multi-Ethnic Study of Atherosclerosis cohort includes 6,814 participants free of clinical cardiovascular disease (CVD) at baseline. Positive family history was defined as reporting a parent, sibling, or child who had a heart attack. Time to incident CHD or CVD event was modeled using the multivariable Cox regression; 3,185 subjects were identified from the original Multi-Ethnic Study of Atherosclerosis cohort as having a baseline CAC score of 0 (mean age 58 years, 37% men). Over a median follow-up of 10 years, 101 participants (3.2%) had CVD events and 56 (1.8%) had CHD events. In age- and gender-adjusted analyses, a family history of CHD was associated with an ∼70% increase in CVD (hazard ratio 1.73, 95% confidence interval 1.17 to 2.56) and CHD (hazard ratio 1.72, 95% confidence interval 1.01 to 2.91) events. CVD events remained significant after further adjustment for ethnicity, risk factors, and baseline medication use. In conclusion, asymptomatic subjects with a 0 CAC score and a positive family history of CHD are at increased risk for CVD and CHD events compared with those without a family history of CHD, although absolute event rates remain low., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Previous studies demonstrated that blacks have less coronary artery calcification (CAC) than whites. We evaluated racial differences in plaque composition and stenosis in the Multicenter AIDS Cohort Study. HIV-positive and HIV-negative men underwent noncontrast cardiac computed tomography (CT) if they were aged 40 to 70 years, weighed <136 kg, and had no history of cardiac surgery or revascularization and, if eligible, coronary CT angiography (CTA). There were 1,001 men who underwent CT scans and 759 men CTA. We measured CAC on noncontrast CT and identified total plaque, noncalcified plaque, calcified plaque, mixed plaque, and coronary stenosis >50% on CTA. The association of presence and extent of plaque with race was determined after adjustment for HIV serostatus, cardiovascular risk factors, and measures of socioeconomic status. The prevalences of any plaque on CTA and noncalcified plaque were not different between black and white men; however, black men had lower prevalences of CAC (prevalence ratio [PR] 0.79, p = 0.01), calcified plaque (PR 0.69, p = 0.002), and stenosis >50% (PR 0.59, p = 0.009). There were no associations between black race and extent of plaque in fully adjusted models. Using log-linear regression, black race was associated with a lower extent of any plaque on CTA in HIV-positive men (estimate = -0.24, p = 0.051) but not in HIV-negative men (0.12, p = 0.50, HIV interaction p = 0.005). In conclusion, a lower prevalence of CAC in black compared with white men appears to reflect less calcification of plaque and stenosis rather than a lower overall prevalence of plaque., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Fractures are associated with cardiovascular diseases in the elderly. The purpose of the present study was to investigate the association between aortic calcification (AC) and the risk of vertebral fractures in postmenopausal Chinese women., Methods: A prospective study with 5 years of follow-up in 1724 postmenopausal women (aged 50 years old and older) was conducted from July 2005 to June 2010. Dual energy X-ray absorptiometry was utilized to evaluate bone mineral density (BMD). Aortic calcification score (ACS) was determined by a semi-quantitative method and was further categorized into four groups. Cox proportional hazards models were established to assess the association between AC and the risk of vertebral fractures., Results: For subjects with AC, the incidence of vertebral fractures was higher than that of those without AC (p<0.01). After adjustment for age and other potential confounders, it was found that severe AC (G4, ACS>6; G3, ACS = 3-6) was associated with vertebral fractures. Severe AC (G4) was associated with non-vertebral fractures. There were higher risk for the vertebral fractures in two groups and higher risk for non-vertebral fractures in one group., Conclusions: The results of the current study indicate that severe AC is associated with a significantly increased risk of vertebral fractures and non-vertebral fractures in postmenopausal women in China.

