[Coronary lithotripsy in calcified lesions: fragmented calcium]. / Litotricia coronaria en lesiones calcificadas: fragmentando el calcio.

Background: Complex calcified coronary lesions are a frequent finding during percutaneous coronary intervention, representing for decades a challenge and limitation in patients with indication of revascularization, due to suboptimal angiographic results, high incidence of perioperative complications and long-term adverse events despite the multiple strategies employed, such as the use of cutting balloon, high-pressure balloons or rotational or orbital atherectomy, interventions with limitations that have hindered its routine use, recently a new plaque modification technique known as coronary intravascular lithotripsy has burst into the treatment of this complex entity, which consists in the use of a specially modified balloon for the emission of pulsatile mechanical energy (sonic pressure waves) that allows modifying the calcified plate. Clinical case: By presenting a series of clinical cases and reviewing the literature, our initial experience is presented, key elements are summarized and discussed in the understanding of this new intervention technique necessary for decision making. Conclusion: Coronary intravascular lithotripsy is projected as a promising technique for the modification and preparation of superficial and deep calcified coronary lesions, through microfractures that allow the apposition and effective expansion of the stent, strategy that according to different trials (Disrupt CAD series, SOLSTICE assay) and records presents a high efficiency and good safety profile, data consistent with our initial experience.

Introducción: las lesiones coronarias calcificadas complejas son un hallazgo frecuente durante el intervencionismo coronario percutáneo, han representado durante décadas un desafío y limitante en pacientes con indicación de revascularización, debido a resultados angiográficos subóptimos, alta incidencia de complicaciones perioperatorias y eventos adversos a largo plazo a pesar de las múltiples estrategias empleadas, como el uso de balones de corte, balones de alta presión o la aterectomía rotacional u orbital, intervenciones con limitantes que han dificultado su uso rutinario. Recientemente, una nueva técnica de modificación de placa conocida como litotricia intravascular coronaria ha irrumpido en el tratamiento de esta compleja entidad, la cual consiste en la utilización de un balón especialmente modificado para la emisión de energía mecánica pulsátil (ondas de presión sónicas) que permite modificar la placa calcificada. Caso clínico: mediante la presentación de una serie de casos clínico y revisión de literatura se presenta nuestra experiencia inicial, se resume y discuten elementos claves en el entendimiento de esta nueva técnica de intervencionismo necesarios para la toma de decisiones. Conclusión: la litotricia intravascular coronaria se proyecta como una técnica prometedora para la modificación y preparación de lesiones coronarias calcificadas superficiales y profundas, mediante microfracturas que permiten la aposición y expansión efectiva del stent; estrategia que de acuerdo con diferentes ensayos (serie Disrupt CAD, ensayo SOLSTICE) y registros presenta una eficacia alta y buen perfil de seguridad, datos concordantes con nuestra experiencia inicial.

AGEs accumulation is related to muscle degeneration and vascular calcification in peritoneal dialysis patients / O acúmulo de AGEs está relacionado à degeneração muscular e calcificação vascular em pacientes em diálise peritoneal

Abstract Background: Patients with chronic kidney disease (CKD) are affected by dynapenia, sarcopenia, and vascular calcification. Advanced glycation end products (AGEs) may accumulate in peritoneal dialysis (PD) patients and favor sarcopenia via changes in collagen cross-linking, muscle protein breakdown, and the calcification of arterial smooth muscle cells via p38-MAPK activation. The aim of this study is to explore the relationships between AGEs, muscle degeneration, and coronary artery calcification. Methods: This was a clinical observational study in patients with CKD undergoing PD, in which serum and skin AGEs (AGEs-sAF), cumulative glucose load, muscle strength and functional tests, muscle ultrasounds with elastography, coronary artery calcium (CAC) quantification, and muscle density by multislice computed tomography were measured. Results: 27 patients aged 48±16 years, dialysis vintage of 27±17 months, had AGEs-sAF levels of 3.09±0.65 AU (elevated in 13 [87%] patients), grip strength levels of 26.2±9.2 kg (11 [42%] patients with dynapenia), gait speed of 1.04±0.3 m/s (abnormal in 14 [58%] patients) and "timed-up-and-go test" (TUG) of 10.5±2.2s (abnormal in 7 [26%] patients). Correlations between AGEs-sAF levels and femoral rectus elastography (R=-0.74; p=0.02), anterior-tibialis elastography (R= -0.68; p=0.04) and CAC (R=0.64; p=0.04) were detected. Cumulative glucose load correlated with femoral rectal elastography (R=-0.6; p=0.02), and serum glycated hemoglobin concentrations correlated with psoas muscle density (R= -0.58; p=0.04) and CAC correlated with psoas muscle density (R=0.57; p=0.01) and lumbar square muscle density (R=-0.63; p=0.005). Conclusions: The study revealed associations between AGEs accumulation and lower muscle stiffness/density. Associations that linked muscle degeneration parameters with vascular calcification were observed.

