Absolute iron deficiency, coronary artery calcification and cardiovascular mortality in maintenance haemodialysis patients.

AIM: The effects of iron on vascular calcification in rats and vascular smooth muscle cells were recently reported, but clinical studies on iron and vascular calcification are scant. We studied the associations of absolute iron deficiency, coronary artery calcification and mortality in patients with maintenance haemodialysis (MHD). METHODS: Transferrin saturation (TSAT), ferritin, mean corpuscular haemoglobin (MCH) and Agatston coronary artery calcium score (CACS) were studied at baseline in MHD patients and followed up for 3 years. Cox proportional hazard analyses for mortality and linear regression analyses for CACS were performed. RESULTS: In 306 patients, the median age was 67 (56-81) years, dialysis duration was 76 (38-142) months, and diabetes prevalence was 42.5%. Fifty-two patients had died by 3 years. Patients with absolute iron deficiency (TSAT <20% and ferritin <100 ng/mL) (n = 102) showed significantly higher CACS (p = .0266) and C-reactive protein (p = .0011), but a lower frequency of iron formulation administration compared with patients without absolute iron deficiency at baseline (n = 204). Absolute iron deficiency was a significant predictor for 3-year cardiovascular (CV) mortality (hazard ratio: 2.08; p = .0466), but not for 3-year all-cause mortality. CACS was significant predictor for both 3-year CV and all-cause mortality (p <.05). Absolute iron deficiency and MCH were significant determinants of CACS (p < .05). CONCLUSION: MHD patients with absolute iron deficiency showed significantly higher CACS than others, and absolute iron deficiency was a significant risk factor for coronary artery calcification and 3-year CV mortality in MHD patients, but was not a significant predictor for 3-year all-cause mortality.

Effects of overhydration, Kt/Vurea, ß2-microglobulin on coronary artery calcification and mortality in haemodialysis patients.

AIM: We studied the effects of overhydration (OH), Kt/Vurea and ß2-microglobulin (ß2-MG) on coronary artery calcification and mortality in patients undergoing haemodialysis (HD). METHODS: The Agatston coronary artery calcium score (CACS), postdialysis body composition using bioimpedance analysis, single-pool Kt/Vurea and predialysis ß2-MG at baseline were assessed and followed up for 3 years in patients undergoing HD. We performed logistic regression analyses for a CACS ≥400 and Cox proportional hazard analyses for all-cause and cardiovascular mortality. RESULTS: The study involved 338 patients with a median age of 67 (56-74) years, dialysis duration of 70 (33-141) months and diabetes prevalence of 39.1% (132/338). Patients with a CACS ≥400 (n = 222) had significantly higher age, dialysis duration, male prevalence, diabetes prevalence, C-reactive protein, predialysis ß2-MG, OH, extracellular water/total body water and overhydration/extracellular water (OH/ECW) but significantly lower Kt/Vurea than patients with a CACS <400 (n = 116) (p < .05). OH/ECW, Kt/Vurea and predialysis ß2-MG were significant predictors of a CACS ≥400 (p < .05) after adjusting for age, dialysis duration, serum phosphate and magnesium. In all patients, cut-off values of OH/ECW, Kt/Vurea and predialysis ß2-MG for a CACS ≥400 were 16%, 1.74 and 28 mg/L, respectively. After adjusting for dialysis duration, OH/ECW ≥16%, Kt/Vurea ≥1.74 and ß2-MG ≥28 mg/L were significant predictors of 3-year all-cause mortality but not 3-year cardiovascular mortality. CONCLUSION: Higher OH/ECW, higher predialysis ß2-MG and lower Kt/Vurea values are significant risk factors for a CACS ≥400 and 3-year all-cause mortality in patients undergoing maintenance HD.

Utility of coronary artery calcium in refining 10-year ASCVD risk prediction using a Thai CV risk score.