Objective: Systemic inflammation has been implicated as an early marker for subclinical cardiovascular disease; however, findings have been inconsistent in the African-American population., Methods: We examined the relation of C-reactive protein (CRP) to subclinical disease in African-American participants of the Jackson Heart Study first examination. Subclinical disease evaluated included aortic valve calcification (AVC), carotid intima-medial thickness (IMT) and peripheral arterial disease (PAD). We assessed the relation of CRP to subclinical disease, adjusting for age, BMI, sex, SBP and DBP, diabetes, total/high-density lipoprotein cholesterol, triglycerides, smoking, antihypertensive therapy, lipid-lowering therapy and hormone replacement therapy., Results: In the study population approximately, 5.1% of participants had AVC and 6.7% had PAD. In the age-adjusted and sex-adjusted model, CRP was significantly related to AVC (P = 0.02) and carotid IMT (P = 0.02). However, in the multivariable-adjusted logistic regression analysis, CRP was significantly related to AVC (P = 0.02) and to PAD (P = 0.04) but not to carotid IMT (P = 0.18)., Conclusion: We describe significant associations between CRP and AVC and PAD in a population-based cohort of African-Americans.

Objectives: The aim of this study was to evaluate the impact of coronary artery calcium (CAC) burden and regional distribution on the need for and type of future coronary revascularization-percutaneous versus surgical (coronary artery bypass graft [CABG])-among asymptomatic subjects., Background: The need for coronary revascularization and the chosen mode of revascularization are thought to be functions of disease burden and anatomic distribution. The association between the baseline burden and regional distribution of CAC and the risk and type of future coronary revascularization remains unknown., Methods: A total of 6,540 participants in the MESA (Multi-Ethnic Study of Atherosclerosis) (subjects aged 45 to 84 years, free of known baseline cardiovascular disease) with vessel-specific CAC measurements were followed for a median of 8.5 years (interquartile range: 7.7 to 8.6 years). Annualized rates and multivariate-adjusted hazard ratios for revascularization and revascularization type were analyzed according to CAC score category, number of vessels with CAC (0 to 4, including the left main coronary artery), and involvement of individual coronary arteries., Results: A total of 265 revascularizations (4.2%) occurred during follow-up, and 206 (78% of the total) were preceded by adjudicated symptoms. Revascularization was uncommon when CAC score was 0.0 (0.6%), with a graded increase over both rising CAC burden and increasingly diffuse CAC distribution. The revascularization rates per 1,000 person-years for CAC scores of 1 to 100, 101 to 400, and >400 were 4.9, 11.7, and 25.4, respectively; for 1, 2, 3, and 4 vessels with CAC, the rates were 3.0, 8.0, 16.1, and 24.8, respectively. In multivariate models adjusting for CAC score, the number of vessels with CAC remained predictive of revascularization and mode of revascularization. Independent predictors of CABG versus percutaneous coronary intervention included 3- or 4-vessel CAC, higher CAC burden, and involvement of the left main coronary artery. Risk for CABG was extremely low with <3-vessel baseline CAC. Results were similar when considering only symptom-driven revascularizations., Conclusions: In this multiethnic cohort of asymptomatic subjects, baseline CAC was highly predictive of future coronary revascularization procedures, with measures of CAC burden and distribution each independently predicting need for percutaneous coronary intervention versus CABG over an 8.5-year follow-up., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Elevated serum uric acid (UA) is associated with cardiovascular disease (CVD) but its association with coronary artery calcium (CAC) is inconsistent. This study examined ethnic differences in the association of UA levels with CAC severity and progression. Participants included 202 white and 166 Filipino postmenopausal women without known CVD. White women originated from the Rancho Bernardo cohort study, whereas Filipino women were convenience sampled from comparable localities. Baseline UA levels and CVD risk factors were measured in 1995 to 1999. CAC was assessed by electron beam computed tomography (EBCT) in 2000 to 2002 (EBCT1) and repeated in 2005 to 2007 (EBCT2). EBCT1 CAC density scores were categorized by severity: minimal 0 to 10, mild 11 to 100, moderate 101 to 399, and severe ≥400. Progression was defined as CAC volume score increases of ≥2.5 mm3 between scans. White women were older at baseline than Filipinas (64.6 vs 59.3 years, p<0.001). Filipinas