Baseline Coronary Artery Calcium Score Research Articles

Impact of Nonalcoholic Hepatic Steatosis on the Warranty Period of a Coronary Artery Calcium Score of 0: Results From the Multi-Ethnic Study of Atherosclerosis.

For individuals with a coronary artery calcium (CAC) score of 0, CAC rescans at appropriate timings are recommended, depending on individual risk profiles. Although nonalcoholic fatty liver disease, recently redefined as metabolic-associated fatty liver disease, is a risk factor for atherosclerotic cardiovascular disease events, its relationship with the warranty period of a CAC score of 0 has not been elucidated. A total of 1944 subjects from the MESA (Multi-Ethnic Study of Atherosclerosis) with a baseline CAC score of 0, presence or absence of nonalcoholic hepatic steatosis, and at least 1 follow-up computed tomography scan were included. Nonalcoholic hepatic steatosis was defined using nonenhanced computed tomography and liver/spleen attenuation ratio <1. The association between nonalcoholic hepatic steatosis and new CAC incidence (CAC score >0) was evaluated using a Weibull survival model. Nonalcoholic hepatic steatosis was identified in 268 (14%) participants. Participants with nonalcoholic hepatic steatosis had higher CAC incidence than those without nonalcoholic hepatic steatosis. Nonalcoholic hepatic steatosis was independently associated with new CAC incidence after adjustment for atherosclerotic cardiovascular disease risk factors (hazard ratio, 1.28 [95% CI, 1.05-1.57]; P=0.015). Using a 25% testing yield (25% of participants with zero CAC at baseline would be expected to have developed a CAC score >0), the warranty period of a CAC score of 0 in participants with nonalcoholic hepatic steatosis was shorter than in those without nonalcoholic hepatic steatosis (4.7 and 6.3 years). This association was consistent regardless of sex, race/ethnicity, age, and 10-year atherosclerotic cardiovascular disease risk. Nonalcoholic hepatic steatosis had an impact on the warranty period of a CAC score of 0. The study suggests that the time period until a CAC rescan should be shorter in those with nonalcoholic hepatic steatosis and a CAC score of 0.

#1200 Coronary artery calcium modifies the relationship between blood pressure and adverse kidney outcome: results from KNOW-CKD

Abstract Background and Aims Previous studies evidenced that elevated coronary artery calcium (CAC) score is associated with higher chronic kidney disease (CKD) progression. However, the use of CAC score to guide CKD management has not been adequately evaluated. Here, we evaluated whether presence of CAC modify the association between systolic blood pressure (SBP) and CKD progression in patients with CKD. Method We analyzed 1693 participants with CKD stages G1 to G5 from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Key exclusion criteria were kidney failure with replacement therapy (KFRT) and missing data for CAC and SBP information. We categorized participants according to baseline SBP and CAC score (Controlled BP, SBP &amp;lt; 120 mmHg; Elevated BP without CAC, SBP 120-140 mmHg and CAC score = 0; Elevated BP with CAC, SBP 120-140 mmHg and CAC score &amp;gt;0; Uncontrolled BP, SBP &amp;gt;140 mmHg) and compared the CKD progression. The CKD progression was defined as a composite of halving eGFR from baseline value or onset of KFRT. Results During 10,023 person-years of follow-up (median 6.2 years), the composite outcome occurred in 689 (40.7%) participants, and 108 (6.4%) participants died among the KNOW-CKD participants. There was significant interaction between CAC score and SBP for CKD progression (P &amp;lt; 0.001). There were 181/568 (31.9%), 167/424 (39.4%), 128/314 (40.8%) 213/387 (55.0%), composite outcomes in controlled BP, elevated BP without CAC, elevated BP with CAC, uncontrolled BP group, respectively. In crude Cox regression, compared to controlled BP, elevated BP with CAC group showed similar CKD progression risk (Hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.95-1.44), whereas other strata group showed increased risk of CKD progression (elevated BP with CAC; HR, 1.59; 95% CI 1.31-1.94 and uncontrolled BP, HR, 1.94; 95% CI 1.56-2.41). Similar elevated risk in elevated BP with CAC was observed even after adjustment of age, sex, diabetes mellitus, estimated glomerular filtration ratio, and proteinuria (HR, 1.26; 95% CI, 1.02-1.56). However, the risk of CKD progression in elevated BP without CAC group was comparable to controlled BP group (HR, 1.20; 95% CI, 0.87-1.66). Conclusion Elevated SBP was more strongly associated with an increased risk of adverse kidney outcomes in patients with coronary calcification.

