High Coronary Artery Calcium Score Research Articles

Additional value of the coronary artery calcium score in patients for whom myocardial perfusion imaging is challenging.

BACKGROUND Determination of prognosis based on ischemia detection, using single‑photon emission computed tomography myocardial perfusion imaging (SPECT‑MPI), can be challenging in patients with multiple affected coronary arteries. AIMS The aim of the study was to examine the outcomes of SPECT‑MPI combined with the coronary artery calcium score (CACS) to identify predictors of adverse cardiac events (ACEs) in patients for whom ischemia detection may be difficult using SPECT‑MPI. METHODS The study group included 195 patients with a history of chronic kidney disease, suspected ischemic cardiomyopathy, or left bundle branch block. All patients underwent SPECT‑MPI and CACS evaluation. During the follow‑up, ACEs were recorded. Perfusion and functional parameters as well as the CACS were analyzed to find the predictors of ACEs. RESULTS The ACEs were recorded in 58 individuals (29.7%) and were significantly associated with ischemia (P <0.001), abnormal functional parameters (P = 0.04), and higher CACSs (P <0.001). The optimal cutoff value of the CACS to predict an ACE was 530. Cox proportional hazards models revealed that age, mild and severe ischemia, functional abnormalities, and a CACS of 530 or higher were significant predictors of ACEs. In the subgroup of individuals without ischemia, a CACS of 530 or higher was significantly associated with poor outcome, while we recorded only 3 ACEs in these patients when the CACS was lower than 530. CONCLUSIONS The addition of the CACS to SPECT‑MPI improves the identification of patients at higher risk for ACEs, even in individuals for whom SPECT‑MPI is challenging.

Differences in association of lower bone mineral density with higher coronary calcification in female and male end-stage renal disease patients

BackgroundRisk of cardiac events and cardiovascular disease (CVD) in end-stage renal disease (ESRD) patients are predicted by coronary artery calcification (CAC) independently. It is not clear to what extent low bone mineral density (BMD) is associated with higher risk of CAC and if sex interacts. We investigated the sex-specific associations of CAC score with total body BMD (tBMD) as well as with BMD of different skeletal sub-regions.MethodsIn 174 ESRD patients, median age 57 (10th–90th percentiles 29–75) years, 63% males, BMD (measured by dual-energy X-ray absorptiometry; DXA), CAC score (measured by cardiac CT) and circulating inflammatory biomarkers were analysed.ResultsA total of 104 (60%) patients with CAC > 100 AUs were older, had higher prevalence of both clinical CVD and diabetes, higher level of high sensitivity C-reactive protein, tumour necrosis factor, interleukin-6 and lower T-score of tBMD. Female patients had significantly lower tBMD and BMD of all skeletal sub-regions, except head, than male patients. Female patients with high CAC (> 100 AUs) had significantly decreased T-score of tBMD, and lower BMD of arms, legs than those low CAC (≤ 100 AUs); elevated CAC score were associated with tBMD, T-score, Z-score of tBMD and BMD of arms and legs, while no such differences was observed in males. Multivariate generalized linear model (GLM) analysis adjusted for age, diabetes and hsCRP showed that in females per SD higher CAC score (1057 AUs) was predicted by either per SD (0.13 g/cm2) lower tBMD or per SD (0.17 g/cm2) lower BMD at legs. No such associations were found in male ESRD patients.ConclusionsIn female, but not male, lower BMD, in particular sub-regions of legs, was associated with higher CAC score independently. Low BMD has the potential to identify increased risk for high CAC score in ESRD patients.

The Predictive Value of Coronary Artery Calcium Scoring for Major Adverse Cardiac Events According to Renal Function (from the Coronary Computed Tomography Angiography Evaluation for Clinical Outcomes: An International Multicenter [CONFIRM] Registry)