had increased UA levels (235.8 vs 294.2 μmol/L, p<0.001), diabetes (35.5% vs 5.2%, p<0.001), hypertension (69.6% vs 45.2%, p<0.001), and statin use (32.8% vs 18.7%, p=0.002). CAC severity did not vary by ethnicity (p=0.502), but Filipinas experienced more CAC progression than whites (53.0% vs 39.1%, p=0.016). Adjustment for CVD risk factors identified a positive association between UA levels and increasing CAC severity at EBCT1 in Filipinas (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.05 to 1.71) but not whites (OR 0.94, 95% CI 0.71 to 1.25). Higher UA levels predicted CAC progression in both cohorts (OR 1.26, 95% CI 1.02 to 1.56). In conclusion, these results support use of UA as an ethnicity-specific marker of CAC severity and as a marker of CAC progression among postmenopausal women., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: This study sought to investigate associations of phosphate metabolism biomarkers with aortic valve calcification (AVC)., Background: Calcific aortic valve disease (CAVD) is a common progressive condition that involves inflammatory and calcification mediators. Currently there are no effective medical treatments, but mineral metabolism pathways may be important in the development and progression of disease., Methods: We examined associations of phosphate metabolism biomarkers, including serum phosphate, urine phosphate, parathyroid hormone (PTH) and serum fibroblast growth factor (FGF)-23, with CT-assessed AVC at study baseline and in short-term follow-up in 6814 participants of the Multi-Ethnic Study of Atherosclerosis (MESA)., Results: At baseline, AVC prevalence was 13.2%. Higher serum phosphate levels were associated with significantly greater AVC prevalence (relative risk 1.3 per 1 mg/dL increment, 95% confidence incidence: 1.1 to 1.5, p<0.001). Serum FGF-23, serum PTH, and urine phosphate were not associated with prevalent AVC. Average follow-up CT evaluation was 2.4 years (range 0.9-4.9 years) with an AVC incidence of 4.1%. Overall, phosphate metabolism biomarkers were not associated with incident AVC except in the top FGF-23 quartile., Conclusions: Serum phosphate levels are significantly associated with AVC prevalence. Further study of phosphate metabolism as a modifiable risk factor for AVC is warranted., (Published by Elsevier Ireland Ltd.)

IMPORTANCE Rib cartilage from the sixth, seventh, and eighth ribs offers a long cartilaginous curvature, making the material reliable for grafting. Calcification of cartilage causes unexpected absorption, difficult manipulation, and donor site morbidity. Most studies of calcification were performed in Western countries. OBJECTIVE To investigate the incidence, degree, and pattern of rib cartilage calcification in Asian patients. DESIGN, SETTING, AND PARTICIPANTS Retrospective study of computed tomographic scans of the chest in 120 patients (60 male and 60 female). The incidence, degree, and pattern of cartilage calcification of the sixth through eighth ribs were noted. The patients were stratified into 6 age groups, and 20 patients (10 male and 10 female) were selected for each group. The degree of calcification was assessed as 0%, 1% to 25%, 26% to 50%, 51% to 75%, and 76% to 100%. Meaningful calcification was defined as 26% or greater. The pattern of calcification was classified as marginal, granular, and central. EXPOSURE Computed tomographic scans of the chest. MAIN OUTCOMES AND MEASURES Degree of calcification, presence of meaningful calcification, and calcification pattern. RESULTS Overall, 50.8% of cartilage was calcified, and female patients showed more frequent calcification than male patients (59.4% vs 42.2% [P < .001]). Calcification rates of the sixth and seventh rib cartilage were higher than those of the eighth rib cartilage in all age groups except teenagers, who had a similar rate for all 3 ribs. Calcification of the sixth and seventh rib cartilage significantly increased with age. A meaningful calcification rate was very low in males younger than 60 years, whereas the rate was relatively higher in females than males for all age groups. Males predominantly had the marginal type of calcification, whereas females predominantly had a granular type. The rate and pattern of calcification had no relationship to age. CONCLUSIONS AND RELEVANCE In Asian patients, males younger than 60 years show a very low incidence of calcification, whereas females 30 years or older show a relatively high incidence of meaningful calcification. Asian females also show a predominantly granular or central pattern of calcification that may hinder proper harvest and incision of the rib cartilage. These differences in the incidence and pattern of rib cartilage calcification need appropriate preoperative attention.

