Quantitative aortic Na[18F]F positron emission tomography computed tomography as a tool to associate vascular calcification with major adverse cardiovascular events.

PURPOSE: Sodium[18F]fluoride (Na[18F]F) used in positron emission tomography (PET) binds to active calcification and correlates consistently with higher cardiovascular risk. This study aims to investigate the feasibility of aortic Na[18F]F-PET in hybrid combination with low-dose computed tomography (CT) as a risk model for major adverse cardiovascular events (MACE). METHODS: Patient data and Na[18F]F-PET/CT scans from January 2019 to February 2022 were retrospectively collected at the University Medical Center Groningen (UMCG), the Netherlands. MACE-outcome was a composite of time to first documented myocardial infarction, cerebral vascular accident (CVA), acute heart failure hospitalization, and aortic aneurysms. MACE dates were recorded from the day of the scan until follow-up in December 2023. The aorta was manually segmented in all low-dose CT scans. To minimize spill-over effects from the vertebrae, the vertebrae were automatically segmented using an open-source model, dilated with 10 mm, and subtracted from the aortic mask. The total aortic Na[18F]F corrected maximum standardized uptake value (cSUVmax) and total aortic Agatston score were automatically calculated using SEQUOIA. Kaplan-Meier and Cox regression survival analysis were performed, stratifying patients into high, medium, and low cSUVmax and Agatston categories. Cox regression models were adjusted for age. RESULTS: Out of 280 identified scans, 216 scans of unique patients were included. During a median follow-up of 3.9 years, 12 MACE occurred. Kaplan-Meier survival analysis demonstrated a significant difference in MACE-free survival among the high cSUVmax group compared to the medium and low groups (p = 0.03 and p < 0.01, respectively). Similarly, patients with high Agatston scores had a significantly lower MACE-free survival probability compared to those with medium and low scores (both p < 0.01). CONCLUSION: This study highlights the potential clinical utility of Na[18F]F-PET/CT as an imaging tool to predict the risk of MACE. Clinical validation of this novel proof-of-concept method is needed to confirm these results and expand the clinical context.

High prevalence of coronary artery calcification and increased risk for coronary artery disease in patients with Sheehan syndrome-A case-control study.

OBJECTIVE: Patients with Sheehan syndrome (SS) are predisposed to coronary artery disease (CAD) due to risk factors like abdominal obesity, dyslipidemia and chronic inflammation. In addition to estimate CAD risk enhancers like high sensitive C reactive protein (hsCRP), apolipoprotein B (ApoB) and lipoprotein A [Lp(a)], this study applies Framingham risk score (FRS) and coronary artery calcium (CAC) score to compute a 10-year probability of cardiovascular (CV) events in SS patients. DESIGN: Case-control study Sixty-three SS patients, on a stable hormonal replacement treatment except for growth hormone and 65 age, body mass index and parity-matched controls. MEASUREMENTS: Measurement of serum hsCRP, ApoB and Lp(a) and estimation of CAC with 16-row multislice computed tomography scanner. RESULTS: The concentrations of hsCRP, ApoB and Lp(a) were significantly higher in SS patients than in controls (p < .01). After calculating FRS, 95.2% of SS patients were classified as low risk, 4.8% as intermediate risk and all controls were classified as low risk for probable CV events. CAC was detected in 50.7% SS patients and 7.6% controls (p = .006). According to the CAC score, 26.9% SS patients were classified as at risk (CAC > 10) for incident CV events as against 1.6% controls. The mean Multi-Ethnic Study of Atherosclerosis (MESA) score was significantly higher in patients with SS than controls. CAC corelated significantly with fasting blood glucose (r = .316), ApoB (r = .549), LP(a) (r = .310) and FRS (r = .294). CONCLUSION: Significant number of asymptomatic SS patients have high coronary artery calcium score and are classified at risk for CAD.

Atherosclerosis of the iliac arteries for the prediction of erectile dysfunction and epistaxis in men undergoing abdominal CT scan.

