Incident Coronary Artery Calcification Research Articles

Incidence and Progression of Coronary Artery Calcium in South Asians Compared With 4 Race/Ethnic Groups.

BackgroundSouth Asians have a relatively high prevalence of coronary artery calcium (CAC) compared with other race/ethnic groups. We determined CAC incidence and progression among South Asians, and compared them with 4 race/ethnic groups.Methods and ResultsData from the MASALA (Mediators of Atherosclerosis in South Asians Living in America) study were used to calculate CAC incidence and progression rates and any CAC change. Data from the MESA (Multi‐Ethnic Study of Atherosclerosis) were used to compare the CAC incidence and progression rates. A total of 698 South Asians had repeat CAC measurements after 4.8±0.8 years. Among those with no CAC at baseline, the age‐adjusted CAC incidence was 8.8% (95% CI, 6.8–10.8%) in men and 3.6% (2.5–4.8%) in women. The median annual CAC progression was 26 (interquartile range, 11–62) for men and 13 (interquartile range, 4–34) for women. Compared with MESA, age‐adjusted CAC incidence was similar in South Asian men compared with white, black, and Latino men, but significantly higher than Chinese men (11.1% versus 5.7%, P=0.008). After adjusting for age, diabetes mellitus, hypertension, and statin medication use, Chinese, black, and Latino men had significantly less CAC change compared with South Asian men, but there were no differences between South Asian and white men. There was no difference in CAC incidence or progression between South Asian women and women in MESA.ConclusionsSouth Asian men had greater CAC change than Chinese, black, and Latino men but similar change to that of whites after adjusting for traditional risk factors.

The impact of non-alcoholic fatty liver disease and metabolic syndrome on the progression of coronary artery calcification

It is unclear whether non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for cardiovascular disease. We examined the independent impact of NAFLD on the progression of the coronary artery calcification (CAC) score, a well-known marker of atherosclerosis progression. We examined 1,173 asymptomatic participants who underwent repeated CAC score measurement during routine health examinations. The subjects were categorised into four groups based on the presence (+) or absence (−) of NAFLD and metabolic syndrome (MetS). The progression of CAC score was defined as either incident CAC in a CAC-free population at baseline or an increase of ≥2.5 units between the baseline and the final square roots of the CAC scores of participants with detectable CAC at baseline. CAC progression was seen in 18.6% (98/526), 28.3% (77/272), 29.1% (30/103) and 32.0% (87/272) of the subjects with NAFLD(−)/MetS(−), NAFLD(+)/MetS(−), NAFLD(−)/MetS(+) and NAFLD(+)/MetS(+), respectively. The subjects with NAFLD(+)/MetS(+) and NAFLD(+)/MetS(−) had a significantly higher risk of CAC progression than those with NAFLD(−)/MetS(−) (multivariate-adjusted odds ratio [OR]: 1.76; 95% confidence interval [CI]: 1.18–2.62 and multivariate-adjusted OR: 1.53, 95% CI: 1.05–2.23, respectively). NAFLD is an independent risk factor for CAC progression, irrespective of the presence of MetS.

The Impact of Fatty Liver Disease and Metabolic Syndrome on the Progression of Coronary Artery Calcification

Objectives: Fatty liver disease (FLD) is a well-known risk factor for cardiovascular disease (CVD). However, it is unclear whether FLD per se is an independent risk factor of CVD or combined unfavorable metabolic components with metabolic syndrome (MetS). In this study, we examined the independent impact of FLD on the coronary artery calcification (CAC) score progression. Methods: We examined 1,173 asymptomatic participants who underwent repeated CAC score measurement during routine health examinations. Subjects were categorized into 4 groups according to the presence (+) or absence (-) of FLD and MetS. The CAC score progression was defined as either incident CAC in a population free of CAC at baseline or increase ≥ 2.5 units between the baseline and final square root of CAC scores participants who had detectable CAC at baseline examination. Results: Among the participants, 44.8% (526), 23.2% (272), 8.8% (103) and 23.2% (272) were classified as FLD(-)/MetS(-), FLD(+)/MetS(-), FLD(-)/MetS(+), and FLD(+)/MetS(+), respectively. The proportions of subjects who developed CAC progression was 18.6% (98), 28.3% (77), 29.1% (30) and 32.0% (87) in FLD(-)/Mets(-), FLD(+)/Mets(-), FLD(-)/MetS(+), and FLD(+)/MetS(+), respectively. In logistic regression analysis, FLD(+)/MetS(+) were at significantly higher risk of CAC progression compared to FLD(-)/MetS(-) [multivariate adjusted-odds ratio (OR) 1.76, 95% confidence interval (CI) 1.18-2.62]. FLD(+)/MetS(-) also demonstrated higher risk of CAC progression [multivariate adjusted-OR 1.53, 95% CI 1.05-2.23]. Conclusions: FLD is an independent risk factor for CAC progression irrespective of the presence of metabolic syndrome. Special attention should be paid to subjects with FLD for the prevention of future cardiovascular events, even though MetS does not coexist. Disclosure Y. Cho: None. Y. Kang: None. C. Park: None. S. Park: None. W. Lee: None. J. Park: None. C. Jung: None.