Objectives: This study examines whether the coronary artery calcium (CAC) score can be used to define the target population to treat with a polypill., Background: Prior studies have suggested a single polypill to reduce cardiovascular disease (CVD) at the population level., Methods: Participants from MESA (Multi-Ethnic Study of Atherosclerosis) were stratified using the criteria of 4 polypill studies (TIPS [The Indian Polycap Study], Poly-Iran, Wald, and the PILL [Program to Improve Life and Longevity] Collaboration). We compared coronary heart disease (CHD) and CVD event rates and calculated the 5-year number needed to treat (NNT) after stratification based on the CAC score., Results: Among MESA participants eligible for TIPS, Poly-Iran, Wald, and the PILL Collaboration, CAC = 0 was observed in 58.6%, 54.5%, 38.9%, and 40.8%, respectively. The rate of CHD events among those with CAC = 0 varied from 1.2 to 1.9 events per 1,000 person-years, those with CAC scores from 1 to 100 had event rates ranging from 4.1 to 5.5, and in those with CAC scores >100 the event rate ranged from 11.6 to 13.3. The estimated 5-year NNT to prevent 1 CVD event ranged from 81-130 for patients with CAC = 0, 38-54 for those with CAC scores from 1 to 100, and 18-20 for those with CAC scores >100., Conclusions: In MESA, among individuals eligible for treatment with the polypill, the majority of CHD and CVD events occurred in those with CAC scores >100. The group with CAC = 0 had a very low event rate and a high projected NNT. The avoidance of treatment in individuals with CAC = 0 could allow for significant reductions in the population considered for treatment, with a more selective use of the polypill and, as a result, avoidance of treatment in those who are unlikely to benefit., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Non-high-density lipoprotein cholesterol (non-HDLc) is an independent predictor of cardiovascular disease risk, with elevated levels signifying an increased risk beyond low-density lipoprotein. Previous data have shown inconsistent association of lipid subfractions with progression of coronary artery calcium (CAC), a surrogate marker of incident cardiovascular disease. We sought to evaluate the association between non-HDLc and development (incident) and progression of CAC in a cohort of multiethnic asymptomatic subjects. The cohort (n = 5,705) was derived from the limited access data set of the Multi-Ethnic Study of Atherosclerosis obtained from the National Heart Lung and Blood Institute. Multivariable regression analysis was performed to derive the association between non-HDLc and incident CAC (n = 2,927) and non-HDLc and progression of CAC (n = 2,778). In the population without CAC at baseline, non-HDLc, especially >190 mg/dl, was independently associated with incident CAC (relative risk 1.40, 95% confidence interval 1.09 to 1.79, p = 0.008) after adjustments with age, gender, race, systolic blood pressure, antihypertension medication use, smoking, diabetes, lipid-lowering therapy use, follow-up duration, and waist-hip ratio. Similarly, among those with CAC at baseline, non-HDLc levels >190 mg/dl were associated with significant CAC progression in the overall population (β 16.4, 95% confidence interval -5.63 to 27.2, p = 0.003) after adjustments. In conclusion, non-HDLc levels, especially >190 mg/dl, are consistently associated with increased risk of CAC progression. Our results suggest that among lipid fractions, non-HDLc may be best suited for the prediction of future CAC