BACKGROUND: To investigate the association between erectile dysfunction (ED) as well as epistaxis (ES) in relation to the extent of iliac atherosclerosis. METHODS: In this retrospective cross-sectional study, all consecutive male patients treated at our institution from 01/2016 to 12/2020 undergoing abdominal CT scan were evaluated. Patients (n = 1272) were invited by mail to participate in the study in returning two questionnaires for the evaluation of ED (IIEF-5) and ES. Patients who returned filled-in questionnaires within a 3-month deadline were included in the study. The extent of atherosclerosis in the common iliac artery (CIA) and the internal iliac artery (IIA) was assessed by calcium scoring on unenhanced CT. Stratification of results was performed according to reported IIEF-5 scores and consequential ED groups. RESULTS: In total, 437 patients (34.4% of contacted) met the inclusion criteria. Forty-two patients did not fulfill predefined age requirements (< 75 years) and 120 patients had to be excluded as calcium scoring on nonenhanced CT was not feasible. Finally, 275 patients were included in the analysis and stratified into groups of "no-mild" (n = 146) and "moderate-severe" (n = 129) ED. The calcium score (r=-0.28, p < 0.001) and the number of atherosclerotic lesions (r=-0.32, p < 0.001) in the CIA + IIA showed a significant negative correlation to the IIEF-5 score, respectively. Patients differed significantly in CIA + IIA calcium score (difference: 167.4, p < 0.001) and number of atherosclerotic lesions (difference: 5.00, p < 0.001) when belonging to the "no-mild" vs. "moderate-severe" ED group, respectively. A multivariable regression model, after adjusting for relevant baseline characteristics, showed that the number of atherosclerotic CIA + IIA lesions was an independent predictor of ED (OR = 1.05, p = 0.036), whereas CIA + IIA calcium score was not (OR = 1.00031, p = 0.20). No relevant correlation was found between ES episodes and IIEF-5 scores (r=-0.069, p = 0.25), CIA + IIA calcium score (r=-0.10, p = 0.87) or number of atherosclerotic CIA + IIA lesions (r=-0.032, p = 0.60), respectively. CONCLUSIONS: The number of atherosclerotic lesions in the iliac arteries on nonenhanced abdominal CT scans is associated with the severity of ED. This may be used to identify subclinical cardiovascular disease and to quantify the risk for cardiovascular hazards in the future. TRIAL REGISTRATION: BASEC-Nr. 2020 - 01637.

Association between vertebral fractures and coronary artery calcification in current and former smokers in the ECLIPSE cohort.

In smokers and former smokers from the ECLIPSE cohort, there is an association between prevalent vertebral fractures (VFs) and coronary artery calcification (CAC). Chest CT scans provide the opportunity to evaluate VFs and CAC, which are potentially important comorbidities, each of which is amenable to effective interventions. INTRODUCTION: Prevalence of VFs among smokers and patients with chronic obstructive pulmonary disease (COPD) is high, and an association between CAC and osteoporosis has been described. We investigated the associations between VFs and CAC (expressed in Agatston score) in (former) smokers. METHODS: Current and former smokers from the ECLIPSE study (designed to determine underlying COPD progression mechanisms) were studied. Baseline Agatston score (zero (0), medium (1-400), or high (> 400)), baseline bone attenuation (BA), and prevalent and incident VFs (vertebrae T1-L1) were assessed on CT. RESULTS: A total of 586 subjects were included (mean age 59.8 ± 8.3; 62.3% men; 70.1% with COPD; 21.0% with prevalent VFs; 196 with zero, 266 with medium, and 124 with high Agatston score). Of these, 23.4% suffered incident VFs within 3 years. In multivariate models, prevalent VFs were associated with medium (1.83 [95% CI 1.01-3.30]) and with high (OR = 3.06 [1.45-6.47]) Agatston score. After adjustment for BA, prevalent VFs were still associated with high (OR = 2.47 [1.13-5.40]), but not significantly with medium Agatston score (OR = 1.57 [0.85-2.88]). Similarly, after adjustment for BA, high (OR = 2.06 [1.02-4.13]) but not medium Agatston score (OR = 1.61 [0.88-2.94]) was associated with prevalent VFs. Agatston score at baseline was not associated with short-term VF incidence. CONCLUSION: In (former) smokers, there was an association between prevalent VFs and Agatston score. Chest CT scans provide the opportunity to also evaluate for VFs and CAC, which are potentially important comorbidities, each of which is amenable to effective interventions.

Optimization of HU threshold for coronary artery calcium scans reconstructed at 0.5-mm slice thickness using iterative reconstruction.