Abstract P122: Racial/Ethnic Variation in Incidence and Progression of Coronary Artery Calcification: Implications for Understanding the Hispanic Paradox

Background: Previous studies show that Hispanic persons have similar or lower levels of coronary artery calcium (CAC) and slower progression than non-Hispanic whites (NHW), even after adjustment for traditional risk factors. We examined whether this health advantage in CAC incidence and progression among Hispanic adults extends across all levels of risk factor (RF) burden, and whether associations vary by nativity (foreign-born, US-born) and by heritage group (Mexican, non-Mexican). Methods: We analyzed data on Hispanic and NHW participants aged 45-84 years from the Multi-Ethnic Study of Atherosclerosis (MESA). Follow-up CAC measurements and complete covariate data were available for 3694 participants with an average of 6.6 years between the follow-up and baseline scans (2000-2002). Baseline measures of the following traditional RFs were considered: current cigarette smoking, high total cholesterol, hypertension, diabetes, and obesity, with RF burden scores ranging from 0-5. Outcomes were incident CAC (any follow-up CAC >0 Agatston units) among individuals without detectable CAC at baseline, and CAC progression (any positive increase in CAC) among all participants estimated using relative risk regression. All models were adjusted for age, sex, RF burden, race/ethnicity, education, income, and time between scans Results: Although a higher proportion of Hispanics had RF burden scores ≥3 compared to NHW (14.6% vs 8.9%, p<0.0001), Hispanics had a lower adjusted incidence (risk ratio (RR) = 0.83, 95% CI: 0.72-0.96) and less progression of CAC (RR=0.90, 95% CI: 0.86-0.95) than NHW. However, there was evidence of heterogeneity in this pattern. For example, among individuals with no detectable baseline CAC, a Hispanic health advantage was only seen among individuals with RF burden scores of 0 (RR=0.66, 95% CI: 0.48-0.91 for Hispanics vs. NHW at RF=0), with race/ethnic differences getting progressively smaller with increasing RF burden (for RF ≥3: RR=1.01, 95% CI: 0.69-1.48). Compared to NHW, lower adjusted incidence and progression of CAC was evident to an even greater extent among foreign-born Hispanics, but a health advantage was still present for US-born Hispanics, and for both Hispanic heritage groups. However, these patterns also only remained among individuals with lower RF burden scores. Conclusions: The Hispanic health advantage in CAC incidence and progression was primarily evident among individuals with fewer traditional risk factors for CVD, but was present among different Hispanics groups. Future research is necessary to identify the factors underlying this advantage, and the dynamics that erode it as RF burden increases.

Sleep characteristics and progression of coronary artery calcification: Results from the Heinz Nixdorf Recall cohort study

Background and aimsSleep characteristics are associated with incident cardiovascular diseases (CVD), but there is a lack of studies on the association between sleep characteristics and incidence/progression of coronary artery calcification (CAC). MethodsIn the Heinz Nixdorf Recall Study, a population-based cohort study in Germany, CAC was assessed by electron-beam tomography at baseline and at 5-year follow-up. In an analysis set of 3043 subjects (age at baseline 45–74 years; 47% men), we fitted logistic and linear regression models to assess associations between self-rated sleep characteristics (nocturnal and total sleep duration; napping; various sleep disorders) and CAC incidence/CAC progression. Progression was measured as 5-year progression factor, as categories of absolute CAC change, and additionally characterized as rapid or slow compared to an extrapolation of baseline CAC values. ResultsWe observed barely any association between sleep characteristics and CAC progression regardless of the chosen statistical approach; associations between sleep and CAC incidence were slightly larger, e.g., the geometric mean of the 5-year CAC progression factor was 6.8% (95% confidence interval: −9.5; 25.9) larger for ≤5 h, 2.9% (−7.3; 14.3) larger for 5.1–6.9 h and 7.1% (−2.4; 15.7) smaller for ≥7.5 h total sleep compared to 7- <7.5 h total sleep. For subjects with any regular sleep disorder, the geometric mean of the 5-year CAC progression was 3.5% (−4.7; 11.2) smaller compared to subjects without any regular sleep disorder. ConclusionsIn this German cohort study, sleep characteristics were barely associated with CAC progression.

