Aterectomía rotacional complicada en una paciente anciana con enfermedad coronaria multivaso. Reporte de caso

La aterectomía rotacional es un procedimiento específico utilizado para el manejo de lesiones coronarias complejas, especialmente cuando existe calcificación de las arterias coronarias (CAC). Esta técnica fue muy utilizada hasta la última década del siglo pasado; actualmente, aunque es poco usada, juega un papel importante en pacientes que podrían ser candidatos a revascularización quirúrgica pero que, por diferentes patologías ―como la enfermedad ateromatosa difusa, en la que se requieren estents largos, reestenosis in-stent, lesiones ostiales calcificadas y oclusiones totales crónicas―, se rechaza la opción quirúrgica. La aterectomía rotacional es un método que utiliza una fresa recubierta de diamante para reducir el volumen de las placas ateroescleróticas y la calcificación de los vasos. Este dispositivo dispersa la placa en microfragmentos, con lo que se consigue un aumento del diámetro luminal. Estos fragmentos, que tienen un diámetro mínimo, pasan predominantemente a la circulación capilar y luego son absorbidos por el sistema reticuloendotelial. Dentro de las complicaciones de esta técnica destacan la disección arterial, el atrapamiento del dispositivo, la bradicardia y la microperforación de arterias coronarias. Esta última puede ser corregida con el uso de trombina, de grasa subcutánea o de perlas. Este artículo reporta el caso de una paciente anciana con enfermedad coronaria multivaso asociada a calcificación extensa de todas las arterias coronarias, por una historia de radioterapia recibida en años anteriores por cáncer de mama y que, al no ser candidata a terapia quirúrgica por cirugía cardiovascular, requirió manejo con aterectomía rotacional que se vio complicada por microperforación de una arteria coronaria, pero que posteriormente evolucionó de manera satisfactoria.

Rotational atherectomy is a specific procedure for managing complex coronary artery lesions, especially when there is coronary artery calcification (CAC). This technique was widely used until the last decade of the 20th century; however, although it is rarely used, it currently plays an important role in patients who could be candidates for surgical revascularization but reject surgeries due to different pathologies-such as diffuse atheromatous disease requiring long stents, in-stent restenosis, calcified ostial lesions and chronic total occlusions. Rotational atherectomy is a method that uses a diamond-coated burr to reduce the volume of atherosclerotic plaques and calcification of vessels. This device breaks up plaque into microfragments, leading to an increase in lumen diameter. These fragments, which have a tiny diameter, pass predominantly into the capillary circulation and are then absorbed by the reticuloendothelial system. Among the complications of this technique are arterial dissection, device entrapment, bradycardia and microperforation of coronary arteries. The latter can be corrected with the use of thrombin, subcutaneous fat or beads. This article reports the case of an elderly female patient with multivessel coronary artery disease associated with extensive calcification of all the coronary arteries secondary to radiotherapy received in previous years for breast cancer. The patient, not being a candidate for cardiovascular surgery, required a rotational atherectomy that resulted in a microperforation of a coronary artery but with good subsequent progress.

Limitaciones de los puntajes de riesgo cardiovascular en prevención primaria. ¿Una oportunidad para los moduladores de riesgo? / Limitations of cardiovascular risk scores in primary prevention. An opportunity for risk modulators?

RESUMEN Introducción : Los puntajes de riesgo cardiovascular tienen limitaciones relacionadas con la calibración, la discriminación y la baja sensibilidad. Se han identificado diferentes "moduladores de riesgo" que permiten mejorar la estratificación del riesgo cardiovascular: placa aterosclerótica carotídea (PAC), puntaje de calcio arterial coronario (pCAC) y lipoproteína(a) [Lp(a)]. Objetivos : 1) determinar la prevalencia de los moduladores de riesgo citados en una población en prevención primaria; 2) determinar la concordancia entre los 2 métodos de detección de aterosclerosis subclínica; 3) establecer qué proporción de pacientes deberían recibir estatinas inicialmente, según su puntaje de riesgo, y posteriormente con el conocimiento de los moduladores de riesgo. Material y métodos : Se incluyeron individuos de 18 a 79 años, que asistieron para una evaluación de riesgo cardiovascular y que no estaban recibiendo tratamiento hipolipemiante. Se calculó el puntaje de riesgo (ASCVD Risk Estimator) en cada paciente. Se evaluó la presencia de PAC, el pCAC y el nivel plasmático de Lp(a). Resultados : Se incluyeron 348 pacientes (edad media 55,6 ± 12,2 años, 45,4% hombres). En la población total, 29,8%, 36,8% y 53,2% de los pacientes mostraron un valor de Lp(a) ≥ 50 mg/dL, PAC o un pCAC > 0, respectivamente. La prevalencia de PAC y pCAC fue progresivamente mayor según la categoría de riesgo cardiovascular; sin embargo, la proporción de sujetos de bajo riesgo que tenían moduladores de riesgo fue considerable (Lp(a) ≥ 50 mg/dl: 25,7%; PAC: 22%; pCAC > 0: 33%). En los 60 individuos menores de 45 años la prevalencia de pCAC > 0 y PAC fue de 18,3% y 10%, respectivamente. La concordancia entre los dos métodos para determinar la presencia de ateromatosis subclínica fue discreta (kappa 0,33). La indicación del tratamiento con estatinas aumentó un 31,6% luego de evaluar la presencia de moduladores. Conclusión : La presencia de moduladores de riesgo fue frecuente en esta población en prevención primaria, incluso en sujetos de bajo riesgo o menores de 45 años. La detección de moduladores de riesgo podría mejorar la estratificación inicial y llevar a reconsiderar el tratamiento con estatinas.