Association of Lipoprotein(a) with Progression of Coronary Artery Calcification: Retrospective Longitudinal Study.

Atherosclerotic cardiovascular disease (ASCVD) is a major health concern, and lipoprotein(a) (Lp(a)) is an independent risk factor. However, there is limited evidence regarding Lp(a) and the risk of ASCVD in Asian populations. This study aimed to assess the predictive value of changes in coronary artery calcification (CAC) for ASCVD risk associated with Lp(a) level. Participants (n=2,750) were grouped according to their Lp(a) levels, and the association between Lp(a) and CAC progression was examined. CAC progression was defined as the occurrence of incident CAC or a difference ≥2.5 between the square root (√) of baseline and follow-up coronary artery calcium scores (CACSs) (Δ√transformed CACS). To adjust for differences in follow-up periods, Δ√transformed CACS was divided by the follow- up period (in years). Over an average follow-up of 3.07 years, 18.98% of participants experienced CAC progression. Those with disease progression had notably higher Lp(a) levels. Higher Lp(a) tertiles correlated with increased baseline and follow-up CACS, CAC progression (%), and Δ√transformed CACS. Even after adjustment, higher Lp(a) levels were associated with CAC progression. However, annualized Δ√transformed CACS analysis yielded no significant results. This study demonstrated an association between elevated Lp(a) levels and CAC progression in a general population without ASCVD. However, longer-term follow-up studies are needed to obtain meaningful results regarding CAC progression. Further research is necessary to utilize Lp(a) level as a predictor of cardiovascular disease and to establish clinically relevant thresholds specific to the Korean population.

Impact of Arterial Calcification on Cardiovascular and Renal Outcomes in Kidney Transplant Patients

Plain Language SummaryArterial calcification, accumulation of calcium in the arterial walls, vascular stiffness, and loss of elasticity of blood vessels can contribute to the development of cardiovascular diseases. Patients with chronic kidney disease and those undergoing dialysis have a considerably increased risk of vascular calcification. Even after kidney transplantation when kidney function has been restored, the prevalence of vascular calcification and subsequent cardiovascular disease remains high. Coronary artery calcification score and abdominal aortic calcification score are both well-established markers of vascular calcification. However, the impact of pretransplant vascular calcification scores on cardiovascular and renal outcomes in kidney transplant patients has not been established. When we analyzed 944 Korean kidney transplant patients, both vascular calcification scores were significantly associated with cardiovascular outcomes after kidney transplantation, but were not associated with renal outcomes. We also demonstrated that the addition of coronary artery calcification scores led to a modest improvement in the prediction performance for kidney transplant outcomes. Our findings suggest a potential role of pretransplant screening of coronary calcification scores and aortic calcification scores in risk stratification for post-kidney transplant outcomes.

Abstract P336: The Association of Coronary Artery Calcium Progression and Cognitive Function in Midlife - The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Background: Little is known about the impact of coronary artery calcium (CAC) and its progression on cognitive function in midlife, a time of importance for cognitive aging. Methods: In CARDIA, CAC was measured using computed tomography at years 15 (baseline), 20 and 25. CAC progression was defined as: (1) CAC&gt;0 at follow-up among participants with baseline CAC=0; (2) an annualized change of ≥10 units at follow-up among those with 0&lt;baseline CAC&lt;100; or (3) an annualized percent change (annualized change in CAC score divided by baseline CAC score) ≥10% among those with baseline CAC≥100. Cognitive function was measured with Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), Stroop Interference, Montreal Cognitive Assessment (MoCA) and Verbal Fluency (Letter and Category Fluency) at year 35. We used linear regression to estimate the difference between marginal means with 95% confidence intervals (CIs) of each cognitive test by CAC score (0 vs &gt;0) and CAC progression. Results: Among 2,341 participants (mean age 40.3 ± 3.6 years, 56% female, 43% Black at baseline), higher CAC score and CAC progression were associated with significantly lower cognitive performance in all cognitive tests. After adjustment for demographics, the association remained for CAC progression, compared to no progression, for most test scores: DSST (-2.70 95% CI: -4.05 to -1.36, p &lt; 0.001), MoCA (-0.44 95% CI: -0.74 to -0.13, p = 0.005) and verbal fluency (-0.85 95% CI: -1.57 to -0.12, p = 0.02). Similar associations were observed for higher CAC score (&gt;0 vs 0): DSST (-3.11 95% CI: -5.16 to -1.06, p = 0.003), MoCA (-0.81 95% CI: -1.28 to -0.34, p = 0.001) and RAVLT (-0.67 95% CI: -1.12 to -0.23, p = 0.003). Additional adjustment for physical activity, depressive symptoms, and APOE, and mutually for baseline CAC score and progression did not materially change the association. Conclusions: CAC score and progression were associated with lower cognitive function in midlife. CAC progression may be an independent risk factor for early cognitive aging, independent of baseline CAC score and other risk factors.