Longitudinal Associations of Pericardial and Intrathoracic Fat With Progression of Coronary Artery Calcium (from the Framingham Heart Study)

Cross-sectional studies have shown that pericardial fat is associated with atherosclerotic burden above and beyond generalized and central adiposity. Whether pericardial fat is longitudinally associated with coronary artery calcium (CAC) has not been firmly established. We examined the associations between cardiac ectopic fat including pericardial and intrathoracic fat with CAC progression and incidence in a community-based study setting. Study participants were from the Framingham Heart Study Offspring and Third Generation Cohorts who underwent multidetector computed tomography at 2 consecutive examinations (2002 to 2005 and 2008 to 2011) for the assessment of CAC. Multivariable-adjusted regression models were used to evaluate the associations between cardiac ectopic fat with CAC. Nonlinear associations were also examined. We included 1,732 participants (49.6% women, mean age 49.9 years). Of the 1,024 participants with a CAC score = 0 at baseline, 197 individuals developed a CAC score > 0 (19.2%) during 6.1 years of follow-up. The remaining 708 participants with a CAC score > 0 at baseline were eligible for CAC progression analysis. We identified nonlinear association between pericardial fat and CAC progression. Higher pericardial fat was associated with higher CAC progression only for those participants with pericardial fat higher than the median value (β = 56.0, p = 0.04). Intrathoracic fat was linearly associated with CAC progression (β = 23.0, p = 0.02). However, all of these associations did not persist after additional adjustment for body mass index, abdominal visceral adipose tissue, or waist circumference (all p ≥ 0.14). Neither pericardial nor intrathoracic fat were associated with CAC incidence (all p ≥ 0.33). Overall, both of the cardiac ectopic fat measures were longitudinally associated with CAC progression.

APOL1 nephropathy risk variants do not associate with subclinical atherosclerosis or left ventricular mass in middle-aged black adults

Prior studies reported associations of APOL1 nephropathy risk variants with subclinical atherosclerosis. However, these findings were limited to older individuals with high comorbidities. To evaluate this in younger individuals, we calculated associations of APOL1 risk variants (high risk [2 risk variants] vs. low risk [0-1 risk variant]) with prevalent, incident, or progressive coronary artery calcification, a carotid intima media thickness over the 90th percentile, and left ventricular hypertrophy in 1315 black participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study. The mean age of this cohort was 44.6 years and their mean estimated glomerular filtration rate was 102.5 ml/min/1.73m2. High-risk participants were found to be younger and have a higher prevalence of albuminuria than low-risk participants. In Poisson regression models adjusted for comorbidities and kidney function, the risk of prevalent coronary artery calcification (relative risk [95% confidence interval] 1.12 [0.72,1.71]), the incident coronary artery calcification (1.50 [0.87,2.59]), and the progression of coronary artery calcification (1.40 [0.88,2.23]) did not significantly differ in high vs. low-risk participants. Furthermore, the risk of carotid intima media thickness over the 90th percentile (1.28 [0.78,2.10]) and left ventricular hypertrophy (1.02[0.73,1.43]) did not significantly differ in high vs. low-risk participants in fully-adjusted models. Thus, APOL1 risk variants did not associate with subclinical markers of atherosclerosis or left ventricular hypertrophy in middle-aged black adults with preserved kidney function.

Association Between Coronary Artery Calcification and the Hemoglobin Glycation Index: The Kangbuk Samsung Health Study.