ABSTRACT Background : Cardiovascular risk scores have limitations related to calibration, discrimination, and low sensitivity. Different "risk modulators" have been identified to improve cardiovascular risk stratification: carotid atherosclerotic plaque (CAP), coronary artery calcium (CAC) score and lipoprotein(a) [Lp(a)]. Objectives : The aims of this study were: 1) to determine the prevalence of risk modulators mentioned in a primary prevention population; 2) determine the concordance between the 2 methods of detecting subclinical atherosclerosis; and 3) establish which proportion of patients should receive statins according to the initial risk stratification and after being recategorized by screening for risk modulators. Methods : Individuals aged 18 to 79 years who consulted for cardiovascular risk assessment and who were not receiving lipid-lowering treatment were included. The risk score was calculated in each patient using ASCVD Risk Estimator. The presence of CAP, CAC score and Lp(a) level were evaluated. Results : The cohort was made up of 348 patients; mean age was 55.6 ± 12.2 years and 45.4% were men. In the total population, 29.8%, 36.8%, and 53.2% of patients showed Lp(a) value ≥50 mg/dL, CAP, or a CAC score >0, respectively. The prevalence of CAP and CAC score was progressively higher according to the cardiovascular risk category; however, the proportion of low-risk subjects who had risk modulators was considerable (Lp(a) ≥50 mg/dl: 25.7%; CAP: 22%; CAC score >0: 33%). In the 60 subjects <45 years, the prevalence of CAC score >0 and CAP was 18.3% and 10%, respectively. The agreement between the two methods for quantifying subclinical atheromatosis was fair (kappa= 0.33). The indication for statin treatment increased by 31.6% after evaluating the presence of modulators. Conclusion : The presence of risk modulators was common in this population in primary prevention, even in low-risk subjects or < 45 years. Detection of risk modulators could improve initial stratification and lead to reconsideration of statin treatment.

Vascular Calcification in Chronic Kidney Disease Patients on Hemodialysis: Prevalence and Correlation with Vascular Disease Events

Introduction: With declining kidney function, the prevalence of vascular calcifications increases and calcification occurs years earlier and is more severe in chronic kidney disease (CKD) patients than in general population. We did this study to find the prevalence of vascular calcification in patients on maintenance hemodialysis using simple and inexpensive radiological method and to find out the correlation of vascular calcification score with vascular disease events, cardiovascular and all-cause mortality over a follow-up period of 1 year. Materials and methods: This prospective, observational, comparative, follow-up, single-center study of maintenance hemodialysis patients was performed at a tertiary care center in Haryana. Seventy-one patients on maintenance hemodialysis for more than 3 months were included in the study. Patients who were 18 years of age or below, CKD stage 5 patients not on dialysis and those who had previous history of parathyroidectomy were excluded. Adragao score for vascular calcification was calculated by evaluating bilateral iliac, femoral and radial arteries in plain radiographic films of pelvis and hands. Statistical analyses were performed with the SPSS System 10.0. Results: Seventy-one patients were enrolled in this study out of which, 45 were male and 26 were female. Mean age of patients was 61.92 ± 10.77 years. Majority of patients were elderly (age group ?60 years). Out of 71 patients, 66 (92.9%) were hypertensive and 26 (36.6%) patients were diabetic. Twenty-two (30.9%) patients had cardiovascular disease (CVD) at baseline. Coronary artery disease (CAD) was present in 20 (28.1%) patients, cerebrovascular disease was present in 2 (2.8%) patients and peripheral artery disease (PAD) was present in only 1 patient at baseline. Average dialysis duration received by patients was 21.35 ± 21.17 months. Out of 71 patients, 16 (22.5%) received calcium-containing phosphate binder, 51 (71.8%) received noncalcium-containing phosphate binder and 4 patients received no phosphate binder. Fifty-five (77.4%) patients received therapeutic or prophylactic vitamin D3 therapy during the study period. Vascular calcification detected with plain X-ray of pelvis and both wrists was found in 56.3% of patients on maintenance hemodialysis. The prevalence and severity of vascular calcification was higher with increasing age. Diabetes was found to be significantly associated with the presence of vascular calcification (p < 0.0005). CAD at the time of enrollment was significantly associated with vascular calcification (p = 0.009). Serum levels of calcium, phosphate, vitamin D3, intact parathyroid hormone (PTH), calcium-phosphate product or use of phosphate binders or the types or vitamin D therapy did not correlate clinically with presence of vascular calcification. Hemodialysis duration did not correlate with the presence of vascular calcification (p = 0.113). Presence of vascular calcifications in hemodialysis patients predicted future vascular disease events over 1 year follow-up (p = 0.013) but did not correlate with cardiovascular and all-cause mortality. Conclusion: There is a high prevalence of vascular calcification in maintenance hemodialysis patients in our center. The risk factors of vascular calcification were higher age, diabetes and CAD. These patients should be followed-up regularly for vascular events. We also want to reiterate with this study that plain X-ray is sufficient to rule out vascular calcification in CKD patients and should be employed regularly in dialysis clinics.

