Prevalence Of Calcification Research Articles

Artificial Intelligence-based Software for Breast Arterial Calcification Detection on Mammograms.

The performance of a commercially available artificial intelligence (AI)-based software that detects breast arterial calcifications (BACs) on mammograms is presented. This retrospective study was exempt from IRB approval and adhered to the HIPAA regulations. Breast arterial calcification detection using AI was assessed in 253 patients who underwent 314 digital mammography (DM) examinations and 143 patients who underwent 277 digital breast tomosynthesis (DBT) examinations between October 2004 and September 2022. Artificial intelligence performance for binary BAC detection was compared with ground truth (GT) determined by the majority consensus of breast imaging radiologists. Area under the receiver operating curve (AUC), sensitivity, specificity, positive predictive value and negative predictive value (NPV), accuracy, and BAC prevalence rates of the AI algorithm were compared. The case-level AUCs of AI were 0.96 (0.93-0.98) for DM and 0.95 (0.92-0.98) for DBT. Sensitivity, specificity, and accuracy were 87% (79%-93%), 92% (88%-96%), and 91% (87%-94%) for DM and 88% (80%-94%), 90% (84%-94%), and 89% (85%-92%) for DBT. Positive predictive value and NPV were 82% (72%-89%) and 95% (92%-97%) for DM and 84% (76%-90%) and 92% (88%-96%) for DBT, respectively. Results are 95% confidence intervals. Breast arterial calcification prevalence was similar for both AI and GT assessments. Breast AI software for detection of BAC presence on mammograms showed promising performance for both DM and DBT examinations. Artificial intelligence has potential to aid radiologists in detection and reporting of BAC on mammograms, which is a known cardiovascular risk marker specific to women.

High prevalence of coronary artery calcium and aortic calcification in adults with repaired coarctation of the aorta and interrupted aortic arch

Abstract Background There is a high rate of late cardiovascular mortality in patients with repaired coarctation of the aorta (CoA) and interrupted aortic arch (IAA). Coronary artery calcium (CAC) is a marker of cardiovascular disease and there is growing evidence for aortic calcification as a predictor. Recent research in the general population suggests any CAC in males <35 years old and females ≤45 years places them at ≥90th percentile. Aims We aimed (1) to determine the prevalence of CAC, thoracic aorta calcification (TAC), and abdominal aorta calcification (AAC) in patients with CoA or IAA repair, and (2) to compare patients to a control group of Tetralogy of Fallot (TOF) patients, a condition with no known increased risk of atherosclerotic cardiovascular disease. Methods Retrospective cohort study of adult survivors of CoA/IAA repair followed up at an adult congenital heart disease (ACHD) clinic. Patients with at least 1 chest, abdomen, or pelvis computerised tomography (CT) scan for any indication were included. The presence/absence of calcification in the coronary arteries or aorta was assessed qualitatively. Patients on antihypertensive and statin therapy were considered hypertensive and hypercholesterolaemic, respectively. Patients were compared to adult survivors of TOF repair with CT scans for any indication (controls). Results Ninety-three CoA/IAA patients (87% CoA/13% IAA, median age at latest follow-up 34 years) had a total of 169 chest and 37 abdomen/pelvis CTs; 82, 93, and 37 patients had at least 1 CT suitable for CAC, TAC, and AAC review, respectively. CAC was present in 22% (18/82), TAC in 33% (31/93), and AAC in 23% (5/22) of CoA/IAA patients. CAC was present in 12% (18/153) and TAC in 11% (18/158) of TOF patients. CoA/IAA patients were more likely to have CAC and TAC than TOF patients (p=0.04 and p<0.0001; respectively) and be younger at the time of diagnosis (CAC p=0.03, TAC p=0.0001) despite TOF patients being older at time of latest CT scan (p=0.0003) (Table 1). Males aged <35 years and females ≤45 years represented 44% (8/18) of CoA/IAA patients with CAC. CoA/IAA patients with CAC were more likely to be hypertensive and hypercholesterolaemic than those without (78% [14/18] vs 48% [31/64], p=0.03; and 28% [5/18] vs 0% [0/64], p<0.0001; respectively) and was similar for TAC (hypertension p=0.005, hypercholesterolaemia p=0.04) but not AAC. After a mean follow-up of 11±7 years from first ACHD clinic, of the 93 patients, 2 patients died, 5 had coronary artery disease (at least mild stenosis on invasive angiography), 3 had a stroke, and 70% (65/93) were considered hypertensive at latest follow-up. Conclusions There is a high prevalence of CAC, aortic calcification, and hypertension in young adults with repaired CoA/IAA. Coronary and thoracic aortic calcification occurs at a younger age compared to controls. Further studies are warranted to assess the impact of aggressive cardiovascular risk reduction in this high-risk group.