The prognostic performance of coronary artery calcium score (CACS) for predicting adverse outcomes in patients with decreased renal function remains unclear. We aimed to examine whether CACS improves risk stratification by demonstrating incremental value beyond a traditional risk score according to renal function status. 9,563 individuals without known coronary artery disease were enrolled. Estimated glomerular filtration rate (eGFR, ml/min/1.73 m2) was ascertained using the modified Modification of Diet in Renal Disease formula, and was categorized as: ≥90, 60 to 89, and <60. CACS was categorized as 0, 1 to 100, 101 to 400, and >400. Multivariable Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) for major adverse cardiac events (MACE), comprising all-cause mortality, myocardial infarction, and late revascularization (>90 days). Mean age was 55.8 ± 11.5 years (52.8% male). In total, 261 (2.7%) patients experienced MACE over a median follow-up of 24.5 months (interquartile range: 16.9 to 41.1). Incident MACE increased with higher CACS across each eGFR category, with the highest rate observed among patients with CACS >400 and eGFR <60 (95.1 per 1,000 person-years). A CACS >400 increased MACE risk with HR 4.46 (95% CI 1.68 to 11.85), 6.63 (95% CI 4.03 to 10.92), and 6.14 (95% CI 2.85 to 13.21) for eGFR ≥90, 60 to 89, and <60, respectively, as compared with CACS 0. Further, CACS improved discrimination and reclassification beyond Framingham 10-year risk score (FRS) (AUC: 0.70 vs 0.64; category free-NRI: 0.51, all p <0.001) for predicting MACE in patients with impaired renal function (eGFR < 90). In conclusion, CACS improved risk stratification and provided incremental value beyond FRS for predicting MACE, irrespective of eGFR status.

Abstract 43: Characteristics of Intracranial Cerebral Aneurysms According to the Coronary Artery Calcium

Introduction: Several vascular risk factors are known to be associated with the presence of intracranial cerebral aneurysm. Coronary artery calcium (CAC) which reflects the atherosclerotic burden of coronary artery is a known predictor of cardiovascular event and stroke. We investigated the relationship between cerebral aneurysm and CAC. Methods: We retrospectively enrolled subjects who had both brain magnetic resonance angiography and cardiac computed tomography as part of health examinations from January 2010 to July 2017. Subjects were categorized into four groups according to the CAC score by cardiac computed tomography; none (0), low (1-99), intermediate (100-399) and high (&gt; 400). The prevalence of cerebral aneurysm according to the CAC score groups was assessed. We also performed subgroup analysis by the sex, age and location of intracranial cerebral aneurysm. Results: Total 4934 subjects (age 54.1 ± 9.8 years, female 42.2%) were included for analysis. Cerebral aneurysms were detected in 258 subjects (5.23%). The prevalence of cerebral aneurysm was significantly increased as the CAC score increased (4.8%, 5.4%, 6.4% and 11.1%, respectively, p for trend = 0.004). This correlation was more prominent in women than in men over the age of 50 (7.1% vs 3.7, 8.8% vs 4.4%, 8.6% vs 6.3%, and 21.1% vs 10.0%, respectively). As to the aneurysm location, non-bifurcation aneurysm was more common than bifurcation aneurysm in high CAC score group (p=0.02). In multivariate analysis, the group of high CAC score had significantly more cerebral aneurysm than group of no CAC score (adjust odds ratio = 2.16, 95% confidence interval 1.18-3.95). Conclusions: CAC which reflects coronary artery atherosclerosis is also an important risk factor of intracranial cerebral aneurysm. This correlation is more prominent in female and non-bifurcation aneurysm.

Association of Retinal Artery Occlusion with Subclinical Coronary Artery Disease.

BackgroundTo evaluate the association between retinal artery occlusion (RAO) and subclinical coronary artery disease (CAD).MethodsWe studied 41 patients with non-arteritic RAO without any history or symptoms of CAD, who had undergone coronary computed tomographic angiography (CCTA) for systemic atherosclerotic evaluation between 2007 and 2012. The age- and gender-matched control group comprised 4-fold subjects who were randomly selected from asymptomatic subjects who underwent CCTA during general health evaluation. Medical records and CCTA findings were compared between RAO patients and control groups. Multiple logistic regression analysis was carried out to assess the risk factors associated with CAD.ResultsCardiovascular risk factors were not significantly different between RAO patients and control groups. RAO patients showed higher coronary artery calcium score than did control subjects (267.9 ± 674.9 vs. 120.2 ± 289.5). On CCTA, the prevalence of obstructive CAD (diameter stenosis ≥ 50%) in RAO patients was significantly higher than that in controls (29% vs. 15%; odds ratio [OR], 3.0). RAO patients demonstrated a significantly higher segment-involvement score (SIS) (2.6 ± 3.0 vs. 1.6 ± 2.4) and segment-stenosis score (SSS) (3.6 ± 4.8 vs. 2.0 ± 3.3) than did controls. After adjustment of associated factors, RAO showed significant association (OR, 3.0) with obstructive CAD and extensive CAD (SIS > 4: OR, 2.8; SSS > 8: OR, 3.4).ConclusionPatients with RAO had a higher prevalence of subclinical obstructive CAD with a more extensive and heavier burden of coronary artery plaques than did age- and gender-matched controls. Physicians should understand the potential risk of CAD in RAO patients.