Eicosapentaenoic and docosahexaenoic acid supplementation and coronary artery calcium progression in patients with coronary artery disease: A secondary analysis of a randomized trial

Background and aimsWe previously reported that an omega-3 fatty acid index ≥4% with high-dose eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) prevented progression of noncalcified plaque. Higher coronary artery calcium (CAC) scores and progression of CAC are associated with increased cardiovascular events and mortality. We examined the effect of EPA + DHA on CAC score. MethodsA total of 242 patients with coronary artery disease (CAD) on statin therapy were randomized to 1.86 g EPA and 1.5 g DHA daily or none (control) for 30 months. The CAC score was measured at baseline and 30-months with non-contrast, cardiac computed tomography. ResultsBoth EPA + DHA and control groups had significant progression in CAC scores over 30 months (median change:183.5 vs 221.0, respectively, p < 0.001) despite a 13.6% reduction in triglyceride level with EPA + DHA. No significant difference was observed between groups for the total group, by baseline CAC scores of <100, 100–399, 400–999 and ≥1000 or quartiles of achieved levels of EPA, DHA and the omega-3 fatty acid index. Similar rates of CAC progression were noted in those on high-intensity statin compared to low- and moderate-intensity statin. ConclusionsEPA and DHA added to statin resulted in similar CAC progression over 30 months regardless of baseline CAC categories, statin intensity and achieved levels of EPA, DHA and the omega-3 fatty acid index.

Differences in left anterior descending coronary artery disease in participants without standard modifiable cardiovascular risk factors: the Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract Background/Introduction The development of coronary artery disease (CAD) and myocardial infarction (MI) in the absence of standard modifiable cardiovascular risk factors (SMuRFs) has been highlighted as an unmet clinical need, accounting for between 10-27% of ST elevation MI and associated with higher 30-day mortality. One potential contributor to the early mortality is the higher observed rates of LAD territory culprit lesions in SMuRFless patients compared to those with at least one SMuRF. Purpose To characterise the differential proportion of LAD disease in an asymptomatic population with no prior cardiovascular disease (CVD) history, comparing individuals with CAD despite no SMuRFs to those with at least one SMuRF in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods A MESA sub-cohort with a baseline coronary artery calcium score (CACS) &amp;gt;0 Agatston units (AU) was prepared. SMuRF status was assigned by self-report, treatment, or biomarkers for hypertension, hypercholesterolaemia, diabetes, and smoking. Proportion of disease in the left main, LAD, circumflex, and right coronary arteries were calculated by the vessel CACS divided by the total CACS. Standard descriptive statistics were used to characterise baseline differences. Group comparisons were completed with Wilcoxon rank sum for continuous measures and Chi-square for categorical. Results A CAC positive cohort of 3,417 participants was prepared from participants with SMuRF and CT imaging data, 14.3% of whom were considered SMuRFless. Total CACS was lower in SMuRFless participants compared to those with ≥1 SMuRF (58 AU vs. 102 AU, p&amp;lt;0.0001). However, proportion of calcium burden in the LAD was significantly higher in SMuRFless participants with CAD (74.2% vs. 56.8%, p&amp;lt;0.0001). When considering clinically significant CACS strata, proportion of LAD calcium burden was not significantly different between SMuRFless vs. ≥1 SMuRF participants with a total CACS of 1-99 AU (93.7% vs. 80.0%). However, statistically significant differences in LAD calcium proportion were observed between SMuRFless vs. ≥1 SMuRF participants with a total CACS 100-400 AU (69.5% vs. 57.8%) and CACS&amp;gt;400AU (45.2% vs. 40.5%). This difference remained significant during multivariate modelling, including consideration of absolute CACS. Conclusion Of patients with evidence of CAD (CACS&amp;gt;0) in the MESA cohort, SMuRFless status was associated with a higher proportion of LAD disease compared to participants with ≥1 SMuRF. This adds to previous observations in STEMI cohorts suggesting a heightened susceptibility to atherosclerosis development in the LAD territory against a lower traditional risk burden, and highlights the need for consideration of distinct biology and clinical significance in future studies.Fig. 1Fig. 2

Incorporating a polygenic risk score into cardiovascular disease examinations to identify subclinical coronary artery disease: rationale and design of the ESCALATE trial

