Traditional Coronary Artery Calcium Research Articles

Association of Cardiovascular Risk Factors and Coronary Calcium Burden with Epicardial Adipose Tissue Volume Obtained from PET-CT Imaging in Oncological Patients.

Whole-body positron emission tomography (PET)-computed tomography (CT) imaging performed for oncological purposes may provide additional parameters such as the coronary artery calcium (CAC) and epicardial adipose tissue (EAT) volume with cost-effective prognostic information in asymptomatic people beyond traditional cardiovascular risk factors. We evaluated the feasibility of measuring the CAC score and EAT volume in cancer patients without known coronary artery disease (CAD) referred to whole-body 18F-FDG PET-CT imaging, regardless of the main clinical problem. We also investigated the potential relationships between traditional cardiovascular risk factors and CAC with EAT volume. A total of 109 oncological patients without overt CAD underwent whole-body PET-CT imaging with 18F-fluorodeoxyglucose (FDG). Unenhanced CT images were retrospectively viewed for CAC and EAT measurements on a dedicated platform. Overall, the mean EAT volume was 99 ± 49 cm3. Patients with a CAC score ≥ 1 were older than those with a CAC = 0 (p < 0.001) and the prevalence of hypertension was higher in patients with detectable CAC as compared to those without (p < 0.005). The EAT volume was higher in patients with CAC than in those without (p < 0.001). For univariable age, body mass index (BMI), hypertension, and CAC were associated with increasing EAT values (all p < 0.005). However, the correlation between the CAC score and EAT volume was weak, and in multivariable analysis only age and BMI were independently associated with increased EAT (both p < 0.001), suggesting that potential prognostic information on CAC and EAT is not redundant. This study demonstrates the feasibility of a cost-effective assessment of CAC scores and EAT volumes in oncological patients undergoing whole-body 18F-FDG PET-CT imaging, enabling staging cancer disease and atherosclerotic burden by a single test already included in the diagnostic work program, with optimization of the radiation dose and without additional costs.

Coronary Artery Calcium for Risk Stratification Among Persons With Very High HDL Cholesterol

BackgroundCompared to normal high-density lipoprotein (HDL) cholesterol values, very high HDL cholesterol is associated with a higher incidence of mortality and atherosclerotic cardiovascular disease (ASCVD). As such, clinical risk stratification among persons with very high HDL cholesterol is challenging. ObjectivesAmong persons with very high HDL cholesterol, the purpose was to determine the prevalence of coronary artery calcium (CAC) and compare the association between traditional risk factors vs CAC for all-cause mortality and ASCVD. MethodsThe primary analysis was completed among 446 participants from the Cedars-Sinai Medical Center of the CAC Consortium with very high HDL cholesterol (≥77 mg/dL in men, ≥97 mg/dL in women). Cox proportional hazards regression assessed the association of CAC and traditional risk factors with all-cause mortality during a median follow-up of 10.7 years. Replication and validation analyses were performed for all-cause mortality among 119 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with very high HDL cholesterol, who also had information on incident ASCVD. ResultsThe mean age was 57.9 years old, 49% were women, and the median HDL cholesterol was 98 mg/dL. One-half of participants (50%) had prevalent CAC, in whom the median CAC score was 118. Prevalent CAC conferred a 3.6-fold higher risk of all-cause mortality (HR: 3.64; 95% CI: 1.21-11.01), which appeared to be a more robust predictor than individual traditional risk factors beyond age. In the validation sample, prevalent CAC but not individual traditional risk factors were associated with all-cause mortality (HR: 2.39; 95% CI: 1.07-5.34) and a 4.0-fold higher risk of ASCVD (HR: 4.06; 95% CI: 1.11-14.84). ConclusionsMeasurement of CAC may facilitate clinical risk assessment among individuals with very high HDL cholesterol.

Visual Ordinal Coronary Artery Calcium Score from Non-Gated Chest CT Predicts Mortality After Severe Chronic Obstructive Pulmonary Disease Exacerbation.

Chronic obstructive pulmonary disease (COPD) patients often undergo chest CT for various indications. Coronary artery calcium (CAC) can be quantified visually on ungated chest CT using an ordinal score that has been shown to correlate well with traditional Agatston CAC scoring. The prognostic role of CAC was studied mainly in stable COPD patients. We aim to study the association between ordinal CAC and mortality amongst patients admitted for acute exacerbation of COPD (AECOPD). Retrospective study of AECOPD cases with no previous coronary revascularization admitted between 1st January 2016 to 30th June 2017 with a chest CT performed during admission or within 365 days prior. Ordinal CAC scoring (scale of 0-12) was performed by an experienced CT cardiologist blinded to patient data and outcomes. Patient demographics and future clinical events were retrieved from electronic medical records. There were 93 patients included (87.1% male, mean age 75 years) with the majority (59.1%) in GOLD Stage III. There were 21 (22.6%) patients with no CAC as well as 39 (41.9%) and 33 (35.5%) with ordinal CAC of 1-3 and 4-12, respectively. There were no significant differences in Charlson Comorbidity Index (CCI) and the proportion of patients with traditional cardiovascular risk factors (namely hypertension, dyslipidaemia, diabetes and smoking status) between the ordinal CAC score groups. Over a median follow-up period of 2.9 (1.1-3.9) years, there were 51 (54.8%) deaths. An ordinal CAC score of 4-12 was the only significant predictor of mortality after multivariate Cox-regression analysis adjustment for age, gender, body mass index, prior exacerbations, FEV1, cardiovascular risk factors and CCI [HR 3.944, (95% confidence interval 1.647-9.433, p = 0.002)]. Ordinal CAC measured from a current or recent ungated chest CT is an independent predictor of all-cause mortality in admitted AECOPD patients with no previous coronary revascularization.