Inverse J-shaped relation between coronary arterial calcium density and mortality in advanced chronic kidney disease.

The coronary artery calcium (CAC) score from cardiac computed tomography (CT) is a composite of CAC volume and CAC density. In the general population, CAC volume is positively and CAC density inversely associated with cardiovascular disease (CVD) events, implying that decreased CAC density reflects atherosclerotic plaque instability. We analysed associations of CAC indices with mortality risk in patients with end-stage renal disease [chronic kidney disease Stage 5 (CKD5)]. In 296 CKD5 patients undergoing cardiac CT (median age 55 years, 67% male, 19% diabetes, 133 dialysed), the Framingham risk score (FRS), presence of CVD and protein-energy wasting (PEW; subjective global assessment) and high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) were determined at baseline. During follow-up for a median of 35 months, 51 patients died and 75 patients underwent renal transplantation. All-cause mortality risk was analysed with competing-risk regression models. Vascular calcification was analysed in biopsies of the arteria epigastrica inferior in 111 patients. Patients in the middle tertile of CAC density had the highest CAC score, CAC volume, age, CVD, PEW, FRS, hsCRP and IL-6. In competing risk analysis, the middle {subhazard ratio [sHR] 10.7 [95% confidence interval (CI) 2.0-57.3]} and high [sHR 8.9 (95% CI 1.5-51.8)] tertiles of CAC density associated with increased mortality, independent of CAC volume. The high tertile of CAC volume, independent of CAC density, associated with increased mortality [sHR 8.9 (95% CI 1.5-51.8)]. Arterial media calcification was prominent and associated with CAC volume and CAC density. In CKD5, mortality increased linearly with higher CAC score and CAC volume whereas for CAC density an inverse J-shaped pattern was observed, with the crude mortality rate being highest for the middle tertile of CAC density. CAC volume and CAC density were associated with the extent of arterial media calcification.

Increased burden of coronary artery calcium from elevated blood pressure in low-risk young adults

Background and aimsThe relationship between blood pressure (BP) levels given in the new hypertension guidelines by the American College of Cardiology and the American Heart Association (ACC/AHA) and subclinical coronary atherosclerosis in low-risk young adults is unknown. We evaluated the association between the new BP categories and coronary artery calcium (CAC) in low-risk, young and middle-aged adults. MethodsWe performed a cross-sectional study of 96,166 Koreans who underwent a health examination including cardiac tomography estimation of CAC scores in 2012–2017. BP categories were defined according to the 2017 ACC/AHA guidelines. We used Poisson regression models with robust variance to calculate prevalence ratios (PRs) with 95% confidence intervals (CIs) for prevalent CAC >0. ResultsOverall, higher BP categories were associated with higher CAC scores in both young (aged 20–39) and middle-aged people (aged 40 years or more). After adjusting for possible confounders, including traditional cardiovascular disease (CVD) risk factors, the multivariable-adjusted PRs (95% CI) for prevalent CAC, comparing elevated BP and stage 1 and 2 hypertension to normal BP, were 1.27 (1.08–1.49), 1.45 (1.28–1.63), and 2.02 (1.67–2.43), respectively, among those aged 20–39 years and 1.25 (1.15–1.36), 1.29 (1.23–1.35), and 1.46 (1.36–1.57), respectively, among those aged ≥40 years. This association was also evident in those with a 10-year CVD risk of <10%. ConclusionsHigher BP categories were positively associated with prevalent CAC, and that association began in the elevated BP category, even in a young and low-risk population.

Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease

IntroductionProteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex CVD-1, Olink Bioscience, Uppsala, Sweden) in a discovery cohort of dialysis patients, the Mapping of Inflammatory Markers in Chronic Kidney disease cohort [MIMICK; n = 183, 55% women, mean age 63 years, 46 cardiovascular deaths during follow-up (mean 43 months)]. Significant results were replicated in the incident and prevalent hemodialysis arm of the Salford Kidney Study [SKS dialysis study, n = 186, 73% women, mean age 62 years, 45 cardiovascular deaths during follow-up (mean 12 months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n = 89, 37% women, mean age 46 years).ResultsIn age and sex-adjusted Cox regression in MIMICK, 11 plasma proteins were nominally associated with cardiovascular mortality (in order of significance: Kidney injury molecule-1 (KIM-1), Matrix metalloproteinase-7, Tumour necrosis factor receptor 2, Interleukin-6, Matrix metalloproteinase-1, Brain-natriuretic peptide, ST2 protein, Hepatocyte growth factor, TNF-related apoptosis inducing ligand receptor-2, Spondin-1, and Fibroblast growth factor 25). Only plasma KIM-1 was associated with cardiovascular mortality after correction for multiple testing, but also after adjustment for dialysis vintage, cardiovascular risk factors and inflammation (hazard ratio) per standard deviation (SD) increase 1.84, 95% CI 1.26–2.69, p = 0.002. Addition of KIM-1, or nine of the most informative proteins to an established risk-score (modified AROii CVM-score) improved discrimination of cardiovascular mortality risk from C = 0.777 to C = 0.799 and C = 0.823, respectively. In the SKS dialysis study, KIM-1 predicted cardiovascular mortality in age and sex adjusted models (hazard ratio per SD increase 1.45, 95% CI 1.03–2.05, p = 0.034) and higher KIM-1 was associated with higher CACscores in the CKD5-LD-RTx-cohort.ConclusionsOur proteomics approach identified plasma KIM-1 as a risk marker for cardiovascular mortality and coronary artery calcification in three independent ESRD-cohorts. The improved risk prediction for cardiovascular mortality by plasma proteomics merit further studies.

Abstract 17248: Statin Therapy Increases Coronary Artery Calcification Scores

Introduction: Coronary artery calcification (CAC) assessment is a noninvasive test to determine atherosclerotic burden. There has been a discordance with the well-known lipid lowering and cardiovascular protection of statins and the progression of CAC in small trials with narrow inclusion criteria. We performed a subgroup analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) dataset to assess the impact of statins on patients with a baseline CAC score of 0. Hypothesis: Statin usage will cause patients to have a higher CAC scores despite lowering LDL and reducing cardiac mortality. Methods: A subgroup analysis (3235 patients) was performed on the MESA dataset to identify patients with a CAC score of 0 at baseline. Statin usage and cholesterol values were reviewed at 4 examination points. Multivariate regression was performed. Results: The number of patients using statins (Table 1) and lipid levels (Table 2) increased throughout the study as expected for an aging population. A consistently larger increase in CAC score was noted in patients receiving statins; this difference was demonstrated in all stratified groups by Framingham score (Table 3). Table 4 shows the results of multivariate linear regression. Excluding gender, statins had the largest impact on CAC; more than any established cardiovascular risk factor. Conclusion: This large subgroup analysis of the MESA dataset demonstrates that statins are associated with increasing CAC score. While this is in contrast to the well-established cardiovascular protection of statin therapy, it adds to the growing literature that statin use is associated with progression of CAC, even in low risk patients with baseline CAC of 0. One hypothesis for this finding is that statins promote coronary atheroma calcification which ultimately results in plaque stabilization and less likelihood for progression to unstable plaques. It is therefore necessary for clinicians to take into account statins when interpreting CAC scores.

Coronary artery calcium score in predicting periprocedural myocardial infarction in patients undergoing an elective percutaneous coronary intervention.

This study aimed to evaluate whether the coronary artery calcium score (CACS) measured with computed tomography coronary angiography (CTCA) predicts periprocedural myocardial infarction (PMI) in patients undergoing an elective percutaneous coronary intervention (PCI). A total of 197 patients with stable angina underwent elective PCI after CTCA. We evaluated CACS using CTCA and assessed the clinical risk factors for PMI. PMI was defined as an elevation of troponin I levels exceeding five times the upper limit of normal within 24 h after PCI. Patients were followed up for major adverse cardiovascular events for a median of 4.6 years. The prevalence of PMI was 18.7% (37 patients) and patients with PMI showed a trend toward a higher CACS (721±779 vs. 498±842, P=0.142). The prevalence of PMI showed a positive correlation with the CACS distribution [8.0%, first interquartile range (IQR); 14.3%, second IQR; 22.4%, third IQR; 30.6%, fourth IQR; P=0.002]. The CACS cut-off value for PMI was greater than 113 (area under the curve: 0.670; 95% confidence interval: 0.600-0.736; P<0.001). Patients with CACS greater than 113 before PCI showed a higher prevalence of PMI (26.2 vs. 5.6%, odds ratio: 5.994; P<0.001). Multivariate analysis showed that CACS greater than 113 was the main predictor for PMI (odds ratio: 3.61, 95% confidence interval: 1.145-11.363; P=0.028). In this study, the cumulative incidence of major adverse cardiovascular event was higher in patients with PMI (54.1 vs. 10.6%; P<0.001). This study suggests that high CACS measured with CTCA influences the occurrence of PMI, which is associated with worse cardiovascular outcomes.