Resumo Histórico: Pacientes com doença renal crônica (DRC) são afetados pela dinapenia, sarcopenia e calcificação vascular. Produtos finais da glicação avançada (AGEs) podem se acumular em pacientes em diálise peritoneal (DP) e favorecer a sarcopenia por meio de alterações em ligações cruzadas do colágeno, quebra da proteína muscular e calcificação das células do músculo liso arterial por meio da ativação da p38-MAPK. O objetivo deste estudo é explorar as relações entre AGEs, degeneração muscular e calcificação da artéria coronária. Métodos: Este foi um estudo clínico observacional em pacientes com DRC submetidos à DP, no qual foram medidos os AGEs séricos e teciduais (AGEs-sAF), a carga cumulativa de glicose, a força muscular e testes funcionais, ultrassonografias musculares com elastografia, quantificação do cálcio da artéria coronária (CAC), e a densidade muscular por tomografia computadorizada multislice. Resultados: 27 pacientes com idade entre 48±16 anos, tempo de diálise entre 27±17 meses, tinham níveis de AGEs-sAF de 3,09±0,65 UA (elevado em 13 [87%] pacientes), níveis de força de preensão de 26,2±9,2 kg (11 [42%] pacientes com dinapenia), velocidade de marcha de 1,04±0,3 m/s (anormal em 14 [58%] pacientes) e teste "timed-up-and-go" (TUG) de 10,5±2,2s (anormal em 7 [26%] pacientes). Foram detectadas correlações entre os níveis AGEs-sAF e a elastografia do reto femoral (R=-0,74; p=0,02), a elastografia tibial anterior (R= -0,68; p=0,04) e a CAC (R=0,64; p=0,04). A carga cumulativa de glicose se correlacionou com a elastografia do reto femoral (R=-0,6; p=0,02), as concentrações séricas de hemoglobina glicada se correlacionaram com a densidade muscular do psoas (R= -0,58; p=0,04) e o CAC se correlacionou com a densidade do músculo psoas (R=-0,57; p=0,01) e a densidade do músculo quadrado lombar (R=-0,63; p=0,005). Conclusões: O estudo revelou associações entre o acúmulo de AGEs e menor rigidez/densidade muscular. Foram observadas associações que ligavam parâmetros de degeneração muscular com a calcificação vascular.

AGEs accumulation is related to muscle degeneration and vascular calcification in peritoneal dialysis patients.