A better understanding of coronary artery disease molecular biology through an intermediate phenotype

Abstract Coronary Artery Disease (CAD) remains a common cause of death worldwide; over half of these deaths are asymptomatic until the first fatal presentation. Previous studies have often compared coronary artery calcification (CAC) with coronary stenosis or its sequelae. However, the genetic contribution to CAC in sub-clinical atherosclerosis is controversial. Purpose This study intended to assess the relationship between a set of single nucleotide polymorphisms associated with CAD (GWAS) and CAC score in an asymptomatic population. Methods Prospective study performed in an asymptomatic cohort from GENEMACOR population-based sample of 1207 subjects aged 51.7±8.3, 73.8 male, without apparent prior CAD. CAC score was performed by cardiac computed tomography and reported as Agatston units according to the Hoff nomogram (Low, Moderate and High-risk categories). For the present work, we considered two groups: Group 1 (0≤CAC&amp;lt;100 and Percentile&amp;lt;50) and Group 2 (CAC≥100 or Percentile≥50). We genotyped thirty-three single nucleotide polymorphisms (SNP) associated with CAD by TaqMan real-time PCR. Anthropometric, conventional, and biochemical risk factors were assessed. The association of these SNPs with CAC score groups were evaluated by bivariate and multivariate logistic regression analysis, and the dominant genetic model was considered for comparison. Results After bivariate analysis, only PHACTR1 rs1332844 C&amp;gt;T (CT+TT genetic model) showed a significative association with CAC score (OR=1.45; 95%CI 1.09-1.94; p=0.011). Multivariate logistic regression analysis, adjusted to traditional risk factors, genetic model and CAC score showed that PHACTR1 rs1332844 remained in the equation as significantly associated to CAC score (P=0.009) together with age (0.0001), hypertension (0.006), Diabetes (0.0001), smoking (0.001) and obesity (0.028). Conclusion PHACTR1 genetic variant is known to contribute to atherosclerosis and plaque formation. In the present study it showed a significant association with plaque calcium. More research in this field is critical to understanding the genetic basis of CAD through an intermediate phenotype, plaque calcification. We highlight this point since it can be crucial for the prognosis and therapy of the asymptomatic population.

Abstract 13721: Coronary Artery Calcium for Risk Stratification Among Persons With Very-High High-Density Lipoprotein Cholesterol

Introduction: Persons with very-high high-density lipoprotein-cholesterol (HDL-C) may experience an increased mortality risk. However, the predictors of mortality among those with very-high HDL-C remain unknown. Hypothesis: Compared to traditional risk factors, coronary artery calcium (CAC) will more strongly stratify risk among individuals with very-high HDL-C. Aims: Among individuals with very-high HDL-C, to 1) calculate crude all-cause mortality rates across the burden of traditional risk factors and CAC, and 2) identify independent risk factors associated with all-cause mortality. Methods: There were 335 primary prevention patients from the CAC Consortium who had very-high HDL-C ( &gt; 80 mg/dL in men, &gt; 100 mg/dL in women) and available information on traditional CVD risk factors. Crude all-cause mortality rates were calculated per 1,000 person-years. Multivariable Cox proportional hazards regression assessed the association of traditional risk factors and CAC with mortality. Results: The mean age was 58.6 years old, 51.0% were women, 51.3% had prevalent CAC, and the median HDL-C was 100 mg/dL. There were 20 deaths (6.0%) over a median follow-up of 10.5 years, 7 (2.1%) of which were attributable to CVD. There was a stepwise higher crude mortality rate per 1,000 person-years across increasing CAC burden ( Central Illustration ). Independent of traditional risk factors, each 100 Agatston Unit increase in CAC score was associated with a 7% higher hazard of all-cause mortality (HR: 1.07, 95% CI: 1.01-1.12) and individuals with CAC &gt; 1000 experienced a 5.75-fold higher hazard of mortality when compared to CAC=0 (HR: 5.75, 95% CI: 1.26-26.24). Beyond age, no traditional risk factor was associated with mortality in multivariable analyses. Conclusion: Measurement of CAC on non-contrast cardiac computed tomography may facilitate risk assessment among individuals with very-high HDL-C.