progression., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Worldwide clinical practice guidelines for dyslipidemia emphasize allocating statin therapy to those at the highest absolute atherosclerotic cardiovascular disease (CVD) risk., Methods and Results: We examined 5534 Multi-Ethnic Study of Atherosclerosis (MESA) participants who were not on baseline medications for dyslipidemia. Participants were classified by baseline coronary artery calcium (CAC) score (>0, ≥ 100) and the common clinical scheme of counting lipid abnormalities (LA), including low-density lipoprotein cholesterol ≥ 3.36 mmol/L (130 mg/dL), high-density lipoprotein cholesterol <1.03 mmol/L (40 mg/dL) for men or <1.29 mmol/L (50 mg/dL) for women, and triglycerides ≥ 1.69 mmol/L (150 mg/dL). Our main outcome measure was incident CVD (myocardial infarction, angina resulting in revascularization, resuscitated cardiac arrest, stroke, cardiovascular death). Over a median follow-up of 7.6 years, more than half of events (55%) occurred in the 21% of participants with CAC ≥ 100. Conversely, 65% of events occurred in participants with 0 or 1 LA. In those with CAC ≥ 100, CVD rates ranged from 22.7 to 29.5 per 1000 person-years across LA categories. In contrast, with CAC=0, CVD rates ranged from 2.7 to 5.9 per 1000 person-years across LA categories. Individuals with 0 LA and CAC ≥ 100 had a higher event rate compared with individuals with 3 LA but CAC=0 (22.7 versus 5.9 per 1000 person-years). Similar results were obtained when we classified LA using data set quartiles of total cholesterol/high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, or low-density lipoprotein particle concentration and guideline categories of low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol., Conclusions: CAC may have the potential to help match statin therapy to absolute CVD risk. Across the spectrum of dyslipidemia, event rates similar to secondary prevention populations were observed for patients with CAC ≥ 100.

Background: The coronary artery calcium (CAC) score predicts coronary heart disease (CHD) events, but methods for interpreting the score in combination with conventional CHD risk factors have not been established., Methods and Results: We analyzed CAC scores and CHD risk factor measurements from 6757 black, Chinese, Hispanic, and white men and women aged 45 to 84 years in the Multi-Ethnic Study of Atherosclerosis (MESA). CAC was associated with age, sex, race/ethnicity, and all conventional CHD risk factors. Multivariable models using these factors predicted the presence of CAC (C statistic=0.789) and degree of elevation (16% of variation explained) and can be used to update a "pretest" CHD risk estimate, such as the 10-year Framingham Risk Score, that is based on an individual's conventional risk factors. In scenarios in which a high CAC score is expected, a moderately elevated CAC score of 50 is reassuring (eg, reducing risk from 10% to 6% in a healthy older white man), but when a low/zero CAC score is expected, even with identical pretest CHD risk, the same CAC score of 50 may be alarmingly high (eg, increasing risk from 10% to 20% in a middle-aged black woman with multiple risk factors). Both the magnitude and direction of the shift in risk varied markedly with pretest CHD risk and with the pattern of risk factors., Conclusions: Knowledge of what CAC score to expect for an individual patient, based on their conventional risk factors, may help clinicians decide when to order a CAC test and how to interpret the results.