PURPOSE: This work investigated the simultaneous influence of tube voltage, tube current, body size, and HU threshold on calcium scoring reconstructed at 0.5-mm slice thickness using iterative reconstruction (IR) through multivariate analysis. Regression results were used to optimize the HU threshold to calibrate the resulting Agatston scores to be consistent with those obtained from the conventional protocol. METHODS: A thorax phantom set simulating three different body sizes was used in this study. A total of 14 coronary artery calcium (CAC) protocols were studied, including 1 conventional protocol reconstructed at 3-mm slice thickness, 1 FBP protocol, and 12 statistical IR protocols (3 kVp values*4 SD values) reconstructed at 0.5-mm slice thickness. Three HU thresholds were applied for calcium identification, including 130, 150, and 170 HU. A multiple linear regression method was used to analyze the impact of kVp, SD, body size, and HU threshold on the Agatston scores of three calcification densities for IR-reconstructed CAC scans acquired with 0.5-mm slice thickness. RESULTS: Each regression relationship has R2 larger than 0.80, indicating a good fit to the data. Based on the regression models, the HU thresholds as a function of SD estimated to ensure the quantification accuracy of calcium scores for 120-, 100-, and 80-kVp CAC scans reconstructed at 0.5-mm slice thickness using IR for three different body sizes were proposed. Our results indicate that the HU threshold should be adjusted according to the imaging condition, whereas a 130-HU threshold is appropriate for 120-kVp CAC scans acquired with SD = 55 for body size of 24.5 cm. CONCLUSION: The optimized HU thresholds were proposed for CAC scans reconstructed at 0.5-mm slice thickness using IR. Our study results may provide a potential strategy to improve the reliability of calcium scoring by reducing partial volume effect while keeping radiation dose as low as reasonably achievable.

Coronary artery CT calcium score assessed by direct calcium quantification using atomic absorption spectroscopy and compared to macroscopic and histological assessments.

The Agatston score (AS) is the gold standard CT calcium scoring method in clinical practice. However, the AS is an indirect method of determining calcium amount, whereas atomic absorption spectroscopy (AAS) can directly measure the calcium amount. Our primary aim was to investigate the association between the AS and the coronary calcium amount measured by AAS. Furthermore, we compared our outcome to the macroscopic and histological coronary calcification and stenosis assessment, thus allowing us to infer a clinical coronary artery status based on post-mortem findings. Deceased individuals were examined with a 64-slice multidetector CT scanner, and the AS was determined. At autopsy, the degree of CAC and stenosis was determined, and the coronary arteries were excised and weighed. The coronary arteries were decalcified in a solution that was examined using AAS to measure the calcium amount. The degree of CAC and stenosis was also assessed by a histological examination. One hundred thirty-two coronary arteries were examined, and AS was highly correlated to the coronary calcium amount, measured by AAS, (r2 = 0.72, Pearson 0.85, p < 0.0001). In cases with AS 0, AAS measurements showed zero or very low calcium amounts. AS was also correlated to macroscopic and histological calcification assessments (Spearman's rho 0.68, p < 0.0001, Spearman's rho 0.82, p < 0.0001). Furthermore, an underestimation of subclinical atherosclerosis was seen and AS 0 could not rule out stenosis.

Hypercalcemia Is a Risk Factor for the Progression of Aortic Calcification in Kidney Transplant Recipients.

BACKGROUND/AIMS: Vascular calcification is common and progressive in chronic kidney disease, including kidney transplant recipients (KTRs). However, the risk factors associated with the progression of aortic calcification (AoC) in KTRs have not been fully elucidated. In the present study, we evaluated AoC and examined the factors associated with its advancement in KTRs. MATERIALS: This was a prospective longitudinal study that included 98 KTRs. We quantitatively investigated infrarenal abdominal AoC using the Agatston score, as measured by multi-slice computed tomography. After the baseline investigation, a follow-up scan was performed after 3 years, and the Agatston scores were obtained again. The changes in laboratory data affecting the 2nd Agatston scores were examined by multivariable analysis using non-linear regression after adjustment for several confounders. RESULTS: The 2nd Agatston scores were significantly greater than the baseline Agatston scores (p < 0.001). After adjustment for the confounders, the change in corrected serum calcium exhibited a significant non-linear correlation with the 2nd Agatston scores (p = 0.022 for non-linearity/p = 0.031 for the effect of corrected serum calcium). Moreover, an interaction was present from the baseline AoC in the effect of corrected serum calcium on the progression of AoC, and the effect of hypercalcemia was greater in patients with higher baseline Agatston scores (p = 0.049). CONCLUSION: The present study revealed that hypercalcemia is a risk factor for the development of infrarenal abdominal AoC in KTRs. Furthermore, the effect of hypercalcemia was greater in patients with more severe vascular calcification.