Abstract 14960: Coronary Artery Calcium Distribution Patterns Are Independently Predictive of Adverse Cardiovascular Events: Observations From the Dallas Heart Study

Introduction: The coronary artery calcium (CAC) diffusivity index (DI) may improve risk stratification for those with Agatston CAC &gt; 0 in older individuals. We aimed to assess whether the distribution of CAC would improve risk prediction of cardiovascular (CV) events beyond the traditional Agatston CAC score in a younger population. Methods: Among Dallas Heart Study 2 (DHS2) participants with Agatston CAC &gt; 0 and no history of CVD (35% of entire cohort), we studied 1013 participants with CAC DI at DHS2. The raw CAC DI was calculated as 1 - (CAC in most affected vessel/total CAC) and categorized into concentrated (&lt;25th%), standard (25-75th%), and diffuse (&gt;75th%) patterns. Multivariable Cox proportional hazards regression and C statistics were calculated for coronary events (CHD) and all CVD, and all-cause mortality. Models were adjusted for total Agatston score, race, gender, BSA, smoking history, diabetes, and statin use. Results: Mean age of the DHS2 study cohort was 55 ± 9.4 years (48% women, 45% Black). The median follow up was 9 ± 2.5 years (55 CHD, 97 CVD, and 120 all-cause mortality events) (Figure, A) . CAC DI was modestly correlated with Agatston CAC (Spearman rho = 0.60, p&lt;0.01). In models adjusted for total Agatston score, risk factors, and demographics, compared with a concentrated pattern, a diffuse CAC pattern was associated with incident CHD (HR [95%CI]: 5.32 [1.68-16.86]); CVD (HR [95%CI]: 3.21 [1.66-6.21]), and all-cause mortality (HR [95%CI]: 2.02 [1.18-3.47] (Figure, B) . Findings were similar for continuous CAC DI. Addition of continuous CAC DI to adjusted models including Agatston CAC improved the C-statistic for CHD (0.79 to 0.81, p&lt;0.01) and CVD (0.71 to 0.73, p&lt;0.01). Conclusions: Beyond the validated Agatston score, higher CAC DI at baseline improves risk prediction of incident CHD and CVD events in a younger population-based cohort. Further studies are warranted to evaluate the clinical utility of assessing distribution patterns of CAC.

Social disadvantage, coronary artery calcium, and their interplay in the prediction of atherosclerotic cardiovascular disease events

Background and aimsSocial determinants of health (SDOH) are key for the identification of populations at increased risk of atherosclerotic cardiovascular disease (ASCVD). However, whether at the individual level SDOH improve current ASCVD risk prediction paradigms beyond traditional risk factors and the coronary artery calcium (CAC) score, is unknown. We evaluated the interplay between CAC and SDOH in ASCVD risk prediction. MethodsMESA is a prospective study of US adults free of clinical ASCVD at baseline. We used an SDOH index inclusive of 14 determinants from 5 domains. The index ranged 0–1 and was divided into quartiles, with higher ones representing worse SDOH. Cox regression was used to evaluate the adjusted associations between CAC, SDOH, their interplay, and ASCVD events. The C-statistic was computed to assess improvement in risk discrimination for prediction of ASCVD events. ResultsWe included 6479 MESA participants (50% with CAC = 0, 24% CAC>100). ASCVD incidence increased with increasing CAC scores across SDOH quartiles. The lowest incidence was noted in those with CAC = 0 and favourable SDOH (2/1000 person-years) and highest in those with CAC>100 and most unfavourable SDOH (20.6/1000 person-years). While CAC was strongly associated with ASCVD across SDOH quartiles, SDOH was weakly associated with ASCVD across CAC strata. CAC improved the discriminatory ability of all prediction models beyond traditional risk factors, the improvement in C-statistic ranging +0.02 - +0.05. Improvements with SDOH were smaller, and were none on top of CAC. ConclusionsCAC improves ASCVD risk stratification across the spectrum of social vulnerability, while SDOH fail to improve risk prediction beyond traditional RFs and CAC.

Epicardial fat volume, an independent risk factor for major adverse cardiovascular events, had an incremental prognostic value to myocardial perfusion imaging in Chinese populations with suspected or known coronary artery disease with a normal left ventricular ejection fraction.

