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Background: Cardiac biomarkers Troponin T (TnT) and N-terminal pro-B-type natriuretic peptide (proBNP) and abdominal aortic calcification score (AAC) are associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). The effects of cardiac biomarkers and AAC on maximal exercise capacity in CKD are unknown and were studied.Methods: One hundred seventy-four CKD 4-5 patients not on maintenance dialysis underwent maximal bicycle ergometry stress testing, lateral lumbar radiograph to study AAC, echocardiography and biochemical assessments.Results: The subjects with proportional maximal ergometry workload (WMAX%) less than 50% of the expected values had higher TnT, proBNP, AAC, left ventricular end-diastolic diameter, left ventricular mass index, E/e' and pulse pressure, and lower global longitudinal strain compared to the better performing patients. TnT (β = - 0.09, p = 0.02), AAC (β = - 1.67, p < 0.0001) and diabetes (β = - 11.7, p < 0.0001) remained significantly associated with WMAX% in the multivariable model. Maximal ergometry workload (in Watts) was similarly associated with TnT and AAC in addition to age, male gender, hemoglobin and diastolic blood pressure in a respective multivariate model. AAC and TnT showed fair predictive power for WMAX% less than 50% of the expected value with AUCs of 0.70 and 0.75, respectively.Conclusions: TnT and AAC are independently associated with maximal ergometry stress test workload in patients with advanced CKD.Trial Registration: http://www.ClinicalTrials.gov NCT04223726. [ABSTRACT FROM AUTHOR]

Purpose: Abdominal aorta calcium (AAC) burden and dilatation are associated with an increased risk of mortality. The purpose of this study was to investigate determinants of AAC and abdominal aorta size in patients with essential hypertension., Materials and Methods: Patients with uncomplicated essential hypertension who had undergone non-enhanced abdominal CT to rule out secondary hypertension in addition to biological test were recruited between 2010 and 2018. A semi-automatic system was designed to estimate the aortic size (diameter, length, volume) and quantify the AAC from mesenteric artery to bifurcation using the Agatston score. Determinants of aortic size and those related to AAC were searched for using uni- and multivariables analyses., Results: Among 293 randomly selected patients with hypertension (age 52 ± 11 [SD] years) included, 23% had resistant hypertension. Mean abdominal aorta diameter was 20.1 ± 2.1 (SD) mm. Eight (3%) patients had abdominal aorta aneurysm ≥ 30 mm and 58 (20%) had dilated abdominal aorta ≥ 27 mm. Median AAC score was 38 and calcifications were detected in the infra- and supra-renal abdominal aortic portions in 59% and 26% of the patients, respectively. After adjustment for age, male sex and body surface area, abdominal aorta diameter was positively associated with diastolic blood pressure (P = 0.0019). Smoking was the single variable associated with calcified abdominal aorta (P < 0.001) after adjustment for cofactors. In patients with calcifications of abdominal aorta, the score increased with smoking history (P < 0.001), statins treatment (P < 0.01), greater number of anti-hypertensive drugs (P < 0.01), larger abdominal aorta (P < 0.05) and greater systolic blood pressure (P < 0.05). Patients with resistant hypertension had more AAC in the supra-renal abdominal aorta portion than those without resistant hypertension (P < 0.01)., Conclusion: In patients with essential hypertension, abdominal aorta dilation is related with diastolic blood pressure while AAC is associated with smoking history and resistant hypertension when located to the supra-renal abdominal aorta portion., Competing Interests: Declaration of Competing Interest The authors have no disclosures related to the content of this study., (Copyright © 2023. Published by Elsevier Masson SAS.)

Ischaemic heart disease, sudden cardiac death and arrhythmias, heart failure, stroke and peripheral arterial disease make up >50% of the causes of death in advanced chronic kidney disease (CKD). Calcification of the vascular tree and heart valves is partially related to these complications and has received growing attention in the literature. However, the main focus of research has been on the pathophysiology and consequences of vascular calcification, with less attention being paid to valvular calcification (VC) and its impact on the survival of CKD patients. Although VC has long been seen as an age-related degenerative disorder with minimal functional impact, several studies proved that it carries an increased risk of death and clinical consequences different from those of vascular calcification. In dialysis patients, the annual incidence of aortic valve calcification is nearly 3.3% and the reported prevalence of aortic and mitral VC varies between 25% and 59%. Moreover, calcification of both valves occurs 10–20 years earlier in CKD patients compared with the general population. Therefore, the purpose of this review is to summarize the current knowledge on the pathophysiology and relevance of VC in CKD patients, and to highlight specific clinical consequences and potential therapeutic implications. [ABSTRACT FROM AUTHOR]

Background Vascular calcification (VC) is associated with high morbidity and mortality among older adults, a population that exhibits a higher tendency for developing frailty at the same time. Whether VC serves as a risk factor for the development of frailty in this population remains unclear. Methods and Results We analyzed a prospectively assembled cohort of community‐dwelling older adults between 2014 and 2017 (n=1783). Frailty and prefrailty were determined on the basis of the Study of Osteoporotic Fractures criteria, and VC was measured using semiquantitative aortic arch calcification (AAC) and abdominal aortic calcification scoring. We conducted multiple logistic regression with prefrailty or frailty as the dependent variable, incorporating sociodemographic profiles, comorbidities, medications, laboratory data, AAC status/severity, and other geriatric phenotypes. Among all participants, 327 (18.3%) exhibited either prefrailty (15.3%) or frailty (3.1%), and 648 (36.3%) exhibited AAC. After adjusting for multiple confounders, we found that AAC incidence was associated with a substantially higher probability of prefrailty or frailty (odds ratio [OR], 11.9; 95% CI, 7.9–15.4), with a dose‐responsive relationship (OR for older adults with AAC categories 1, 2, and 3 was 9.3, 13.6, and 52.5, respectively). Similar association was observed for older adults with abdominal aortic calcification (OR, 5.0; 95% CI, 1.3–19.5), and might be replicable in another cohort of patients with end‐stage renal disease. Conclusions Severity of VC exhibited a linear positive relationship with frailty in older adults. Our findings suggest that a prompt diagnosis and potential management of VC may assist in risk mitigation for patients with frailty.

Saud Alsahli,1,2 Dalal K Bubshait,3 Zuhair A Rahbeeni,4 Majid Alfadhel1,2 1Medical Genomic Research Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 2Division of Genetics, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs (MNGHA), Riyadh, Saudi Arabia; 3Department of Pediatrics, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 4Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia Abstract: Gaucher disease is the most common sphingolipid storage disease and is present in all ethnic groups. Its symptoms span all systems including the cardiovascular system. The health care provider should be vigilant regarding this potentially fatal complication. Gaucher disease type IIIC has been linked to causing oculomotor apraxia and cardiac calcification. We report a Saudi girl who developed valvular and aortic calcification in late childhood and died as a result of her cardiovascular complications. This report further strengthens the association and reminds the clinicians that patients with D409H mutation need echocardiographic evaluation annually. Keywords: Gaucher disease, aortic calcification, D409H

Background/Aims: Potential relationships between serum sclerostin levels and the levels of bone metabolic markers in maintenance hemodialysis (MHD) patients have yet to be evaluated. This study sought to determine whether serum sclerostin levels are associated with mortality in MHD patients. Methods: We measured serum sclerostin levels in a Japanese MHD cohort, classified the patients into tertiles according to these levels, and followed their course for a 42-month period. Results: The cohort consisted of 389 MHD patients and there were 75 deaths. Kaplan-Meier analyses showed that the tertile of serum sclerostin was not associated with mortality risk. Cox analyses showed that there were no significant associations between serum sclerostin level and mortality. Conclusion: Serum sclerostin level was not an independent predictor of mortality in MHD patients after adjustment for several confounders. However, whether clinical interventions to modulate serum sclerostin levels in MHD patients would improve their survival remains to be determined.