Atherosclerosis and Microvascular Complications: Results From the Canadian Study of Longevity in Type 1 Diabetes.

Type 1 diabetes carries a significant risk for cardiovascular mortality, but it is unclear how atherosclerosis associates with microvascular complications. We aimed to determine the relationships between atherosclerotic burden and neuropathy, retinopathy, and diabetic kidney disease (DKD) in adults with a ≥50-year history of type 1 diabetes. Adults with type 1 diabetes (n = 69) underwent coronary artery calcification (CAC) volume scoring by wide-volume computerized tomography. Microvascular complications were graded as follows: neuropathy by clinical assessment, electrophysiology, vibration and cooling detection thresholds, heart rate variability, and corneal confocal microscopy; retinopathy by ultra-wide-field retinal imaging; and DKD by renal hemodynamic function measured by inulin and para-aminohippurate clearance at baseline and after intravenous infusion of angiotensin II. The cohort was dichotomized to high (≥300 Agatston units [AU]) or low (<300 AU) CAC and was stratified by diabetes status. A comparator group without diabetes (n = 73) matched for age and sex also underwent all study procedures except for retinal imaging. CAC scores were higher in participants with type 1 diabetes (median Agatston score 1,000 [interquartile range = 222, 2,373] AU vs. 1 [0.75] AU in comparators, P < 0.001). In participants with type 1 diabetes, high CAC scores associated with markers of neuropathy and retinopathy, but not with DKD, or renal hemodynamic function at baseline or in response to angiotensin II. The presence of high CAC in adults with longstanding type 1 diabetes was associated with large nerve fiber neuropathy and retinopathy but not with renal hemodynamic function, suggesting that neuropathy, retinopathy, and macrovascular calcification share common risk factors.

The associated risk factors for coronary artery calcium in asymptomatic individuals with and without diabetes in rural Central Appalachia

AimTo examine the risk factor of coronary artery calcium (CAC) in individuals with diabetes and those without diabetes in Central Appalachia. MethodsStudy population included 2479 asymptomatic participants who underwent CAC screening between August 2012 and November 2016. CAC score was classified into four categories [0 (no plaque), 1–99 (mild plaque), 100–399 (moderate plaque), and ≥400 (severe plaque)]. Multinomial logistic regression analyses were conducted to test the association between CAC and cardiovascular disease (CVD) risk factors among participants with diabetes, age and gender matched controls, and randomly selected controls. Results13.6% of total participants had diabetes. Around 69%, 59.8%, and 57.7% of the participants with diabetes, matched controls, and randomly selected controls had CAC score ≥1, respectively. Participants with diabetes had higher prevalence of all CVD risk factors than controls. Among participants with diabetes, hypertension and physical inactivity increased the odds of CAC = 100–399, while among those without diabetes, hypertension and hypercholesteremia increased the odds of having CAC = 1–99 and CAC ≥ 400. ConclusionHalf of study participants had subclinical atherosclerosis (i.e., CAC), and individuals with diabetes had higher CAC scores. This study suggests that individuals with diabetes in Central Appalachia might benefit from screening for CAC.

Extracellular Fluid Excess Is Significantly Associated With Coronary Artery Calcification in Patients With Chronic Kidney Disease.

BackgroundExtracellular fluid (ECF) excess is an independent predictor of cardiovascular morbidity in patients undergoing dialysis. This study aimed to investigate the relationship between ECF status, which is affected by renal function, and coronary artery calcification (CAC), which is a marker of cardiovascular disease, in patients with chronic kidney disease (CKD).Methods and ResultsA total of 1741 patients at all stages of pre‐dialysis CKD from the prospective observational cohort of CMERC‐HI (Cardiovascular and Metabolic Disease Etiology Research Center‐High Risk) were analyzed for the association between ECF status and CAC. ECF status was defined as extracellular water‐to‐total body water ratio (ECW/TBW) measured using bioelectrical impedance analysis. ECF excess was defined as ECW/TBW ≥0.390 or ≥0.400 depending on its severity. To define CAC, Agatston coronary artery calcium scores were measured. A total coronary artery calcium score of ≥400 was defined as CAC. The CKD stages were defined according to estimated glomerular filtration rate calculated using the CKD Epidemiology Collaboration equation. ECW/TBW and the proportion of ECF excess increased with progressing CKD stages. Multivariable logistic regression analyses showed that ECW/TBW was independently associated with CAC (per 0.01 increase of ECW/TBW, odds ratio 1.168, 95% confidence interval, 1.079–1.264, P<0.001). The adjusted R 2 for predicting higher coronary artery calcium scores and CAC significantly improved after ECW/TBW was added to conventional factors. This association was further confirmed by net reclassification and integrated discriminant improvements, sensitivity analysis, and subgroup analysis.Conclusions ECF status is independently associated with a high risk of CAC in patients with CKD.Study Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02003781.