Most coronary artery disease (CAD) patients with a normal left ventricular ejection fraction (LVEF) experience a poor prognosis. Single-photon emission computerized tomography (SPECT)-myocardial perfusion imaging (MPI), a routine examination, is useful in assessing risk and predicting major adverse cardiovascular events (MACEs) in populations with suspected or known CAD. SPECT/CT is a "one-stop shop" examination, which, through non-contrast CT, can produce attenuation correction for MPI and obtain information on coronary artery calcium (CAC) and epicardial fat volume (EFV) simultaneously. This study aims to investigate the predictive and incremental value of EFV to MPI for MACE in Chinese populations with suspected or known CAD with a normal LVEF. We retrospectively studied 290 suspected or known CAD inpatients with a normal LVEF who underwent SPECT/CT between February 2014 and December 2017. Abnormal MPI was defined as a summed stress score ≥4 or summed difference score ≥2. EFV and CAC were calculated using non-contrast CT. The end date of follow-ups was in February 2022. The follow-up information was obtained from the clinical case notes of the patients or reviews of telephone calls. MACE was defined as cardiac death, late coronary revascularization ≥3 months after MPI, non-fatal myocardial infarction, angina-related rehospitalization, heart failure, and stroke. During the 76-month follow-up, the event rate was 32.0% (93/290). Univariate and multivariate Cox regression analyses concluded that high EFV (>108.3 cm3) [hazard ratio (HR): 3.3, 95% CI: 2.1-5.2, P < 0.000] and abnormal MPI (HR: 1.8, 95% CI: 1.1-2.8, P = 0.010) were independent risk factors for MACE. The event-free survival of patients with high EFV was significantly lower than that of the low EFV group (log-rank test P < 0.001). In the subgroup with normal MPI, high EFV was associated with reduced event-free survival (log-rank P < 0.01), with a higher annualized event rate (8.3% vs. 1.9%). Adding high EFV to MPI could predict MACEs more effectively, with a higher concordance index (0.56-0.69, P < 0.01), higher global chi square (7.2-41.4, P < 0.01), positive integrated discrimination improvement (0.10, P < 0.01), and net reclassification index (0.37, P < 0.01). In Chinese populations with suspected or known CAD with normal LVEF, high EFV was an independent risk factor for MACE after adjusting for traditional risk factors, CAC and MPI. In subgroups with normal MPI, EFV could also improve risk stratification. Adding EFV to MPI had an incremental value for predicting MACE.

Incremental value of epicardial fat volume on predicting obstructive coronary artery disease with myocardial ischemia

Objective: This study aimed to investigate the association between epicardial fat volume (EFV) and obstructive coronary artery disease (CAD) with myocardial ischemia, and evaluate the incremental value of EFV on top of traditional risk factors and coronary artery calcium (CAC) in predicting obstructive CAD with myocardial ischemia. Methods: This study was a retrospective cross-sectional study. Patients with suspected CAD who underwent coronary angiography (CAG) and single photon emission computerized tomography-myocardial perfusion imaging (SPECT-MPI) at the Third Affiliated Hospital of Soochow University from March 2018 to November 2019 were consecutively enrolled. EFV and CAC were measured by non-contrast chest computed tomography (CT) scan. Obstructive CAD was defined as coronary artery stenosis≥50% in at least one of the major epicardial coronary arteries, and myocardial ischemia was defined as reversible perfusion defects in stress and rest MPI. Obstructive CAD with myocardial ischemia was defined in patients with coronary stenosis severity≥50% and reversible perfusion defects in the corresponding areas of SPECT-MPI. Patients with myocardial ischemia bot without obstructive CAD were defined as none-obstructive CAD with myocardial ischemia group. We collected and compared the general clinical data, CAC and EFV between the two groups. Multivariable logistic regression analysis was performed to identify the relationship between EFV and obstructive CAD with myocardial ischemia. ROC curves were performed to determine whether addition of EFV improved predictive value beyond traditional risk factors and CAC for obstructive CAD with myocardial ischemia. Results: Among the 164 patients with suspected CAD, 111 patients were males, and average age was (61.4±9.9) years old. 62 (37.8%) patients were included into the obstructive CAD with myocardial ischemia group. 102 (62.2%) patients were included into the none-obstructive CAD with myocardial ischemia group. EFV was significantly higher in obstructive CAD with myocardial ischemia group than in none-obstructive CAD with myocardial ischemia group ((135.63±33.29)cm3 and (105.18±31.16)cm3, P<0.01). Univariate regression analysis showed the risk of obstructive CAD with myocardial ischemia increased by 1.96 times for each SD increase in EFV(OR 2.96; 95%CI, 1.89-4.62; P<0.01). After adjustment for traditional risk factors and CAC, EFV remained as an independent predictor for obstructive CAD with myocardial ischemia (OR, 4.48, 95%CI, 2.17-9.23; P<0.01). Addition of EFV to CAC and traditional risk factors was related to larger AUC for predicting obstructive CAD with myocardial ischemia (0.90 vs. 0.85, P=0.04, 95%CI: 0.85-0.95) and the global chi-square increased by 21.81 (P<0.05). Conclusions: EFV is an independent predictor for obstructive CAD with myocardial ischemia. Addition of EFV to traditional risk factors and CAC has incremental value for predicting obstructive CAD with myocardial ischemia in this patient cohort.