Achados tomográficos incidentais de calcificações coronarianas: um estudo de prevalência na região sul do Brasil / Incidental tomographic findings of coronary artery calcifications: a prevalence study in southern Brazil

Fundamento: As calcificações de artérias coronárias (CAC) mostram-se como fator preditivo de doenças cardiovasculares (DCV). A tomografia computadorizada (TC) de tórax com protocolo de aquisição de baixa dose apresenta acurácia na identificação de CAC e propicia achados incidentais dessas calcificações, que são comumente negligenciados. Este estudo analisará a prevalência de achados incidentais de calcificação em artérias coronárias em indivíduos não cardiopatas submetidos à TC de tórax. Métodos: Estudo transversal consecutivo de caráter analítico e descritivo. Foram incluídos indivíduos de ambos os sexos que realizaram TC de tórax por encaminhamento, acima de 18 anos e não cardiopatas. A coleta de dados foi realizada por meio de prontuários e ficha de anamnese auto aplicada. As variáveis referentes às CAC e à extensão do comprometimento foram obtidas a partir da reavaliação das imagens de TC de tórax disponíveis no sistema da instituição. Os exames foram anonimizados e avaliados por dois médicos radiologistas experientes. Considerou-se como estatisticamente significativo p≤0,05. Resultados: Foram analisados 397 exames. Encontrou-se prevalência de calcificações em 176 (44%) dos casos. A existência dessas calcificações coronárias está relacionada à idade (p<0,001). As calcificações possuem relação com o sexo (p = 0,03) com maior razão de chance de desenvolvimento em homens (odds ratio [OR] = 1,55). O tabagismo (p<0,001), o sedentarismo (p<0,001), a hipertensão arterial sistêmica (p<0,001), o diabetes mellitus (p = 0,04) e as dislipidemias (p<0,001) mostraram associação positiva. Conclusão: A prevalência de achados incidentais de CAC foi de 44%; variam em maior número entre leve e grave; maior razão de chance no sexo masculino e aumento da prevalência com a idade. Portanto, a TC de tórax mostra-se um efetivo método para avaliar as CAC, e juntamente com a história clínica do paciente pode ser utilizada para medir os fatores de risco para doenças cardiovasculares e intervir no desfecho do quadro.(AU)

Introduction: Coronary artery calcifications (CAC) are shown to be a predictive factor of cardiovascular diseases. Computed tomography (CT) of the chest with a low-dose acquisition protocol is accurate in identifying CAC and provides incidental findings of these calcifications, which are commonly overlooked. This study will analyze the prevalence of incidental findings of calcification in coronary arteries in non-cardiac individuals undergoing chest CT. Methods: Consecutive cross-sectional study of an analytical and descriptive nature. Individuals of both genders who underwent chest CT by referral, over 18 years of age and without heart disease were included. Data collection was carried out using medical records and a self-applied anamnesis form. The variables referring to the CAC and the extension of the impairment were obtained from the reassessment of the chest CT images available in the institution's system. The exams were anonymized and evaluated by two experienced radiologists. P≤0.05 was considered statistically significant. Results: 397 exams were analyzed. A prevalence of calcifications was found in 176 (44%) of the cases. The existence of these coronary calcifications is related to age (p<0.001). Calcifications are related to gender (p = 0.03) with a higher odds ratio of development in men (odds ratio [OR] = 1.55). Smoking (p<0.001), sedentary lifestyle (p<0.001), systemic arterial hypertension (p<0.001), Diabetes Mellitus (p = 0.04), and dyslipidemia (p<0.001) showed a positive association. Conclusion: The prevalence of incidental CAC findings was 44%; vary in greater numbers between mild and severe; higher odds ratio in males and increased prevalence with age. Therefore, chest CT proves to be an effective method to assess CAC, and together with the patient's clinical history, it can be used to measure risk factors for CVD and intervene in the outcome of the condition.(AU)

Determinação da Idade Vascular em Homens Através do Escore de Cálcio Coronariano e seu Impacto na Reestratificação do Risco Cardiovascular / Determination of Vascular Age in Men Using the Coronary Calcium Score and its Impact on Restratification of Cardiovascular Risk

Resumo Fundamento Identificar os indivíduos assintomáticos sob risco de desenvolver doenças cardiovasculares é um dos principais objetivos da cardiologia preventiva. O escore de cálcio coronariano (ECC) permite estimar a idade vascular, que se mostrou mais fidedigna que a idade cronológica na determinação do risco cardiovascular. Objetivos Reclassificar o risco cardiovascular com base na idade arterial e avaliar a progressão do escore de cálcio durante o seguimento. Métodos 150 homens assintomáticos foram submetidos a avaliação clínica e do ECC em 2 avaliações com intervalo de 7,6 anos. Classificamos os pacientes pelos escores de risco tradicionais e pela idade arterial. Avaliamos quais variáveis se associaram a maior progressão do ECC durante o período. O nível de significância estatística considerado foi de 5% (p < 0,05). Resultados A utilização da idade arterial na estratificação do risco cardiovascular em comparação ao escore de risco de Framingham (ERF) reclassificou 29% dos indivíduos para uma categoria de risco superior e 37% para uma categoria inferior. Em relação ao escore da AHA e ACC (ASCVD), 31% passaram para um risco maior e 36% para um risco menor. A classificação inicial pela idade arterial teve relação direta com a progressão do ECC ao longo do seguimento (p < 0,001), fato que não foi observado para o ERF (p = 0,862) e ASCVD (p = 0,153). As variáveis individuais que mais se associaram à progressão do ECC foram a pressão arterial sistólica e o HDL baixo. Conclusão A estratificação de risco cardiovascular utilizando a idade arterial apresentou melhor associação que o ERF e ASCVD na identificação de indivíduos com maior risco de progressão da aterosclerose.