Osteocalcin (OC) is produced by osteoblasts and vascular smooth muscle cells. In animal models, serum OC levels are strongly correlated with vascular calcium content, however, the association of OC with vascular calcification in humans is uncertain. The Study of Osteoporotic Fractures (SOF) enrolled community-living women, age ≥65 years. The present study included a subsample of 363 randomly selected SOF participants. Serum total OC was measured by ELISA, and abdominal aortic calcification (AAC) was evaluated on lateral lumbar radiographs. We examined the cross-sectional association between serum OC and AAC. The mean serum OC level was 24 ± 11 ng/ml and AAC was present in 188 subjects (52%). We observed no association of OC and AAC in either unadjusted or adjusted analyses. For example, each standard deviation higher OC level was associated with an odds ratio (OR) for AAC prevalence (AAC score >0) near unity (OR = 1.06; 95% CI, 0.82–1.36) in models adjusted for CVD risk factors. Further adjustment for intact parathyroid hormone, bone-specific alkaline phosphatase, 25-hydroxyvitamin D, and hip and spine bone mineral density did not materially change the results (OR = 1.22; 95% CI, 0.86–1.75). Similarly, higher OC levels were not associated with severity of AAC (P = 0.87). In conclusion, among community-living older women, serum OC is not associated with AAC. These findings suggest that serum OC levels may more closely reflect bone formation than vascular calcification in humans.

Patients with severely calcified aorta undergoing conventional cardiac surgery are at increased risk for postoperative neurologic deficits. Implementation of cerebroprotective devices may substantially reduce or even eliminate the risk of the adverse neurologic events, thus enabling surgical therapy, especially when interventional treatment cannot be considered an alternative option. [ABSTRACT FROM AUTHOR]

Screening of cardiovascular risk is essential in preventing cardiac events and quantifying asymptomatic risk. Coronary artery calcium (CAC) scores are a well-established in predicting cardiovascular risk, but require specialized computed tomography (CT) scans. Given the relationship of aortic calcification with cardiovascular risk, we sought to determine whether aortic calcification measures from incidental CT scans may approximate CAC. Retrospective CT scans and corresponding volumetric CAC scores were obtained from patients at the University of Michigan. Aortic calcifications were measured in 166 scans. Correlations between a novel morphomic calcium (MC) percent score and CAC score were evaluated using Kendall's correlation coefficients. Comparison of receiver operating characteristic (ROC) curves based on MC at different vertebral levels showed the highest predictive values for measures taken at L4. MC at L4 shows promise in predicting CAC (AUC 0.90 in non-contrast scans, 0.70 in post-contrast scans). Proposed MC threshold are (4.21% for best sensitivity, B 12.93% for balance, C = 19.26% for specificity) in scans without contrast enhancement and (D = 7.31 for sensitivity, E 8.06 for specificity) in scans with contrast enhancement. The MC score demonstrates promising potential in approximating CAC, particularly at the L4 level. The utilization of MC from incidental CT scans may be useful for assessment of cardiovascular risk. The ability to extract MC from contrast scans makes it especially valuable to patients receiving additional medical or surgical care. Recognition of high-risk patients would allow the use of indicated preventative strategies to avoid hard cardiovascular events in at risk patients. • CAC scores are established personalized predictors of cardiovascular risk, but require a specialized scan • Analytic morphomics were used to obtain granular measurements of aortic calcium from incidental CT scans • In this study, the morphomic calcium score had the strongest correlation with CAC at the lowest observed vertebral levels [ABSTRACT FROM AUTHOR]

Summary: This study evaluated whether zoledronic acid (ZA) inhibited the progression of abdominal aortic calcification (AAC) over 3 years in 502 postmenopausal women with osteoporosis. AAC progressed in a similar proportion of participants in the ZA (29%) and placebo (31%) groups, suggesting no effect of ZA on AAC progression. Introduction: Bisphosphonate use is associated with reduced risk of all-cause mortality and cardiovascular events. The underlying mechanisms are uncertain but may include effects on vascular calcification. This study aimed to evaluate the effect of zoledronic acid (ZA) on abdominal aortic calcification (AAC) in postmenopausal women with osteoporosis. Methods: This was a post hoc analysis of the HORIZON Pivotal Fracture Trial that included 502 postmenopausal women (mean age 72.5 years) with osteoporosis (234 received ZA and 268 placebo). AAC scores (range, 0–8) were assessed from paired spine X-rays at baseline and after 3 years. Progression of AAC was defined as any increase in AAC score. The association between change in hip and femoral neck bone mineral density and change in AAC score was also assessed. Results: At baseline, 292 (58.2%) participants had AAC (i.e., AAC score > 0), with AAC scores similar in the two intervention groups (median [interquartile range], 1 [0 to 2] for both; p = 0.98). Over 3 years, AAC progressed in a similar proportion of participants in both groups (ZA 29% and placebo 31%; p = 0.64). Change in bone mineral density and change in AAC score were not correlated. Conclusion: Once-yearly zoledronic acid did not affect progression of AAC over 3 years in postmenopausal women with osteoporosis. Trial registration: ClinicalTrials.gov identifier: NCT00049829 [ABSTRACT FROM AUTHOR]

Background: Patients with advanced chronic kidney disease (CKD stage 4-5) have an increased risk of death. To study the determinants of all-cause mortality, we recruited 210 consecutive CKD stage 4-5 patients not on dialysis to the prospective Chronic Arterial Disease, quality of life and mortality in chronic KIDney injury (CADKID) study.Methods: One hundred seventy-four patients underwent maximal bicycle ergometry stress testing and lateral lumbar radiography to study abdominal aortic calcification score and echocardiography. Carotid and femoral artery intima-media thickness and elasticity and brachial artery flow-mediated dilatation were measured in 156 patients.Results: The duration of follow-up was 42 ± 17 months (range 134-2,217 days). The mean age was 61 ± 14 years, and the estimated glomerular filtration rate was 12 (11-15) mL/min/1.73 m2. Thirty-six (21%) patients died during follow-up (time to death 835 ± 372 days). Seventy-five and 21 patients had diabetes and coronary artery disease, respectively, and all but one had hypertension. In the respective multivariate proportional hazards models adjusted for age, sex, and coronary artery disease, the significant determinants of mortality were troponin T, N-terminal pro-B-type natriuretic peptide, maximal ergometry performance, abdominal aortic calcification score, E/e' ratio, and albumin.Conclusion: Stress ergometry performance, abdominal aortic calcification score, E/e' of echocardiography, and plasma cardiac biomarkers and albumin predict mortality in advanced CKD. [ABSTRACT FROM AUTHOR]