Predictive value of CAC score combined with clinical features for obstructive coronary heart disease on coronary computed tomography angiography: a machine learning method

ObjectiveWe investigated the predictive value of clinical factors combined with coronary artery calcium (CAC) score based on a machine learning method for obstructive coronary heart disease (CAD) on coronary computed tomography angiography (CCTA) in individuals with atypical chest pain.MethodsThe study included data from 1,906 individuals undergoing CCTA and CAC scanning because of atypical chest pain and without evidence for the previous CAD. A total of 63 variables including traditional cardiovascular risk factors, CAC score, laboratory results, and imaging parameters were used to build the Random forests (RF) model. Among all the participants, 70% were randomly selected to train the models on which fivefold cross-validation was done and the remaining 30% were regarded as a validation set. The prediction performance of the RF model was compared with two traditional logistic regression (LR) models.ResultsThe incidence of obstructive CAD was 16.4%. The area under the receiver operator characteristic (ROC) for obstructive CAD of the RF model was 0.841 (95% CI 0.820–0.860), the CACS model was 0.746 (95% CI 0.722–0.769), and the clinical model was 0.810 (95% CI 0.788–0.831). The RF model was significantly superior to the other two models (p < 0.05). Furthermore, the calibration curve and Hosmer–Lemeshow test showed that the RF model had good classification performance (p = 0.556). CAC score, age, glucose, homocysteine, and neutrophil were the top five important variables in the RF model.ConclusionRF model was superior to the traditional models in the prediction of obstructive CAD. In clinical practice, the RF model may improve risk stratification and optimize individual management.

Sex Differences in Coronary Arterial Calcification in Symptomatic Patients

Despite the increasing use of Coronary Artery Calcium (CAC) scoring for cardiovascular risk stratification in asymptomatic patients, the gender differences in CAC among symptomatic patients have not been well evaluated. We analyzed patients presenting to the emergency department (ED) with chest pain suggesting possible coronary artery disease (CAD) who received coronary computed tomography angiography (CCTA). Ordinal logistic regression was used to determine the odds ratio for the association of traditional cardiovascular risk factors and CAC. Patients with a CAC score ≥ 100 were followed for cardiovascular events or changes in medical management. Our cohort included 542 individuals (263 male, 279 female). Ordinal logistic regression model showed that among traditional cardiovascular risk factors, male sex had the highest odds ratio (OR) of 3.04 (p < 0.001, 95% CI [2.01, 4.59]) for the presence of CAC. Also, males had more diffuse distribution of coronary atherosclerosis (p=0.01). Subgroup analysis revealed that obesity was a bigger risk factor in male patients (OR 2.16), while smoking showed the greatest effect (OR 4.27) on CAC in women. Of patients who had CAC > 100 with an average follow-up of 346 days, there was an increase in both aspirin and statin use, yet significant sex differences were observed especially in patients with non-obstructive lesions on CCTA. Among male patients with non-obstructive lesions, 68.2% were on aspirin and 86.4% were on statin therapy after the CCTA compared to 27.3% and 45.5% respectively in their female counterparts. In conclusion, sex not only is the most powerful predictor for higher CAC among traditional cardiovascular risk factors in symptomatic patients but also influences the contribution of various traditional risk factors to elevated CAC. Furthermore, the discovery of CAD led to the initiation of medical therapy in male patients more frequently than in female patients, even after adjusting for the degree of luminal stenosis detected on coronary CT angiography.

Thoracic Aortic Calcium for the Prediction of Stroke Mortality (from the Coronary Artery Calcium Consortium)

Thoracic aortic calcium(TAC) is an important marker of extracoronary atherosclerosis with established predictive value for all-cause mortality. We sought to explore the predictive value of TAC for stroke mortality, independent of the more established coronary artery calcium (CAC) score. The CAC Consortium is a retrospectively assembled database of 66,636 patients aged ≥18 years with no previous history of cardiovascular disease, baseline CAC scans for risk stratification, and follow-up for 12 ± 4 years. CAC scans capture the adjacent thoracic aorta, enabling assessment of TAC from the same images. TAC was available in 41,066 (62%), and was primarily analyzed as present or not present. To account for competing risks for nonstroke death, we utilized multivariable-adjusted Fine and Gray competing risk regression models adjusted for traditional cardiovascular risk factors and CAC score. The mean age of participants was 53.8 ± 10.3 years, with 34.4% female. There were 110 stroke deaths during follow-up. The unadjusted subdistribution hazard ratio (SHR) for stroke mortality in those who had TAC present compared with those who did not was 8.80 (95% confidence interval [CI]: 5.97, 12.98). After adjusting for traditional risk factors and CAC score, the SHR was 2.21 (95% CI:1.39,3.49). In sex-stratified analyses, the fully adjusted SHR for females was 3.42 (95% CI: 1.74, 6.73) while for males it was 1.55 (95% CI: 0.83, 2.90). TAC was associated with stroke mortality independent of CAC and traditional risk factors, more so in women. The presence of TAC appears to be an independent risk marker for stroke mortality.