Background: Coronary artery calcium (CAC) scanning is a valuable additional tool for calculating the risk of cardiovascular (CV) events. We aimed to determine if a CAC score could improve performance of a Thai CV risk score in prediction of 10-year atherosclerotic cardiovascular disease (ASCVD) risk for asymptomatic patients with CV risk factors. Methods: This was a retrospective cohort study that enrolled asymptomatic patients with CV risk factors who underwent CAC scans between 2005 and 2013. The patients were classified as low-, intermediate-, or high-risk (<10%, 10%-<20%, and ≥20%, respectively) of having ASCVD within 10-years based on a Thai CV risk score. In each patient, CAC score was considered as a categorical variable (0, 1-99, and ≥100) and natural-log variable to assess the risk of developing CV events (CV death, non-fatal MI, or non-fatal stroke). The C statistic and the net reclassification improvement (NRI) index were applied to assess whether CAC improved ASCVD risk prediction. Results: A total of 6,964 patients were analyzed (mean age: 59.0 ± 8.4 years; 63.3% women). The majority of patients were classified as low- or intermediate-risk (75.3% and 20.5%, respectively), whereas only 4.2% were classified as high-risk. Nearly half (49.7%) of patients had a CAC score of zero (no calcifications detected), while 32.0% had scores of 1-99, and 18.3% of ≥100. In the low- and intermediate-risk groups, patients with a CAC ≥100 experienced higher rates of CV events, with hazard ratios (95% CI) of 1.95 (1.35, 2.81) and 3.04 (2.26, 4.10), respectively. Incorporation of ln(CAC + 1) into their Thai CV risk scores improved the C statistic from 0.703 (0.68, 0.72) to 0.716 (0.69, 0.74), and resulted in an NRI index of 0.06 (0.02, 0.10). To enhance the performance of the Thai CV risk score, a revision of the CV risk model was performed, incorporating ln(CAC + 1), which further increased the C statistic to 0.771 (0.755, 0.788). Conclusion: The addition of CAC to traditional risk factors improved CV risk stratification and ASCVD prediction. Whether this adjustment leads to a reduction in CV events and is cost-effective will require further assessment.

Computed Tomography-Based Coronary Artery Calcium Score Calculation at a Reduced Tube Voltage Utilizing Iterative Reconstruction and Threshold Modification Techniques: A Feasibility Study.

BACKGROUND: The coronary artery calcium score (CACS) indicates cardiovascular health. A concern in this regard is the ionizing radiation from computed tomography (CT). Recent studies have tried to introduce low-dose CT techniques to assess CACS. We aimed to investigate the accuracy of iterative reconstruction (IR) and threshold modification while applying low tube voltage in coronary artery calcium imaging. METHODS: The study population consisted of 107 patients. Each subject underwent an electrocardiogram-gated CT twice, once with a standard voltage of 120 kVp and then a reduced voltage of 80 kVp. The standard filtered back projection (FBP) reconstruction was applied in both voltages. Considering Hounsfield unit (HU) thresholds other than 130 (150, 170, and 190), CACS was calculated using the FBP-reconstructed 80 kVp images. Moreover, the 80 kVp images were reconstructed utilizing IR at different strength levels. CACS was measured in each set of images. The intraclass correlation coefficient (ICC) was used to compare the CACSs. RESULTS: A 64% reduction in the effective dose was observed in the 80 kVp protocol compared to the 120 kVp protocol. Excellent agreement existed between CACS at high-level (strength level = 5) IR in low-kVp images and the standard CACS protocol in scores ≥ 11 (ICC > 0.9 and p < 0.05). Increasing the threshold density to 190 HU in FBP-reconstructed low-kVp images yielded excellent agreement with the standard protocol in scores ≥ 11 (ICC > 0.9 and p < 0.05) and good agreement in score zero (ICC = 0.84 and p = 0.02). CONCLUSIONS: The modification of the density threshold and IR provides an accurate calculation of CACS in low-voltage CT with the potential to decrease patient radiation exposure.

Detecting obstructive coronary artery disease with machine learning: rest-only gated single photon emission computed tomography myocardial perfusion imaging combined with coronary artery calcium score and cardiovascular risk factors.