BACKGROUND: Patients with chronic kidney disease (CKD) are affected by dynapenia, sarcopenia, and vascular calcification. Advanced glycation end products (AGEs) may accumulate in peritoneal dialysis (PD) patients and favor sarcopenia via changes in collagen cross-linking, muscle protein breakdown, and the calcification of arterial smooth muscle cells via p38-MAPK activation. The aim of this study is to explore the relationships between AGEs, muscle degeneration, and coronary artery calcification. METHODS: This was a clinical observational study in patients with CKD undergoing PD, in which serum and skin AGEs (AGEs-sAF), cumulative glucose load, muscle strength and functional tests, muscle ultrasounds with elastography, coronary artery calcium (CAC) quantification, and muscle density by multislice computed tomography were measured. RESULTS: 27 patients aged 48±16 years, dialysis vintage of 27±17 months, had AGEs-sAF levels of 3.09±0.65 AU (elevated in 13 [87%] patients), grip strength levels of 26.2±9.2 kg (11 [42%] patients with dynapenia), gait speed of 1.04±0.3 m/s (abnormal in 14 [58%] patients) and "timed-up-and-go test" (TUG) of 10.5±2.2s (abnormal in 7 [26%] patients). Correlations between AGEs-sAF levels and femoral rectus elastography (R=-0.74; p=0.02), anterior-tibialis elastography (R= -0.68; p=0.04) and CAC (R=0.64; p=0.04) were detected. Cumulative glucose load correlated with femoral rectal elastography (R=-0.6; p=0.02), and serum glycated hemoglobin concentrations correlated with psoas muscle density (R= -0.58; p=0.04) and CAC correlated with psoas muscle density (R=0.57; p=0.01) and lumbar square muscle density (R=-0.63; p=0.005). CONCLUSIONS: The study revealed associations between AGEs accumulation and lower muscle stiffness/density. Associations that linked muscle degeneration parameters with vascular calcification were observed.

Role of Uremic Toxins in Early Vascular Ageing and Calcification.

In patients with advanced chronic kidney disease (CKD), the accumulation of uremic toxins, caused by a combination of decreased excretion secondary to reduced kidney function and increased generation secondary to aberrant expression of metabolite genes, interferes with different biological functions of cells and organs, contributing to a state of chronic inflammation and other adverse biologic effects that may cause tissue damage. Several uremic toxins have been implicated in severe vascular smooth muscle cells (VSMCs) changes and other alterations leading to vascular calcification (VC) and early vascular ageing (EVA). The above mentioned are predominant clinical features of patients with CKD, contributing to their exceptionally high cardiovascular mortality. Herein, we present an update on pathophysiological processes and mediators underlying VC and EVA induced by uremic toxins. Moreover, we discuss their clinical impact, and possible therapeutic targets aiming at preventing or ameliorating the harmful effects of uremic toxins on the vasculature.

Mineral Bone Abnormalities and Vascular Calcifications.

Vascular calcification (VC) is common in chronic kidney disease, increases in prevalence as patients progress to end-stage renal disease, and is significantly associated with mortality. VC is a complex and highly regulated process similar to bone formation whereby hydroxyapatite crystals deposit in the intimal or medial layer of arteries. Mineral bone abnormalities are common in chronic kidney disease; reduction in glomerular filtration rate and changes in vitamin D, parathyroid hormone, and fibroblast growth factor 23 result in the dysregulation of phosphorus and calcium metabolism. Cell culture studies, animal models, and observational and clinical studies all suggest this abnormal mineral metabolism plays a role in the initiation and progression of VC in kidney disease. This review will focus on these mineral bone abnormalities and how they may contribute to mechanisms that induce VC in kidney disease.

Type 1 Diabetes Accelerates Progression of Coronary Artery Calcium Over the Menopausal Transition: The CACTI Study.

OBJECTIVE: Type 1 diabetes is associated with a higher risk of cardiovascular disease (CVD) in women. Although menopause increases risk of CVD, it is uncertain how menopause affects risk of CVD in women with type 1 diabetes. We examined whether risk of CVD changes differentially in women with and those without type 1 diabetes over the transition through menopause. RESEARCH DESIGN AND METHODS: Premenopausal women with type 1 diabetes (n = 311) and premenopausal women without diabetes (n = 325) enrolled in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study and attended up to four study visits over 18 years. Coronary artery calcium (CAC) volume was measured from computed tomography scans obtained at each visit. Longitudinal repeated-measures modeling estimated the effect of diabetes on CAC volume over time and the effect of menopause on the diabetes-CAC relationship. RESULTS: CAC volume was higher at baseline and increased more over time in women with type 1 diabetes than in women without diabetes. A significant diabetes-by-menopause interaction was found (P < 0.0001): postmenopausal women with type 1 diabetes had significantly higher CAC volumes than premenopausal women (5.14 ± 0.30 vs. 2.91 ± 0.18 mm3), while there was no difference in women without diabetes (1.78 ± 0.26 vs. 1.78 ± 0.17 mm3). This interaction remained significant after adjusting for CVD risk factors. CONCLUSIONS: Type 1 diabetes was associated with higher CAC volume and accelerated progression of CAC over time. Menopause increased CAC progression more in women with diabetes than in women without diabetes independent of age and other CVD risk factors known to worsen with menopause.