The hemoglobin glycation index (HGI) is known to be correlated with the risk for cardiovascular disease. To analyze the association between incident coronary artery calcification (CAC) and the changes in HGI among participants without diabetes, over 4 years. A retrospective study of 2052 nondiabetic participants in whom the coronary artery calcium score was measured repeatedly over 4 years, as part of a health checkup program in Kangbuk Samsung Hospital in Korea, and who had no CAC at baseline. The HGI was defined as the difference between the measured and predicted hemoglobin A1c (HbA1c) levels. A total of 201 participants developed CAC after 4 years, and the mean baseline HGI was significantly higher in those patients. The incidence of CAC gradually increased from the first to the fourth quartile groups of baseline HGI. The odds ratio (OR) for incident CAC was the highest among the four groups divided by the quartiles of the baseline HGI and was significant after adjustment for confounding variables (vs first quartile group: OR, 1.632; 95% confidence interval, 1.024 to 2.601). The incidence of and risk for CAC development were significantly higher than in other groups compared with the low-to-low group after adjustment for confounding factors; however, when baseline HbA1c level was included in the model, only participants with a low-to-high HGI over 4 years showed a significantly increased OR for CAC development compared with the low-to-low group (OR, 1.722; 95% confidence interval, 1.046 to 2.833). The participants with a high baseline HGI and consistently high HGI showed a higher risk for incident CAC than those with a low baseline HGI. An increased HGI over 4 years significantly increased the risk for CAC regardless of the baseline HbA1c levels.

CT-Detected Growth of Coronary Artery Calcification in Asymptomatic Middle-Aged Subjects and Association With 15 Biomarkers

ObjectivesThis study sought to determine the incidence and progression of coronary artery calcification (CAC) in asymptomatic middle-aged subjects and to evaluate the value of a broad panel of biomarkers in the prediction of CAC growth. BackgroundCAC continues to be a major risk factor, but the value of biochemical markers in predicting CAC incidence and progression remains unresolved. MethodsAt baseline, 1,227 men and women underwent traditional risk assessment and a computed tomography (CT) scan to determine the CAC score. Biomarkers of calcium-phosphate metabolism (calcium, phosphate, vitamin D3, parathyroid hormone, osteoprotegerin), lipid metabolism (triglyceride, high- and low-density lipoprotein, total cholesterol), inflammation (C-reactive protein, soluble urokinase-type plasminogen activator receptor), kidney function (creatinine, cystatin C, urate), and myocardial necrosis (cardiac troponin I) were analyzed. A second CT scan was scheduled after 5 years. General linear models were performed to examine the association between biomarkers and ΔCAC score, and additionally, sensitivity analyses were performed in terms of binary and ordinal logistic regressions. ResultsA total of 1,006 participants underwent a CT scan after 5 years. Among the 562 participants with a baseline CAC score of 0, 189 (34%) had incident CAC, whereas 214 (48%) of the 444 participants with baseline CAC score >0 had significant progression (>15% annual increase in CAC score). In the multivariate models (n = 1,006), age, sex, hypertension, diabetes, dyslipidemia, and smoking were associated with ΔCAC, whereas the strongest predictor was baseline CAC score. Low-density lipoprotein and total cholesterol levels were independently associated with CAC incidence (n = 562; incidence rate ratio [IRR]: 1.47; 95% confidence interval [CI]: 1.05 to 2.05; and IRR: 1.34; 95% CI: 1.01 to 1.77, respectively), whereas phosphate level was associated with CAC progression (n = 444; IRR: 3.60; 95% CI: 1.42 to 9.11). ConclusionsIn this prospective study, a large part of participants had incident CAC or progression of prevalent CAC at 5 years of follow-up. Low-density lipoprotein and total cholesterol were associated with CAC incidence and phosphate with CAC progression, whereas 12 other biomarkers had little value.

Fatty liver disease determines the progression of coronary artery calcification in a metabolically healthy obese population.

ObjectivesMetabolically healthy obese (MHO) phenotype describes an obese state with a favorable metabolic profile. However, the prognosis of this subpopulation remains controversial. We aimed to examine whether MHO phenotype is associated with progression of atherosclerotic activity, reflected as the changes in coronary artery calcification (CAC) over time. If so, we sought to determine the role of fatty liver disease (FLD), the hallmark of hepatic steatosis, in this progression.MethodsWe enrolled 1,240 asymptomatic subjects who underwent repeated CAC score measurement during routine health examinations. CAC score progression was defined as either incident CAC in a population free of CAC at baseline, or an increase by ≥2.5 units between the baseline and final square root of CAC scores in participants with detectable CAC at baseline. Subjects were stratified by body mass index (cut-off, 25.0 kg/m2) and metabolic health state using Adult Treatment Panel-III criteria. FLD was assessed via ultrasonography.ResultsOver 2.9 years of follow-up, 25.2% of total subjects exhibited CAC score progression. The MHO phenotype was not significantly associated with CAC score progression (multivariate adjusted-odds ratio [OR], 1.45; 95% confidence interval [CI], 0.93–2.25), as compared to the metabolically healthy non-obese (MHNO) phenotype. However, subgroup analysis indicated that the MHO/FLD phenotype was significantly associated with CAC score progression (multivariate adjusted-OR, 2.37; 95% CI, 1.34–4.16), as compared to the MHNO/no FLD phenotype, whereas the MHO/no FLD phenotype was not (multivariate adjusted OR, 1.25; 95% CI, 0.71–2.24).ConclusionsObese individuals with FLD have an increased risk of atherosclerosis progression, despite their healthy metabolic profile. Preventive interventions targeting cardiometabolic risk factors should be considered in such individuals, regardless of the weight status.