Abstract Background Identifying asymptomatic individuals at risk of developing cardiovascular disease is one of the main goals of preventive cardiology. The coronary calcium score (CCS) makes it possible to estimate vascular age, which has shown to be more reliable than chronological age for determining cardiovascular risk. Objectives To reclassify cardiovascular risk based on arterial age and evaluate CCS progression during follow-up. Methods We included 150 asymptomatic men who underwent clinical and CCS evaluation in 2 evaluations with an interval of 7.6 years. We classified patients by traditional risk scores and arterial age. We evaluated which variables were associated with greater CCS progression during the period, considering a statistical significance level of 5% (p < 0.05). Results The use of arterial age in the stratification of cardiovascular risk in comparison with the Framingham risk score (FRS) reclassified 29% of individuals to a higher risk category and 37% to a lower risk category. Regarding the American Heart Association and American College of Cardiology score (ASCVD), 31% were reclassified as higher risk and 36% as lower risk. The initial classification by arterial age was directly related to the progression of CCS throughout follow-up (p < 0.001). This was not observed for the FRS (p = 0.862) or ASCVD (p = 0.153). The individual variables most associated with CCS progression were high systolic blood pressure and low HDL. Conclusion Cardiovascular risk stratification using arterial age showed a better association than the FRS and ASCVD in identifying individuals with higher risk of atherosclerosis progression.

Association of coronary artery calcium with heart rate variability in the Brazilian Longitudinal Study of Adult Health - ELSA-Brasil

Current data shows that the autonomic and vascular systems can influence each other. However, only a few studies have addressed this association in the general population. We aimed to investigate whether heart rate variability (HRV) was associated with coronary artery calcium (CAC) in a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We examined baseline data from 3138 participants (aged 35 to 74 years) without previous cardiovascular disease who underwent CAC score assessment and had validated HRV recordings. Prevalent CAC was defined as a CAC score>0, and HRV analyses were performed over 5-min segments. We detected CAC score>0 in 765 (24.4%) participants. Subgroup analyses in older participants (≥49 years) adjusted for sociodemographic and clinical variables revealed that CAC score>0 was associated with lower values of standard deviation of NN intervals (SDNN) (odds ratio [OR]=1.32; 95%CI: 1.05,1.65), root mean square of successive differences between adjacent NN intervals (RMSSD) (OR=1.28; 95%CI: 1.02,1.61), and low frequency (LF) (OR=1.53, 95%CI: 1.21,1.92). Interaction analysis between HRV indices and sex in age-stratified groups revealed significant effect modification: women showed increased OR for prevalent CAC in the younger group, while for men, the associations were in the older group. In conclusion, participants aged ≥49 years with low SDNN, RMSSD, and LF values were more likely to present prevalent CAC, suggesting a complex interaction between these markers in the pathogenesis of atherosclerosis. Furthermore, our results suggested that the relationship between CAC and HRV might be sex- and age-related.

Hemodialysis with mesenteric artery calcified stenosis and mesenteric ischemia: a case report / 中国医师杂志

Objective:To improve the understanding of hemodialysis complicated with mesenteric artery calcified stenosis and mesenteric ischemia through the analysis of the case and review of related literature.Methods:A case of hemodialysis with intractable abdominal pain as the main manifestation was reported, and its clinical features, diagnosis and treatment were summarized.Results:The case was a maintenance hemodialysis patient with persistent dull pain around the umbilicus, which worsens after meal and hemodialysis. The results showed multiple vascular calcification, superior mesenteric artery stenosis so the patient was diagnosed with chronic mesenteric ischemia. Mesenteric revascularization under intervention was planned but the guide wire failed to enter the superior mesenteric artery after repeated attempts during the operation. Surgical treatment was recommended, but the patient and family refused surgery and were discharged.Conclusions:Dialysis patients with intractable abdominal pain should be carefully identified and alert for mesenteric artery disease and mesenteric ischemia.

Terpine-4-ol on inhibiting vascular smooth muscle cell calcification by improving mitochondrial dynamics / 药学学报

The aim of this study was to investigate the role and mechanism of terpinen-4-ol (T4O) on high glucose (HG) -induced calcification in vascular smooth muscle cell (VSMC). To investigate the role of T4O on HG-induced calcium deposition, osteogenic phenotypic transformation and mitochondrial dynamics in VSMC, Mdivi-1, a mitochondrial dynamin-related protein 1 (Drp-1) inhibitor, was used to analyze the correlation between mitochondrial dynamics and VSMC calcification and the role of T4O. Alizarin red S staining was used to observe calcium salt deposition and flow cytometry to detect intracellular Ca2+ content; Western blot and immunofluorescence were used to detect the expression of phenotypic switching-related markers α-smooth muscle actin (α-SMA), bone morphogenetic protein 2 (BMP2) and Runt related transcription factor 2 (Runx2), and mitochondrial dynamics-related markers mitofusin 1 (MFN1), mitofusin 2 (MFN2) and Drp-1. The results showed that low and high doses of T4O could inhibit HG-induced down-regulation of α-SMA, MFN1 and MFN2 expression levels, and up-regulation of BMP2, Runx2 and Drp-1 expression levels, reduce intracellular Ca2+ content and calcium salt deposition, and effectively inhibit HG-induced VSMC calcification and mitochondrial dynamics disorders. The T4O group, Mdivi-1 group and T4O+Mdivi-1 group were able to up-regulate the expression levels of HG-induced α-SMA, MFN1 and MFN2, down-regulate the protein expression levels of BMP2, Runx2 and Drp-1, and inhibit calcium salt deposition, and there was no significant difference between the above indexes in the T4O and T4O+Mdivi-1 groups. The above findings suggest that T4O can inhibit the expression level of Drp-1, regulate the disturbance of mitochondrial dynamics, and suppress HG-induced VSMC calcification.