Evaluation of non-target lesions in femoropopliteal disease using near-infrared spectroscopy intravascular ultrasound imaging

Abstract Aim This study aims to assess the plaque morphology of non-target lesions, especially lipid-core-containing plaque (LCP), and compare it to target lesions using near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) in patients with femoropopliteal disease. Methods We conducted a single-center prospective observational study on 14 patients who underwent endovascular therapy for femoropopliteal disease between July 2022 and November 2023. NIRS-IVUS assessment was performed on the whole femoropopliteal arterial segment. Forty-one LCP lesions > maximum lipid-core burden index in any 4-mm region (max LCBI4mm) 100 were detected by NIRS-IVUS. We evaluated patient and lesion characteristics. In addition, the LCP lesions were divided into two groups, the target lesion group (n=18) and the non-target lesion group (n=23), and compared. Results Patient characteristics were notable for advanced age (76.8±6.6 years), high incidence of male (78.7%), hypertension (100%), dyslipidemia (78.6%), diabetes (64.3%), statin use (71.4%). Lipid profiles were as follows: LDL-cholesterol 85.9±26.7 mg/dl, HDL-cholesterol 48.9±12.7 mg/dl, triglyceride 138.9±80.3 mg/dl, lipoprotein(a) 19.6±16.3 mg/dl. Ten participants had LCPs in the non-target lesion (71.4%). For IVUS findings, the target lesion group had significantly longer lesion length (34.6±11.9 mm vs. 22.6±8.7 mm, p=0.001), smaller minimum lumen area (7.0±2.8 mm2 vs. 14.8±5.4 mm2, p<0.001), and larger plaque burden (78.0±5.0 % vs. 53.0±12.0 %, p<0.001) than those in the non-target lesion group. No significant differences were observed in the prevalence of calcification (target lesion group vs. non-target lesion group: 83.3 % vs. 91.3 %, p=0.64) and the extent of calcification (p=0.76). For NIRS findings, the target lesion group contained a significantly smaller proportion of LCP in the lesion length (25.9±15.7 % vs. 50.6±29.2 %, p=0.002) than the non-target lesion group. On the other hand, there were no significant differences in the value of max LCBI4mm (284.4±153.4 vs. 289.5±113.1, p=0.90) and the length of LCP lesion (9.8±9.7 mm vs. 10.7±6.9 mm, p=0.74) and distribution of LCP (p=0.08) between both groups. In addition, the number of LCPs in the target femoropopliteal artery was positively correlated with max LCBI4mm in the target femoropopliteal artery (r=0.671, p=0.008) Conclusion NIRS-IVUS findings in this study demonstrated that the non-target lesions contained LCPs to the same degree as the target lesions.

Arterio-Venous Fistula Calcifications—Risk Factors and Clinical Relevance

(1) Background: Arterio-venous fistulas (AVFs) are considered the gold-standard vascular access (VA) in patients on maintenance hemodialysis (HD) therapy. AVF calcifications represent a less studied VA related complication, even though HD patients are at a higher risk for extraosseous calcifications. The aim of this study is to assess the prevalence and risk factors of AVF calcifications, as well as the 5-year impact on AVF functionality and on overall mortality. (2) Methods: We conducted a 5-year prospective study including 161 patients on maintenance HD therapy. At baseline, we collected data related to VA history, comorbidities, demographics, subjective global assessment scale (SGA), and biochemical parameters. All patients underwent a complete AVF ultrasound and we recorded AVF blood flow and the presence of AVF calcifications, stenoses, and aneurysms. (3) Results: In our study, we found an AVF calcification prevalence of 39%. In a univariate analysis, we found that patients with AVF calcifications were associated with other AVF complications as well (stenoses, aneurysms), had longer AVF and HD vintage, as well as higher serum calcium and PTH values. In a multivariate analysis, we found that patients with a longer HD vintage and higher calcium values were independently associated with AVF calcifications. AVF calcifications did not affect 5-year fistula patency, nor were they associated with a higher mortality risk in our group of patients. (4) Conclusions: AVF calcifications were a frequent finding in our analysis, but their presence does not seem to affect the 5-year AVF patency.

The triglyceride glucose: high-density lipoprotein cholesterol ratio is associated with coronary artery calcification evaluated via non-gated chest CT

BackgroundCoronary artery calcification (CAC) is a common risk factor of cardiovascular disease. Although triglyceride glucose (TYG) index and high-density lipoprotein cholesterol (HDL-c) are both associated with CAC, no study has evaluated the correlation between the TYG/HDL-c ratio and CAC. In the present study, we investigated the relationships between CAC and the TYG index and the TYG/HDL-c ratio.MethodsA total of 9585 participants who underwent computed tomography (CT) screening for lung cancer from 2018 to 2020 were included in this cross-sectional study. Demographic data, laboratory test data and medical history data were collected from medical records. TYG = Ln[fasting glucose (mg/dL)×fasting TG (mg/dL/2]. The triglyceride glucose-HDL-c ratio was calculated as TYG/HDL-c. CAC was evaluated on chest CT images. Multivariate logistic regression analysis and restricted cubic splines were used to determine the relationships among the TYG index, TYG/HDL-c ratio and risk of CAC. The receiver operating characteristic (ROC) curve was used to evaluate the performance of the TYG index and TYG/HDL-c ratio in identifying CACs in individuals aged 60 years and above.ResultsCAC was detected in 2515 of 9585 participants (mean age 51.8 ± 15.5 years, 61.2% men). The prevalence of CAC was significantly greater in participants with a high TYG/HDL-c ratio (32.6% in the fourth quartile vs. 19.1% in the first quartile, p < 0.001). Multivariate logistic regression revealed that both the TYG index (odds ratio (OR) = 1.06, 95% confidence interval (CI): 1.02–1.10) and the TYG/HDL-c ratio were associated with coronary artery calcification (OR = 1.32, 95% CI: 1.14–1.51). No such association was observed between the TYG index and CAC when further adjusted for the serum lipid level (OR = 1.23, 95% CI: 0.99–1.54). The TYG/HDL-c ratio was still associated with CAC after further adjustment for low-density lipoprotein cholesterol and total cholesterol (OR = 1.21, 95% CI: 1.09–1.35). TYG/HDL-c ratio was associated both with single vessel and multivessel calcification (OR = 1.14, 95%CI:1.05–1.23; OR = 1.15, 95%CI: 1.05–1.21). Similar trends were observed when we categorized individuals by TYG index and TYG/HDL-c quartiles and in subjects older than 60 years. Restricted cubic splines revealed that the TYG/HDL ratio had a better dose‒responsive relationship than did the TYG index. Subgroup analysis revealed that the association between the TYG/HDL-c ratio and coronary artery calcification was mainly observed in nondiabetic or nonhypertensive participants, regardless of low-density lipoprotein cholesterol levels. The ROC curve also revealed that the TYG/HDL-c ratio was better able to identify CAC than the TYG index was (area under the curve = 0.54 vs. 0.52, p < 0.01) in subjects older than 60 years.Conclusion An increase in the TYG/HDL-c ratio is significantly positively associated with the risk of CAC, and the TYG/HDL-c ratio has a more stable association with CAC than TYG.