Despite increased social awareness, marketing restraints, tobacco taxation, and available smoking cessation rehab programs, active and passive smoking remain a worldwide challenging epidemic and a key risk factor for cardiovascular diseases development. Although cardiovascular (CV) protection is more pronounced in women than in men due to estrogenic effects, tobacco cigarette smoking exposure seems to alter this protection by modulating estrogen actions via undefined mechanisms. Premenopausal cigarette smoking women are at higher risk of adverse CV effects than non‐smokers. In this study, we investigated the impact of cigarette smoking on early CV injury after myocardial infarction (MI) in non‐menopausal female mice. Aortic arch calcification, fibrosis, reactive oxygen species, and gene expression of inflammatory and calcification genes were exaggerated in mice exposed to cigarette smoke (CS). These findings suggest that aortic injury following MI, characterized by vascular smooth muscle cells transdifferentiation, calcification, inflammation, and collagen deposition but not cardiac dysfunction is exacerbated with CS exposure. The novel findings of this study highlight the importance of aortic injury on short and long‐term prognosis in CS‐exposed MI females. Linking those findings to estrogen alteration is probable and entails investigation. [ABSTRACT FROM AUTHOR]

Vascular calcification (VC) involves the deposition of calcium apatite in vascular intima or media. Individuals of advanced age, having diabetes mellitus or chronic kidney disease (CKD) are particularly at risk. The pathogenesis of CKD-associated VC evolves considerably. The core driver is the phenotypic change involving vascular wall constituent cells toward manifestations similar to that undergone by osteoblasts. Gender-related differences are observed regarding the expressions of osteogenesis-regulating effectors, and presumably the prevalence/risk of CKD-associated VC exhibits gender-related differences as well. Despite the wealth of data focusing on gender-related differences in the risk of atherosclerosis, few report whether gender modifies the risk of VC, especially CKD-associated cases. We systematically identified studies of CKD-associated VC or its regulators/modifiers reporting data about gender distributions, and extracted results from 167 articles. A significantly higher risk of CKD-associated VC was observed in males among the majority of original investigations. However, substantial heterogeneity exists, since multiple large-scale studies yielded neutral findings. Differences in gender-related VC risk may result from variations in VC assessment methods, the anatomical segments of interest, study sample size, and even the ethnic origins of participants. From a biological perspective, plausible mediators of gender-related VC differences include body composition discrepancies, alterations involving lipid profiles, inflammatory severity, diversities in matrix Gla protein (MGP), soluble Klotho, vitamin D, sclerostin, parathyroid hormone (PTH), fibroblast growth factor-23 (FGF-23), and osteoprotegerin levels. Based on our findings, it may be inappropriate to monotonously assume that male patients with CKD are at risk of VC compared to females, and we should consider more background in context before result interpretation.

Abstract Background Arterial stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease (CKD). There are limited prospective data however on progression of arterial stiffness in CKD, including evaluating associations with bone mineral markers such as fibroblast growth factor 23 (FGF23) and soluble α-klotho (sKl). Methods In this prospective, single-center, observational study, arterial stiffness [measured by pulse wave velocity (PWV)] and hormones influencing mineral homeostasis, including serum FGF23 and sKl, were compared between non-dialysis CKD stages 4/5 and healthy controls at baseline and 12 months (12 m). Abdominal aortic calcification (AAC) was quantitated using lateral lumbar radiography at baseline. Results Forty patients with CKD [mean estimated glomerular filtration rate (eGFR) 19.5 ± 6.7 mL/min/1.73m2] and 42 controls (mean eGFR 88.6 ± 12.9 mL/min/1.73m2) completed follow-up. There were no differences in age, gender and body mass index between groups. A significant increase in FGF23 [240.6 (141.9–1129.8) to 396.8 (160.3–997.7) pg/mL, p = 0.001] was observed in the CKD group but serum phosphate, corrected calcium, parathyroid hormone and sKl did not change significantly over 12 m. At baseline, CKD subjects had higher AAC prevalence [83.8% versus (vs.) 43.6%, p = 0.002] and higher aortic PWV [9.7(7.6–11.7) vs. 8.1 (7.2–9.7) m/s, p = 0.047] compared to controls. At 12 m, aortic PWV increased by 1.3 m/s (95% confidence interval, 0.56 to 2.08, p 10 m/s). Serum FGF23 was associated with AAC, abnormal PWV and progression of PWV at 12 m. Conclusions Arterial stiffness and serum FGF23, both of which are associated with increased cardiovascular risk, increased over one year in individuals with CKD. Additionally, a significant association was found between serum FGF23 and arterial calcification and stiffness. Larger clinical studies and further experimental work are warranted to delineate the temporal relationship as well as the pathological mechanisms linking FGF23 and vascular disease.

Abstract Background The aim of the present study is to investigate the clinical relevance of aortic calcification in urolithiasis patients. Methods Between January 2010 and September 2014, 1221 patients with urolithiasis were treated in Oyokyo Kidney Research Institute and Hirosaki University Hospital. Among these, 287 patients (Stone group) on whom adequate data were available were included in this retrospective study. We also selected 148 subjects with early stage (pT1N0M0) renal cell carcinoma from 607 renal cell carcinoma patients who underwent radical nephrectomy at Hirosaki University Hospital (Non-stone group) as control subjects. Validity of the Non-stone group was evaluated by comparison with pair-matched 296 volunteers from 1166 subjects who participated in the Iwaki Health Promotion Project in 2014. Thereafter, age, body mass index, aortic calcification index (ACI), renal function, serum uric acid concentrations, and comorbidities (diabetes, hypertension, or cardiovascular disease) were compared between the Non-stone and Stone groups. Independent factors for higher ACI and impaired renal function were assessed using multivariate logistic regression analysis. Results We confirmed relevance of Non-stone group patients as a control subject by comparing the pair-matched community-dwelling volunteers. Backgrounds of patients between the Non-stone and Stone groups were not significantly different except for the presence of hypertension in the Stone group. ACI was not significantly high in the Stone group compared with the Non-stone group. However, age-adjusted ACI was greater in the Stone group than the Non-stone group. Among urolithiasis patients, ACI was significantly higher in uric acid containing stone patients. The number of patients with stage 3B chronic kidney disease (CKD) was significantly higher in the Stone group than in the Non-stone group (12% vs. 4%, P = 0.008). Multivariate logistic regression analysis showed higher aortic calcification index (>13%), and being a stone former were independent factors for stage 3B CKD at the time of diagnosis. Conclusion Aortic calcification and being a stone former had harmful influence on renal function. This study was registered as a clinical trial: UMIN: UMIN000022962.