Abstract Background Identifying and targeting established modifiable risk factors such as hyperlipidaemia, blood pressure, smoking, and diabetes have led to a successful reduction in poor outcomes from coronary artery disease (CAD) at the population-level. However, up to one-in-four patients who present with ST elevation myocardial infarction do so in the absence of such risk factors. There is a significant unmet need for new diagnostic strategies independent of these factors to detect CAD in its subclinical phase. Polygenic risk scores (PRS) have demonstrated an ability in cohort studies to improve risk prediction models independent of traditional risk factors and self-reported family history. However, there is a lack of data from implementation and interventional studies demonstrating efficacy, participant and provider experience, and cost effectiveness of utilising PRS. Aim The aim of this study is to examine the incorporation of a CAD PRS during primary care-based cardiovascular disease (CVD) risk assessments to identify low or intermediate risk individuals with newly diagnosed CAD and subsequent impact on shared treatment decisions, participant experience, and provider experience. Our hypothesis is that incorporating a CAD PRS-based decision tool for a coronary calcium scan into CVD risk assessments will identify new, potentially missed individuals with subclinical CAD. Methods The ESCALATE study is a 12-month, prospective, multi-centre implementation study incorporating CAD PRS into otherwise standard primary care CVD risk assessments, identifying patients at increased lifetime CAD risk, for non-invasive CT coronary imaging. 1,000 eligible participants aged 45-65 years old will enter the PPP-CAD Diagnostic Pathway, which applies CAD PRS to those considered low or moderate 5-year absolute CVD risk based on traditional risk factors and triages those with CAD PRS ≥80% for a coronary calcium scan (Figure 1). The primary outcome will be the identification of subclinical CAD, defined as a coronary artery calcium score (CACS) &amp;gt;0 Agatston units (AU). Multiple secondary outcomes will be assessed, including baseline CACS ≥100 AU or ≥75th age-/sex-matched percentile, medical management strategies, cholesterol and blood pressure levels, health-related quality of life (HRQOL), and patient experience. Results Study recruitment was initiated recruitment in August 2022 and is actively recruiting across Australia. 298 participants have been enrolled as of 27th February 2022. Conclusion The ESCALATE study is the first prospectively registered clinical trial testing the ability of a CAD PRS to: a) identify individuals with subclinical CAD by non-invasive coronary imaging; and b) measure the impact of this diagnostic strategy on personalised diagnosis and shared decision-making. The top-line study results are expected in mid-2025.

Incorporating a polygenic risk score-triaged coronary calcium score into cardiovascular disease examinations to identify subclinical coronary artery disease (ESCALATE): Protocol for a prospective, nonrandomized implementation trial

Identifying and targeting established modifiable risk factors has been a successful strategy for reducing the burden of coronary artery disease (CAD) at the population-level. However, up to 1-in-4 patients who present with ST elevation myocardial infarction do so in the absence of such risk factors. Polygenic risk scores (PRS) have demonstrated an ability to improve risk prediction models independent of traditional risk factors and self-reported family history, but a pathway for implementation has yet to be clearly identified. The aim of this study is to examine the utility of a CAD PRS to identify individuals with subclinical CAD via a novel clinical pathway, triaging low or intermediate absolute risk individuals for noninvasive coronary imaging, and examining the impact on shared treatment decisions and participant experience. The ESCALATE study is a 12-month, prospective, multicenter implementation study incorporating PRS into otherwise standard primary care CVD risk assessments, to identify patients at increased lifetime CAD risk for noninvasive coronary imaging. One-thousand eligible participants aged 45 to 65 years old will enter the study, which applies PRS to those considered low or moderate 5-year absolute CVD risk and triages those with CAD PRS ≥80% for a coronary calcium scan. The primary outcome will be the identification of subclinical CAD, defined as a coronary artery calcium score (CACS) >0 Agatston units (AU). Multiple secondary outcomes will be assessed, including baseline CACS ≥100 AU or ≥75th age-/sex-matched percentile, the use and intensity of lipid- and blood pressure-lowering therapeutics, cholesterol and blood pressure levels, and health-related quality of life (HRQOL). This novel trial will generate evidence on the ability of a PRS-triaged CACS to identify subclinical CAD, as well as subsequent differences in traditional risk factor medical management, pharmacotherapy utilization, and participant experience. Australian New Zealand Clinical Trials Registry, ACTRN12622000436774. Trial was prospectively registered on March 18, 2022. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383134.