Aims: Conflicting evidence exists regarding whether obesity is independently associated with coronary artery calcium (CAC), a measure of coronary atherosclerosis. We examined an independent association of obesity with prevalent CAC among samples of multi-ethnic groups whose background populations have varying levels of obesity and coronary heart disease (CHD)., Methods and Results: We analysed a population-based sample of 1212 men, aged 40-49 years free of clinical cardiovascular disease recruited in 2002-06; 310 Japanese in Japan (JJ), 294 Koreans in South Korea (KN), 300 Japanese Americans (JA), and 308 Whites in the USA (UW). We defined prevalent CAC as an Agatston score of ≥10. Prevalent CAC was calculated by tertile of the body mass index (BMI) in each ethnic group and was plotted against the corresponding median of tertile BMI. Additionally, logistic regression was conducted to examine whether an association of the BMI was independent of conventional risk factors. The median BMI and crude prevalence of CAC for JJ, KN, JA, and UW were 23.4, 24.4, 27.4, and 27.1 (kg/m2); 12, 11, 32, and 26 (%), respectively. Despite the absolute difference in levels of BMI and CAC across groups, higher BMI was generally associated with higher prevalent CAC in each group. After adjusting for age, smoking, alcohol, hypertension, lipids, and diabetes mellitus, the BMI was positively and independently associated with prevalent CAC in JJ, KN, UW, but not in JA., Conclusion: In this multi-ethnic study, obesity was independently associated with subclinical stage of coronary atherosclerosis among men aged 40-49 years regardless of the BMI level.

Background: The association between non-steroidal anti-inflammatory drugs (NSAIDs) and the incidence of valvular and arterial calcification is not well established despite known associations between these drugs and cardiovascular events., Objective: To compare the association between the baseline use of aspirin with other NSAID class medications with the incidence and prevalence of aortic valve calcification (AVC) and coronary artery calcification (CAC)., Methods: The relationship of NSAID use to AVC and CAC detected by computed tomography was assessed in 6814 participants within the Multi-Ethnic Study of Atherosclerosis (MESA) using regression modeling. Results were adjusted for age, sex, ethnicity, study site, anti-hypertensive medication use, education, income, health insurance status, diabetes, smoking, exercise, body mass index, blood pressure, serum lipids, inflammatory markers, fasting glucose, statin medication use, and a simple diet score. Medication use was assessed by medication inventory at baseline which includes the use of non-prescription NSAIDs. MESA collects information on both incident and prevalent calcification. The 4814 participants of the Heinz Nixdorf Recall (HNR) Study, a German prospective cohort study with similar measures of calcification, were included in this analysis to enable replication., Results: Mean age of the MESA participants was 62 years (51% female). After adjustment for possible confounding factors, a possible association between aspirin use and incident AVC (Relative Risk(RR): 1.60; 95%Confidence Interval (CI): 1.19-2.15) did not replicate in the HNR cohort (RR: 1.06; 95%CI: 0.87-1.28). There was no significant association between aspirin use and incident CAC in the MESA cohort (RR 1.08; 95%CI: 0.91-1.29) or in the HNR cohort (RR 1.24; 95%CI: 0.87-1.77). Non-aspirin NSAID use was not associated with either AVC or CAC in either cohort. There were no associations between regular cardiac dose aspirin and incident calcification in either cohort., Conclusion: Baseline NSAID use, as assessed by medication inventory, appears to have no protective effect regarding the onset of calcification in either coronary arteries or aortic valves., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: The prevalence of coronary artery calcification (CAC) in Japanese men is lower than in white and Japanese-American men. It is unclear if aortic calcification (AC) strongly linked to smoking is also lower in Japanese men who have many times higher smoking prevalence compared to US men., Methods: We conducted a population-based study of 903 randomly-selected men aged 40-49 years: 310 Japanese men in Kusatsu, Japan, 301 white men in Allegheny County, US, and 292 Japanese men in Hawaii, US (2002-2006). The presence of AC was assessed by electron-beam tomography. AC was defined as Agatston aortic calcium scores (AoCaS) >0 and ≥ 100., Results: Japanese (35.8%) had significantly less AoCaS>0 