Background/aim: The aim of the study was to analyze the association between abdominal aortic calcification (AAC) and patient prognosis following resection of colorectal liver metastases (CRLM). AAC potentially reflects intrahepatic immunity and is involved in tumor development and progression. However, the clinical effects of AAC on colorectal cancer (CRC) prognosis after curative-intent liver resection for CRLM remain unclear., Patients and Methods: We evaluated the effect of AAC on the clinical prognosis and metastatic patterns in 99 patients who underwent hepatectomy for CRLM between 2010 and 2019., Results: The high-AAC group had significantly worse overall survival (OS) and remnant liver recurrence rate (RR) after propensity score matching to adjust for differences in baseline characteristics of patients and tumors. In multivariate Cox regression analyses, high AAC volume was an independent risk factor for poor OS and liver RR, but not poor lung RR. The expression of tumor necrosis factor-related apoptosis-inducing ligand, known as an anti-tumor marker, in liver natural killer (NK) cells was lower in the high-AAC group than in the low-AAC group., Conclusion: High AAC volume showed a strong relationship with remnant liver RR after curative resection of CRLM. High AAC volume may be responsible for the suppression of anti-tumor activity of liver NK cells, which results in an increased risk of liver recurrence and poor prognosis., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Pulse wave velocity (PWV) is a noninvasive measure of arterial stiffness and predictor of cardiovascular disease. However, the association between PWV and vascular calcification across different vascular beds has not been fully investigated. This study aimed to quantify the association between PWV and multiterritory calcification and to explore whether PWV can identify individuals with vascular calcification beyond traditional risk factors., Methods and Results: Among 1351 older adults (mean age, 79.2 years [SD, 4.1]) from the ARIC (Atherosclerosis Risk in Communities) study, we measured segment-specific PWVs: heart-carotid, heart-femoral, carotid-femoral, heart-ankle, brachial-ankle, and femoral-ankle. Dependent variables were high calcium score (≥75th percentile of Agatston score) across different vascular beds: coronary arteries, aortic valve ring, aortic valve, mitral valve, ascending aorta, and descending aorta. Quartiles of carotid-femoral, heart-femoral, heart-ankle, and brachial-ankle PWV were significantly associated with coronary artery calcium (eg, adjusted odds ratio [OR] for the highest versus lowest quartile of carotid-femoral PWV, 1.84 [95% CI, 1.24-2.74]). Overall, PWVs were most strongly associated with descending aorta calcification, with significant results for carotid-femoral, heart-femoral, heart-ankle, and brachial-ankle PWV (eg, adjusted OR for the highest versus lowest quartile of carotid-femoral PWV, 3.99 [95% CI, 2.61-6.17]). In contrast, femoral-ankle PWV was inversely associated with descending aorta calcification. Some PWVs improved the discrimination of coronary artery calcium and descending aorta calcification beyond traditional risk factors., Conclusions: The associations of PWV with vascular calcification varied substantially across segments, with descending aorta calcification most closely linked to PWVs. Our study suggests that some PWVs, especially carotid-femoral PWV, are helpful to identify individuals with coronary artery calcium and descending aorta calcification.

Background: The factors affecting cardiovascular risk associated with vascular calcification in patients with chronic kidney disease are less well addressed. Distinct risk factors may contribute synergistically to this elevated cardiovascular risk in this population., Objectives: We aimed to determine whether echocardiographic left ventricular hypertrophy (LVH) affects the risk of major adverse cardiac events (MACE) associated with vascular calcification in end-stage kidney disease (ESKD) patients., Methods: In this retrospective cohort study, ESKD patients underwent chest radiography and echocardiography to assess aortic arch calcification (AoAC) and LVH, respectively, and were classified into three groups accordingly: non-to-mild AoAC without LVH, non-to-mild AoAC with LVH, and moderate-to-severe AoAC. The risks of MACE, cardiovascular mortality, and overall mortality were assessed using Cox proportional hazard analysis., Results: Of the 283 enrolled ESKD patients, 44 (15.5%) had non-to-mild AoAC without LVH, 117 (41.3%) had non-to-mild AoAC with LVH, and 122 (43.1%) had moderate-to-severe AoAC. After 34.1 months, 107 (37.8%) participants developed MACE, including 6 (13.6%), 40 (34.2%), and 61 (50%) from each respective group. Those with moderate-to-severe AoAC (Hazard ratio, 3.72; 95% confidence interval, 1.58-8.73) had a significantly higher risk of MACE than did those with non-to-mild AoAC without LVH or with non-to-mild AoAC and LVH (Hazard ratio, 2.73; 95% confidence interval, 1.16-6.46). A similar trend was observed for cardiovascular and overall mortality., Conclusion: Echocardiographic LVH could modify the risk of adverse cardiovascular events associated with vascular calcification in ESKD patients. Interventions aiming to ameliorate both morbidities might be translated into a lower MACE risk in this population., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Visceral and ectopic fat accumulation might have an impact on the atherosclerotic calcification of abdominal arteries. The pattern of calcification of the abdominal aorta and its branches is not fully investigated. We retrospectively analyzed the abdominopelvic MSCT images and calculated calcification volumes of the abdominal aorta, celiac trunk, superior and inferior mesenteric arteries, and both common and external iliac arteries. On the same MSCT scans, a visceral fat volume and ectopic fat deposits (liver-to-spleen ratio (L/S) and pancreas-to-spleen (P/S) ratio) were also measured. The results showed that calcifications of the abdominal aorta and its branches were associated with visceral fat volume, less strongly associated with L/S, and not associated with the P/S ratio. The abdominal aorta, the common iliac and external iliac arteries were more calcified arteries compared to the celiac trunk and superior and mesenterial arteries. In conclusion, visceral fat has a stronger effect on abdominopelvic arteries' calcification than ectopic fat. Visceral aortic branches are generally less calcified than iliac arteries.

Background and Objectives: Aortic arch calcification (AoAC) is associated with a variety of cardiovascular complications. The measurement and grading of AoAC using posteroanterior (PA) chest X-rays are well established. The cardiothoracic ratio (CTR) can be simultaneously measured with PA chest X-rays and used as an index of cardiomegaly. The genetic and environmental contributions to the degree of the AoAC and CTR are not well understood. The purpose of this study was to investigate the effect of genetics and environmental factors on the AoAC and CTR. Materials and Methods: A total of 684 twins from the South Korean twin registry (261 monozygotic, MZ and 81 dizygotic, DZ pairs; mean age 38.6 ± 7.9 years, male/female = 264/420) underwent PA chest X-rays. Cardiovascular risk factors and anthropometric data were also collected. The AoAC and CTR were measured and graded using a standardized method. A structural equation method was used to calculate the proportion of variance explained by genetic and environmental factors behind AoAC and CTR. Results: The within-pair differences were low regarding the grade of AoAC, with only a few twin pairs showing large intra-pair differences. We found that the thoracic width showed high heritability (0.67, 95% CI: 0.59–0.73, p = 1). Moderate heritability was detected regarding cardiac width (0.54, 95% CI: 0.45–0.62, p = 0.572) and CTR (0.54, 95% CI: 0.44–0.62, p = 0.701). Conclusions: The heritable component was significant regarding thoracic width, cardiac width, and the CTR.