Relationship between left main and left anterior descending arteries bifurcation angle and coronary artery calcium score in chronic kidney disease: A 3-dimensional analysis of coronary computed tomography.

BackgroundA high coronary artery calcium score (CACS) predicts a poor prognosis in patients with coronary artery disease. We examined the relationship between the bifurcation angle and the CACS of the left main (LM) and left anterior descending (LAD) arteries in patients suffering from chronic kidney disease (CKD).MethodsWe analyzed the data of 121 patients who underwent coronary computed tomography between October 2014 and June 2015 and whose estimated glomerular filtration rate (eGFR) was <60 ml/min/1.73 m2. The LM-LAD bifurcation angle was measured by 3-dimensional coronary computed tomography. The CACS of the LM-LAD arteries was also calculated. We excluded stent recipients and patient who had undergone coronary artery bypass graft surgery.ResultsIn the overall sample, the mean ± standard deviation (range) LM-LAD bifurcation angle was 35.9 ± 11.4° (6.8–79.4°) and mean CACS was 227 ± 351 (0 to 1,695). The mean LM-LAD arteries angle was 40.3° ± 10.0° in 39 patients whose CACS was ≥200, versus 33.8° ± 11.6° in 82 patients with CACS <200 (p = 0.003). A weak, but positive correlation (r = 0.269, p = 0.003) was observed between the LM-LAD arteries angle and CACS of the LM-LAD arteries. By multiple variable analysis, hemoglobin A1c, triglycerides, eGFR and the LM-LAD arteries angle were independent predictors of a high CACS of the LM-LAD arteries.ConclusionIn patients with CKD, a wide LM-LAD arteries angle was associated with a high CACS of the LM-LAD arteries. The prognostic value of this observation warrants further evaluation.

Commonly available hematological biomarkers are associated with the extent of coronary calcifications

Background and aimsWe aimed to improve the understanding of potential associations between commonly available hematological biomarkers and the coronary artery calcification (CAC) score, which may help unravel the pathophysiology of coronary calcifications and subclinical coronary artery disease. MethodsA cross-sectional study was performed within the Utrecht Patient Oriented Database (UPOD). Patients with suspected or known coronary artery disease who underwent CT CAC scoring as well as standard hematology analysis that was part of routine clinical care (within 3 months of CT acquisition) were included. Complete hematology datasets were extracted from hematology analyzers. Linear regression adjusted for potential confounders was used to assess if hematological biomarkers were related to the CAC score. ResultsIn total, 1504 patients were included, of whom 43% (n = 647) had a CAC score of 0. Mean age (±SD) was 53 ± 13 years, and 34% of patients were women. Red blood cell distribution width (RDW, β = 0.20 [0.05–0.36], p=0.007), the fraction of immature reticulocytes (β = 0.97 [0.10–6.43], p=0.004), coefficient of variation of neutrophil lobularity (β = 0.13 [0.01–0.25], p=0.040) and mean lymphocyte cell size (β = 0.21 [0.08–0.34], p=0.001) were positively associated with the CAC score after adjustment for age, sex, body mass index (BMI), diabetes, glomerular filtration rate (GFR) and high-density lipoprotein (HDL). ConclusionsThis study confirms the known association of RDW with the CAC score, and presents the fraction of immature reticulocytes, coefficient of variation of neutrophil lobularity, and mean lymphocyte cell size as new markers associated with a higher CAC score.

Prognostic relevance of subclinical coronary and carotid atherosclerosis in a diabetic and nondiabetic asymptomatic population.