Risk of cardiovascular mortality predicted by the serum calcium level and calcification score at the initiation of dialysis.

BACKGROUND: The relationship between serum corrected calcium (CCa) level and vessel calcification at dialysis initiation and survival has seldom been evaluated. Therefore, we evaluated the efficacy of CCa levels and the calcification score at the initiation of dialysis for predicting all-cause and cardiovascular (CV) mortality in patients with end-stage renal disease (ESRD). METHODS: The study group included 407 patients with ESRD, who started hemodialysis between January 2009 and December 2016 at the Red Cross Ishinomaki Hospital. The primary outcomes were the 1- and 3-year all-cause and CV mortality rate, with the association between CCa level and CVD-specific mortality evaluated using the Kaplan-Meier method and Cox proportional hazard regression analysis. RESULTS: Patients with a high initial CCa level were at higher risk for CVD-related, but not all-cause, mortality than patients with a low initial CCa level [hazard ratio (HR) 2.81; 95% confidence interval 1.05-7.55]. The HR for CVD-related mortality was also higher for patients with an Agatston vessel calcification score > 2000 (HR 13.9; 95% CI 1.63-118.2). Overall, the 3-year CVD-free rate was 88.2% (range 76.4-94.3%). Higher CCa level was associated with a higher Agatston score and cardiac valve calcification. CONCLUSION: High serum CCa levels and an Agatston score > 2000 are independent risk factors of CVD mortality due to advanced vessel calcification.

Technical feasibility and validation of a coronary artery calcium scoring system using CT coronary angiography images.

OBJECTIVES: We validate a novel CT coronary angiography (CCTA) coronary calcium scoring system. METHODS: Calcium was quantified on CCTA images using a new patient-specific attenuation threshold: mean + 2SD of intra-coronary contrast density (HU). Using 335 patient data sets a conversion factor (CF) for predicting CACS from CCTA scores (CCTAS) was derived and validated in a separate cohort (n = 168). Bland-Altman analysis and weighted kappa for MESA centiles and Agatston risk groupings were calculated. RESULTS: Multivariable linear regression yielded a CF: CACS = (1.185 × CCTAS) + (0.002 × CCTAS × attenuation threshold). When applied to CCTA data sets there was excellent correlation (r = 0.95; p < 0.0001) and agreement (mean difference -10.4 [95% limits of agreement -258.9 to 238.1]) with traditional calcium scores. Agreement was better for calcium scores below 500; however, MESA percentile agreement was better for high risk patients. Risk stratification was excellent (Agatston groups k = 0.88 and MESA centiles k = 0.91). Eliminating the dedicated CACS scan decreased patient radiation exposure by approximately one-third. CONCLUSION: CCTA calcium scores can accurately predict CACS using a simple, individualized, semiautomated approach reducing acquisition time and radiation exposure when evaluating patients for CAD. This method is not affected by the ROI location, imaging protocol, or tube voltage strengthening its clinical applicability. KEY POINTS: • Coronary calcium scores can be reliably determined on contrast-enhanced cardiac CT • This score can accurately risk stratify patients • Elimination of a dedicated calcium scan reduces patient radiation by a third.

Coronary calcification in SLE: comparison with the Multi-Ethnic Study of Atherosclerosis.

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

Distribution of calcification in carotid endarterectomy tissues: comparison of micro-computed tomography imaging with histology.