Purpose: The correlation between serum levels of homocysteine and bone mineral density remains controversial. The aim of this study was to identify the potential factors associated with the levels of serum total homocysteine (S-Hcy) and urinary N-terminal telopeptide of type I collagen (U-NTX) in female osteoporotic patients. Materials and Methods: This cross-sectional study included 163 female osteoporotic patients, aged between 48 and 91 years, who had never been treated with anti-osteoporosis therapy. Background data including spine and hip bone mineral density, ongoing therapy for the metabolic disease, aortic calcification score as evaluated by lateral lumbar X-ray film, and recent fragility fracture history were obtained. S-Hcy, U-NTX levels, and creatinine clearance were measured. Results: Multiple linear regression analysis revealed a significant correlation between S-Hcy levels and aortic calcification score (p = 0.022), creatinine clearance (p = 0.004), and recent fracture history (within 1 year after fracture) (p = 0.028); conversely, U-NTX levels correlated significantly with total hip bone mineral density (p < 0.0001) and recent fracture history (p = 0.0007). Conclusions: S-Hcy levels had no correlation with bone mineral density, but were associated with the degree of aortic calcification, renal function, and fracture events. These confounding factors should be taken into consideration when the relationship between S-Hcy and bone mineral density is discussed. [ABSTRACT FROM AUTHOR]

Introduction: Aortic calcification as detected by computed tomography is associated with arterial stiffening and is an important predictor of cardiovascular morbidity and mortality. Uptake of 18F-sodium fluoride (18F-NaF) in the aortic wall reflects metabolically active areas of calcification. The aim of this study was to determine if 18F-NaF uptake in the aorta is associated with calcification and progression of calcification as detected by computed tomography. Methods: Twenty-one postmenopausal women (mean age 62 ± 6 years) underwent assessment of aortic 18F-NaF uptake using positron emission tomography/computer tomography at baseline and a repeat computed tomography scan after a mean follow-up of 3.8 ± 1.3 years. Tracer uptake was quantified by calculating the target-to-background (TBR) ratios at baseline and follow-up. Calcification was assessed at baseline and follow-up using computed tomography. Results: Over the follow-up period, aortic calcium volume increased from 0.46 ± 0.62 to 0.71 ± 0.93 cm³ (P < 0.05). However, the change in calcium volume did not correlate with baseline TBR either unadjusted (r = 0.00, P = 1.00) or adjusted for age and baseline calcium volume (beta coefficient = -0.18, P = 0.42). TBR at baseline did not differ between participants with (n = 16) compared to those without (n = 5) progression in calcium volume (2.43 ± 0.46 vs. 2.31 ± 0.38, P = 0.58). In aortic segments identified to have the highest tracer uptake at baseline, calcium volume did not significantly change over the follow-up period (P = 0.41). Conclusion: In a cohort of postmenopausal women, 18F-NaF uptake as measured by TBR in the lumbar aorta did not predict progression of aortic calcification as detected by computed tomography over a four-year follow-up. [ABSTRACT FROM AUTHOR]

Aims: To assess the contribution of aortic valve calcification to the occurrence of transient or permanent atrioventricular block (AVB) and the need for permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) in a large single-centre cohort.Methods and Results: We retrospectively analysed pre-operative contrast-enhanced multidetector computed tomography scans of patients who underwent TAVI in our centre between 2012 and 2016. Calcium volume was calculated for each aortic cusp above (aortic valve), and below [left ventricular outflow tract (LVOT)] the basal plane. Clinical and procedural data as well as pre-operative electrocardiograms were evaluated. Multivariate analysis was performed to evaluate risk factors for transient and permanent AVB. A total of 342 patients receiving a balloon-expandable prosthesis were included in the study. Overall incidence of transient and permanent AVB was 4% (n = 14) and 7.6% (n = 26), respectively. On logistic regression analysis, baseline right bundle branch block [odds ratio (OR) 7.36, 95% confidence interval (CI) 2.6-20.6; P < 0.01], degree of oversizing (OR 1.04, 95% CI 1.01-1.07 P = 0.02), prior percutaneous coronary intervention (OR 2.8, 95% CI 1.1-7.3), and LVOT calcification beneath the non-coronary cusp (OR for an increase of 10 mm3 = 1.06, 95% CI 1-1.1; P = 0.03) were found to be independently associated with permanent AVB and PPI, whereas calcification of LVOT beneath the right coronary cusp (OR for an increase of 10 mm3 = 1.16, 95% CI 1.02-1.3; P = 0.02) and balloon post-dilation (OR 3.8, 95% CI 1.2-11.8; P = 0.02) were associated with reversible AVB.Conclusion: Left ventricular outflow tract calcifications are associated with transient and non-reversible AVB after TAVI, and its evaluation could help in predicting onset and reversibility of AVB. [ABSTRACT FROM AUTHOR]

Background/Aims: Although hypomagnesemia was found to be a risk for cardiovascular diseases in the general population, the relationship between serum magnesium (Mg) levels and prognosis of patients on maintenance hemodialysis (MHD) has not been extensively studied. This study sought to determine the relationship of serum Mg levels with aortic arch calcification (AoAC) and mortality in Japanese MHD patients. Methods: We measured serum Mg levels in a cohort of 392 patients on MHD, classified the patients into 3 groups according to these levels, and followed their course for 4 years. AoAC was assessed using chest-X-rays. Results: During follow-up, there were 117 deaths. Kaplan-Meier analyses showed that the high serum Mg group tended to have better survival rates than the low and middle serum Mg groups but this did not reach statistical significance. We also found that patients in the high serum Mg group had better nutritional status associated with higher serum albumin, triglyceride, and phosphate levels and had a significantly lower serum C-reactive protein level. In total, 83 patients (59.3%) in the high serum Mg group had been prescribed Mg oxide (MgO). Conclusions: Hypermagnesemia tended to be associated with better survival and a higher prescription rate of MgO. Interventional studies are needed to clarify whether Mg supplementation is beneficial for improving patient prognosis. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the inhibitory effects of 10-dehydrogingerdione (10-DHGD) and pentoxifylline (PTX) either individually or in combined form on calcium deposition in high cholesterol diet (HCD)-fed rabbits as compared to atorvastatin (ATOR), and to clarify the underlying mechanisms. Three-months-old male New Zealand white rabbits received either normal chow or HCD for 12 weeks. The latter group was subdivided into five groups and concurrently treated either with vehicle (dyslipidemic control), ATOR, 10-DHGD, PTX or combined 10-DHGD and PTX. Blood samples and aortic tissue were collected for biochemical and histological analyses. HCD-fed rabbits displayed dyslipidemia, inflammation, atherosclerotic lesions, and calcium deposition in aortas as compared to normal group. This was associated with up-regulation of bone morphogenetic protein-2 (BMP-2), wingless-type MMTV integration site family 3A (Wnt3a) mRNA levels and osteopontin expression in their aortic tissue, along with higher serum alkaline phosphatase and osteocalcin levels. Furthermore, a marked decrease in osteoprotegerin, along with a significant increase in receptor activator of NF-κB(RANK) levels, was found in aortic tissue of dyslipidemic rabbits. 10-DHGD and PTX monotherapy significantly modulated the afore-mentioned calcification markers and attenuated aortic calcification to greater extent than ATOR. Combination of 10-DHGD and PTX exerted more anti-calcifying effect than either individual drug. Our findings suggested therapeutic roles of 10-DHGD and PTX against aortic calcium deposition in dyslipidemic rabbits, likely mediated by HDL-raising effect and attenuation of associated inflammation. Combination of 10-DHGD and PTX may represent a promising therapeutic strategy for aortic calcification associated with atherosclerosis. [ABSTRACT FROM AUTHOR]