Abstract 14240: Thoracic Aortic Calcium for the Prediction of Stroke Mortality: The Coronary Artery Calcium Consortium

Introduction: Thoracic aortic calcium(TAC) is an important marker of extra-coronary atherosclerosis with known predictive value for all-cause mortality. We sought to explore the predictive value of TAC for stroke mortality, independent of the more established coronary artery calcium score. Methods: The Coronary Artery Calcium(CAC) Consortium is a retrospectively assembled database of 66,636 patients aged ≥18 years with no prior history of cardiovascular disease, who had CAC scans done for risk stratification and were followed-up for an average of 12±4years. CAC scans capture a view of the adjacent thoracic aorta, enabling us to assess TAC at no extra cost. TAC was analyzed as present or not present and we restricted analysis to those with this information available. To account for competing risks for death from other causes, we utilized multivariable-adjusted competing risk regression models adjusted for traditional cardiovascular risk factors (age, sex, hypertension, hyperlipidemia, cigarette smoking, diabetes, family history of CHD) and CAC score. We report the relationship between TAC and stroke mortality using sub-distribution hazard ratios(SHR) with 95% CI. Results: There were 41,066 patients with information on TAC, 110 of whom had stroke mortality. The mean age of participants was 53.8±10.3 years, with 34.4% female. The unadjusted SHR for stroke mortality among those who had TAC compared to those who did not was 8.80(95%CI:5.97,12.98). After adjusting for traditional risk factors and CAC score, the SHR was 2.21(95%CI:1.39,3.49). The fully adjusted SHR for females was 3.42(95%CI:1.74,6.73) while for males it was 1.55(95%CI:0.83,2.90). Conclusion: TAC was predictive of stroke mortality independent of traditional risk factors and CAC, more so in females. The presence of TAC appears to be an independent marker of stroke mortality risk though further research is needed to study its incremental value over existing cardiovascular risk prediction models.

Calcium scores distribution across coronary artery by age and sex: the ImaLife study

Abstract Background The distribution of coronary artery calcium (CAC) across the coronary system increases the ability to predict coronary events compared to traditional CAC scoring alone. Reference values for regional distribution of CAC by age and sex are not yet available for a general European population. Purpose To investigate the distribution of CAC across the coronary arteries by age and sex in the population-based ImaLife study. Methods ImaLife is part of Lifelines, a multi-generational, prospective cohort study with over 167,000 participants from the northern Netherlands. From 2017–2019, 5,531 participants aged 45–84 years underwent non-contrast cardiac CT using third-generation dual-source CT. Total and vessel-specific CAC scores (Agatston's method) were acquired semi-automatically using dedicated software. Participants with a positive CAC score were classified into three groups: total CAC score 1–100, 101–300 and &amp;gt;300. The diffusivity index (equation: 1 – [highest one-vessel CAC/total CAC]) was calculated. The diffusivity index is an expression of the relative distribution of CAC across the coronary arteries. Data were analyzed for the whole population and by sex and age groups. Mann-Whitney U test was used to analyze the diffusity index in men and women. Kruskal-Wallis H tests were performed to test the diffusivity index in different age groups. Results In total 2,376 men (mean age 56.4±7.7 years) and 3,155 women (mean age 56.0±7.5 years) were analyzed. In participants with CAC, 1, 2, 3 or 4 vessels were affected in 523 (22.0%), 560 (17.7%), 371 (15.6%) and 257 (8.1%) of men, respectively, and in 385 (16.2%), 175 (5.5%), 185 (7.8%) and 81 (2.6%) of women, respectively (P&amp;lt;0.001). The number of 1, 2, 3 or 4 vessels affected were significantly different by age (p&amp;lt;0.001). In age category 45–49 years, CAC in 1, 2, 3, and 4 vessels was present in 60.1%, 21.6%, 15.5%, and 2.9%, respectively; for age 74+ years, these percentages were 19.3%, 19.3%, 31.1% and 30.3%, respectively. The number of affected vessels were significantly different in different CAC categories (p&amp;lt;0.001), see Figure. More vessels were affected in higher CAC categories. The median diffusivity index was higher in men than in women (0.10 (IQR: 0–0.36) vs 0 (IQR: 0–0.24), p&amp;lt;0.001) and increased by increasing age. For age categories of 45–49, 50–54, 55–59,60–64, 65–69, 70–74, and &amp;gt;74 years, diffusivity indexs were 0 (IQR: 0–0.12), 0 (IQR: 0–0.22), 0.02 (IQR: 0–0.28), 0.10 (IQR: 0–0.35), 0.16 (IQR: 0–0.42), 0.20 (IQR: 0–0.44), and 0.28 (IQR: 0.03–0.45) (p&amp;lt;0.001). Conclusions In this Dutch population-based study, male participants had higher prevalence of CAC with higher number of involved vessels, and a higher diffusivity index compared to women. For both sexes, involved vessels and diffusivity index increased with age. The reference values of this regional distribution of CAC in a European population can assist in risk categorization of cardiovascular events. The CAC distribution in ImaLife Funding Acknowledgement Type of funding source: Other. Main funding source(s): Siemens Healthineers

The Future of Concurrent Automated Coronary Artery Calcium Scoring on Screening Low-Dose Computed Tomography.