Prevalence, Radiological, and Pathological Findings of Ossification and Calcification of the Lumbar Spinal Ligamentum Flavum: A Comparative Study with Thoracic Lesions.

This study aimed to determine the prevalence of lumbar ligamentum flavum lesions and identify correlations between radiological and pathological findings. We conducted an observational cross-sectional study of 349 patients (lumbar: n = 296, thoracic: n = 39, lumbar and thoracic: n = 14, mean age: 69 ± 12 years, male: 74%) who underwent posterior surgery for thoracolumbar spinal canal stenosis between January 2008 and April 2023 at our hospital.Computed tomography (CT) revealed that the prevalence of ligamentum flavum lesions defined as a high-density area with a CT value of 200 Hounsfield Unit or higher in the lumbar and thoracic spine was 47% (147/310) and 85% (45/53), respectively. CT showed that most patients had radiologically suspected ossification in the lumbar (90%) and thoracic spine (98%) than radiologically suspected calcification. Lumbar lesions were thinner than the thoracic lesions (2.5 vs 3.7 mm, p < 0.01). Pathological examinations were performed in specimens collected from 34 cases (lumbar: n = 13, thoracic: n = 21), and ossification was found in 62% (8/13) and 95% (20/21) of lumbar and thoracic lesions (p = 0.02), respectively. Lastly, ossification was confirmed pathologically in 72% (8/11) and 95% (19/20) of lumbar and thoracic lesions that showed ossification on imaging (p = 0.13), respectively. The literature review revealed that the prevalence of the lumbar ligamentum flavum lesions varied from 1.5 to 35% and the patient population was mostly asymptomatic.Collectively, we found that the prevalence of lumbar ligamentum flavum lesions in symptomatic patients was greater than previously reported. Histologically confirmed ossification was less common in lumbar lesions than in thoracic lesions.

Investigation of genetic polymorphisms in genes encoding growth factors and dental pulp calcification in orthodontic patients

Background and objectivesPulp calcification is associated with many factors and triggers, including individual genetic predisposition and orthodontic forces. This study aimed to investigate whether genetic polymorphisms in epidermal growth factor (EGF), epidermal growth factor receptor (EGFR1), transforming growth factor-beta 1 (TGFβ1), and transforming growth factor-beta receptor 2 (TGFβR2) are associated with a risk of dental pulp calcifications in orthodontic patients. Materials and methodsDigital orthopantomography (OPG) and genomic DNA from 132 patients were analyzed in this cross-sectional study. Pulp calcification was observed in the maxillary and mandibular first molars. Genomic DNA extracted from saliva cells was used to genotype eight genetic polymorphisms using real-time polymerase chain reaction: EGF (rs2237051 and rs4444903), EGFR (rs2227983 and rs763317), TGFβ1 (rs1800469 and rs4803455), and TGFβR2 (rs3087465 and rs764522). The association between pulp calcification and genetic polymorphisms was analyzed using allelic and genotypic distributions, and haplotype frequencies (P < 0.05). ResultsThe prevalence of pulp calcification was 42.4 % in 490 molars. Genotypic analysis and allelic distribution showed no statistically significant association between the evaluated growth factors and molar calcification (P > 0.05). No haplotype combinations showed a statistically significant difference (P > 0.05). ConclusionThe genetic polymorphisms investigated were not associated with dental pulp calcification in orthodontic patients. Further studies should investigate other polymorphisms in genes encoding growth factors.