Background: The rest-only single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) has low diagnostic performance for obstructive coronary artery disease (CAD). Coronary artery calcium score (CACS) is strongly associated with obstructive CAD. The aim of this study was to investigate the performance of rest-only gated SPECT MPI combined with CACS and cardiovascular risk factors in diagnosing obstructive CAD through machine learning (ML). Methods: We enrolled 253 suspected CAD patients who underwent the 1-stop rest-only SPECT MPI and computed tomography (CT) scan due to stress test-related contraindications. Myocardial perfusion and wall motion were assessed using quantitative perfusion SPECT + quantitative gated SPECT (QPS + QGS) automated quantification software. The Agatston algorithm was used to calculate CACS. The clinical data of patients, including cardiovascular risk factors, were collected. Based on feature selection and clinical experience, 8 factors were identified as modeling variables. Subsequently, patients were divided randomly into 2 groups: the training (70%) and test (30%) groups. The performance of 8 supervised ML algorithms was evaluated in the training and test groups. Results: Obstructive CAD was diagnosed by coronary angiography in 94 (37.2%, 94/253) patients. In the training group, the area under the receiver operator characteristic (ROC) curve (AUC) of the random forest was the highest, and the AUCs of Logistic, extreme gradient boosting (XGBoost), support vector machine (SVM), and adaptive boosting (AdaBoost) were all above 0.9. In the test group, the AUC of recursive partitioning and regression trees (Rpart) was the highest (0.911). Rpart and Naïve Bayes had the highest accuracy (0.840). Rpart had a sensitivity and specificity of 0.851 and 0.821, respectively; Naïve Bayes had a sensitivity and specificity of 0.809 and 0.893, respectively. Next was Logistic, with an accuracy of 0.827, a sensitivity of 0.872, and a specificity of 0.750. The random forest and XGBoost algorithms also had high accuracy, which was 0.813 for each algorithm. Conclusions: Rest-only SPECT MPI combined with CACS and cardiovascular risk factors using an ML algorithm to detect obstructive CAD is feasible. Among the algorithms validated in the test group, Rpart, Naïve Bayes, XGBoost, Logistic, and random forest are all highly accurate for diagnosing obstructive CAD. The application of ML in resting MPI and CACS may be used for screening obstructive CAD.

Validation of deep learning-based fully automated coronary artery calcium scoring using non-ECG-gated chest CT in patients with cancer.

This study aimed to demonstrate clinical feasibility of deep learning (DL)-based fully automated coronary artery calcium (CAC) scoring software using non-electrocardiogram (ECG)-gated chest computed tomography (CT) from patients with cancer. Overall, 913 patients with colorectal or gastric cancer who underwent non-contrast-enhanced chest CT between 2013 and 2015 were included. Agatston scores obtained by manual segmentation of CAC on chest CT were used as reference. Reliability of automated CAC score acquisition was evaluated using intraclass correlation coefficients (ICCs). The agreement for cardiovascular disease (CVD) risk stratification was assessed with linearly weighted k statistics. ICCs between the manual and automated CAC scores were 0.992 (95% CI, 0.991 and 0.993, p<0.001) for total Agatston scores, 0.863 (95% CI, 0.844 and 0.880, p<0.001) for the left main, 0.964 (95% CI, 0.959 and 0.968, p<0.001) for the left anterior descending, 0.962 (95% CI, 0.956 and 0.966, p<0.001) for the left circumflex, and 0.980 (95% CI, 0.978 and 0.983, p<0.001) for the right coronary arteries. The agreement for cardiovascular risk was excellent (k=0.946, p<0.001). Current DL-based automated CAC software showed excellent reliability for Agatston score and CVD risk stratification using non-ECG gated CT scans and might allow the identification of high-risk cancer patients for CVD.

Coronary artery calcium score scan at 100 kVp with tin filtration (Sn100 kVp) prior to coronary computed tomography angiography for overall radiation dose reduction: a prospective cohort study.

Background: Reducing radiation dose is a global concern in coronary computed tomography angiography (CCTA). We aimed to investigate whether a coronary artery calcium score (CACS) scan would lead to an overall reduction of radiation dose in CCTA examination and determine its necessity in routine CCTA imaging. Methods: A total of 297 patients with suspected coronary heart disease were consecutively enrolled in this prospective cohort study between March 1, 2021, and September 1, 2021. All patients were scanned using a prospective electrocardiogram-triggered sequence acquisition mode on a dual-source computed tomography (CT) scanner. The first 1-150 patients (group A, n=150) were scanned with CACS using tin filtration with low voltage (Sn100 kVp) to guide the CCTA scanning range, whereas the subsequent 151-297 patients (group B, n=147) were scanned using a scout view for the CCTA range. Participant characteristics, number of scans, scan length, actual heart length, CT dose index (CTDIvol), dose-length product (DLP), effective dose (ED), and qualitative analysis were statistically analyzed between the groups. Results: There was no significant difference in sex, age, height, weight, body mass index (BMI), or heart rate between the 2 groups. The number of scans and scan length (149 of 3 scans at 10.35 cm, 1 of 4 scans at 13.80 cm; P<0.001), CTDIvol of CCTA (16.13 mGy; P<0.04), DLP of CCTA (166.90 mGy*cm; P<0.001), ED of CCTA (4.34 mSv; P<0.001), and overall ED (4.57 mSv; P<0.001) of group A showed significant differences compared with group B (36 of 3 scans at 10.35 cm, 109 of 4 scans at 13.80 cm, 2 of 5 scans at 17.25 cm; CTDIvol of CCTA at 18.30 mGy; DLP of CCTA at 235.60 mGy*cm; ED of CCTA at 6.13 mSv; overall ED at 6.13 mSv); meanwhile, actual heart length, qualitative analysis, and diagnostic CT reports were similar between the groups. Conclusions: The CACS scan with Sn100 kVp prior to CCTA imaging on dual-source CT could reduce overall radiation dose.