Risk Factors for Coronary Artery Calcifications in Overweight or Obese Persons with Prediabetes: Can They Predict T2 Diabetes and Coronary Vascular Events?

It is difficult to predict the risk of developing atherosclerotic cardiovascular disease in subjects with prediabetes and obesity. The aim of this study was to assess risk factors for coronary artery calcifications (CACs) and the development of type 2 diabetes (T2D) and coronary vascular events (CVEs) after 7 years in 100 overweight or obese persons with prediabetes, according to the baseline coronary artery calcium score (CACS). Lipids, HbA1c, uric acid, and creatinine were assessed. Glucose, insulin, and c-peptide were determined during an oral glucose tolerance test. Multi-sliced computerized tomography with evaluation of CACS was performed. After 7 years, the subjects were assessed for T2D/CVE. CACs were present in 59 subjects. No single biochemical marker could predict presence of a CAC. After 7 years, T2D developed in 55 subjects (61.8% initially had both IFG and IGT). A gain in weight was the only contributing factor for T2D. Nineteen subjects developed a CVE; increased initial clustering of HOMA-IR > 1.9, LDL > 2.6, and mmol/Land TGL > 1.7 mmol/L and higher CACS were present in that group. No risk factors for CACs could be identified. A gain in weight is associated with T2D development, as are higher CACS and clustering of high LDL+TGL+HOMA-IR with CVEs.

Coronary artery calcium and cystatin C for risk stratification of MACCEs and all-cause death in symptomatic patients.

The aim of this study was to examine the independent and joint associations of baseline coronary artery calcium score (CACS) and cystatin C (Cys-C) with the risk of major adverse cardiac and cerebrovascular events (MACCEs) and all-cause death in symptomatic populations. The study included 7140 patients with symptom of chest pain who underwent cardiac computerized tomography examinations to measure CACS. All of them had serum Cys-C results. Endpoints were set for MACCEs and all-cause death events. A total of 7140 participants were followed for a median of 1106 days. A total of 305 patients had experienced MACCEs and 191 patients had experienced all-cause death. CACS ≥ 100 and Cys-C ≥ 0.995 mg/L were independently associated with an increased risk of MACCEs (adjusted hazard ratio [HR]: 1.46; 95% confidence interval [CI]: 1.15-1.85; p = .002 and adjusted HR: 1.57; 95% CI: 1.24-2.00; p < .001, respectively). Compared with CACS < 100 and Cys-C < 0.995 mg/L patients, CACS ≥ 100 and Cys-C ≥ 0.995 mg/L patients had the highest risk of MACCEs and all-cause death (adjusted HR: 2.33; 95% CI: 1.64-3.29; p < .001 and adjusted HR: 2.85; 95% CI: 1.79-4.55; p < .001, respectively). Even in patients with CACS < 100, Cys-C ≥ 0.995 mg/L was also associated with a higher risk of MACCEs and all-cause death than Cys-C < 0.995 mg/L (adjusted HR: 1.76; p = .003 and adjusted HR: 2.02; p = .007, respectively). The combined stratification of CACS and Cys-C showed an incremental risk of MACCEs and all-cause death, reflecting complementary prognostic value. Our results support the combination of the two indicators for risk stratification and event prediction.

Dietary patterns and subclinical atherosclerosis incidence and progression: Results from ELSA-Brasil

Background and aimsCardiovascular disease (CVD) is the main cause of disease burden worldwide. Coronary artery calcification (CAC) score is a subclinical atherosclerosis marker able to predict the risk of CVD in asymptomatic patients, and few studies have investigated the association between dietary patterns (DP) and CAC score prospectively. Thus, the aim of this study was to estimate the association between baseline DP and CAC score incidence and progression on the ELSA-Brasil cohort. Methods and resultsThis study is a longitudinal prospective analysis of the ELSA-Brasil participants who underwent a CAC exam on baseline and follow-up (n = 2,824). CAC incidence was defined as a baseline CAC score equal to zero (n = 2,131) and subsequent follow-up CAC score greater than zero. CAC progression was defined according to the Hokanson method for the individuals who presented a CAC score greater than zero at the baseline (n = 639). Dietary data were assessed at the baseline using a food frequency questionnaire (FFQ), and factor analysis was applied to identify DP. Poisson regression models with robust variance and linear regression models were applied to estimate the association between baseline DP and CAC incidence and progression. The incidence of CAC was 14.6%, while 60.3% of the individuals presented CAC progression. Three DP were identified: convenience, Brazilian traditional, and prudent. We did not find a significant association between baseline DP and CAC incidence or progression. ConclusionOur findings from this longitudinal prospective analysis showed that baseline DP are not associated with CAC incidence or progression.