Study on mechanism of inhibition effect of N 6-methyladenosine methyltransferase-like 3 on vascular calcification in chronic kidney disease through Bax/Bcl-2 / 中华肾脏病杂志

Objective:To investigate the role and mechanism of N 6-methyladenosine (m 6A) methyltransferase-like 3 (METTL3) in vascular calcification (VC) of chronic kidney disease (CKD) through apoptosis-associated protein. Methods:(1) Real-time fluorescence quantitative PCR was used to test METTL3 mRNA in serum of maintenance hemodialysis (MHD) patients. (2) Western blotting was used to detect the expression of METTL3 protein in high-phosphorus stimulated vascular smooth muscle cells (VSMCs), and immunofluorescence double lable was used to observe the distribution of METTL3 and Runt-related transcription factor 2 (Runx2). The METTL3 overexpressed and knockdown plasmids were constructed and transfected into VSMCs. Alizarin red staining was used to detect calcification degree. Western blotting was used to detect the expressions of osteogenic markers [Runx2, bone morphogenetic protein-2(BMP-2), collagen Ⅰ] and apoptosis- related proteins Bax and Bcl-2. (3) SD rats were randomly divided into control group, CKD-VC group and S-adenosylhomocysteine (SAH) intervention group. The calcification of thoracic aorta was evaluated by von Kossa staining, and the protein expressions of Runx2, Bax and Bcl-2 were detected by immunohistochemistry and Western blotting.Results:(1) METTL3 mRNA expression in MHD patients with VC was significantly lower than that in non-VC patients ( P<0.05), and was negatively correlated with coronary artery calcium score ( r=-0.65, P<0.001). (2) The expression of METTL3 in VSMCs stimulated by high phosphorus was decreased and showed a time dependence. Immunofluorescence double label showed that METTL3 and Runx2 were co-expressed in the nucleus. METTL3 was overexpressed in high-phosphorus induced VSMCs, and the expressions of Runx2, collagen I and BMP-2 were significantly decreased, accompanied by the decrease of calcified nodules and Bax/Bcl-2 ratio (all P<0.05). Conversely, METTL3 knockdown aggravated VSMCs calcification by inducing apoptosis. (3) Furthermore, METTL3 inhibitor SAH was administered in vivo, and it was found that inhibition of METTL3 expression significantly increased the calcification of rat thoracic aorta, and the Bax/Bcl-2 ratio and Runx2 expression were up-regulated. Conclusions:Serum METTL3 level is reduced in MHD patients with VC. In vivo and in vitro studies demonstrate that METTL3 inhibits VC in CKD by mediating the apoptosis-related protein Bax/Bcl-2.

Role and diagnostic value of miRNA-205 on vascular calcification in patients with chronic kidney disease / 中华肾脏病杂志

Objective:To investigate the role and diagnostic value of miRNA-205 in chronic kidney disease (CKD) patients with vascular calcification.Methods:It was divided into in vitro cell experiment and retrospective cohort study. In vitro experiments were conducted by using rat thoracic aortic smooth muscle cells. Alizarin red staining and calcium content detection were used to detect the calcification of vascular smooth muscle cells (VSMCs). Alkaline phosphatase (ALP) test kit was used to measure ALP activity. Western blotting was used to detect the protein expression levels of osteogenic transcription factors runt-related transcription factor 2 (Runx2), α smooth muscle actin (α-SMA) and smooth muscle-22α (SM-22α) in VSMCs. qRT-PCR was used to detect miRNA-205 and Runx2 expression levels. The double luciferase reporter gene assay was used to verify the targeted relationship between miRNA-205 and Runx2. The non-dialysis patients with CKD 3-5 stage from June 2020 to January 2021 in the Department of Nephrology of Fourth Hospital, Hebei Medical University were selected. According to coronary artery calcium score (CACs), the patients were divided into non-calcification group (CACs=0), mild-moderate calcification group (0<CACs≤400), and severe calcification group (CACs > 400). Spearman correlation analysis was used to analyze the correlation between miRNA-205 and Runx2 and vascular calcification. Logistic regression model and receiver operating characteristic (ROC) curve analysis were used to analyze the ability of miRNA-205 to predict the vascular calcification in patients with CKD. Results:(1)Compared with the control group, calcium nodules were more, and the calcium content, ALP activity and Runx2 protein level were higher, and the expression levels of miRNA-205, α-SMA and SM-22α were significantly lower in high phosphorus group (all P<0.05). Overexpression of miRNA-205 significantly reduced the calcification of VSMCs and Runx2 protein level, and increased the protein levels of α-SMA and SM-22α (all P<0.05). miRNA-205-5p reduced the activity of luciferase in the wild-type Runx2-3'-end non-coding region plasmid. (2) Eighty CKD patients were enrolled, with age of (57.50±14.93) years old and 49 males (61.3%). The results of comparison of miRNA-205 and Runx2 expression levels in non-calcification group ( n=26), mild- moderate calcification group ( n=30) and severe calcification group ( n=24) showed that, the higher degree of calcification, the lower miRNA-205 expression level and the higher Runx2 mRNA expression level (all P<0.05). miRNA-205 was negatively correlated with CACs ( r=-0.50, P<0.01) and Runx2 was positively correlated with CACs ( r=0.55, P<0.01). Multivariate logistic regression analysis results suggested that miRNA-205 ( OR=0.451, 95% CI 0.122-0.873) was an independent influencing factor of vascular calcification in CKD patients. The area under the ROC curve of miRNA-205 and miRNA-205 combined with Runx2 for predicting vascular calcification were 0.796 (95% CI 0.697-0.859) and 0.924 (95% CI 0.866-0.982), respectively. Conclusions:miRNA-205 inhibits vascular calcification by targeting Runx2 to negatively regulate osteogenetic phenotype transformation of VSMCs and is expected to be an early diagnostic marker of vascular calcification in CKD patients.