Bariatric surgery and the coronary artery calcium score. / Cirurgia bariátrica e o escore de cálcio coronariano.

OBJECTIVE: to investigate the impact of bariatric surgery on the coronary artery calcium score (CACS), and to establish predictors of progression of this score in patients with obesity. METHODS: prospective study that evaluated 18 obese patients before and after bariatric surgery. All patients were submitted to computed tomography scans and blood tests (total cholesterol, LDL, HDL, triglycerides, fasting plasma glucose, A1C, insulin, serum calcium, C-peptide and C-Reactive Protein) in order to determine CACS and Framingham risk score (FRS). RESULTS: the FRS decreased 50% between the pre and postoperative evaluations. The mean CACS increased significantly at the late postoperative period, going from 8.5 to 33.1. HDL levels had also increased between the pre and postoperative periods. All of the other quantitative variables reduced significantly at the postoperative evaluation. When dividing CACS into four degrees, it was observed that 22.2% presented CACS=0 at the postoperative evaluation. The prevalence of mild CACS decreased from 77.8% to 50%, while moderate CACS remained the same (11.1%). Severe CACS increased from 11.1% to 16.7%. Older ages were linked to CACS progression, and this was the only variable that presented statistical association with progression. CONCLUSION: bariatric surgery leads to positive cardiovascular outcomes, apparently regardless of CACS.

OBJETIVO: investigar o impacto da cirurgia bariátrica no escore de cálcio coronariano (ECC) e estabelecer fatores preditivos de progressão desse escore em pacientes obesos. MÉTODOS: estudo prospectivo de 18 pacientes obesos antes e depois da cirurgia bariátrica. Todos os pacientes foram submetidos à tomografia computadorizada e a exames laboratoriais com dosagens sanguíneas de colesterol total, LDL, HDL, triglicerídeos, glicose de jejum, A1C, insulina, cálcio sérico, peptídeo C e proteína C-reativa, para determinar o ECC e o escore de risco de Framingham (ERF). RESULTADOS: o ERF reduziu 50% entre as avaliações pré e pós-operatórias. O ECC médio aumentou significativamente no período pós-operatório, aumentando de 8,5 para 33,1. Os níveis de HDL também aumentaram no pós-operatório. Todas as outras variáveis quantitativas reduziram significativamente no pós-operatório. Ao estratificar o ECC em quatro categorias, foi observado que 22,2% da amostra apresentou ECC=0 no pós-operatório. A prevalência de ECC leve reduziu de 77,8% para 50%, enquanto que ECC moderado permaneceu igual no pré e no pós-operatório (11,1%). ECC grave aumentou de 11,1% para 16,7%. Idade avançada foi associada à progressão do ECC, e essa foi a única variável que apresentou correlação estatística com a progressão do ECC. CONCLUSÃO: cirurgia bariátrica produz desfechos cardiovasculares positivos, que, aparentemente, ocorrem de forma independente do ECC.

Risk factors associated with coronary artery calcification in midlife women: a population-based study.