Abstract A large number of epidemiological studies in ethnically diverse populations show that lipoprotein(a) [Lp(a)] levels above 30–50 mg/dL are significantly associated with calcific aortic valve stenosis, although less so in African Americans. Patients with heterozygous familial hypercholesterolemia (he-FH) have a marked lifelong elevation of serum low-density lipoprotein cholesterol (LDL-C) level, and the prevalence of aortic valve calcification (AVC) is at least two-fold higher among adult he-FH patients compared with healthy controls. Additionally, Lp(a) levels above 50 mg/dL were recently found to be an independent risk factor for AVC among asymptomatic statin-treated he-FH patients. Given that worldwide an estimated 1.4 billion people have an Lp(a) level over 50 mg/dL, and that one out of 250 individuals has he-FH, then globally about 5 million he-FH patients should have an Lp(a) level higher than 50 mg/dL. However, because Lp(a) levels are, on average, significantly higher in he-FH patients than the general population, the actual number of he-FH patients with such high Lp(a) levels must be even higher. We proposed recently that Lp(a) life-years is a useful metric of cumulative burden of risk for atherosclerotic cardiovascular disease (ASCVD), and now posit that this metric may be extended to the development of AVC. The Lp(a) life-years illustrates the age-dependent exposure to a given Lp(a) level (years x mg/dL). Effective novel pharmacotherapies using apo(a) antisense oligonucleotides (ASOs) or small interfering RNA (siRNA)-based therapies targeting the hepatic expression of apo(a) offer unprecedented potential for significant reduction in the cumulative exposure of the aortic valves to Lp(a), and need to be tested in controlled clinical trials on the progression of AVC. Highlights • Lp(a) levels above 30–50 mg/dL associate with calcific aortic valve stenosis. • he-FH patients have marked lifelong elevation of serum LDL-cholesterol level. • AVC among he-FH patients is more frequent than in the general population. • Lp(a) life years is a useful metric of cumulative burden of Lp(a). • Apo(a) antisense oligonucleotides effectively lower Lp(a) concentration. [ABSTRACT FROM AUTHOR]

The objective of the study was to determine the association between AAC and neuromuscular function over 5 years. Participants in this study were ambulant women over 70 years old residing in Perth, Western Australia who participated in the Calcium Intake Fracture Outcomes Study, a randomised controlled trial of calcium supplementation. 1046 women (mean age = 74.9 ± 2.6 years; BMI = 27.1 ± 4.4 kg/m2) were included. Lateral spine images captured during bone density testing were scored for AAC (AAC24; 0-24) at baseline. Severe AAC (AACsev) was defined using established cut points (AAC24 ≥ 6). At baseline and follow-up, isometric grip strength was assessed using a dynamometer. Mobility was assessed by the Timed-Up-and-Go (TUG) test. Using pre-defined criteria, muscle weakness was considered as grip strength < 22 kg and poor mobility defined as TUG > 10.2 s. A subset of women had appendicular lean mass (ALM) determined by dual-energy X-ray absorptiometry at baseline and follow-up (n = 261). AACsev was evident in 193 (18.5%) women. Average decline in grip strength after 5 years was greater in those with AACsev than those without (3.6 ± 3.7 vs. 2.9 ± 4.2 kg; p = 0.034). This remained significant after adjustment for age, treatment allocation, diabetes, smoking history, renal function, medical record-derived prevalent vascular disease, BMI and physical activity (β = - 0.184; 95% confidence interval: - 0.361, - 0.008; p = 0.040). AACsev was not associated with 5-year changes in TUG or ALM in univariable or multivariable analyses (all p > 0.05). In older women, severe aortic calcification was associated with greater 5-year decline in muscle strength, but not TUG or ALM. These findings support the concept that vascular disease may have an effect on the loss of muscular strength. [ABSTRACT FROM AUTHOR]

Uremic vascular calcification (VC) commonly occurs during advanced chronic kidney disease (CKD) and significantly increases cardiovascular morbidity and mortality. Uremic toxins are integral within VC pathogenesis, as they exhibit adverse vascular influences ranging from atherosclerosis, vascular inflammation, to VC. Experimental removal of these toxins, including small molecular (phosphate, trimethylamine-N-oxide), large molecular (fibroblast growth factor-23, cytokines), and protein-bound ones (indoxyl sulfate, p-cresyl sulfate), ameliorates VC. As most uremic toxins share a gut origin, interventions through gastrointestinal tract are expected to demonstrate particular efficacy. The “gastrointestinal decontamination” through the removal of toxin in situ or impediment of toxin absorption within the gastrointestinal tract is a practical and potential strategy to reduce uremic toxins. First and foremost, the modulation of gut microbiota through optimizing dietary composition, the use of prebiotics or probiotics, can be implemented. Other promising strategies such as reducing calcium load, minimizing intestinal phosphate absorption through the optimization of phosphate binders and the inhibition of gut luminal phosphate transporters, the administration of magnesium, and the use of oral toxin adsorbent for protein-bound uremic toxins may potentially counteract uremic VC. Novel agents such as tenapanor have been actively tested in clinical trials for their potential vascular benefits. Further advanced studies are still warranted to validate the beneficial effects of gastrointestinal decontamination in the retardation and treatment of uremic VC.

Twin-to-twin transfusion syndrome (TTTS) at times complicates monochorionic twin gestations, resulting in conditions ranging from discordant sizes to fetal demise of one baby. Various types of cardiac defects have been described in the recipient twin of this syndrome. Isolated great artery calcification, i.e. aortic and pulmonary artery calcification is one such uncommon condition associated with TTTS. Calcification of the walls of great vessels may be due to chronic vascular injury sustained as a result of circulatory volume overload in the recipient twin. It may also cause severe systemic hypertension and cardiomyopathy. An accurate diagnosis is important for an optimal follow-up and appropriate genetic counseling. We report a case of aortic and pulmonary artery calcification in association with TTTS.

Vascular calcification (VC) is a critical contributor to the rising cardiovascular risk among at-risk populations such as those with diabetes or renal failure. The pathogenesis of VC involves an uprising of oxidative stress, for which antioxidants can be theoretically effective. However, astaxanthin, a potent antioxidant, has not been tested before for the purpose of managing VC. To answer this question, we tested the efficacy of astaxanthin against VC using the high phosphate (HP)-induced vascular smooth muscle cell (VSMC) calcification model. RNAs from treated groups underwent Affymetrix microarray screening, with intra-group consistency and inter-group differential expressions identified. Candidate hub genes were selected, followed by validation in experimental models and functional characterization. We showed that HP induced progressive calcification among treated VSMCs, while astaxanthin dose-responsively and time-dependently ameliorated calcification severities. Transcriptomic profiling revealed that 3491 genes exhibited significant early changes during VC progression, among which 26 potential hub genes were selected based on closeness ranking and biologic plausibility. SOD2 was validated in the VSMC model, shown to drive the deactivation of cellular senescence and enhance antioxidative defenses. Astaxanthin did not alter intracellular reactive oxygen species (ROS) levels without HP, but significantly lowered ROS production in HP-treated VSMCs. SOD2 knockdown prominently abolished the anti-calcification effect of astaxanthin on HP-treated VSMCs, lending support to our findings. In conclusion, we demonstrated for the first time that astaxanthin could be a potential candidate treatment for VC, through inducing the up-regulation of SOD2 early during calcification progression and potentially suppressing vascular senescence.