Effect of muscle mass reduction on the progression of coronary artery calcification in maintenance hemodialysis patients / 中华肾脏病杂志

Objective:To evaluate the extent and progression of coronary artery calcification in maintenance hemodialysis (MHD) patients, and to explore the risk factors of rapid progression of coronary artery calcification in MHD patients.Methods:The patients who underwent MHD in the Huashan Hospital affiliated to Fudan University from January 1, 2013 to December 31, 2017 were enrolled. This study included cross-sectional study and prospective cohort study. Multi-slice spiral computed tomography was used to measure coronary artery calcification, and coronary artery calcium score (CACS) was calculated. In the cross-sectional study, 62 MHD patients were enrolled. According to baseline CACS, the patients were divided into low calcification group (CACS < 100) and high calcification group (CACS ≥ 100). The nutritional and bone mineral metabolism indexes were compared between the two groups. Multiple linear regression analysis was used to analyze the correlation between CACS and muscle mass and laboratory indicators. Since 6 patients were lost to follow-up, 56 MHD patients who were followed-up regularly were enrolled in the prospective cohort study. According to the progression of CACS, the patients were divided into slow progression group (ΔCACS/year < 100) and rapid progression group (ΔCACS/year ≥ 100). Logistic regression equation was used to analyze the risk factors of coronary calcification progression. Hosmer-Lemeshow goodness of fit test and receiver operating characteristic curve were used to evaluate the performance of multivariate logistic regression model.Results:In the cross-sectional study, the age of 62 patients was (62.34±10.82) years old, and the median dialysis age was 78 (39,139) months. Among the 33 male patients, compared with the low calcification group ( n=7), the high calcification group ( n=26) had older age ( t=-2.281, P=0.030) and higher blood triglyceride ( Z=-1.985, P=0.047), and there was no statistically significant difference in muscle mass between the two groups; among the 29 female patients, the muscle mass/height 2 ( t=-2.600, P=0.015) and serum calcium ( t=-2.641, P=0.014) in the high calcification group ( n=15) were both higher than those in the low calcification group ( n=14), and the hemoglobin level was lower ( t=2.531, P=0.018), and the difference in muscle mass between the two groups was not statistically significant. High sensitivity C-reactive protein ( β=0.425, P=0.022) was independently correlated with CACS in male patients, and muscle mass/extracellular water ( β=-0.580, P=0.001) was independently correlated with CACS in female patients. In the prospective cohort study, the age of 56 patients was (59.82±11.14) years old, and the median dialysis age was 82 (40, 146) months. There was no significant difference in all-cause mortality between slow progression group ( n=22) and rapid progression group ( n=34), but the proportion of cardiovascular events in rapid progression group was significantly higher than that in slow progression group ( P=0.017). Compared with the slow progression group, the rapid progression group had higher proportion of males ( χ2=4.791, P=0.029), older age ( Z=-2.131, P=0.038), lower baseline muscle mass/extracellular water ( Z=2.482, P=0.016) and high-density lipoprotein cholesterol ( t=2.133, P=0.042), and faster rate of muscle mass loss (Δmuscle mass·height -2·year -1) ( Z=-2.282, P=0.023). Multivariate logistic regression analysis results showed that muscle mass loss ( OR=0.089, 95% CI 0.010-0.792, P=0.030) and baseline CACS ( OR=1.003, 95% CI 1.000-1.005, P=0.021) were influencing factors for progression of coronary artery calcification in MHD patients. Conclusion:Increasing baseline CACS and rapid reduction in muscle mass are risk factors for the progression of coronary artery calcification in MHD patients.

Evaluation of left ventricular structural and functional abnormalities and vascular calcification in kidney transplant recipients and the effect of bone metabolism on them / 中华器官移植杂志