BACKGROUND: Calcification in atherosclerotic plaques has been viewed as a marker of plaque stability, but whether calcification accumulates in specific anatomic sites in the carotid artery is unknown. We determined the burden and distribution of calcified plaque in carotid endarterectomy (CEA) tissues. METHODS: A total of 22 CEA tissues were imaged with high-resolution micro-computed tomography (micro-CT). Total plaque burden and total calcium score using the Agatston method were quantified. The Agatston score (AS) was also normalized for tissue size. Plaque and calcium distribution were analyzed separately for three CEA regions: common segment (CS), bulb segment (BS), and internal/external segments (IES). RESULTS: The average CEA tissue length was 40.83 (interquartile range [IQR] 33.31-42.41) mm with total plaque burden of 103.45 (IQR: 78.84-156.81) mm(3) and total AS of 38.58 (IQR 11.59-89.97). Total plaque volume was 21.02 (IQR: 14.47-25.42) mm(3) in the CS, 37.89 (22.59-48.32) mm(3) in the BS, and 54.05 (36.87-74.52) mm(3) in the IES. Of the 22 tissues, 15 had no calcium in the CS compared with three in the bulb and two in the IES. Normalized calcified plaque was most prevalent in the BS, the IES and was least prevalent in the CS. The overall correlation of calcification between histology sections and matched micro-CT images was 0.86 (p<0.001). CONCLUSIONS: Calcified plaque is heterogeneously distributed in CEA tissues with most in the bulb and IES regions. The amount of calcification in micro-CT slices shows a high correlation with matched histology sections.

Automated detection of incidental abdominal aortic aneurysms on computed tomography.

PURPOSE: To detect and assess abdominal aortic aneurysms (AAAs) on CT in a large asymptomatic adult patient population using fully-automated deep learning software. MATERIALS AND METHODS: The abdominal aorta was segmented using a fully-automated deep learning model trained on 66 manually-segmented abdominal CT scans from two datasets. The axial diameters of the segmented aorta were extracted to detect the presence of AAAs-maximum axial aortic diameter greater than 3 cm were labeled as AAA positive. The trained system was then externally-validated on CT colonography scans of 9172 asymptomatic outpatients (mean age, 57 years) referred for colorectal cancer screening. Using a previously-validated automated calcified atherosclerotic plaque detector, we correlated abdominal aortic Agatston and volume scores with the presence of AAA. RESULTS: The deep learning software detected AAA on the external validation dataset with a sensitivity, specificity, and AUC of 96%, (95% CI 89%, 100%), 96% (96%, 97%), and 99% (98%, 99%) respectively. The Agatston and volume scores of reported AAA-positive cases were statistically significantly greater than those of reported AAA-negative cases (p < 0.0001). Using plaque alone as a AAA detector, at a threshold Agatston score of 2871, the sensitivity and specificity were 84% (73%, 94%) and 87% (86%, 87%), respectively. CONCLUSION: Fully-automated detection and assessment of AAA on CT is feasible and accurate. There was a strong statistical association between the presence of AAA and the quantity of abdominal aortic calcified atherosclerotic plaque.

Circulating miR-6821-5p levels and coronary calcification in asymptomatic familial hypercholesterolemia patients.

BACKGROUND AND AIMS: Premature atherosclerotic cardiovascular disease (CVD) is a clinic characteristic of familial hypercholesterolemia (FH). Coronary calcium score (CCS) is a highly used imaging modality to evidence atherosclerotic plaque burden. microRNAs (miRNAs) are non-coding RNAs that epigenetically regulate gene expression. Here, we investigated whether CCS associates with a specific miRNA-signature in FH-patients. METHODS: Patients with genetic diagnosis of FH (N = 86) from the nationwide SAFEHEART-cohort were investigated by computed tomography angiography imaging and classified depending on the presence of coronary calcification in FH-CCS (+) and FH-CCS (-) groups by the Agatston score. Differential miRNA profiling was performed in two stages: first by Affymetrix microarray technology (high-throughput differential profiling-studies) and second by RT-PCR using TaqMan-technology (analytical RT-qPCR study) in plasma of the two patient groups. RESULTS: miR-193a-5p, miR-30e-5p and miR-6821-5p levels were significantly higher in FH-CCS (+) compared to FH-CCS (-). miR-6821-5p was the best miRNA to discriminate FH-patients CCS(+), according to receiver operating characteristic (ROC) analysis (AUC: 0.70 ± 0.06, p = 0.006). High miR-6821-5p levels were associated with older age (p = 0.03) and high LDL-burden (p = 0.014) using a ROC-derived cut-off value. However, miR-6821-5p did not correlate with age in either the CCS- or CCS + group. Genes involved in calcification processes were identified by in silico analysis. The relation of cell-calcification and expression levels of miR-6821-5p, BMP2 and SPP1 was validated experimentally in human vascular smooth muscle cell cultures. CONCLUSIONS: Up-regulated levels of miR-6821-5p are found in the plasma of asymptomatic FH-patients with coronary calcified atherosclerotic plaques, as well as in isolated human vascular smooth muscle cells expressing the pro-calcification genes BMP2 and SPP1. These findings highlight the impact of epigenetic regulation on the development of subclinical atherosclerosis.