Incremental prognostic value of triglyceride glucose index additional to coronary artery calcium score in asymptomatic low-risk population

BackgroundThe triglyceride glucose (TyG) index has been suggested as a reliable surrogate marker of insulin resistance which is a substantial risk factor for atherosclerotic cardiovascular disease (ASCVD). Several recent studies have shown the relationship between the TyG index and cardiovascular disease; however, the role of the TyG index in coronary artery calcification (CAC) progression has not been extensively assessed especially in low-risk population.MethodsWe enrolled 5775 Korean adults who had at least two CAC evaluations. We determined the TyG index using ln (fasting triglycerides [mg/dL] x fasting glucose [mg/dL]/2). The CAC progression was defined as either incident CAC in a CAC-free population at baseline or an increase of ≥ 2.5 units between the square roots of the baseline and follow-up coronary artery calcium scores (CACSs) of subjects with detectable CAC at baseline.ResultsCAC progression was seen in 1,382 subjects (23.9%) during mean 3.5 years follow-up. Based on the TyG index, subjects were stratified into four groups. Follow-up CACS and incidence of CAC progression were markedly elevated with rising TyG index quartiles (group I [lowest]:17.6% vs. group II:22.2% vs. group III:24.6% vs. group IV [highest]: 31.3%, p < 0.001). In multivariate logistic regression analysis, the TyG index was independent predictor of CAC progression (odds ratio: 1.57; 95% confidence interval: 1.33 to 1.81; p < 0.001) especially in baseline CACS ≤ 100 group.ConclusionThe TyG index is an independent predictor of CAC progression in low-risk population. It adds incremental risk stratification over established factors including baseline CACS.

Relationship Between Coronary Artery Calcium and Atherosclerosis Progression Among Patients With Suspected Coronary Artery Disease

BackgroundAmong symptomatic patients, it remains unclear whether a coronary artery calcium (CAC) score alone is sufficient or misses a sizeable burden and progressive risk associated with obstructive and nonobstructive atherosclerotic plaque. ObjectivesAmong patients with low to high CAC scores, our aims were to quantify co-occurring obstructive and nonobstructive noncalcified plaque and serial progression of atherosclerotic plaque volume. MethodsA total of 698 symptomatic patients with suspected coronary artery disease (CAD) underwent serial coronary computed tomographic angiography (CTA) performed 3.5 to 4.0 years apart. Atherosclerotic plaque was quantified, including by compositional subgroups. Obstructive CAD was defined as ≥50% stenosis. Multivariate linear regression models were used to measure atherosclerotic plaque progression by CAC scores. Cox proportional hazard models estimated CAD event risk (median of 10.7 years of follow-up). ResultsAcross baseline CAC scores from 0 to ≥400, total plaque volume ranged from 30.4 to 522.4 mm3 (P < 0.001) and the prevalence of obstructive CAD increased from 1.4% to 49.1% (P < 0.001). Of those with a 0 CAC score, 97.9% of total plaque was noncalcified. Among patients with baseline CAC <100, nonobstructive CAD was prevalent (40% and 89% in CAC scores of 0 and 1-99), with plaque largely being noncalcified. On the follow-up coronary CTA, volumetric plaque growth (P < 0.001) and the development of new or worsening stenosis (P < 0.001) occurred more among patients with baseline CAC ≥100. Progression varied compositionally by baseline CAC scores. Patients with no CAC had disproportionate growth in noncalcified plaque, and for every 1 mm3 increase in calcified plaque, there was a 5.5 mm3 increase in noncalcified plaque volume. By comparison, patients with CAC scores of ≥400 exhibited disproportionate growth in calcified plaque with a volumetric increase 15.7-fold that of noncalcified plaque. There was a graded increase in CAD event risk by the CAC with rates from 3.3% for no CAC to 21.9% for CAC ≥400 (P < 0.001). ConclusionsCAC imperfectly characterizes atherosclerotic disease burden, but its subgroups exhibit pathogenic patterns of early to advanced disease progression and stratify long-term prognostic risk.