Objective:To evaluate left ventricular structural and functional abnormalities and vascular calcification in kidney transplant (KT) recipients, explore their influencing factors and examine the effects of mineral and bone disorders.Methods:From January 2017 to December 2019, retrospective analysis was performed for 292 KT recipients. Biochemical markers of bone metabolism, bone mineral density (BMD), left ventricular hypertrophy (LVH), left ventricular ejection fraction (LVEF), left ventricular diastolic function, coronary artery calcification (CAC) score and thoracic aortic calcification (TAC) score were assessed. Linear regression and binary Logistic regression analyses were employed for evaluating the influencing factors of cardiovascular parameters and the influence of abnormal mineral and bone metabolism.Results:Postoperative abnormalities in mineral and bone disorders were manifested mostly as hypercalcemia (8.9%, 26/292), hypophosphatemia (27.1%, 79/292), low 25-hydroxyvitamin D (25(OH)vitD) (67.0%, 196/292), hyperparathyroidismhigh parathyroid hormone (PTH) (50.6%, 148/292), elevated bone turnover markers and bone loss rate of 25%-30%. The prevalence of LVH, LVEF<50%, left ventricular diastolic dysfunction, high CAC score and high TAC score were 39.9%(116/292), 0%, 13.1%(38/292), 17.3%(50/292) and 39.9%(116/292) respectively. The results of multivariate analysis indicated that LVH was correlated positively with hypertension and serum calcium (Ca) (95% CI: 1.242-28.080, P=0.026; 95% CI: 1.714-277.584, P=0.018); LVEF was correlated positively with lumbar vertebrae BMD (95% CI: 0.000 1-0.005 5, P=0.041); Left ventricular diastolic dysfunction was correlated positively with age, diabetes and parathyroid hyperplasia/nodules (95% CI: 1.050-1.176, P<0.001; 95% CI: 2.118-43.813, P=0.003 and 95% CI: 1.419-9.103, P=0.007); High CAC score was correlated positively with recipient age and dialysis time (95% CI: 1.036-1.160, P=0.001; 95% CI: 1.009-1.041, P=0.002); High TAC score was correlated positively with age (95% CI: 1.095-1.215, P<0.001). Correlation analysis indicated that TAC was correlated positively with serum Ca ( r=0.233, P=0.003), bone-specific alkaline phosphatase (BALP)( r=0.325, P<0.001) and type Ⅰ collagen cross-linked N-terminal peptide (NTX)( r=0.204, P=0.011) and negatively with femoral neck BMD ( r=0.194, P=0.017). Conclusions:There is a high prevalence of left ventricular structural and functional abnormalities and vascular calcification. It is closely correlated with mineral and bone disorders.

Preliminary application of CT on accessing aortic arch calcification during parathyroid SPECT/CT in patients with renal secondary hyperparathyroidism / 中华核医学与分子影像杂志

Objective:To access the clinical value and related risk factors of aortic arch calcification (AoAC) in patients with renal secondary hyperparathyroidism (SHPT) on CT during parathyroid SPECT/CT imaging.Methods:From January 2014 to May 2021, 136 renal SHPT patients (70 males, 66 females, age (50.1±11.4) years) who underwent parathyroid 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT/CT in Affiliated Jiangyin Hospital of Nantong University were retrospectively enrolled. AoAC score was estimated with CT(1-5), and patients were divided into none-light AoAC group (AoAC score<3) and moderate-severe AoAC group (AoAC score≥3). Independent-sample t test or Mann-Whitney U test was used to compare differences of various indicators between two groups. Univariate binary logistic regression was used to analyze the influencing factors of AoAC. Results:Of 136 renal SHPT patients, 111(81.62%) were AoAC detected by CT. There were 84 patients in none-light AoAC group and 52 patients in moderate-severe AoAC group. The age ((46.7±9.8) vs (55.7±11.6) years; t=-4.84, P<0.001), pulse pressure (52(41, 64) vs 60(51, 70) mmHg (1 mmHg=0.133 kPa); z=-3.27, P=0.001), serum corrected calcium (2.41(2.28, 2.53) vs (2.49±0.22) mmol/L; z=-2.50, P=0.013), serum phosphorus ((1.95±0.39) vs (2.14±0.48) mmol/L; t=-2.54, P=0.012), calcium phosphorus product ((4.68±1.07) vs (5.29±1.10) mmol 2/L 2;t=-3.21, P=0.013) and parathyroid hormone (PTH) level (106.30(90.15, 127.45) vs 109.90(87.93, 157.63) pmol/L; z=-2.09, P=0.036) between non-light AoAC group and moderate-severe AoAC group were significantly different. Logistic regression analysis showed that serum phosphorus (odds ratio ( OR)=7.261, 95% CI: 2.416-21.819, P<0.001), calcium and phosphorus product ( OR=1.598, 95% CI: 1.073-2.380, P=0.021) and PTH level ( OR=1.018, 95% CI: 1.007-1.029, P=0.001) were independent risk factors of AoAC. Conclusions:Hybrid SPECT/CT can be used for an effective method of evaluating AoAC in patients with renal SHPT. High serum phosphorus, high calcium phosphorus product and high PTH level may be independent risk factors of AoAC.

Pathogenesis and Traditional Chinese Medicine Prevention and Treatment Strategy of Diabetic Vascular Calcification Based on Theory of Stasis-toxin-deficiency / 中国实验方剂学杂志

Vascular complications are the primary cause of the high disability and mortality in diabetic patients. Vascular calcification is a pathological basis of diabetic vascular complications and increases the risk of adverse cardiovascular events and the difficulty of revascularization in diabetic patients. It is of great clinical value to explore the measures for prevention and treatment of diabetic vascular calcification with integrated traditional Chinese and Western medicine. This paper explores the intrinsic association of stasis， toxin， and deficiency with diabetic vascular calcification to reveal the pathogenesis of diabetic vascular calcification. Stasis and toxin are causally affected by and combined with each other； deficiency refers to the deficiency of healthy Qi and the loss of Qi and blood. The three elements are associated with the occurrence and development of blood vessel diseases. This paper proposes the evolutional law of stasis， toxin， and deficiency in traditional Chinese medicine （TCM） for diabetic vascular calcification. Specifically， diabetic vascular calcification is rooted in the stasis of meridians and collaterals， develops due to the combination of stasis and toxin， and is aggravated by middle Qi deficiency. Furthermore， this paper proposes the TCM intervention principle of activating blood， removing toxin， tonifying deficiency， and dredging collaterals for the prevention and treatment of diabetic vascular calcification. The aim is to provide a theoretical basis for clinical and translational research on the prevention and treatment of diabetic vascular calcification with integrated Chinese and Western medicine.