We sought to evaluate the incremental prognostic benefit of carotid artery disease and subclinical coronary artery disease (CAD) features in addition to clinical evaluation in an asymptomatic population. Over a 6-year period, 10-year Framingham risk score together with carotid ultrasound and coronary computed tomography angiography were evaluated for prediction of major adverse cardiac events (MACE). We enrolled 517 consecutive asymptomatic patients (63% male, mean age 64 ±10 years; 17.6% with diabetes). Median (interquartile range) coronary artery calcium score (CACS) was 34 (0-100). Over a median follow-up of 4.4 (3.4-5.1) years, there were 53 MACE (10%). Patients experiencing MACE had higher CACS, incidence of carotid disease, presence of CAD ≥50%, and remodeled plaque as compared with patients without MACE. At multivariable analyses, presence of CAD ≥50% (HR: 5.14, 95% CI: 2.1-12.4) and percentage of segments with remodeled plaque (HR: 1.04, 95% CI: 1.03-1.06) independently predicted MACE (P < 0.001). Models adding CAD ≥50% or percentage of segments with remodeled plaque resulted in higher discrimination and reclassification ability compared with a model based on 10-year FRS, carotid disease, and CACS. Specifically, the C-statistic improved to 0.75 with addition of CAD and 0.84 when adding percentage of segments with remodeled plaque, whereas net reclassification improvement indices were 0.86 and 0.92, respectively. In an asymptomatic population, CAD and plaque positive remodeling increase MACE prediction compared with a model based on 10-year FRS, carotid disease, and CACS estimation. In the diabetes subgroup, percentage of segments with remodeled plaque was the only predictor of MACE.

Association of epicardial adipose tissue with cardiovascular risk factors and coronary artery calcification in the community residents

Objective: This cross-sectional study aimed to address the relationship between the volume of epicardial adipose tissue (EAT) with cardiovascular risk factors and coronary artery calcification(CAC) in the community residents. Methods: Individuals were recruited from the Jidong Community (Tangshan City, Northern China) which mainly comprised employees of the Jidong Co. Ltd. and their family members. From July 2013 to August 2014, 2 647 participants aged ≥40 years were included in this study. The volume of EAT and coronary artery calcification score (CAC score) were determined by a 64-slice CT. Carotid intima-media thickness (CIMT) was measured by a trained sonographer using a high-resolution B-mode topographic ultrasound system. Venous blood samples were analyzed by automated analyzers in the central laboratory. A validated questionnaire specifically designed for this study was used to collect demographic data from all participants by trained doctors. Characteristics of study cohort were compared according to quartiles of EAT volume (n=660, 663, 662, 662, repectively). Results: (1) The mean age of participants was (55.31±7.76) years and 49.94% (n=1 322) were men. The median EAT volume (interquartile) was 129.42 (95.66, 176.51)cm(3). (2) Age, BMI, waist circumference and hip circumference, systolic blood pressure, LDL-C, triglycerides, and fasting blood glucose were significantly higher, while HDL-C level was significantly lower in participants with higher EAT volume than participants with lower EAT volume (all P<0.05). Carotid intima-media thicken (CIMT) and higher CAC score were also significantly higher in participants with higher volume of EAT. Furthermore, percentage of diabetes mellitus, hypertension, hyperlipidemia increased in proportion with increasing EAT volume (P<0.05). (3) In the linear regression, significant positive relations were found for age (β=0.019 3, 95%CI 0.017-0.021, P<0.001), waist circumference (β=0.012 7, 95%CI 0.009-0.016, P<0.001), BMI (β=0.022 4, 95%CI 0.013-0.032, P<0.001), LDL-C (β=0.048 4, 95%CI 0.021-0.076, P<0.001), and HDL-C (β=-0.098 1, 95%CI-0.164--0.032, P<0.001) was inversely related to the EAT volume. (4) Logistic regression analysis indicated that EAT volume was an independent risk factor for CAC score>0 (OR=1.233, 95%CI 1.205-1.262, P<0.001) . Conclusions: Our findings indicate that EAT volume is strongly correlated to cardiovascular risk factors and coronary calcification and is an independent risk factor of increased coronary calcification in community residents.

The Value of Big Endothelin-1 in the Assessment of the Severity of Coronary Artery Calcification

Progression of coronary artery calcification (CAC) was significantly associated with all-cause mortality, and high coronary artery calcium score (CACS) portends a particularly high risk of cardiovascular events. But how often one should rescan is still an unanswered question. Preliminary screening by testing circulating biomarker may be an alternative before repeat computed tomography (CT) scan. The aim of this study was to investigate the value of big endothelin-1 (bigET-1), the precursor of endothelin-1 (ET-1), in predicting the severity of CAC. A total of 428 consecutively patients who performed coronary computed tomography angiography (CCTA) due to chest pain in Fuwai Hospital were included in the study. The clinical characteristics, CACS, and laboratory data were collected, and plasma bigET-1 was detected by enzyme-linked immunosorbent assay (ELISA). The bigET-1 was positively correlated with the CACS (r = .232, P < .001), and the prevalence of CACS >400 increased significantly in the highest bigET-1 tertile than the lowest tertile. Multivariate analysis showed that bigET-1was the independent predictor of the presence of CACS >400 (odds ratio [OR] = 1.721, 95% confidence interval [CI], 1.002-2.956, P = .049). The receiver operating characteristic (ROC) curve analysis showed that the optimal cutoff value of bigET-1 for predicting CACS >400 was 0.38 pmol/L, with a sensitivity of 59% and specificity of 68% (area under curve [AUC] = 0.65, 95% CI, 0.58-0.72, P < .001). The present study demonstrated that the circulating bigET-1 was valuable in the assessment of the severity of CAC.