The aim of this study was to investigate the association between individual risk factors and coronary artery calcification (CAC), as a marker of subclinical cardiovascular disease, in a population-based nested cross-sectional study of midlife women. Anthropometric and metabolic data from 295 women from the South of Brazil were analyzed. Habitual physical activity was assessed by pedometer. CAC was assessed by a multi-detector computed tomography system. Average Agatston score was used to stratify participants as CAC > 0 and CAC = 0. Women with CAC > 0 (34.7%) were older (58.7 ± 5.4 vs. 56.3 ± 5.2 years, p < .001) and had higher prevalence of central adiposity (71 vs. 59%, p = .04) and hypertension (71 vs. 52%, p = .002) than women in the CAC = 0 group. Hormone therapy (HT) was more prevalent in the group with CAC = 0 (19.7 vs. 9.8%, p = .029). The prevalence ratios for CAC > 0 were 0.545 (95%CI:0.309-0.962, p = .036) for HT and 1.752 (95%CI:1.207-2.541, p = .003) for hypertension, after adjustment for age, educational level, smoking, alcohol intake, and physical activity. The present data in a population-based sample of midlife women indicate that hypertension and age were positively associated with higher risk for CAC > 0 and HT was related with CAC = 0.

The Effect of Long-Term Cholecalciferol Supplementation on Vascular Calcification in Chronic Kidney Disease Patients With Hypovitaminosis D.

OBJECTIVE: The role of vitamin D supplementation on vascular calcification (VC) in patients with chronic kidney disease (CKD) is controversial. The objective of this study was to evaluate the effects of long-term cholecalciferol supplementation on VC in nondialysis patients with CKD stages 3-4 with hypovitaminosis D. DESIGN AND METHODS: Eighty patients aged 18-85 years with creatinine clearance between 15 and 60 mL/min/1.73 m2 and serum 25(OH)D level < 30 ng/mL were enrolled in a 18-month prospective study. Individuals with vitamin D insufficiency (25-hydroxyvitamin D [25(OH)D] level between 16 and 29 ng/mL) were included in a randomized, double-blind, two-arm study to receive cholecalciferol or placebo. Patients with vitamin D deficiency [25(OH)D < 15 ng/mL] were included in an observational study and mandatorily received cholecalciferol. The coronary artery calcium score was obtained by multislice computed tomography at baseline and the 18th month. RESULTS: During the study, VC did not change in the treated insufficient group (418 [81-611] to 364 [232-817] AU, P = 0.25) but increased in the placebo group (118 [37-421] to 199 [49-490] AU, P = 0.01). The calcium score change was inversely correlated with 25(OH)D change (r = -0.45; P = 0.037) in the treated insufficient group but not in the placebo group. Renal function did not change in the insufficient, treated, and placebo groups. In multivariate analysis, there was no difference in VC progression between the treated and placebo insufficient groups (interaction P = 0.92). In the deficient group, VC progressed (265 [84-733] to 333 [157-745] AU; P = 0.006) and renal function declined (33 [26-43] to 23 [17-49] mL/min/1.73 m2; P = 0.04). The calcium score change was inversely correlated with cholecalciferol cumulative doses (r = -0.41; P = 0.048) and kidney function change (r = -0.43; P = 0.033) but not with 25(OH)D change (r = -0.08; P = 0.69). CONCLUSION: Vitamin D supplementation did not attenuate VC progression in CKD patients with hypovitaminosis D. CONCLUSION: Vitamin D supplementation did not attenuate VC progression in CKD patients with hypovitaminosis D.

Is arterial calcification in children and adolescents with end-stage renal disease a rare finding?

AIM: To investigate if calcification and intimal media thickness (IMT) of arteries are present in children and adolescents with end-stage renal disease and to describe the risk factors associated with these alterations. METHODS: In an observational, cross-sectional prospective study, 68 patients were evaluated at the time of renal transplantation. A fragment of the inferior epigastric artery was removed during surgery for histopathological analysis to verify the presence or not of arterial calcification. Two outcomes were considered: the presence of calcium deposition and the measurement of the IMT of the artery. The potential exposure variables were: age, chronic kidney disease aetiology, diagnosis time, systolic blood pressure (SBP), use of oral active vitamin D, homocysteine and C-reactive protein. RESULTS: No arterial calcification was observed in the studied sample. The median value of the IMT of the inferior epigastric artery was 166 µm (interquartile range = 130-208). SBP standard deviation score and age were the only factors associated with this outcome. There was no statistical interaction between SBP and age with the IMT (P = 0.280). CONCLUSION: Arterial calcification is rare in children and adolescents with end-stage renal disease. The factors associated with IMT were age and SBP.