Effects of Low-density Lipoprotein Cholesterol on Coronary Artery Calcification Progression According to High-density Lipoprotein Cholesterol Levels

Previous studies reported that many patients are at high risk for cardiovascular disease (CVD) despite achieving recommended low-density lipoprotein cholesterol (LDL-C) levels. Therefore, we investigated whether the association between LDL-C and the risk for incident CVD differed according to high-density lipoprotein cholesterol (HDL-C) levels using coronary artery calcium score (CACS) progression as a surrogate marker for predicting CVD. We investigated 2132 Korean men in a health screening program, in which CACS was measured at baseline and after 4years. Coronary artery calcification (CAC) progression was defined as a change in CACS ≥0 over 4years. We divided the subjects into nine groups according to baseline HDL-C and LDL-C levels and compared their risks for CAC progression. After 4years, 475 subjects (22.3%) exhibited CAC progression. We identified a positive relationship between baseline LDL-C levels and the risk for incident CAC. However, this association was attenuated by high baseline HDL-C levels. Multivariate logistic regression analysis adjusted for age, body mass index, systolic blood pressure, fasting glucose, smoking, and exercise status revealed that the odds ratios for incident CAC in the lowest HDL-C tertile were 3.08 for LDL-C tertile 3 and 2.02 for LDL-C tertile 2 compared to LDL-C tertile 1. However, these differences disappeared in the highest HDL-C tertile (HDL-C ≥54.0mg/dL). In this longitudinal study, we found that the positive relationship between LDL-C and the relative risk for incident CAC was attenuated by higher HDL-C levels. Therefore, HDL-C levels should be considered when estimating CVD risk.

Abstract P037: Epigenetic Markers of Cardiovascular Health Trajectories and Coronary Artery Calcification in the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Background: Trajectory of AHA’s cardiovascular health (CVH) through young adulthood are associated with subclinical CVD. The human epigenome is modifiable by lifestyle and environmental factors and may be an important mechanism of CVH outcomes. We sought to determine associations of epigenetic markers with CVH trajectories and with coronary artery calcification (CAC) through young adulthood. Methods: Among CARDIA ppts, we performed methylome analysis at follow up year (Y) 15 and Y20 using Illumina Methylation EPIC array (~850K CpG loci). We compared methylome between those with optimal CVH at baseline and remained stable (optimal-stable, n=645) and individuals with baseline optimal but declining CVH during follow up (n=100) to identify methylomic biomarkers of CVH trajectories. Differentially methylated CpGs were further examined in association with incident CAC risk at Y25 (n=745), and for their potential mediating role in CVH-associated CAC risk. Results: In 1,087 CARDIA ppts (mean age=25 at baseline), we identified 25 hypermethylated CpGs (18 at Y15, 13 at Y20, including 6 seen at both Y15 and Y20) significantly associated with optimal-stable CVH trajectories. The 6 common CpGs were stable (mean ICC = 0.66) whereas the remaining 19 CpGs were dynamic (mean ICC = 0.39) over a 5-year interval. Hypermethylation of 6 stable CpGs was associated with a decreased risk of having future CAC incidence ( Table 1 ). Hypermethylation of 10 (out of 19) dynamic CpGs at Y20 was associated with a decreased risk for incident CAC while the associations was less pronounced at Y15. Mediation analyses showed that hypermethylation of these 16 CpGs at Y15 and Y20 contributed 15% and 23% reduction in the CVH-associated relative risks (RRs) of CAC incidence at Y25. Conclusion: We observed distinct methylomic patterns in young adulthood with stable optimal CVH trajectories relative to those with declining CVH. CVH associated methylomic marks may predict CAC incidence and potentially mediate the associations of CVH trajectories with incident CAC risk.