Low-dose computed tomography (LDCT) has been extensively validated for lung cancer screening in selected patient populations. Additionally, the use of gated cardiac CT to assess coronary artery calcium (CAC) burden has been validated to determine a patient's risk for major cardiovascular adverse events. This is typically performed by calculating an Agatston score based on density and overall burden of calcified plaque within the coronary arteries. Patients that qualify for LDCT for lung cancer screening commonly share major risk factors for coronary artery disease and would frequently benefit from an additional gated cardiac CT for the assessment of CAC. Given the widespread use of LDCT for lung cancer screening, we evaluated current literature regarding the use of non-gated chest CT, specifically LDCT, for the detection and grading of coronary artery calcifications. Additionally, given the evolving and increasing use of artificial intelligence (AI) in the interpretation of radiologic studies, current literature for the use of AI in CAC assessment was reviewed. We reviewed primary scientific literature dating up to April 2020 using Pubmed and Google Scholar, with the search terms low dose CT, lung cancer screening, coronary artery calcium, EKG/cardiac gated CT, deep learning, machine learning, and AI. These publications were then independently evaluated by each member of our team. Overall, there was a consensus within these papers that LDCT for lung cancer screening plays a role in the evaluation of CAC. Most studies note the inherent problems with the evaluation of the density of coronary calcifications on LDCT to give an accurate numeric calcium or Agatston score. The current method of evaluating CAC on LDCT involves using a qualitative categorical system (none, mild, moderate, or severe). When performed by cardiac imaging experts, this method broadly correlates with traditional CAC score groups (0, 1 to 100, 101 to 400, and > 400). Furthermore, given the high sensitivity of a properly protocolled LDCT for coronary calcium, a negative study for CAC precludes the need for a dedicated gated CT assessment. However, qualitative methods are not as accurate or reproducible when performed by general radiologists. The implementation of AI in the LDCT screening process has the potential to give a quantifiable and reproducible numeric value to the calcium score, based on whole heart volume scoring of calcium. This more closely aligns with the Agatston score and serves as a better guide for treatment and risk assessment using current guidelines.We conclude that CAC should be assessed on all LDCT performed for lung cancer screening and that a qualitative categorical scoring system should be provided in the impression for each patient. Early studies involving AI for the assessment of CAC are promising, but more extensive studies are needed before a final recommendation for its use can be given. The implementation of an accurate, automated AI CAC assessment tool would improve radiologist compliance and ease of overall workflow. Ultimately, the potential end result would be improved turnaround time, better patient outcomes, and reduced healthcare costs by maximizing preventative care in this high-risk population.

Coronary Artery Calcium Trajectory Predicts Coronary Artery Disease Events—The CACTI Study

Coronary artery calcium (CAC), a marker of subclinical atherosclerosis, predicts coronary artery disease (CAD) events, but the best use of CAC in risk prediction remains unclear. We examined whether group-based trajectory modeling of CAC in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study could independently predict CAD events. Four CAC trajectory groups (Figure 1a) were identified using longitudinal CAC in people free from CAD (Proc TRAJ in SAS Version 9.4), and these groups were used to predict a subsequent CAD event (myocardial infarction or coronary revascularization) using survival analysis. People with type 1 diabetes (T1D) were more likely to be in higher CAC trajectory groups than those without diabetes (non-DM, p&amp;lt;0.0001). Over 17,417 person-years of follow-up, 75 CAD events occurred (56 in T1D and 19 in non-DM individuals). Higher CAC trajectory group predicted CAD events in a dose-response manner (Figure 1b). In cox proportional hazards adjusted for age, sex, T1D, smoking, LDL, HDL, triglycerides and systolic blood pressure, being in a higher CAC group increased CAD risk, with a 33-fold increased risk in Group 4 (95% CI 12-91). A 3.3-fold excess risk (95% CI 1.7-6.4) for CAD remained for people with T1D. CAC trajectory group modeling can identify individuals at very high risk for a CAD event. However, T1D increases CAD risk independently of traditional risk factors and CAC trajectory. Disclosure J.K. Snell-Bergeon: Stock/Shareholder; Self; Abbott. Research Support; Self; Roche Diagnostics Corporation. A. Keshawarz: None. G.L. Kinney: None. I.E. Schauer: None. V.N. Shah: None. L. Pyle: None.