The Sensitivity and Specificity of Susceptibility Weighted Imaging Phase (Swip) in Detecting Intracranial Large Artery Calcium Stenosis Compared to Cone Beam CT

Introduction: Intracranial calcifications are common and often associated with advanced stages of atherosclerosis. Studies estimating the prevalence of intracranial calcifications using other imaging modalities are common, however, studies comparing the diagnostic accuracies of cone-beam computed tomography (CBCT) and susceptibility-weighted imaging (SWI) and generated scoring systems for SWI are not well established. Aims: The objectives of the present study are to identify locations of intracranial calcifications; estimate the sensitivity and specificity rates for each intracranial vessel and each modality; estimate the sensitivity and specificity rates for diagnosing each grade of stenosis for each modality; and generate cutoff value for predicting each grade of intracranial stenosis and for each modality; as well as to develop a scoring system for estimating intracranial stenosis using SWI. Material and Methods: The study employs a prospective cross-sectional study design to collect brain data from 146 stroke patients who had initially undergone CBCT and SWI examinations. Data were collected using pro forma from January 2021 to December 2022 at Hospital Pengajar Universiti Putra Malaysia. Results: The results show an estimated prevalence of intracranial calcification of 87.7% and 92.5% for CBCT and SWI respectively. Regarding intracranial calcium grades, the prevalence of minimum – mild, moderate, and severe grade stenosis were 18.5%, 58,9%, and 10.3% respectively for CBCT and 2.7%, 33.8%, and 57.5% for SWI. Further, the results revealed that CBCT attained a sensitivity of 100% for the anterior cerebral artery, 71% for the middle cerebral artery, and 100% for the vertebral artery as well as a specificity of 90%, 80%, and 42% for the anterior cerebral artery, middle cerebral artery, and vertebral artery respectively. However, with the SWI modality, basilar, vertebral, and middle cerebral arteries reached a sensitivity of 90%, 63%, and 87% and a specificity of 82%, 95%, and 59%. Conclusion: In conclusion, both CBCT and SWI demonstrate reliable means of detecting intracranial calcifications and vessel stenosis with SWI outperforming CBCT.

BRCC36 regulates β-catenin ubiquitination to alleviate vascular calcification in chronic kidney disease

BackgroundThe prevalence of vascular calcification (VC) in chronic kidney disease (CKD) patients remains substantial, but currently, there are no effective pharmaceutical therapies available. BRCA1/BRCA2-containing complex subunit 36 (BRCC36) has been implicated in osteoblast osteogenic conversion; however, its specific role in VC remains to be fully elucidated. The aim of this study was to investigate the role and underlying mechanisms of BRCC36 in VC.MethodsThe association between BRCC36 expression and VC was examined in radial arteries from patients with CKD, high-adenine-induced CKD mice, and vascular smooth muscle cells (VSMCs). Western blotting, real-time polymerase chain reaction, immunofluorescence, and immunohistochemistry were used to analyse gene expression. Gain- and loss-of-function experiments were performed to comprehensively investigate the effects of BRCC36 on VC. Coimmunoprecipitation and TOPFlash luciferase assays were utilized to further investigate the regulatory effects of BRCC36 on the Wnt/β-catenin pathway.ResultsBRCC36 expression was downregulated in human calcified radial arteries, calcified aortas from CKD mice, and calcified VSMCs. VSMC-specific BRCC36 overexpression alleviated calcium deposition in the vasculature, whereas BRCC36 depletion aggravated VC progression. Furthermore, BRCC36 inhibited the osteogenic differentiation of VSMCs in vitro. Rescue experiments revealed that BRCC36 exerts the protective effects on VC partly by regulating the Wnt/β-catenin signalling pathway. Mechanistically, BRCC36 inhibited the Wnt/β-catenin pathway by decreasing the K63-linked ubiquitination of β-catenin. Additionally, pioglitazone attenuated VC partly through upregulating BRCC36 expression.ConclusionsOur research results emphasize the critical role of the BRCC36-β-catenin axis in VC, suggesting that BRCC36 or β-catenin may be promising therapeutic targets to prevent the progression of VC in CKD patients.Graphical

Coronary artery calcification is prevalent in systemic sclerosis and is associated with adverse prognosis.

Coronary artery calcification assessed on thoracic computed tomography represents the calcific component of established coronary artery disease, is a biomarker of total atheromatous plaque burden and predicts mortality. Systemic sclerosis is a pro-inflammatory condition, and inflammation is also a driver of coronary artery disease. We assessed coronary artery calcification prevalence, mortality risk and potential clinical impact on primary prevention in a cohort of patients with systemic sclerosis, differentiated by clinical phenotype including the presence of interstitial lung disease and pulmonary arterial hypertension. Retrospective analysis of 258 computed tomographies in systemic sclerosis patients from three prospectively maintained clinical and research databases at a single tertiary rheumatology/pulmonary hypertension (PH) service between March 2007 and September 2020 (mean age = 65 ± 12, 14% male). Co-morbidities, statin prescription and all-cause mortality were recorded. Patients were subtyped according to underlying systemic sclerosis complications. Computed tomographies were re-reviewed for coronary artery calcification; severity was graded using a 4-point scale per vessel and summed for total coronary artery calcification score. The impact of reporting coronary artery calcification was assessed against pre-existing statin prescriptions. Coronary artery calcification was present in 58% (149/258). Coronary artery calcification was more prevalent in systemic sclerosis-pulmonary arterial hypertension than in systemic sclerosis subgroups with interstitial lung disease or without pulmonary arterial hypertension, controlling for age, sex, co-morbidities and smoking status (71%; χ 2(13) = 81.4; p < 0.001). The presence and severity of coronary artery calcification were associated with increased risk of mortality independently of age and co-morbidities (hazard ratio = 2.8; 95% confidence interval = 1.2-6.6; p = 0.018). The 'number needed to report' coronary artery calcification presence to potentially impact management was 3. Coronary artery calcification is common in systemic sclerosis. Coronary artery calcification predicts mortality independently of age and confounding co-morbidities which suggests this finding has clinical relevance and is a potential target for screening and therapeutic intervention.