Traditional Chinese Medicine Intervenes in Signaling Pathways Associated with CKD-MBD： A Review / 中国实验方剂学杂志

Traditional Chinese medicine （TCM） has certain advantages in the treatment of chronic kidney disease-mineral and bone disorder （CKD-MBD）. In recent years， there have been many studies on the treatment of CKD-MBD by Chinese medicinal compounds and monomers. As revealed by literature retrieval， the research on the mechanism of Chinese medicine in intervening in signaling pathways related to CKD-MBD was mainly based on self-made Chinese medicinal compounds， and the action pathways involved fibroblast growth factor 23/Klotho （FGF23/Klotho） signaling pathway， Wnt/β-catenin signaling pathway， receptor activator of nuclear factor-κB/receptor activator of nuclear factor-κB ligand/osteoprotegerin （RANK/RANKL/OPG） system， and other signaling pathways. TCM can improve calcium and phosphorus metabolism and bone metabolism disorder， and regulate inflammatory reaction， oxidative stress， apoptosis， and autophagy by regulating this series of signaling pathways for the treatment of CKD-MBD. This paper introduced the research results of these signaling pathways and the mechanism of TCM in the treatment of CKD-MBD in order to provide ideas and references for the related research of Chinese medicine in the treatment of CKD-MBD.

Concern about the prevention and treatment of parathyroid hyperfunction or hyperparathyroidism associated metastatic vascular calcification or calcinosis universalis / 中华内分泌外科杂志

Metastatic vascular calcification and calcinosis universalis, as severe complications of parathyroid hyperfunction and hyperparathyroidism, have attracted more attention in patients with renal secondary hyperparathyroidism and primary hyperparathyroidism. But, they are of little concern in patients with long-term negative calcium balance related parathyroid hyperfunction or hyperparathyroidism caused by calcium and/or vitamin D insufficiency (CVI). CVI is common in the population. Relatively low level of serum calcium and negative calcium balance caused by long-term CVI result in parathyroid hyperfunction or hyperparathyroidism, which may cause secretion of PTH beyond the physiological level, leading to bone absorption and release of a large amount of bone calcium into the blood. It may not only cause bone loss and osteoporosis, but also form metastatic vascular calcification or calcinosis universalis presented by cardiovascular diseases and other multi-organ lesions. Early calcium deposition can gradually fade after reasonable treatment, but middle arterial calcification is not easy to fade once it occurs. Therefore, vascular calcification and calcium deposition should be actively prevented and early screened and diagnosed. The early prevention, diagnosis and treatment of parathyroid hyperfunction or hyperparathyroidism can prevent, delay, or even reverse the occurrence and development of metastatic vascular calcification and calcinosis universalis, which is significant for disease prevention and protecting the patients' health influenced by these diseases.

A nonobstructive condition: Medial arterial calcification / 中南大学学报(医学版)

Vascular calcification, including intimal and medial calcification, is closely associated with a significant increase in cardiovascular diseases. Although increased understandings were achieved, people still know much more about intimal calcification than medial calcification because the latter doesn't obstruct the arterial lumen, commonly considered as a non-significant finding. We clarified the pathologic characteristic of medial calcification, its difference from intimal calcification, principally focused on its clinical relevance, such as diagnosis, nosogenesis, and hemodynamics. We underline the importance of identifying and distinguishing medial calcification, understanding its effect to local/systematic arterial compliance, and relationship to diabetic neuropathy. Recent studies emphasize do not ignore its predictive role in cardiovascular mortality. It is of great clinical significance to summarize the mechanisms of occurrence, lesion characteristics, diagnostic methods, pathogenic mechanisms, hemodynamic changes, and the distinction as well as association of intimal calcification with intimal calcification.

Association between monocyte lymphocyte ratio and abdominal aortic calcification in US adults: A cross-sectional study

Abstract Background This study aimed to evaluate the association between Monocyte Lymphocyte Ratio (MLR) and Abdominal Aortic Calcification (AAC) in adults over 40 years of age in the United States. Methods Data were collected from the 2013-2014 National Health and Nutrition Examination Survey (NHANES). AAC was quantified by the Kauppila score system based on dual-energy X-Ray absorptiometry. Severe AAC was defined as a total AAC score > 6. The lymphocyte count and monocyte count can be directly obtained from laboratory data files. Multivariable logistic regression models were used to determine the association between MLR and the AAC score and severe AAC. Results A total of 3,045 participants were included in the present study. After adjusting for multiple covariates, MLR was positively associated with higher AAC score (β = 0.21, 95% CI 0.07, 0.34, p = 0.0032) and the odds of severe AAC increased by 14% per 0.1 unit increase in the MLR (OR = 1.14, 95% CI 1.00, 1.31, p = 0.0541). The Odds Ratio (OR) (95% CI) of severe AAC for participants in MLR tertile 3 was 1.88 (1.02, 3.47) compared with those in tertile 1 (p for trend = 0.0341). Subgroup analyses showed that a stronger association was detected in the elderly compared with non-elderly (p for interaction = 0.0346) and diabetes compared with non-diabetes (borderline significant p for interaction = 0.0578). Conclusion In adults in the United States, MLR was associated with higher AAC scores and a higher probability of severe AAC. MLR may become a promising tool to predict the risk of AAC.