Prognostic value of suPAR and hs-CRP on cardiovascular disease

Background and aimsStudies have shown that soluble urokinase Plasminogen Activator Receptor (suPAR) and CRP (both inflammatory markers) and coronary artery calcification (CAC) are independent risk predictors for cardiovascular (CV) disease. The aim of this study is to assess whether suPAR and CRP have an increased predictive prognostic value beyond the traditional CV risk factors and the CAC score. MethodsA population sample of 1179 subjects, free of CV disease was included. The subjects underwent traditional CV risk evaluation, CAC assessment and blood sampling for suPAR and CRP. CV events were extracted from The Danish National Patient Register after 6.5 years. The additive values of suPAR and CRP were evaluated by unadjusted Kaplan Meier analysis, adjusted hazard ratio and ROCAUC models. Results1179 participants (47.6% males, mean age 55 years) were included. 73 events occurred. In Kaplan Meier analyses, suPAR and CRP were significantly associated with CV events (p = 0.03 and p = 0.002). Adjusted for the CV risk factors and the CAC score, the hazard ratios for suPAR and CRP were 1.17 (95% confidence interval [CI] 1.01–1.34) and 1.04 (95% CI 1.01–1.06), respectively. suPAR was associated with a substantial risk among women (2.03; 95% CI 1.45–2.84) and 60-year-old subjects (1.44; 95% CI 1.09–1.90). By ROCAUC, neither suPAR nor CRP provided significant estimates (0.7100 and 0.7054) compared to the traditionally CV risk factors (0.6952, p = 0.24 and p = 0.16) and CAC score (0.7481, p = 0.33 and p = 0.32). ConclusionsAdjusted for traditional CV risk factors and CAC score, suPAR and CRP were of minor importance in risk prediction.

Thoracic extra-coronary calcification for the prediction of stroke: The Multi-Ethnic Study of Atherosclerosis

Background and aimsAtherosclerosis is a systemic disease. We examined whether the cumulative burden of thoracic extra-coronary calcification (ECC) improves prediction of stroke, transient ischemic attack (TIA), and stroke mortality beyond traditional risk factors and coronary artery calcium (CAC). MethodsWe followed a total of 6805 participants (mean age 62.1 ± 10.2 years, 47.2% male) from the Multi-Ethnic Study of Atherosclerosis (MESA) over a median of 12.1 years. The presence or absence of calcification at 4 thoracic ECC sites (mitral valve annulus, aortic valve, aortic root, and thoracic aorta) was determined from baseline cardiac-gated non-contrast CT scans. A multisite thoracic ECC score, ranging 0–4, was calculated by summing the 4 individual sites, which were treated as binary variables. Multivariable Cox proportional hazards regression models, controlled for traditional risk factors and CAC, were used to estimate hazard ratios for ischemic (primary endpoint) and hemorrhagic stroke, total stroke, TIA, and stroke mortality with increasing thoracic ECC. ResultsWith an increasing number of thoracic ECC sites, there was a significant (p < 0.05) multivariable adjusted step-wise increase in the risk for ischemic stroke (n = 184), total stroke (n = 235), and TIA (n = 85), but not hemorrhagic stroke (n = 32) and stroke mortality (n = 42). Thoracic ECC increased the c-statistic and net reclassification index beyond traditional risk factors and CAC, but the results were not significant (p > 0.10). ConclusionsAlthough multisite thoracic ECC is independently associated with ischemic stroke, total stroke, and TIA, the incremental predictive value of thoracic ECC beyond traditional risk factors and CAC appears to be minimal.

Adult Height, Prevalent Coronary Artery Calcium Score, and Incident Cardiovascular Disease Outcomes in a Multiethnic Cohort.

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

Improving the CAC Score by Addition of Regional Measures of Calcium Distribution: Multi-Ethnic Study of Atherosclerosis

ObjectivesThe aim of this study was to investigate whether inclusion of simple measures of calcified plaque distribution might improve the ability of the traditional Agatston coronary artery calcium (CAC) score to predict cardiovascular events. BackgroundAgatston CAC scoring does not include information on the location and distributional pattern of detectable calcified plaque. MethodsWe studied 3,262 (50%) individuals with baseline CAC >0 from MESA (Multi-Ethnic Study of Atherosclerosis). Multivessel CAC was defined by the number of coronary vessels with CAC (scored 1 to 4, including the left main). The “diffusivity index” was calculated as: 1 − (CAC in most affected vessel/total CAC), and was used to group participants into concentrated and diffuse CAC patterns. Multivariable Cox proportional hazards regression, area under the curve, and net reclassification improvement analyses were performed for both coronary heart disease (CHD) and cardiovascular disease (CVD) events to assess whether measures of regional CAC distribution add to the traditional Agatston CAC score. ResultsMean age of the population was 66 ± 10 years, with 42% women. Median follow-up was 10.0 (9.5 to 10.7) years and there were 368 CHD and 493 CVD events during follow-up. Considerable heterogeneity existed between CAC score group and number of vessels with CAC (p < 0.01). Addition of number of vessels with CAC significantly improved capacity to predict CHD and CVD events in survival analysis (hazard ratio: 1.9 to 3.5 for 4-vessel vs. 1-vessel CAC), area under the curve analysis (C-statistic improvement of 0.01 to 0.033), and net reclassification improvement analysis (category-less net reclassification improvement 0.10 to 0.45). Although a diffuse CAC pattern was associated with worse outcomes in participants with ≥2 vessels with CAC (hazard ratio: 1.33 to 1.41; p < 0.05), adding this variable to the Agatston CAC score and number of vessels with CAC did not further improve global risk prediction. ConclusionsThe number of coronary arteries with calcified plaque, indicating increasingly “diffuse” multivessel subclinical atherosclerosis, adds significantly to the traditional Agatston CAC score for the prediction of CHD and CVD events.