Fully Automated Agatston Score Calculation From Electrocardiography-Gated Cardiac Computed Tomography Using Deep Learning and Multi-Organ Segmentation: A Validation Study.

To evaluate deep learning-based calcium segmentation and quantification on ECG-gated cardiac CT scans compared with manual evaluation. Automated calcium quantification was performed using a neural network based on mask regions with convolutional neural networks (R-CNNs) for multi-organ segmentation. Manual evaluation of calcium was carried out using proprietary software. This is a retrospective study of archived data. This study used 40 patients to train the segmentation model and 110 patients were used for the validation of the algorithm. The Pearson correlation coefficient between the reference actual and the computed predictive scores shows high level of correlation (0.84; P < .001) and high limits of agreement (±1.96 SD; -2000, 2000) in Bland-Altman plot analysis. The proposed method correctly classifies the risk group in 75.2% and classifies the subjects in the same group. In total, 81% of the predictive scores lie in the same categories and only seven patients out of 110 were more than one category off. For the presence/absence of coronary artery calcifications, the deep learning model achieved a sensitivity of 90% and a specificity of 94%. Fully automated model shows good correlation compared with reference standards. Automating process reduces evaluation time and optimizes clinical calcium scoring without additional resources.

Quantification accuracy in photon-counting detector CT for coronary artery calcium score: a pilot study.

To validate the accuracy of coronary artery calcium score (CACS) using photon-counting detector (PCD) CT under various scanning settings and explore the optimized scanning settings considering both the accuracy and the radiation dose. A CACS phantom containing six hollow cylindrical hydroxyapatite calcifications of two sizes with three densities and 12 patients underwent CACS scans. For PCD-CT, two scanning modes (sequence and flash [high-pitch spiral mode]) and five tube voltages (90kV, 120kV, 140kV, Sn100kV, and Sn140kV) at different image quality (IQ) levels were set for phantom, and patients were scanned with 120kV at IQ19 using flash mode. All acquisitions from PCD-CT were reconstructed at 70keV. Acquisitions in sequence mode at 120kV on an energy-integrating detector CT (EID-CT) was used as the reference. Agatston, mass, and volume scores were calculated. The CACS from PCD-CT exhibited excellent agreements with the reference (all intraclass correlation coefficient [ICC] > 0.99). The root mean square error (RMSE) between the Agatston score acquired from PCD-CT and the reference (5.4-11.5) was small. A radiation dose reduction (16-75%) from PCD-CT compared with the reference was obtained in all protocols using flash mode, albeit with IQ20 only at sequence mode (22-44%). For the patients, ICC ( all ICC > 0.98) and Bland-Altman analysis of CACS all showed high agreements between PCD-CT and the reference, without reclassifying CACS categories(P = 0.317). PCD-CT yields repeatable and accurate CACS across diverse scanning protocols according to our pilot study. Sn100kV, 90kV, and 120kV using flash mode at IQ20 are recommended for clinical applications considering both accuracy and radiation dose.

Associations of Dietary Calcium and Phosphorus With Vascular and Valvular Calcification: The ARIC Study.

