Association between bone mineral metabolism and vascular calcification in end-stage renal disease

Background Development of vascular calcification is accelerated in patients with end-stage renal disease. In addition to traditional risk factors of cardiovascular disease (CVD) abnormal bone and mineral metabolism together with many other factors contribute to the excess cardiovascular burden in patients on dialysis. Aortic calcification score and coronary calcification score are predictive of CVD and mortality. The aim of this study was to evaluate the possible relationship between arterial calcification and bone metabolism. Methods Thirty two patients on dialysis were included. All patients underwent a bone biopsy to assess bone histomorphometry and a 18F-NaF PET scan. Fluoride activity was measured in the lumbar spine (L1 – L4) and at the anterior iliac crest. Arterial calcification scores were assessed by computerized tomography for quantification of coronary artery calcification score and lateral lumbar radiography for aortic calcification score. Results This study group showed high prevalence of arterial calcification and 59% had verified CVD. Both CAC and AAC were significantly higher in patients with verified CVD. Only 22% had low turnover bone disease. There was a weak association between fluoride activity, which reflects bone turnover, measured in the lumbar spine, and CAC and between PTH and CAC. There was also a weak association between erosion surfaces and AAC. No significant association was found between calcification score and any other parameter measured. Conclusions The results in this study highlight the complexity, when evaluating the link between bone remodeling and vascular calcification in patients with multiple comorbidities and extensive atherosclerosis. Several studies suggest an impact of bone turnover on development of arterial calcification and there is some evidence of reduced progression of vascular calcification with improvement in bone status. The present study indicates an association between vascular calcification and bone turnover, even though many parameters of bone turnover failed to show significance. In the presence of multiple other factors contributing to the development of calcification, the impact of bone remodeling might be diminished. Trial registration The study is registered in ClinicalTrials.gov protocol registration and result system, ID is NCT02967042. Date of registration is 17/11/2016.

The diagnosis and prognosis of coronary microvascular disease using PET/CT

OBJECTIVE: This study aimed to evaluate the diagnostic and prognostic value of 13N–NH3·H2O positron emission tomography combined with computed tomography (PET/CT) for non-obstructive coronary microvascular disease (CMVD). METHODS: A retrospective analysis was conducted on 70 patients with clinically suspected non-obstructive CMVD (35 males, 35 females) between March 2017 and August 2019. The average age of the patients was 53.32±7.82 years. The patients underwent 13N–NH3·H2O PET/CT and were divided into two groups based on diagnostic criteria: a CMVD group and a non-CMVD group. They were then followed up for 180–1,095 days. Data were analyzed using an χ 2 test, the logistic regression model, the multiple linear regression model, the Kaplan–Meier method, the Cox proportional hazards regression model, and a receiver operating characteristic (ROC) curve. RESULTS: (1) The incidence of cardiovascular family history and a high calcification score (11–400) was higher in the CMVD group than in the non-CMVD group (58.8% vs. 20.8% and 29.4% vs. 5.7%, respectively; P < 0.05 for all), stress myocardial blood flow (MBF) and coronary flow reserve (CFR) values were lower in the CMVD group than in the non-CMVD group (2.280±0.693 vs. 3.641±1.365 and 2.142±0.339 vs. 3.700±1.123, respectively), and calcification score was higher in the CMVD group than in the non-CMVD group (110.18±165.07 vs. 13.21±41.68, respectively; P < 0.05 for all). Gender and diabetes were risk factors for stress MBF reduction (β= 1.287 and β= –0.636, respectively), calcification score and hypertension were risk factors for CFR reduction (β= –0.004 and β= –0.654, respectively), and hypertension, family history, and calcification score were risk factors in the CMVD group (OR = 7.323, OR = 5.108, OR = 1.012, respectively; P < 0.05 for all). (2) The prognosis of patients with CFR < 2.5 was worse than that of patients with CFR≥2.5 (x 2 value: 27.404, P < 0.001). The risk of adverse cardiovascular events in diabetic patients was also increased (β= 0.328, P < 0.001). When CFR was set to 2.595, the prognostic sensitivity was 94% and the specificity was 80%. CONCLUSION: The technology of 13N–NH3·H2O PET/CT can be used for the diagnosis and prognosis of non-obstructive CMVD. Cardiovascular risk factors are related to the occurrence and prognosis of CMVD.

Analysis of Correlation Between Coronary Tortuosity and Calcification Score

Background: Coronary artery tortuosity (CAT) is regarded as a variation of vascular anatomy, and its relationship with coronary artery calcification (CAC) score is still not well clarified. Studying the correlation between coronary artery calcification scores and CAT to determine specific prevention and intervention populations seems to have more meaningful.Methods: The study is a cross-sectional retrospective study, including 1280 patients with tortuous coronary artery. CAT is defined as the presence of at least three consecutive curvatures of more than 45°measured during systole or diastole of a major epicardial coronary artery. Multivariable regression analysis was used to adjust the clinical parameters directly affecting CAT.Results: Of these individuals, 445 (35%) were evaluated having CAT, of which females are higher than males (59.1% vs. 40.9%). Moderate CAC score (101-400) (odds ratio (OR) 1.49, 95% confidence interval [95%CI] 1.05-2.10, P=0.025) revealed significantly associated with CAT on univariable analysis. However, multivariable analysis after adjusting for confounding factors only indicated that CAT was positively correlated with female (OR 1.60, 95%CI 1.22-2.10, P=0.001), hypertension (OR 1.34, 95% CI 1.03-1.74, P=0.028), and age (OR 1.04, 95% CI 1.01-1.03, P=0.001), while was negatively associated with body mass index (BMI) > 28 (OR 0.48, 95% CI 0.32-0.70, P<0.0001). Further analysis stratified by gender showed that compared with non-CAT, CAT was significantly linked with moderate CAC score (OR 1.79, 95% CI 1.00-3.20, P=0.048), hypertension (OR 1.54, 95% CI 1.07-2.22, P=0.021), and high-density lipoprotein (HDL) (OR 1.86, 95% CI 1.07-3.24, P=0.028), while was negatively related to BMI > 28 (OR 0.51, 95% CI 0.31-0.84, P<0.008) in female patients.Conclusions: CAT is more likely to be found in females, connected with hypertension, age, and BMI. No significant correlation is found between the presence of tortuosity and calcium score or diameter stenosis on multivariable analysis. Whereas the CAT is associated with moderate CAC score in correlation analysis when women are selected as the main group.