Prevalence and clinical implications of calcification in internal carotid artery stenosis: a retrospective study

BackgroundCalcification is common in advanced atheromatous plaque, but its clinical significance remains unclear. This study aimed to assess the prevalence of plaque calcification in the moderate-to-severe internal carotid artery stenosis and investigate its relationship with ipsilateral ischemia.MethodsThe retrospective study included 178 patients detected with proximal internal carotid artery (pICA) stenosis of ≥ 50% on multidetector computed tomography at Zhejiang Hospital from January 2019 to March 2023. Association between plaque calcification characteristics (calcification thickness, position, type, circumferential extent, calcium volume and calcium score) and ipsilateral cerebrovascular events was analyzed.ResultsThe 178 patients (mean age 71.24 ± 10.02 years, 79.78% males) had 224 stenosed pICAs overall. Plaque calcification was noted in 200/224 (89.29%) arteries. Calcification rates were higher in older age-groups. Calcification volume (r = 0.219, p < 0.001) and calcification score (r = 0.230, p < 0.001) were correlated with age. Ipsilateral ischemic events were significantly more common in the noncalcification group than in the calcification group (χ2 = 4.160, p = 0.041). The most common calcification type was positive rim sign calcification (87/200, 43.50%), followed by bulky calcification (66/200, 33.00%); both were significantly associated with ischemic events (χ2 = 10.448, p = 0.001 and χ2 = 4.552, p = 0.033, respectively). Calcification position, thickness, and circumferential extent, and calcification volume and score, were not associated with ischemic events. In multivariate analysis, positive rim signs (OR = 2.795, 95%CI 1.182–6.608, p = 0.019) was an independent predictor of ischemic events.ConclusionsPlaque calcification in proximal internal carotid artery is common, and prevalence increases with age. Calcification characteristics could be predictive of ipsilateral ischemic events. The positive rim sign within plaque is a high-risk factor for a future ischemic event.

Alternative Venous Pathways: A Potential Key Imaging Feature for Early Diagnosis of Sturge-Weber Syndrome Type 1.

Sturge-Weber syndrome is a rare congenital disorder characterized by cortical atrophy and calcifications on late-stage imaging. Understanding the evolution of brain lesions is crucial for effective early interventions, yet the timeline remains unclear. We aimed to evaluate early brain MRI findings and their progression longitudinally on follow up MRI in children diagnosed with Sturge-Weber syndrome. We retrospectively included all children with a confirmed diagnosis of Sturge-Weber syndrome between 2009 and 2023 that had at least 2 available MRIs performed before the age of 2 years. A pediatric radiologist and a pediatric neuroradiologist evaluated all the MRI scans for pial enhancement, choroid plexus enlargement, atrophy, calcifications, a prominent subarachnoid varicose network, trans medullary veins, subependymal veins, and deep extra ventricular veins. Descriptive analysis was used for demographic data and brain lesion prevalence. Cumulative incidence curves were used to show the timeline of emerging lesions. K-means clustering was used to categorize the lesions based on their prevalence at 1, 2, 3, 6, 12, 18, and 24 months after birth. Nine patients met the inclusion criteria. Median ages at the first and last MRIs were 35 days (IQR: 11-123) and 294 days (IQR: 208-465), respectively. The most prevalent lesions at the first MRI were subarachnoid varicose network (88.9%) and trans medullary veins (77.8%), while prevalence of atrophy and calcifications differed most between the first and last MRIs. The results of the elbow method and K-means clustering showed that we can divide Sturge-Weber syndrome lesions into 3 groups based on their timeline of emergence. The first cluster contained subarachnoid varicose network, trans medullary veins, subependymal veins, and choroid plexus enlargement. The second cluster contained deep extra ventricular veins, pial enhancement, accelerated myelination, and atrophy. The last cluster contained calcifications. Our findings suggest that dilated venous channels emerge early as a compensatory mechanism, preceding atrophy and calcification. Additionally, these dilated channels precede the appearance of abnormal contrast enhancement of the pia, often termed leptomeningeal angioma. This underscores the importance of early recognition and monitoring of these initial imaging indicators in clinical practice. ASL = Arterial Spin Labelled; MinIP = Minimum intensity projection; SWS = Sturge-Weber Syndrome.

Structural and molecular imaging-based characterization of soft tissue and vascular calcification in hyperphosphatemic familial tumoral calcinosis.