Abstract MP079: Coronary Artery Calcium Incidence and Progression Among South Asians: Results From the MASALA Study

Background: South Asians have a high burden of cardiovascular disease. We have reported that South Asians have similarly high prevalence of coronary artery calcium (CAC) compared to non-Hispanic Whites, and higher CAC than other U.S. ethnic minority groups. No studies have determined the incidence or progression of CAC among South Asians. Methods: We used data from a community-based cohort of South Asians (MASALA) and calculated change in CAC Agatston score between Exam 1 (2010-2013) and Exam 2 (2015-2016) among 379 South Asians. We calculated the average annual incident CAC for those with no CAC at Exam 1, and CAC progression among those with CAC at Exam 1. We compared these findings to the previously reported CAC incidence and progression in the Multi-Ethnic Study of Atherosclerosis (MESA). We also determined factors associated with a ≥100 change in CAC score. Results: We used data from 240 men and 139 women with repeat CAC measured after 4.5±0.7 years of follow-up. Among those with no detectable CAC at baseline, 6.8% developed incident CAC annually (9.2% of men and 4.4% of women), which was similar to MESA race/ethnic groups. Among those with known CAC at baseline, the median annual CAC progression was 23 (interquartile range, 8-56). The table shows the distribution of annual CAC progression. South Asians overall, but particularly South Asian men, had significantly higher annual CAC progression compared to the reported average in MESA (overall median 18, 4-53). Established risk factors (age, male sex, diabetes and hypertension), pericardial fat volume and visceral fat area were associated with greater CAC progression. Conclusions: These preliminary results suggest that South Asian men have significantly greater CAC progression compared to other race/ethnic groups. Longer follow-up of MASALA will determine whether CAC score or CAC progression are important predictors of cardiovascular disease events.

Relation of Risk Factors and Abdominal Aortic Calcium to Progression of Coronary Artery Calcium (from the Framingham Heart Study)

Coronary artery calcium (CAC) and abdominal aortic calcium (AAC) on multidetector computed tomography (MDCT) permit assessment of the presence and burden of coronary and systemic atherosclerosis. Risk factors for progression of CAC and AAC and the association of AAC with CAC progression have not been well characterized in a community-dwelling cohort. We studied 1,959 asymptomatic participants from the Framingham Heart Study who underwent serial MDCT scans with a median interval of 6.1years. Primary outcomes were (a) the incidence of CAC and AAC (CAC >0 and AAC >0 with baseline CAC= 0 and AAC= 0) and (b) absolute progression of CAC (CAC > baseline CAC and AAC > baseline AAC). Covariates were collected at adjacent cycle examinations and included age, gender, use of antihypertensive therapy, use of lipid-lowering therapy, cigarette smoking, and total and high-density lipoprotein cholesterol. Predictors for CAC and AAC progression included baseline CAC, baseline AAC, lipid-lowering therapy, diabetes, high-density lipoprotein cholesterol, BMI, and serum creatinine. Multivariable stepwise logistic and linear regression models were used to test the association of these risk factors with CAC and AAC. Those who developed incident CAC on follow-up scanning comprised 18.8% of 1,124 participants, and 84.9% of 780 participants, with detectable baseline CAC, had further progression. Baseline AAC was a predictor of both CAC incidence and progression, independent of other risk factors. In stepwise models, addition of baseline AAC slightly improved the area under the curve from 0.72 (0.68 to 0.76) to 0.74 (0.70 to 0.78). In conclusion, standard cardiovascular disease risk factors are associated with incidence and progression of CAC and AAC, and AAC augments CAC incidence and progression above cardiovascular disease risk factors.

Progression of coronary artery calcium in Japanese American men and white men in the ERA JUMP study

BackgroundProgression 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. MethodsPopulation-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. ResultsJapanese 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. ConclusionsIn 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.