Relation of Progression of Coronary Artery Calcium to Dementia (from the Multi-Ethnic Study of Atherosclerosis)

Baseline coronary artery calcification has been shown to be associated with dementia. However, the value of coronary artery calcium (CAC) progression in the prediction of dementia remains unclear. In this study, we examined the association between CAC progression and dementia in the Multi-Ethnic Study of Atherosclerosis. The Multi-Ethnic Study of Atherosclerosis is a prospective study consisting of 6,814 participants 45 to 84years of age, free of overt cardiovascular disease at baseline. A total of 5,570 subjects had baseline and follow-up CAC scans approximately 2.5years apart and were included this analysis. A total of 4,173 of these participants completed cognitive testing with the Cognitive Abilities Screening Instrument (CASI) approximately 10years after the baseline CAC scan. Dementia diagnoses were identified using International Classification of Diseases codes from hospitalizations, death certificates, and medications used to treat dementia. The absolute change between baseline and follow-up CAC was used to assess CAC progression. Cox proportional hazards and multivariable linear regression models were used to examine the association of CAC progression with incident dementia and with CASI score. Over a median follow-up of 13.2 (interquartile range: 11.2 to 15.3) years, 350 participants developed incident dementia. CAC progression showed no association with dementia risk after adjustment for age, gender, race/ethnicity, vascular risk factors, and baseline CAC score. There was no association of CAC progression with CASI score in any adjusted model. In conclusion, progression of CAC over approximately 2.5years was not associated with increased risk of dementia after adjustment for demographic variables, vascular risk factors, and baseline CAC.

Abstract 10417: Parity and Progression of Coronary Artery Calcium: The Multi-Ethnic Study of Atherosclerosis

Introduction: Coronary artery calcium (CAC) is a measure of subclinical atherosclerosis and predicts cardiovascular disease (CVD) events. Higher parity, the number of live births, has been shown to relate to CVD. We examined whether parity is associated with progression of CAC as one pathway to CVD. Methods: We studied 2772 women aged 44 to 84 years free of CVD at baseline in the prospective Multi-Ethnic Study of Atherosclerosis. Parity was examined continuously as number of live births as well as by categories: 0-1 (reference), 2-3, and ≥4 in relation to change in CAC score from baseline to follow-up from repeat exams up to 11 years later. We used linear mixed effect models to account for repeated measures when assessing whether progression of CAC was associated with parity, adjusted for baseline CAC and other risk factors. Results: Women with higher parity had greater annualized progression of CAC scores (unadjusted p&lt;0.01) (figure). Using linear mixed effects modeling adjusted for age, ethnicity, baseline CAC scores, and other risk factors, parity was associated with progression of CAC (parity-CAC progression interaction terms): continuous parity (&lt;0.0001), parity 2-3 vs 0-1 (p=0.06), &gt; 4 vs. 0-1 (p&lt;0.0001). Conclusion: We show parity to be associated with the progression of CAC; this may help explain the increased CVD risk observed with higher parity and lends support to adding parity as a risk enhancing factor in women.

Coronary artery calcification progression and long-term cardiovascular outcomes in renal transplant recipients: an analysis by the joint model.

ABSTRACTBackground Compared with the general population, the risk of death is substantially higher in renal transplant recipients than in age- and sex-matched individuals in the general population. In the general population, coronary artery calcification (CAC) predicts all-cause and cardiovascular mortality. In this study we aimed to analyse these relationships in renal transplant recipients.MethodsWe examined 178 renal transplant patients in this prospective observational cohort study. We measured CAC with multidetector spiral computed tomography using the Agatston score at multiple time points. Overall, 411 scans were performed in 178 patients over an average 12.8 years follow-up. The clinical endpoint was a composite including all-cause death and non-fatal cardiovascular events. Data analysis was performed by the joint model.ResultsDuring a follow-up of 12.8 ± 2.4 years, coronary calcification progressed over time (P < 0.001) and the clinical endpoint occurred in 54 patients. In the analysis by the joint model, both the baseline CAC score and the CAC score progression were strongly associated with the incidence rate of the composite event [hazard ratio 1.261 (95% confidence interval 1.119–1.420), P = 0.0001].ConclusionsCAC at baseline and coronary calcification progression robustly predict the risk of death and cardiovascular events in renal transplant recipients. These findings support the hypothesis that the link between the calcifying arteriopathy of renal transplant patients and clinical end points in these patients is causal in nature.

Physical activity and the progression of coronary artery calcification

BackgroundThe association of physical activity with the development and progression of coronary artery calcium (CAC) scores has not been studied. This study aimed to evaluate the prospective association between physical...