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare disorder caused by deficient FGF23 signaling and resultant ectopic calcification. Here, we systematically characterized and quantified macro- and micro-calcification in a HFTC cohort using CT and 18F-sodium fluoride PET/CT (18F-NaF PET/CT). Fourier-transform infrared (FTIR) spectroscopy was performed on 4 phenotypically different calcifications from a patient with HFTC, showing the dominant component to be hydroxyapatite. Eleven patients with HFTC were studied with CT and/or 18F-NaF PET/CT. Qualitative review was done to describe the spectrum of imaging findings on both modalities. CT-based measures of volume (eg, total calcific burden and lesion volume) and density (Hounsfield units) were quantified and compared to PET-based measures of mineralization activity (eg, mean standardized uptake values-SUVs). Microcalcification scores were calculated for the vasculature of 6 patients using 18F-NaF PET/CT and visualized on a standardized vascular atlas. Ectopic calcifications were present in 82% of patients, predominantly near joints and the distal extremities. Considerable heterogeneity was observed in total calcific burden per patient (823.0 ± 670.1cm3, n = 9) and lesion volume (282.5 ± 414.8cm3, n = 27). The largest lesions were found at the hips and shoulders. 18F-NaF PET offered the ability to differentiate active vs quiescent calcifications. Calcifications were also noted in multiple anatomic locations, including brain parenchyma (50%). Vascular calcification was seen in the abdominal aorta, carotid, and coronaries in 50%, 73%, and 50%, respectively. 18F-NaF-avid, but CT-negative calcification was seen in a 17-year-old patient, implicating early onset vascular calcification. This first systematic assessment of calcifications in a cohort of patients with HFTC has identified the early onset, prevalence, and extent of calcification. It supports 18F-NaF PET/CT as a clinical tool for distinguishing between active and inactive calcification, informing disease progression, and quantification of ectopic and vascular disease burden.

Tenascin-C is a Promising Marker of High Bone Turnover and Vascular Calcification in Prevalent Hemodialysis Patients

Abstract Background and Aims Tenascin-C (TN-C) is an extracellular matrix glycoprotein associated with high cell turnover and vascular calcification and atherosclerosis. This study determines the frequency of Tenascin-C in uncontrolled parathyroid hormone state and its relation to vascular calcification. Method A cross sectional study included 90 prevalent hemodialysis patients divided into 2 equal groups: uncontrolled iPTH level &amp;gt;300 pg /ml and controlled iPTH (150-300 pg/ml) groups. Serum Tenascin-C was measured by ELISA and vascular calcification was assessed by simple vascular calcification score (adragao score): by Plain X ray on hands, pelvis &amp; vascular access for all patients. Results The prevalence of Tenascin-C and vascular calcification in patient with uncontrolled PTH were 84.4% (38 patients), 46.7% (21 patients) respectively. Tenascin-C was positively correlated with PTH level (r 0.494 p &amp;lt; 0.001) in patients with high bone turnover. Tenascin-C was high in patients with uncontrolled PTH [median (IQR) 637 (4245)u/ml] compared with patients with controlled PTH [median (IQR) 211 (143) u/ml] P value &amp;lt;0.0001. According to Adragao calcification score, in uncontrolled PTH: 31.1% (14 patients) had score 1 and 15.6% (7 patients) score 2. In controlled iPTH all patients had score 0. Patients with vascular calcification had high Tenascin-C median [(IQR) 10697 (53974)] compared with patients without vascular calcification [median (IQR)7697 (18000) u/ml)] P value &amp;lt;0.001. Serum Tenascin-C can predict high bone turnover at cutoff value 7377 ng/ml with AUC 0.794, sensitivity 84.4% and specificity 60 % while predict vascular calcification at cut of value &amp;gt; 8859 ng/ml AUC 0.745, sensitivity 72.7 %, specificity 72.1 %. Patients who have elevated level of tenascin C had 10.3, 3.7 times the risk to have high bone turnover and vascular calcification than negative one respectively. Conclusion Tenascin-C appears to be a sensitive marker for assessment of high bone turnover and vascular calcification in Prevalent Hemodialysis Patients.

Effect of Dialysis Modality and Membrane Permeability on FGF 23 Level and Cardiovascular Calcification in ESRD Patients

Abstract Introduction Cardiovascular disease is the most common cause of death in patients with chronic kidney disease (CKD) and vascular calcification is one of the strongest predictors of cardiovascular risk. The prevalence of vascular calcification increases as glomerular filtration rate (GFR) declines and calcification occurs years earlier in CKD patients than in the general population. (26). Aim of the Study To study the effect of hemodialysis modality in controlling FGF-23and to determine the impact of FGF23 on cardiovascular calcification Patients and Methods We selected 50 patients ESRD maintained on hemodialysis divided into 2 groups, Group 1: comprised of 25 patients maintained on hemodialysis with high flux dialyzer and Group 2: comprised of 25 maintained on weekly session of hemodiafiltration and comparison between both groups regarding FGF23 serum level in addition to cardiovascular screening for calcifications using ECHO, Carotid intima-media thickness, and carotid duplex. Results we found that Post dialysis FGF23 was significantly lower in “hemodiafiltration patients” than ‘hemodialysis patients” and Reduction ratio was significantly higher in “hemodiafiltration patients”(P &amp;lt; 0.001).ECHO score and carotid duplex score were insignificantly different between both groups, but carotid intima-media thickness was significantly higher in haemodialysis patients (P value 0.035). Post HDF FGF 23 had a significant positive correlation with IMT (r = 0.579, P = 0.008). Serum FGF23 post-HD and HDF had significant positive correlation with serum Calcium (r = 0.659, P = 0.002), (r = 0.474, P = 0.035), PTH (r = 0.485, P = 0.03), (r = 547, P = 0.013) and CRP (r = 0.646, P = 0.002), (r = 707, P &amp;lt; 0.001) and serum Phosphorus (r = 0.462, P = 0.04), (r = 478, P = 0.033) respectively. In HD group Carotid Duplex Score had significant positive correlation with serum Ca (r = 0.469, P = 0.037), while in HDF group Carotid Duplex Score had significant positive correlation with PTH (r = 0.59, P = 0.006). Conclusion Using online HDF technique showed a significant reduction of FGF23 and improvement of carotid intima-media thickness calcification score.