Background: High dietary calcium and phosphorus may accelerate vascular calcification, but epidemiological data are inconsistent. Most of those studies assessed diet at one point and have not been systematically evaluated. Objectives: The purpose of this study was to assess the associations of dietary calcium and phosphorus intakes in middle age with coronary artery and extra-coronary calcification at older age. Methods: We studied 1,914 participants from the ARIC (Atherosclerosis Risk In Communities) study (mean age 80.5 years) without coronary heart disease who underwent chest computed tomography scans at visit 7 (2018-2019) and completed a 66-item food frequency questionnaire at 2 earlier visits (visit 1 [1987-1989] and visit 3 [1993-1995]). Dietary calcium and phosphorus intakes were averaged between these 2 visits. Calcification was quantified by the Agatston score in coronary artery, ascending aorta, descending aorta, aortic valve ring, aortic valve, and mitral valve. Results: Dietary calcium intake was inversely associated with coronary artery and ascending aorta calcification, whereas the association was not significant for other measures of extra-coronary calcification. For example, the highest vs lowest quartile of calcium intake showed an adjusted OR of 0.66 (95% CI: 0.45-0.98) for coronary artery calcification (Agatston score ≥75th percentile). Dietary phosphorus intake demonstrated similar results, but the magnitude of the association was weaker than dietary calcium intake. Conclusions: Dietary calcium and phosphorus intakes at middle age were not positively associated with vascular and valvular calcification at over 75 years old. Our findings did not support the link between a calcium or phosphorus-rich diet and vascular and valvular calcification.

Combining anatomical and biochemical markers in the detection and risk stratification of coronary artery disease.

AIMS: We aimed to test the hypothesis if combining coronary artery calcium score (Ca-score) as a quantitative anatomical marker of coronary atherosclerosis with high-sensitivity cardiac troponin as a quantitative biochemical marker of myocardial injury provided incremental value in the detection of functionally relevant coronary artery disease (fCAD) and risk stratification. METHODS AND RESULTS: Consecutive patients undergoing myocardial perfusion single-photon emission computed tomography (MPS) without prior CAD were enrolled. The diagnosis of fCAD was based on the presence of ischaemia on MPS and coronary angiography; fCAD was centrally adjudicated in the diagnostic and prognostic domain. Diagnostic accuracy was evaluated using the area under the receiver-operating characteristic curve (AUC). The composite of cardiovascular death and non-fatal acute myocardial infarction (AMI) within 730 days was the primary prognostic endpoint. Among 1715 patients eligible for the diagnostic analysis, 399 patients had fCAD. The combination of Ca-score and high-sensitivity cardiac troponin T (hs-cTnT) had good diagnostic accuracy for the diagnosis of fCAD (AUC 0.79, 95% confidence interval (CI) 0.77-0.81), but no incremental value compared with the Ca-score alone (AUC 0.79, 95% CI 0.77-0.81, P = 0.965). Similar results were observed using high-sensitivity cardiac troponin I (AUC 0.80, 95% CI 0.77-0.82) instead of hs-cTnT. Among 1709 patients (99.7%) with available follow-up, 59 patients (3.5%) suffered the composite primary prognostic endpoint (non-fatal AMI, n = 34; CV death, n = 28). Both Ca-score and hs-cTnT had independent prognostic value. Increased risk was restricted to patients with elevation in both markers. CONCLUSION: The combination of the Ca-score with hs-cTnT increases the prognostic accuracy for future events but does not provide incremental value vs. the Ca-score alone for the diagnosis of fCAD. STUDY REGISTRATION: Clinical trial registration: NCT00470587.

Diagnostic Value of Aortic Valve Calcification Levels in the Assessment of Low-Gradient Aortic Stenosis.

BACKGROUND: In patients with low-gradient aortic stenosis (AS) and low transvalvular flow, dobutamine stress echocardiography (DSE) is recommended to determine AS severity, whereas the degree of aortic valve calcification (AVC) supposedly correlates with AS severity according to current European and American guidelines. OBJECTIVES: The purpose of this study was to assess the relationship between AVC and AS severity as determined using echocardiography and DSE in patients with aortic valve area <1 cm2 and peak aortic valve velocity <4.0 m/s. METHODS: All patients underwent DSE to determine AS severity and multislice computed tomography to quantify AVC. Receiver-operating characteristics curve analysis was used to assess the diagnostic value of AVC for AS severity grading as determined using echocardiography and DSE in men and women. RESULTS: A total of 214 patients were included. Median age was 78 years (25th-75th percentile: 71-84 years) and 25% were women. Left ventricular ejection fraction was reduced (<50%) in 197 (92.1%) patients. Severe AS was diagnosed in 106 patients (49.5%). Moderate AS was diagnosed in 108 patients (50.5%; in 77 based on resting transthoracic echocardiography, in 31 confirmed using DSE). AVC score was high (≥2,000 for men or ≥1,200 for women) in 47 (44.3%) patients with severe AS and in 47 (43.5%) patients with moderate AS. AVC sensitivity was 44.3%, specificity was 56.5%, and positive and negative predictive values for severe AS were 50.0% and 50.8%, respectively. Area under the receiver-operating characteristics curve was 0.508 for men and 0.524 for women. CONCLUSIONS: Multi-slice computed tomography-derived AVC scores showed poor discrimination between grades of AS severity using DSE and cannot replace DSE in the diagnostic work-up of low-gradient severe AS.