Patients with chronic kidney disease (CKD) have an increased risk of vascular calcification (VC), including aortic arch calcification (AAC). Few investigated the influence of gustatory function on the probability of having VC. We examined whether gustatory function results modulated the probability of having VC in patients with CKD. We prospectively enrolled adults with CKD (estimated glomerular filtration rate 2), with their AAC rated semi-quantitatively and gustatory function assessed by objective and subjective approaches. Multiple logistic regression was used to analyze the relationship between gustatory function results and AAC. Those with AAC had significantly better objective gustatory function in aggregate scores (p = 0.039) and categories (p = 0.022) and less defective bitter taste (p = 0.045) and scores (p = 0.037) than those without. Multiple regression analyses showed that higher aggregate scores (odds ratio (OR) 1.288, p = 0.032), or better gustatory function, and higher bitter taste scores (OR 2.558, p = 0.019) were each associated with a higher probability of having AAC among CKD patients; such an association was modulated by serum phosphate levels. In conclusion, better gustatory function was independently correlated with having AAC among CKD patients. A follow-up of VC severity may be an underrecognized component of care for CKD patients with a preserved gustatory function.

Aim: Patients with end-stage kidney disease (ESKD) have an unparalleled risk of left ventricular hypertrophy (LVH) and vascular calcification (VC), both of which introduce excessive cardiovascular risk. However, it remains unclear whether LVH geometry co-modulates cardiovascular outcomes with VC in this population., Methods: A retrospective cohort study was conducted. Patients with ESKD requiring chronic hemodialysis were identified from Shin Kong Wu Ho-Su Memorial Hospital between October and December 2018, with echocardiographic LVH geometry and aortic arch calcification (AoAC) determined. They were divided into four groups according to AoAC severity and eccentric or concentric LVH. We used Kaplan-Meier analysis and Cox proportional hazard regression to analyze their cardiovascular and all-cause mortality after multivariate adjustment., Results: Overall, 223 patients with ESKD with LVH were analyzed, among whom 29.1%, 23.3%, 25.1%, and 22.4% had non-to-mild AoAC with eccentric and concentric LVH and moderate-to-severe AoAC with eccentric and concentric LVH, respectively. After 3.5 years of follow-up, patients with ESKD with moderate-to-severe AoAC and concentric LVH had a significantly higher risk of cardiovascular mortality than those with non-to-mild AoAC and eccentric LVH (hazard ratio 3.35, p=0.002). However, those with moderate-to-severe AoAC but eccentric LVH did not have higher cardiovascular mortality. Similarly, patients with ESKD with moderate-to-severe AoAC and concentric LVH had a significantly higher all-cause mortality than those with non-to-mild AoAC and eccentric LVH, whereas the other two groups did not have higher risk., Conclusion: LVH geometry could help stratify the risk of patients with ESKD when they had severe VC, and co-existing severe VC and concentric LVH aggravated cardiovascular risk.

Background/Aim: Vascular calcification is associated with cardiovascular risk in maintenance hemodialysis (MHD) patients. Previous reports have shown that simple assessment of aortic arch calcification (AoAC) using plain radiography is associated with cardiovascular mortality in the general population. We conducted a prospective study to investigate factors associated with the presence at baseline and progression of AoAC in MHD patients and examined its prognostic value in a short-term outcome. Methods: We prospectively evaluated chest X-rays in 301 asymptomatic MHD patients. The extent of AoAC was divided into three Grades (0, 1, 2+3). Demographic data including age, gender, dialysis vintage, co-morbidity and biochemical data were assessed and the patients were then followed for 3 years. Results: AoAC was observed in 126 patients (41.9%) as Grade 0, in 112 patients (37.2%) as Grade 1, and in 63 patients (20.9%) as Grade 2 and 3 at baseline. An increase in the severity of calcification was associated with older male patients who had lower serum albumin levels. During the follow-up period of 3 years, multivariate Cox proportional hazards analysis revealed that high-grade calcification was associated with cardiovascular and all-cause mortality. Patients with AoAC were associated with a worse outcome in survival analysis and the grade of AAC also influenced their survival. Moreover, all-cause death rates were significantly higher in the progression groups than in the non-progression groups. Conclusions: The presence and progression of AoAC assessed by chest X-ray were independently associated with mortality in MHD patients. Regular follow-up by chest X-ray could be a simple and useful method to stratify mortality risk in MHD patients.

Policosanol (POL) is a hypocholesterolemic drug of natural origin and has been shown to reduce circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) in healthy participants. Recently, we have reported that POL can attenuate aortic calcification in diabetic dyslipidemic rats; however, the underlying mechanism is not fully elucidated. We aimed to investigate the effect of POL on aortic calcification and whether PCSK9 has a contributory role and also to examine whether the combination of POL with pentoxifylline (PTX) as anti-tumor necrosis factor α would offer additional benefits. Thirty adult male New Zealand rabbits weighing 1.5 to 2 kg were randomly assigned to 5 groups. One group received standard chow diet and served as normal control group (NC). The other 4 groups received 0.5% wt/wt cholesterol-rich diet for 12 weeks and concurrently treated with placebo, POL, PTX, or a combination of POL and PTX. Sera samples and aortic tissue were collected for biochemical measurements and histological assessment. Rabbits fed a cholesterol-rich diet demonstrated dyslipidemia, increased inflammatory state, and elevated serum levels of PCSK9, compared to the NC group. Aortic calcification was evident in dyslipidemic rabbits, represented by increased calcium deposition and osteopontin expression in aortic tissue, along with elevated serum levels of alkaline phosphatase and osteocalcin. Dyslipidemic rabbits showed a significant upregulation of wingless-type MMTV integration site family 3A and bone morphogenetic protein 2 genes in their aortic tissue. Policosanol significantly reduced circulating PCSK9 levels, suppressed calcification markers, and attenuated aortic calcification. Combination of POL with PTX alleviated aortic calcification to a greater extent than either monotherapy, which may be attributed to further suppression of PCSK9 and calcification markers. These findings suggested that POL exerted anticalcifying effect partly via inhibition of PCSK9. Combination of POL and PTX offered additional benefits and might represent a promising therapeutic option for aortic calcification. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Cortistatin (CST) is a newly discovered endogenous active peptide that exerts protective effects on the cardiovascular system. However, the relationship between CST and aortic calcification and the underlying mechanism remain obscure. Therefore, we investigated effects of CST on aortic calcification and its signalling pathways. Methods: Calcium content and alkaline phosphatase (ALP) activity were measured using the o‐cresolphthalein colorimetric method and ALP assay kit respectively. Protein expression of smooth muscle (SM)‐ɑ‐actin, osteocalcin (OCN), β‐catenin, glycogen synthase kinase 3β (GSK3β), p‐GSK3β, protein kinase C (PKC), p‐PKC, c‐Jun N‐terminal kinase (JNK) and p‐JNK was determined using Western blotting. Results: In aorta from a rat vitamin D3 calcification model, CST abrogated calcium deposition and pathological damage, decreased the protein expression of OCN and β‐catenin and increased SM‐ɑ‐actin expression. In a rat cultured vascular smooth muscular cell (VSMC) calcification model induced by β‐glycerophosphate (β‐GP), CST inhibited the increase in ALP activity, calcium content and OCN protein and the decrease in SM‐α‐actin expression. CST also inhibited the β‐GP‐induced increase in p‐GSK3β and β‐catenin protein (both P < .05). The inhibitory effects of CST on ALP activity, calcium deposition and β‐catenin protein were abolished by pretreatment with lithium chloride, a GSK3β inhibitor. CST promoted the protein expression of p‐PKC by 68.5% (P < .01), but not p‐JNK. The ability of CST to attenuate β‐GP‐induced increase in ALP activity, calcium content and OCN expression in the VSMC model was abolished by pretreatment with the PKC inhibitor Go6976. Conclusion: These results indicate that CST inhibits aortic calcification and osteogenic differentiation of VSMCs likely via the GSK3β/β‐catenin and PKC signalling pathways, but not JNK signalling pathway. [ABSTRACT FROM AUTHOR]