compared to both white (68.8%, p<0.001) and Japanese-American (62.3%, p<0.001) but similar AoCaS ≥ 100 (19.4%, 18.3%, 22.6%, respectively, p=0.392). The pack-years of smoking, which was highest in Japanese, was the most important single associate of AC in all populations. Additionally age, low-density-lipoprotein cholesterol (LDL-C), and triglycerides in Japanese; body-mass index (BMI) in white; and BMI, LDL-C, hypertension, diabetes, and lipid medications in Japanese-American were independent associates of AC. The risk of AC using either cut points adjusted for pack-years of smoking and additional risk factors was lower in Japanese compared to both white and Japanese-American. AC and CAC had moderately positive and significant correlations in Japanese (r=0.26), white (r=0.39), and Japanese-American (r=0.45)., Conclusions: The prevalence of AC defined both >0 and ≥ 100 was significantly lower in Japanese than in white and Japanese-American men after adjusting for cigarette smoking and additional risk factors., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To examine the relationship of pericardial adipose tissue (PAT) with coronary artery calcification in the Multi-Ethnic Study of Atherosclerosis., Design and Methods: The baseline cohort comprised 6,814 Caucasian (38%), African-American (28%), Chinese American (12%), and Hispanic (22%) adults aged 45-84, without known clinical cardiovascular disease. Cardiac CT was used to measure PAT (cm(3) ) and calcification (Agatston score). We examined cross-sectional associations of PAT with the presence (score >0) and severity (continuous score if >0) of calcification using prevalence ratio (PR) (n = 6,672) and linear regression (n = 3,362), respectively. Main models were adjusted for age, age(2) , gender, race/ethnicity, field site, smoking, physical activity, alcohol, and education., Results: PAT volume (adjusted for age, height, weight, and site) was greatest in Chinese males, whereas Black males had less PAT than all but Black females. PAT was associated with presence [PR per standard deviation (SD): 1.06 (95% CI: 1.04, 1.08)] and severity [difference in log Agatston score per SD: 0.15 (0.09, 0.21)] of calcification, but neither association varied by race/ethnicity. Adjustment for generalized adiposity attenuated but did not eliminate the associations. With further adjustment for traditional risk factors and inflammatory markers, only the association with severity remained statistically significant [PR: 1.02 (1.00, 1.04); difference: 0.10 (0.03, 0.17)]. Heterogeneity by sex was observed for the presence of calcification (PR in men: 1.04; in women: 1.08; P for interaction <0.0001)., Conclusion: PAT was associated with the presence and severity of coronary artery calcification in this cohort, but neither association varied by race/ethnicity., (Copyright © 2013 The Obesity Society.)

Objectives: The study examined whether progression of coronary artery calcium (CAC) is a predictor of future coronary heart disease (CHD) events., Background: CAC predicts CHD events and serial measurement of CAC has been proposed to evaluate atherosclerosis progression., Methods: We studied 6,778 persons (52.8% female) aged 45 to 84 years from the MESA (Multi-Ethnic Study of Atherosclerosis) study. A total of 5,682 persons had baseline and follow-up CAC scans approximately 2.5 ± 0.8 years apart; multiple imputation was used to account for the remainder (n = 1,096) missing follow-up scans. Median follow-up duration from the baseline was 7.6 (max = 9.0) years. CAC change was assessed by absolute change between baseline and follow-up CAC. Cox proportional hazards regression providing hazard ratios (HRs) examined the relation of change in CAC with CHD events, adjusting for age, gender, ethnicity, baseline calcium score, and other risk factors., Results: A total of 343 and 206 hard CHD events occurred. The annual change in CAC averaged 24.9 ± 65.3 Agatston units. Among persons without CAC at baseline (n = 3,396), a 5-unit annual change in CAC was associated with an adjusted HR (95% Confidence Interval) of 1.4 (1.0 to 1.9) for total and 1.5 (1.1 to 2.1) for hard CHD. Among those with CAC >0 at baseline, HRs (per 100 unit annual change) were 1.2 (1.1 to 1.4) and 1.3 (1.1 to 1.5), respectively. Among participants with baseline CAC, those with annual progression of ≥300 units had adjusted HRs of 3.8 (1.5 to 9.6) for total and 6.3 (1.9 to 21.5) for hard CHD compared to those without progression., Conclusions: Progression of CAC is associated with an increased risk for future hard and total CHD events.