Accuracy of aortic valve calcification volume score for identification of significant aortic stenosis on non-electrocardiographic-gated computed tomography compared to the Agatston scoring system.

BACKGROUND: Considering the absence of reports validating the precision of the volume score and the relationship between the volume and Agatston scores, this study evaluated the accuracy of the volume score compared to the Agatston score for the quantitative measurement of aortic valve calcification (AVC) on non-electrocardiographic-gated computed tomography (CT). METHODS: We retrospectively analysed the AVC scores of 5385 patients who underwent transthoracic echocardiography between March 1, 2013 and December 26, 2019 â€‹at our institution, using non-contrast non-electrocardiographic-gated CT. The thresholds for significant aortic stenosis (AS) were computed using receiver operating characteristic curves based on the AVC scores. The area under the curve (AUC) of the Agatston and volume scores for significant AS were compared to evaluate the accuracy of the scoring method. RESULTS: All sex-specific AVC thresholds of the volume score for significant AS (moderate and high AS severity, moderate and high AS severity without discordance, discordant severe AS, and concordant severe AS) showed high sensitivity and specificity (AUC, 0.978-0.996; sensitivity, 94.2-98.4%; specificity, 90.1-100%). No significant differences in the AUC were observed between the Agatston and volume scores for significant AS in male and female patients. CONCLUSION: All volume score threshold values showed high sensitivity and specificity for identifying significant AS. The accuracy of the test for AVC thresholds of the volume score for significant AS was comparable to that of the Agatston score. Our findings raise questions about the significance of weighting calcium density in the Agatston score for assessing AS severity.

Effects of high- versus low-intensity lipid-lowering treatment in patients undergoing serial coronary computed tomography angiography: results of the multi-center LOCATE study.

AIM: To evaluate the effects of lipid-lowering medications of different intensities on total, calcified, and non-calcified plaque volumes in patients undergoing serial cardiac computed tomography angiography (CCTA). METHODS: Individuals with chronic coronary syndromes from 11 centers were included in a retrospective registry. Total, calcified, and non-calcified plaque volumes were quantified and the relative difference in plaque volumes between baseline and follow-up CCTA was calculated. The intensity of lipid-lowering treatment was designated as low, moderate, or high, based on current recommendations. RESULTS: Of 216 patients (mean age 63.1 ± 9.7 years), undergoing serial CCTA (median timespan = 824.5 [IQR = 463.0-1323.0] days), 89 (41.2%) received no or low-intensity lipid-lowering medications, and 80 (37.0%) and 47 (21.8%) moderate- and high-intensity lipid-lowering agents, respectively. Progression of total and non-calcified plaque was attenuated in patients on moderate-/high- versus those on no/low-intensity treatment and arrested in patients treated with high-intensity statins or PCSK9 inhibitors (p < 0.001). Halted increase of non-calcified plaque was associated with LDL-cholesterol reduction (p < 0.001), whereas calcified plaque mass and Agatston score increased irrespective of the lipid-lowering treatment (p = NS). The intensity of lipid-lowering therapy robustly predicted attenuation of non-calcified plaque progression as a function of the time duration between the two CCTA scans, and this was independent of age and cardiovascular risk factors (HR = 3.83, 95% CI = 1.81-8.05, p < 0.001). CONCLUSION: The LOCATE multi-center observational study shows that progression of non-calcified plaques, which have been previously described as precursors of acute coronary syndromes, can be attenuated with moderate-intensity, and arrested with high-intensity lipid-lowering therapy. GERMAN CLINICAL TRIALS REGISTER: DRKS00031954.