Abstract 13839: Differences in Prevalence, Incidence, and Progression of Coronary Artery Calcium among Participants With Chronic Kidney Disease With and Without Diabetes Mellitus: Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: Chronic kidney disease (CKD) is associated with elevated coronary artery calcium (CAC) scores, presumed from altered calcium/phosphorus metabolism. However, differences in prevalence/progression of CAC in CKD with (CKD-DM) and without (CKD-non-DM) diabetes are not known. Methods: The MESA cohort (6780 individuals aged 45-84 yr, with no clinical cardiovascular disease enrolled 2000-02) were followed until 2010-12. Baseline CKD was identified (eGFR&lt;60 ml/min/1.73 m 2 using CKD-EPI creatinine and cystatin C-based eGFR or spot urine albumin/creatinine ≥ 17 mg/g in men; 25 mg/g in women). Prevalent CAC was defined by baseline Agatston score &gt;0, incident CAC by any follow-up Agatston score &gt; 0 in those with baseline CAC=0, and CAC progression by any CAC score increase vs. baseline. CAC progression was adjusted for demographic, clinical and inflammatory biomarker variables using linear regression. Results: 1308 (19.3%) MESA participants had CKD, while 853 (12.5%) had DM. CAC &gt; 0 at baseline was lowest (44.3%) in non-CKD, non-DM, intermediate in those with either condition, and highest (67.1%) in CKD-DM participants (table). CAC incidence (among those with CAC=0 at baseline) was highest in CKD-DM, lowest in non-CKD-non-DM (39.3% vs 18.3%, p&lt;0.0001) &amp; intermediate with either CKD or DM alone (27%). About 90% of those with CAC &gt; 0 at baseline had an increase in Agatston score in follow-up; Agatston score increased 37.0/yr in non-CKD-non-DM, 57.6/yr in CKD-non-DM, 68.3/yr in non-CKD-DM, and 107.6/yr in CKD-DM (all pairwise p&lt;0.001). Extensive adjustment (table) attenuated to similar increases between non-CKD-non-DM and CKD-non-DM (40.6 vs 47.2/yr, p=0.09). Greater increases remained in non-CKD-DM (65.7/yr) and in CKD-DM (95.8/yr, p&lt;0.002). Conclusion: CKD-non-DM participants had slower CAC incidence/progression compared to CKD-DM participants. CAC differences among CKD participants may help identify subgroups at higher risk of future events.

Fasting plasma glucose levels and coronary artery calcification in subjects with impaired fasting glucose.

BACKGROUNDPrediabetes is associated with an increased risk of cardiovascular disease (CVD). While the association of impaired glucose tolerance with CVD has been shown in many studies, the relationship between impaired fasting glucose (IFG) and CVD remains unclear.OBJECTIVESThe purpose of this study was to compare the coronary artery calcium (CAC) scores of participants with normal fasting glucose versus those with IFG, according to fasting plasma glucose (FPG) levels, and to assess whether differences in CAC scores were independent of important confounders.DESIGNRetrospective study.SETTINGHealth Promotion Center of the University Hospital (Gyeonggi-do, South Korea), during the period 2010–2014.PATIENTS AND METHODSParticipants were enrolled from the general population who visited for a medical check-up. CAC was assessed in asymptomatic individuals by multidetector computed tomography. Anthropometric parameters and metabolic profiles were also recorded. Subjects were divided into four fasting glucose groups. Participants with a history of CVD or diabetes mellitus were excluded.MAIN OUTCOME MEASURESCorrelation between FPG and CAC scores, CAC score categories, and association between CAC score and FPG categories.RESULTSOf 1112 participants, 346 (34.2%) had a CAC score >0. FPG values in the IFG patients were positively but weakly correlated with CAC scores (r=0.099, P=.001). The incidence of CAC differed according to FPG level (P<.001) and in Kruskal-Wallis test the mean CAC score differed by FPG group (P<.001). After adjustment for other factors in a multiple logistic regression analysis, those subjects with FPG ≥110 mg/dL had a significantly higher risk of CAC than did subjects with normal fasting glucose (110≤FPG [mg/dL] <120, OR=2.507, P=.002; 120≤FPG [mg/dL] <126, OR=3.568, P=.001 vs. <100 mg/dL)CONCLUSIONIFG (especially FPG≥110 mg/dL) could be an independent risk factor for CAC. These associations were not altered after adjustment for other possible confounders.LIMITATIONSPossible misclassification because data taken from a single blood test. No HbA1c tests or repeated FPG tests. No adjustment for other potentially important confounders.

Antidepressant Use and Subclinical Measures of Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis.

Antidepressants are commonly prescribed medications used in primary care. The cardiovascular safety profile of antidepressant medications, in terms of subclinical atherosclerosis, is underexamined. A total of 6814 participants in the Multi-Ethnic Study of Atherosclerosis were examined. At baseline, the mean age was 62 years with 4 race/ethnic groups represented: European Americans (38%), Hispanic Americans (23%), African Americans (28%), and Chinese Americans (11%). Antidepressants were subgrouped as serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and "other" (bupropion, nefazodone, trazodone, mirtazapine). After adjusting for potential confounders, we estimated the association between antidepressant use and the following measures of subclinical atherosclerosis: coronary artery calcium (CAC), the ankle-brachial index, and carotid intima-media thickness, both cross-sectionally and prospectively. A total of 324 participants were exposed to SSRIs, 88 to TCAs, 41 to SNRIs, and 123 to other antidepressants. For CAC incidence, the fully adjusted longitudinal analyses revealed no consistent associations with SSRIs (relative risk [RR], 0.99; 95% confidence interval [CI], 0.71-1.37), SNRIs (RR, 0.49; 95% CI, 0.13-1.86), TCAs (RR, 0.94; 95% CI, 0.50-1.77), other antidepressant (RR, 0.87; 95% CI, 0.73-1.03) exposure, and subclinical disease. Similar null results were obtained in the cross-sectional and longitudinal exposure to antidepressants with changes in baseline CAC greater than 0, ankle-brachial index, and carotid intima-media thickness. The results of the current study do not support an association between antidepressants and subclinical atherosclerosis.