IL-6 Is Associated with Progression of Coronary Artery Calcification and Mortality in Incident Dialysis Patients

Introduction: Inflammation is important in the pathogenesis of atherosclerosis. Elevated interleukin-6 (IL-6) is associated with cardiovascular events and also predicts mortality in individuals with CKD. Our goal was to determine the association between IL-6, FGF23, and high-sensitivity C-reactive protein (hsCRP) on coronary artery calcification (CAC) progression and mortality in incident dialysis patients without prior coronary events. Methods: A prospective cohort of incident adult dialysis participants had CAC measured by ECG-triggered multislice CT scans at baseline and at least 12 months later. Lipids, mineral metabolism markers, FGF23, and inflammatory markers, such as IL-6 and hsCRP, were measured at the baseline visit. Results: Participants in the high IL-6 tertile had the highest baseline CAC score (133.25 [10.35–466.15]) compared to the low (0.25 [0–212.2]) and intermediate (29.55 [0–182.85]) tertiles. Almost half of the participants with high IL-6 (15 of 32 [46.9%]) experienced progression of CAC compared to participants with low (8 of 32 [25%]) and intermediate (9 of 32 [28.1%]) (p = 0.05) IL-6 levels. Each log increase in IL-6 was associated with increase in death (hazard ratio 2.2, 95% CI: 1.2–3.8; p = 0.01). After adjusting for smoking, age, gender, race, diabetes, phosphate, and baseline calcium score, IL-6 (log) was associated with 2.2 times (95% CI: 1.1–4.6; p = 0.03) increase in death. Conclusion: IL-6 is associated with progression of CAC and mortality in incident dialysis patients.

MO563HIGH DIALYSATE MAGNESIUM AND CORONARY ARTERY CALCIFICATION IN MAINTENANCE HEMODIALYSIS PATIENTS*

Abstract Background and Aims Cardiovascular calcification is highly prevalent among patients with end-stage renal disease (ESRD). Low normal serum magnesium has been linked to a more severe degree of vascular calcification and a decrease in patient survival. An inhibitory effect of extracellular magnesium on osteogenic transformation of vascular smooth muscle cells and the upregulation of anti-calcification protein have been confirmed in vitro. Increased dialysate magnesium concentration has also been shown to lower calcification propensity of the serum of maintenance hemodialysis (HD) patients. Method This study is an investigator initiated, single-blinded, parallel-group, matched case-control clinical trial that investigated the effect of high dialysate magnesium concentration for 24 weeks on the progression of coronary artery calcification (CAC) in maintenance HD patients. The changes in laboratory data and bone mineral density (BMD) were also examined. Seventy-six ESRD patients underwent CAC screening by multi-slice computed tomography and BMD measurement by dual-x-ray absorptiometry. Only patients with Agatston score&amp;gt;300 were included. They were matched according to the initial CAC score that fell within 20% of one another. Twenty patients were assigned to high dialysate magnesium concentration of 1.75 mEq/L and the matched controls were kept on standard dialysate magnesium concentration of 0.7 mEq/L. CAC and BMD measurements were repeated after 24 weeks. Laboratory data were obtained prior to dialysis at study entry, 8-week intervals during the study and 2 weeks after the study ended. Results There were no significant differences in age, sex, BMI, underlying diseases, dialysis vintage, medications, baseline CAC scores and BMD. The median baseline CAC Agatston score (Volume score) were 1923 (720) and 1672 (785) in the standard and high dialysate groups, respectively. At the end of the study, a significant increase in the CAC score was observed in both groups. Because majority of the included patients had severe calcification burden at baseline, patients were categorized into 2 subgroups using the median baseline CAC Agatston (1600) and Volume scores (700) as cut-offs. Among patients with CAC Agatston score &amp;lt;=1600, CAC score increased significantly in the standard dialysate magnesium group (P&amp;lt;0.01) but was stable in the high dialysate magnesium group (P=0.33). Among patients with CAC Agatston score &amp;gt;1600, the severity of CAC worsened in both groups. The progression of CAC was analyzed by the difference between the follow-up and the baseline square root transformed Agatston and Volume scores. In subgroup of patients with less severe calcification, more patients in the standard dialysate magnesium group progressed compared to the high dialysate magnesium group (P=0.03). In subgroup of patients with more severe calcification, the number of progressors were comparable among the 2 groups. Serum and ionized magnesium levels increased substantially during the study and returned to baseline after the return to standard dialysate magnesium concentration. The highest predialysis serum magnesium was 3.8 mg/dL. Most patients who received high dialysate magnesium reported the disappearance of symptoms of muscle cramps (P=0.01) and requested the high dialysate magnesium be continued after the end of the study. There were no significant changes in serum calcium, phosphate or PTH levels. The decline in BMD was observed in both groups but the difference did not reach statistical significance. Conclusion High dialysate magnesium was well tolerated and could ameliorate the progression of CAC in maintenance HD patients with mild to moderate vascular calcification.