The Atherosclerosis Profile by Coronary Computed Tomography Angiography (CTA) in Symptomatic Patients with Coronary Artery Calcium Score Zero.

(1) Background: Whether it is safe to exclude coronary artery disease (CAD) in symptomatic patients with coronary artery calcium score (CACS 0), is an open debate. To compare coronary CTA including high-risk plaque (HRP) features in symptomatic patients with CACS 0 (2) Methods: 1709 symptomatic patients (age, mean 57.5 ± 16 years, 39.6% females) referred to coronary CTA for clinical indications were included. CACS, coronary stenosis (CADRADS) severity and HRP features (low-attenuation-plaque, spotty calcification, positive remodeling, NRS) were recorded. (3) Results: Of 1709 patients, 665 with CACS 0 were finally included. 562 (84.5%) had no CAD by CTA while 103 of 665 (15.4%) had CAD. Stenosis was minimal <25% in 79, mild <50% in 20, moderate in 1 and severe >70% in 3 patients. The rate of obstructive CAD was low with 4/665 (0.61%). The majority of patients had non-obstructive CAD (<50% stenosis) (99/103; 96.1%). A high proportion of patients with non-obstructive CAD had at least one HRP (52/103; 50.4%) per patient. (4) Conclusions: The rate of obstructive CAD is very low in symptomatic patients with CACS 0, and non-obstructive CAD domineering. CACS 0 does not rule out non-obstructive CAD and misses patients in which primary preventive measures are indicated. More than half of patients with non-obstructive CAD had high-risk plaque, highlighting the importance of quantitative plaque analysis.

Case report: 68 yo Chinese-American woman with high HDL-C and ischemic stroke attributed to intracranial atherosclerotic stenosis.

Atherosclerotic cardiovascular disease (ASCVD) events are the most common cause of death in the United States and for most individuals who experience these events, may be predicted by risk identification tools. ASCVD risk calculators enable a clinician-patient discussion and the presence of risk-enhancing factors may further inform decision-making with respect to preventive pharmacotherapy, especially statin prescription. In cases where the decision of whether to treat with medicine is unclear, coronary artery calcium scoring by computed tomography offers enhanced risk stratification and may allow both clinicians and patients to feel more at ease with the decision to withhold statin therapy. Despite this thoughtful approach, individual risk may still be underestimated. We present a case of a woman whose family history suggested increased short- and long-term ASCVD risk due to intracranial atherosclerosis, but whose tests suggested a more equivocal indication for treatment. Neither she nor her clinician appreciated the presence of significant enough risk to persevere through minor statin side effects for primary prevention, but she was lucky to have survived without appreciable harm from an acute cerebrovascular event and is now able to pursue an appropriate secondary preventive strategy. We discuss how exceptional characteristics may mislead clinicians, including misperception about lower risk due to gender, East Asian predisposition to intracranial more than coronary atherosclerosis, high levels of high density lipoprotein cholesterol (HDL-C), and CACS = 0.

Diagnostic accuracy of 13N-ammonia myocardial perfusion imaging with PET-CT in the detection of coronary artery disease.