Vascular calcification in chronic kidney disease associated with pathogenic variants in ABCC6

Vascular calcification is prevalent in chronic kidney disease (CKD). Genetic causes of CKD account for 10–20% of adult-onset disease. Vascular calcification is thought to be one of the most important risk factors for increased cardiovascular morbidity and mortality in CKD patients and is detectable in 80% of patients with end stage kidney disease (ESKD). Despite the high prevalence of vascular calcification in CKD, no single gene cause has been described. We hypothesized that variants in vascular calcification genes may contribute to disease pathogenesis in CKD, particularly in families who exhibit a predominant vascular calcification phenotype.We developed a list of eight genes that are hypothesized to play a role in vascular calcification due to their involvement in the ectopic calcification pathway: ABCC6, ALPL, ANK1, ENPP1, NT5E, SLC29A1, SLC20A2, and S100A12. With this, we assessed exome data from 77 CKD patients, who remained unsolved following evaluation for all known monogenic causes of CKD. We also analyzed an independent cohort (Ontario Neurodegenerative Disease Research Initiative (ONDRI), n = 520) who were screened for variants in ABCC6 and compared this to a control cohort of healthy adults (n = 52).We identified two CKD families with heterozygous pathogenic variants (R1141X and A667fs) in ABCC6. We identified 10 participants from the ONDRI cohort with heterozygous pathogenic or likely pathogenic variant in ABCC6. Replication in a healthy control cohort did not reveal any variants.Our study provides preliminary data supporting the hypothesis that ABCC6 may play a role in vascular calcification in CKD. By screening CKD patients for genetic causes early in the diagnostic pathway, patients with genetic causes associated with vascular calcification can potentially be preventatively treated with new therapeutics with aims to decrease mortality.

Ghrelin Expression in Atherosclerotic Plaques and Perivascular Adipose Tissue: Implications for Vascular Inflammation in Peripheral Artery Disease.

Atherosclerosis, a leading cause of peripheral artery disease (PAD), is driven by lipid accumulation and chronic inflammation within arterial walls. Objectives: This study investigates the expression of ghrelin, an anti-inflammatory peptide hormone, in plaque morphology and inflammation in patients with PAD, highlighting its potential role in age-related vascular diseases and metabolic syndrome. Methods: The analysis specifically focused on the immunohistochemical expression of ghrelin in atherosclerotic plaques and perivascular adipose tissue (PVAT) from 28 PAD patients. Detailed immunohistochemical staining was performed to identify ghrelin within these tissues, comparing its presence in various plaque types and assessing its association with markers of inflammation and macrophage polarization. Results: Significant results showed a higher prevalence of calcification in fibro-lipid plaques (63.1%) compared to fibrous plaques, with a notable difference in inflammatory infiltration between the two plaque types (p = 0.027). Complicated plaques exhibited increased ghrelin expression, suggesting a modulatory effect on inflammatory processes, although this did not reach statistical significance. The correlation between ghrelin levels and macrophage presence, especially the pro-inflammatory M1 phenotype, indicates ghrelin's involvement in the inflammatory dynamics of atherosclerosis. Conclusions: The findings propose that ghrelin may influence plaque stability and vascular inflammation, pointing to its therapeutic potential in managing atherosclerosis. The study underlines the necessity for further research to clarify ghrelin's impact on vascular health, particularly in the context of metabolic syndrome and age-related vascular alterations.

Association between body composition and coronary artery calcification in patients with chronic kidney disease