Abstract 045: Leisure Time Physical Activity is Associated With Higher Coronary Artery Calcium Density: The Multi-Ethnic Study of Atherosclerosis

Introduction: Leisure-time physical activity (LTPA) has favorable effects on many risk factors for cardiovascular disease (CVD). Paradoxically, LTPA has also been associated with higher amounts of coronary artery calcium (CAC) in athletes. Recently, a higher density of CAC was shown to significantly mitigate the risk of CVD associated with a given volume of CAC. The effects of LTPA and non-LTPA on the density and volume components of CAC among individuals with calcified coronary atherosclerosis are unknown. Methods: We evaluated 3,398 participants from the Multi-Ethnic Study of Atherosclerosis with prevalent CAC (50% of cohort). CAC was assessed via cardiac computed tomography, while physical activity was assessed via questionnaire and categorized by quintiles of moderate and vigorous LTPA (e.g. exercise) and non-LTPA (e.g. work). Multiple linear regression with mutual adjustment for LTPA, non-LTPA, demographics, and CVD risk factors was performed. Results: Mean age of the sample was 66 years, 58% were male, 44% were Caucasian, 24% were African-American, 20% were Hispanic, and 12% were Chinese-American. Compared to the lower four quintiles, LTPA above the threshold of 2567 MET-minutes/week (quintile 5) was associated with 0.057 (0.008, 0.105) higher CAC density-units after full adjustment. LTPA at any level was not associated with CAC volume. Conversely, non-LTPA was associated with both lower CAC density and higher CAC volume in a stepwise fashion, with the highest quintile meeting statistical significance for both (see Table). Conclusions: The highest quintile of LTPA was associated with higher CAC density but not higher CAC volume, suggesting a possible explanation for high CAC scores in athletes with favorable CVD risk factor profiles. Non-LTPA was associated with a less favorable CAC composition after adjustment for LTPA, an unexpected finding that merits further investigation.

High-Sensitivity Troponin I and Coronary Computed Tomography in Symptomatic Outpatients With Suspected CAD: Insights From the PROMISE Trial

ObjectivesThe goal of this study was to examine associations between concentrations of high-sensitivity troponin I (hsTnI) (measured by using a single-molecule counting method) and obstructive coronary artery disease (CAD) in 1,838 stable, symptomatic outpatients with suspected CAD randomized to undergo coronary computed tomography angiography (CTA) in the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial. BackgroundElevated concentrations of hsTnI are associated with CAD in patients with myocardial infarction. The meaning of hsTnI concentrations in stable symptomatic outpatients is not well understood. MethodsClinical characteristics and CTA results (including coronary artery calcium [CAC] scores) were expressed across hsTnI quartiles. Determinants of hsTnI concentration were identified. Multivariable logistic regression identified independent predictors of obstructive CAD50 (≥50% stenosis in any vessel) and CAD70 (≥70% stenosis or ≥50% left main). ResultsThe median hsTnI concentration was 1.5 ng/l; nearly all (98.5%) subjects had measurable hsTnI, and 6.1% had concentrations ≥99th percentile concentration for this assay (6 ng/l). Higher CAC scores, as well as more prevalent and diffuse CAD, was seen in upper hsTnI quartiles (all p < 0.001). Independent predictors of hsTnI concentrations included age, sex, and CAC score (all p < 0.05). After adjusting for demographic and clinical characteristics, log-transformed hsTnI concentrations were associated with obstructive CAD50 (odds ratio: 1.15 per interquartile range; p = 0.02) and CAD70 (odds ratio: 1.25 per interquartile range; p = 0.001). ConclusionsIn stable symptomatic outpatients undergoing nonemergent coronary CTA for the diagnosis of suspected CAD, higher concentrations of hsTnI were associated with increasing presence and severity of coronary atherosclerosis. (Prospective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550)