Abstract P025: Trimethylamine N-oxide Not Associated with Coronary Artery Calcium in Healthy, Young Adults with Normal Kidney Function: Coronary Artery Risk Development in Young Adults Study, 2000-2011

Objective: Trimethylamine N-oxide (TMAO), a gut microbiota-dependent nutrient metabolite, has been implicated in the development of cardiovascular disease (CVD). TMAO is excreted in the urine and high levels may reflect poor kidney function, an independent risk factor for CVD. We tested the association between TMAO and coronary artery calcium (CAC) in a young, healthy sample of US adults with normal kidney function. Methods: Study participants were from the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a multicenter cohort of black and white Americans established in 1985/86 (baseline n=5,115; ages 18-30). CAC was measured at follow-up years 15, 20, and 25 with computed tomography (CT). Among a subsample of participants with no detectable CAC at year 15 who had complete CAC data (years 15, 20, 25) and covariate data (year 15) (n=746), we measured TMAO (uM) in year 15 stored plasma (-70 C) and defined incident CAC as having total Agatston units ≥ 0 across all arteries at year 20 or 25. TMAO was measured by using liquid chromatography mass spectrometry. Multivariable-adjusted logistic regression was used to estimate the 10-year incidence of CAC (% who developed any CAC) across quartiles of year 15 TMAO. Results: Among 746 participants without CAC at year 15, 184 developed CAC over the 10-year study period. TMAO was not associated with incident CAC in multivariable-adjusted logistic regression models, controlling for demographic, behavioral, and biologic covariates (see Table). Comparing quintiles 1 and 5 of TMAO, the multivariable-adjusted risk (%) of the cohort who developed CAC over the 10-year period was 26% (95% CI: 18%-36%) and 22% (16%-31%), respectively. Conclusion: In this population-based cohort of healthy middle-aged US adults with normal kidney function (99% eGFR≥60 ml/min/1.73 m2), TMAO was not associated with incident CAC over 10 years of follow-up. These findings do not support a role for TMAO in the progression of atherosclerosis among young (33-45 y) healthy individuals with normal kidney function.

Incidence and progression of coronary artery calcium in HIV-infected and HIV-uninfected men.

The aim of this article is to determine whether HIV-infected (HIV+) men have either higher incidence or more rapid progression of coronary artery calcium (CAC) compared with HIV-uninfected (HIV-) controls. Prospective observational study. Multicenter study in four US academic research centers: University of Pittsburgh, Johns Hopkins University, University of California Los Angeles, and Northwestern University. Eight hundred and twenty-five men (541 HIV+ and 284 HIV-) enrolled in the cardiovascular substudy of the Multicenter AIDS Cohort Study who underwent serial cardiac computed tomography (CT) imaging during a mean follow-up of 5 years (range, 2-8 years). Incidence and progression of CAC assessed by cardiac CT. During follow-up, 21% of HIV+ men developed incident CAC compared with 16% of HIV- men. This association persisted after adjustment for traditional and HIV-associated risk factors: hazard ratio 1.64 (1.13-3.14). However, there was no association between HIV serostatus and CAC progression among men with CAC present at baseline. Current smoking and increased insulin resistance, both modifiable risk factors, were independently associated with increased incidence of CAC. No evidence supporting an elevated risk for either CAC progression or incidence was found for either dyslipidemia or long-term usage of antiretroviral therapy. In this large study of HIV+ and HIV- men who underwent serial cardiac CT scan imaging, HIV+ men were at significantly higher risk for development of CAC: hazard ratio 1.64 (1.13-3.14). In addition, two important and modifiable risk factors were identified for increased incidence of CAC. Taken together, these findings underscore the potential importance for smoking cessation and interventions to improve insulin resistance among HIV+ men.