BACKGROUND: 13N-ammonia positron emission tomography-computed tomography (PET-CT) is being increasingly used as a non-invasive imaging modality for evaluating patients with known or suspected coronary artery disease (CAD), but information about the diagnostic accuracy of PET-MPI is sparse. Objectives: Our objective was to determine the accuracy of 13N-ammonia PET-CT myocardial perfusion imaging (MPI) for detecting CAD. METHODS: We retrospectively evaluated 383 patients with suspected CAD who underwent rest-stress 13N- ammonia PET-CT MPI. Invasive coronary angiography (ICA) was performed within 60 days for all patients with abnormal PET-MPI findings and for selected patients with normal PET-MPI findings. RESULTS: The mean age of the patients was 64±11 years, and the mean body mass index was 32±7 kg/m2. Stress perfusion defects were identified in 147 (34%) out of a total of 383 patients. ICA was performed in 213 patients (145 patients with abnormal PET and 68 patients with normal PET). The sensitivity of PET-MPI for detection of obstructive CAD based on ≥50% stenosis was 90%; specificity, 90%; positive predictive value, 96%; negative predictive value, 76%; and diagnostic accuracy, 80%. CONCLUSIONS: PET-MPI with 13N-ammonia affords high sensitivity and overall accuracy for detecting CAD. The addition of coronary artery calcium score (CACS) can improve CAD risk stratification.

Assessment of the relationship between selected cardiovascular risk factors and the indices of intima-media thickness and coronary artery calcium score in various stages of chronic kidney disease.

Renal diseases pose a growing epidemiological and health problem worldwide. Cardiovascular diseases are the leading cause of deaths among patients with chronic kidney disease. Increased risk of atherosclerosis in these patients results from the occurrence of traditional and non-traditional risk factors. The aim of this study was to assess the relationship between selected risk factors for cardiovascular diseases (age, sex, dyslipidemia, hypertension, etc.), intima-media thickness and coronary artery calcium score in patients with chronic kidney disease stages 2, 3 and 4. This study included 60 patients with chronic kidney disease divided into 3 groups on the basis of disease stage and control group consisting of 20 individuals without diagnosed chronic kidney disease and cardiovascular diseases. Blood analysis and blood pressure measurements were taken. All patients underwent carotid artery ultrasound with the assessment of the intima-media thickness, and heart CT scan in order to assess the index of coronary artery calcification. Logistic regression analysis revealed statistically significant correlation between blood vessels calcification and age--the increase in age by 1 year was associated with the increase in the risk of coronary artery calcification by 6.7 %. The increase in IMT by about 0.1 mm raises the risk of calcification by about 2 %. Second logistic regression model revealed that one-year increase in age was associated with an increase in the risk of intima-media thickening by 6.5 %. Occurrence of hypertension was associated with a ninefold increase in intima-media thickening risk in comparison with patients with normal blood pressure. To sum up, age and hypertension were associated with the growth of IMT in CKD patients, while age and exposure to tobacco smoke were associated with the increase in coronary artery calcium score. The relationship between thickening of IMT and the increase in calcification index in patients was also observed in study group.

Relationship between insulin resistance and subclinical atherosclerosis in individuals with and without type 2 diabetes mellitus.

BACKGROUND: Insulin resistance is of utmost importance as an underlying mechanism for increased risk of cardiovascular disease (CVD). We assessed the association between Homeostatic Model Assessment (HOMA-IR) and two surrogate subclinical atherosclerosis markers (SCA) among individuals with and without type 2 diabetes (DM), those who did not have any clinical presentation of the CVD. METHODS: In a cross-sectional study, 208 participants (105 diabetics and 103 non-diabetics) were enrolled from referred patients with diabetes to an academic outpatient clinic and their non-diabetic relatives in-law. Fasting serum levels of insulin, blood glucose and lipid profile, were measured. Anthropometric and blood pressure were measuremented standardly. Body Mass Index (BMI) and Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) index were calculated. Coronary Artery Calcium Score(CACS) was measured using a Multi-Detctor CT scanner. Flow mediated dilation (FMD) was measured using bimode ultrasonography (with linear transducer 13,000 MHZ). Univariate and multivariate logistic regression models were used to evaluate the association between these SCA markers and HOMA index in adjusting models. RESULTS: CACS and HOMA-IR were higher and FMD was lower in diabetic participants than non-diabetic ones (P < 0.01) In a stepwise logistic regression model, CACS and FMD were associated with HOMA-IR (odds ratio = 1.778; 95 % confidence interval (CI): 1.211-2.726 and odds ratio = 1.557; 95 % CI: 1.601-2.275, respectively) in non-diabetics but not among diabetic participants. CONCLUSIONS: CACS and FMD are related to insulin resistance among non-diabetic individuals, but we could not find this relationship among diabetic patients.