Comparison of Manual versus Semi-Automatic Segmentations of the Stenotic Carotid Artery Bifurcation

Background: The image reconstruction of stenotic carotid bifurcation can be managed by medical practitioners and non-medical investigators with semi-automatic or manual segmentation. The outcome of blood flow simulations may vary because of a single mean voxel difference along the examined section, possibly more in the stenotic lesions, which can lead to conflicting results regarding other research findings. The aim of our project is computational geometry reconstruction for blood flow simulations to make it suitable for comparison with plaque image analysis performed by commercially available software. In this paper, a comparison is made between the manual and semi-automatic segmentations performed by non-medical and medical investigators, respectively. Methods: 30 patients were classified into three homogeneous groups. Our group classification was based on the following parameters: plaque calcification score, thickness, extent, remodeling and plaque localization. The images in the first group were segmented individually by medical practitioners and experienced non-medical investigators, the second group was segmented collectively, and the last group was segmented individually again. Cross-sections along the centerline were extracted, then geometrical and statistical analyses were performed. Exploratory flow simulations were carried out on two patients to showcase the effect of geometrical differences on the hemodynamic flow field. Results: The largest centerline-averaged voxel difference between the medical and non-medical investigators occurred in the first group with a positive difference of 1.16 voxels. In the second and third groups, the average voxel difference decreased to 0.65 and 0.75, respectively. The example case from the first group showed that the difference in maximum wall shear stress in the middle of the stenosis is 30% with an average voxel difference of 1.73. Meanwhile, it can decrease to 4% when the average voxel difference is 0.64 for the example case from the third group. Conclusions: A collective review of the medical images should preceded the manual segmentations before applying them in computational simulations in order to ensure a proper comparison with plaque image analysis. Especially complex pathology such as calcifications should be segmented under medical supervision or after specific training. Non-significant differences in the segmentation can lead to significant differences in the computed flow field.

Alavi–Carlsen Calcification Score (ACCS): A Simple Measure of Global Cardiac Atherosclerosis Burden

Multislice cardiac CT characterizes late stage macrocalcification in epicardial arteries as opposed to PET/CT, which mirrors early phase arterial wall changes in epicardial and transmural coronary arteries. With regard to tracer, there has been a shift from using mainly 18F-fluorodeoxyglucose (FDG), indicating inflammation, to applying predominantly 18F-sodium fluoride (NaF) due to its high affinity for arterial wall microcalcification and more consistent association with cardiovascular risk factors. To make NaF-PET/CT an indispensable adjunct to clinical assessment of cardiac atherosclerosis, the Alavi–Carlsen Calcification Score (ACCS) has been proposed. It constitutes a global assessment of cardiac atherosclerosis burden in the individual patient, supported by an artificial intelligence (AI)-based approach for fast observer-independent segmentation. Common measures for characterizing epicardial coronary atherosclerosis by NaF-PET/CT as the maximum standardized uptake value (SUV) or target-to-background ratio are more versatile, error prone, and less reproducible than the ACCS, which equals the average cardiac SUV. The AI-based approach ensures a quick and easy delineation of the entire heart in 3D to obtain the ACCS expressing ongoing global cardiac atherosclerosis, even before it gives rise to CT-detectable coronary calcification. The quantification of global cardiac atherosclerotic burden by the ACCS is suited for management triage and monitoring of disease progression with and without intervention.

Citric Acid-Based Bicarbonate Dialysate Attenuates Aortic Arch Calcification in Maintenance Haemodialysis Patients: An Observational Study

Introduction: The progression of aortic calcification is associated with mortality in haemodialysis patients. Blood calciprotein particle (CPP) levels are associated with coronary artery calcification, and was reported to be inhibited when using citric acid-based bicarbonate dialysate (CD). Therefore, we examined the effect of CD on the progression of the aortic arch calcification score (AoACS) and blood CPP levels in haemodialysis patients.Methods: A 12-month retrospective observational study of 262 haemodialysis patients who met the eligibility criteria was conducted at Joban Hospital. Patients taking warfarin or bisphosphonates and those with baseline AoACS of 100% were excluded. Progression, defined as ΔAoACS (12 months – baseline) > 0%, was compared between the CD and acetic acid-based bicarbonate dialysate (AD) groups.Results: The CD group had significantly lower AoACS progression than the AD group (P = 0.037). ΔCPP and ΔAoACS were not correlated in the AD group (R2 = 0.030, P = 0.098), but were negatively correlated in the CD group (R2 = 0.065, P = 0.022). Multivariate logistic analysis showed that the CD (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.27‒0.97, P = 0.042) was significantly associated with the AoACS progression.Conclusion: CD may suppress the progression of vascular calcification in haemodialysis patients.