Objective: To investigate the association between body composition and coronary artery calcification in patients with chronic kidney disease (CKD). Methods: This cross-sectional study enrolled patients with CKD hospitalized from May 2019 to April 2022 at Sun Yat-sen Memorial Hospital, Guangzhou, China. Skeletal muscle mass index and visceral fat area were measured by bioelectrical impedance analysis. Coronary artery calcification was assessed by computed tomography. Patients were divided into coronary artery calcification group and non-coronary artery calcification group according to the incidence of coronary artery calcification. Patients were categorized into tertile groups according to their skeletal muscle mass index and visceral fat area levels ranging from the lowest to the highest levels (T1 to T3). We defined skeletal muscle mass index≤30.4% as low muscle mass and visceral fat area≥80.6 cm2 as high visceral fat based on the results of the restricted cubic spline graph. All individuals were divided into 4 phenotypes: normal body composition, low muscle mass, high visceral fat, and low muscle mass with high visceral fat. Spearman correlation analysis and logistic regression analysis were used to assess the association between skeletal muscle mass index, visceral fat area and coronary artery calcification. Results: A total of 107 patients with CKD were enrolled, with an age of (60.0±14.1) years, including 41 female patients (38.3%). Patients of coronary artery calcification group had lower skeletal muscle mass index ((32.0±4.8) vs. (34.3±4.8), P=0.016) and higher visceral fat area ((70.8±32.6) cm2 vs. (47.9±23.8) cm2, P<0.001) than those of non-coronary artery calcification group. Patients in the T3 group of skeletal muscle mass index had a lower prevalence of coronary artery calcification (17 (48.6%) vs. 28 (77.8%)) and a lower coronary artery calcification score (0.5 (0, 124.0) vs. 12.0 (0.3, 131.0)) than those in the T1 group (P<0.05). Similarly, patients in the T1 group of visceral fat area had a lower prevalence of coronary artery calcification (14 (40.0%) vs. 29 (80.6%)) and a lower coronary artery calcification score (0 (0, 3.0) vs. 37.0 (2.0, 131.0)) than those in the T3 group (P<0.05). Likewise, patients with both low muscle mass and low muscle mass with high visceral fat had a higher prevalence of coronary artery calcification (11(78.6%) vs. 33 (47.8%); 15 (83.3%) vs. 33 (47.8%)) and a higher coronary artery calcification score (31.1 (0.8, 175.8) vs. 0 (0, 16.4); 27.6 (6.4, 211.4) vs. 0 (0, 16.4)) than those with normal body composition (P<0.05). Spearman correlation analysis showed that skeletal muscle mass index was inversely correlated with coronary artery calcification score (r=-0.212, P=0.028), and visceral fat area was positively correlated with coronary artery calcification score (r=0.408, P<0.001). Multivariate logistic regression analysis showed that increased skeletal muscle mass index was inversely associated with coronary artery calcification prevalence (T2: OR=0.208, 95%CI: 0.056-0.770, P=0.019; T3: OR=0.195, 95%CI: 0.043-0.887, P=0.034), and reduced visceral fat area was inversely associated with coronary artery calcification prevalence (T1: OR=0.256, 95%CI: 0.071-0.923, P=0.037; T2: OR=0.263, 95%CI: 0.078-0.888, P=0.031). Consistently, both low muscle mass and low muscle mass with high visceral fat were associated with coronary artery calcification prevalence (OR=6.616, 95%CI: 1.383-31.656, P=0.018; OR=5.548, 95%CI: 1.062-28.973, P=0.042). Conclusion: Reduced skeletal muscle mass index and increased visceral fat area are significantly associated with both the prevalence and severity of coronary artery calcification in patients with CKD.

Vascular calcification in kidney stone formers: the impact of age and stone composition.

An increased prevalence of vascular calcification (VC) has been reported in kidney stone formers (KSFs), along with an elevated cardiovascular risk. The aim of the current study is to assess whether VC in these patients develops at a younger age and is influenced by stone composition. This single-center, matched case-control study included KSFs with uric acid or calcium oxalate stones (diagnosed based on stone analysis) and age- and sex-matched controls without a history of nephrolithiasis. The prevalence and severity of abdominal aortic calcification (AAC) and bone mineral density (BMD) were compared between KSFs and non-KSFs. In total, 335 patients were investigated: 134 with calcium oxalate stones, 67 with uric acid stones, and 134 controls. Overall, the prevalence of AAC was significantly higher among calcium stone formers than among the controls (67.9% vs. 47%, p = 0.002). In patients under 60 years of age, those with calcium oxalate stones exhibited both a significantly elevated AAC prevalence (61.9% vs. 31.3%, p = 0.016) and severity (94.8 ± 15.4 vs. 30.3 ± 15.95, p = 0.001) compared to the controls. Within the age group of 40-49, osteoporosis was identified only in the KSFs. Multivariate analysis identified age, smoking, and the presence of calcium stones as independent predictors of AAC. This study highlights that VC and osteoporosis occur in KSFs at a younger age than in non-stone-formers, suggesting potential premature VC. Its pathogenesis is intriguing and needs to be elucidated. Early evaluation and intervention may be crucial for mitigating the cardiovascular risk in this population.

Mammographic breast features and risk of cardiovascular diseases in korean women

BackgroundThere is a growing amount of evidence on the association between cardiovascular diseases (CVDs) and breast calcification. Thus, mammographic breast features have recently gained attention as CVD predictors. ObjectiveThis study assessed the association of mammographic features, including benign calcification, microcalcification, and breast density, with cardiovascular diseases. MethodsThis study comprised 6,878,686 women aged ≥40 who underwent mammographic screening between 2009 and 2012 with follow-up until 2020. The mammographic features included benign calcification, microcalcification, and breast density. The cardiovascular diseases associated with the mammographic features were assessed using logistic regression. ResultsThe prevalence of benign calcification, microcalcification, and dense breasts were 9.6 %, 0.9 % and 47.3 % at baseline, respectively. Over a median follow-up of 10 years, benign calcification and microcalcification were positively associated with an increased risk of chronic ischaemic heart disease whereas breast density was inversely associated with it; the corresponding aOR (95 % CI) was 1.14 (1.10–1.17), 1.19 (1.03–1.15), and 0.88 (0.85–0.90), respectively. A significantly increased risk of chronic ischaemic heart disease (IHD) was observed among women with benign calcifications (aHR, 1.14; 95 % CI 1.10–1.17) and microcalcifications (aOR, 1.19; 95 % CI 1.06–1.33). Women with microcalcifications had a 1.16–fold (95 % CI 1.03–1.30) increased risk of heart failure. ConclusionsMammographic calcifications were associated with an increased risk of chronic ischaemic heart diseases, whereas dense breast was associated with a decreased risk of cardiovascular disease. Thus, the mammographic features identified on breast cancer screening may provide an opportunity for cardiovascular disease risk identification and prevention.