Calcific aortic vasculopathy correlates with bone loss in osteoporosis in an age-independent manner. Prior work suggests that teriparatide, the bone anabolic treatment for postmenopausal osteoporosis, may inhibit the onset of aortic calcification. Whether teriparatide affects the progression of preexisting aortic calcification, widespread among this patient population, is unknown. Female apolipoprotein E-deficient mice were aged for over 1 yr to induce aortic calcification, treated for 4.5 wk with daily injections of control vehicle (PBS), 40 μg/kg teriparatide (PTH40), or 400 μg/kg teriparatide (PTH400), and assayed for aortic calcification by microcomputed tomography (microCT) before and after treatment. In a followup cohort, aged female apolipoprotein E-deficient mice were treated with PBS or PTH400 and assayed for aortic calcification by serial microCT and micropositron emission tomography. In both cohorts, aortic calcification detected by microCT progressed similarly in all groups. Mean aortic 18F-NaF incorporation, detected by serial micropositron emission tomography, increased in the PBS-treated group (+14 ± 5%). In contrast, 18F-NaF incorporation decreased in the PTH400-treated group (-33 ± 20%, P = 0.03). Quantitative histochemical analysis by Alizarin red staining revealed a lower mineral surface area index in the PTH400-treated group compared with the PBS-treated group (P = 0.04). Furthermore, Masson trichrome staining showed a significant increase in collagen deposition in the left ventricular myocardium of mice that received PTH400 [2.1 ± 0.6% vs. control mice (0.5 ± 0.1%), P = 0.02]. In summary, although teriparatide may not affect the calcium mineral content of aortic calcification, it reduces 18F-NaF uptake in calcified lesions, suggesting the possibility that it may reduce mineral surface area with potential impact on plaque stability. [ABSTRACT FROM AUTHOR]

Objective Preoperative chest radiograph screening is widely used before cardiac surgery. The objective of this study was to investigate the frequency of abnormal findings on a routine chest radiograph before cardiac surgery. Methods In this retrospective cohort study, 1136 patients were included. Patients were scheduled for cardiac surgery and underwent a preoperative chest radiograph. The primary outcome was the frequency of abnormalities on the chest radiograph. Secondary outcome was the effect of those abnormalities on surgery. Results One half of the patients (570/1136; 50%) had 1 or more abnormalities on the chest radiograph. Most frequent abnormalities were cardiomegaly, aortic elongation, signs of chronic obstructive pulmonary disease, vertebral fractures or height loss, possible pulmonary or mediastinal mass, pleural effusion, and atelectasis. In 2 patients (2/1136; 0.2%), the chest radiograph led to postponement of surgery, whereas in none of the patients the surgery was cancelled. In 1 patient (1/1136; 0.1%) the surgical approach was altered and in 15 patients (15/1136; 1.3%) further analysis was performed without having an impact on the planned surgical approach. Conclusions Although abnormalities are frequently found on preoperative chest radiographs before cardiac surgery, change in clinical management with regard to planned surgery or surgical approach occurs infrequently. [ABSTRACT FROM AUTHOR]

Gaucher disease (GD) is the most frequent lysosomal storage disorder due to biallelic pathogenic variants in GBA gene. Only homozygous D409H variant has been associated with the cardiovascular phenotype which is also known as Gaucher disease type 3c. In this descriptive study, we presented phenotypic heterogeneity and a novel clinical finding among 13 patients with GD type 3c. Patients presented with varying degrees of cardiac valve and/or aortic calcifications (84,6%) and corneal opacities (76,9%) in addition to visceral (100%), hematological (92,3%), neurological (92,3%), and skeletal (30%) manifestations. Also, cervical dystonia (38,4%) and psychiatric disorders (46,1%) were not infrequent entities with respect to neurological involvement in GD type 3c. In this report, we highlight transient neonatal cholestasis (38,4%) as a novel finding in GD type 3c. Neonatal cholestasis is a finding associated with Gaucher type 2, but transient neonatal cholestasis has not been reported in GD patients, so far. The clinical features of GD type 3c are highly heterogeneous, from disease severity or age of onset to disease progression. Also, we concluded that phenotypic spectrum may be associated with age at onset of clinical symptoms. As, patients presenting in infancy or childhood had mainly visceral and hematological involvement and patients presenting in adolescence and adulthood had mainly cardiac, neurological involvement, and psychiatric behavioral disorders. Identifying the heterogeneous clinical course of these patients in this fatal disease, may lead a sufficient understanding of the pathophysiology which will enable targeted therapeutic interventions. [ABSTRACT FROM AUTHOR]

BackgroundThe DENERHTN (Renal Denervation for Hypertension) trial confirmed the efficacy of renal denervation (RDN) in lowering daytime ambulatory systolic blood pressure when added to standardized stepped‐care antihypertensive treatment (SSAHT) for resistant hypertension at 6 months. Methods and ResultsThis post hoc exploratory analysis assessed the impact of abdominal aortic calcifications (AAC) on the hemodynamic and renal response to RDN at 6 months. In total, 106 patients with resistant hypertension were randomly assigned to RDN plus SSAHT or to the same SSAHT alone (control group). Total AAC volume was measured, with semiautomatic software and blind to randomization, from the aortic hiatus to the iliac bifurcation using the prerandomization noncontrast abdominal computed tomography scans of 90 patients. Measurements were expressed as tertiles. The baseline‐adjusted difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the RDN and control groups was −10.1 mm Hg (P=0.0462) in the lowest tertile and −2.5 mm Hg (P=0.4987) in the 2 highest tertiles of AAC volume. Estimated glomerular filtration rate remained stable at 6 months for the patients in the lowest tertile of AAC volume who underwent RDN (+2.5 mL/min per 1.73 m2) but decreased in the control group (−8.0 mL/min per 1.73 m2, P=0.0148). In the 2 highest tertiles of AAC volume, estimated glomerular filtration rate decreased similarly in the RDN and control groups (P=0.2640). ConclusionsRDN plus SSAHT resulted in a larger decrease in daytime ambulatory systolic blood pressure than SSAHT alone in patients with a lower AAC burden than in those with a higher AAC burden. This larger decrease in daytime ambulatory systolic blood pressure was not associated with a decrease in estimated glomerular filtration rate. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777.