Cirurgia bariátrica e o escore de cálcio coronariano / Bariatric surgery and the coronary artery calcium score

RESUMO Objetivo: investigar o impacto da cirurgia bariátrica no escore de cálcio coronariano (ECC) e estabelecer fatores preditivos de progressão desse escore em pacientes obesos. Métodos: estudo prospectivo de 18 pacientes obesos antes e depois da cirurgia bariátrica. Todos os pacientes foram submetidos à tomografia computadorizada e a exames laboratoriais com dosagens sanguíneas de colesterol total, LDL, HDL, triglicerídeos, glicose de jejum, A1C, insulina, cálcio sérico, peptídeo C e proteína C-reativa, para determinar o ECC e o escore de risco de Framingham (ERF). Resultados: o ERF reduziu 50% entre as avaliações pré e pós-operatórias. O ECC médio aumentou significativamente no período pós-operatório, aumentando de 8,5 para 33,1. Os níveis de HDL também aumentaram no pós-operatório. Todas as outras variáveis quantitativas reduziram significativamente no pós-operatório. Ao estratificar o ECC em quatro categorias, foi observado que 22,2% da amostra apresentou ECC=0 no pós-operatório. A prevalência de ECC leve reduziu de 77,8% para 50%, enquanto que ECC moderado permaneceu igual no pré e no pós-operatório (11,1%). ECC grave aumentou de 11,1% para 16,7%. Idade avançada foi associada à progressão do ECC, e essa foi a única variável que apresentou correlação estatística com a progressão do ECC. Conclusão: cirurgia bariátrica produz desfechos cardiovasculares positivos, que, aparentemente, ocorrem de forma independente do ECC.

ABSTRACT Objective: to investigate the impact of bariatric surgery on the coronary artery calcium score (CACS), and to establish predictors of progression of this score in patients with obesity. Methods: prospective study that evaluated 18 obese patients before and after bariatric surgery. All patients were submitted to computed tomography scans and blood tests (total cholesterol, LDL, HDL, triglycerides, fasting plasma glucose, A1C, insulin, serum calcium, C-peptide and C-Reactive Protein) in order to determine CACS and Framingham risk score (FRS). Results: the FRS decreased 50% between the pre and postoperative evaluations. The mean CACS increased significantly at the late postoperative period, going from 8.5 to 33.1. HDL levels had also increased between the pre and postoperative periods. All of the other quantitative variables reduced significantly at the postoperative evaluation. When dividing CACS into four degrees, it was observed that 22.2% presented CACS=0 at the postoperative evaluation. The prevalence of mild CACS decreased from 77.8% to 50%, while moderate CACS remained the same (11.1%). Severe CACS increased from 11.1% to 16.7%. Older ages were linked to CACS progression, and this was the only variable that presented statistical association with progression. Conclusion: bariatric surgery leads to positive cardiovascular outcomes, apparently regardless of CACS.

Cohort study of cardiovascular risk in asymptomatic young adults: subclinical atherosclerosis and coronary calcium score.

Coronary artery calcification is an early marker of subclinical atherosclerosis, but little research has been done in asymptomatic individuals under 45 years. In this cohort study with 17 years of follow-up, 155 participants were assessed in 2016 with a coronary calcium score for the association with cardiovascular risk factors. During follow-up, there was a significant increase in anthropometric measurements, cholesterol and fractions, and diastolic pressure. Participants who gained 1 cm in waist circumference had a mean reduction of 0.36 mg/dL in HDL-cholesterol and those who gained 1 kg/m2 in body mass index had a reduction of 0.72 mg/dL in HDL-cholesterol. Married participants had a 4.78 mg/dL reduction in HDL-cholesterol levels compared to singles. There was an increase of 2.09 mg/dL in HDL-cholesterol at each higher level of self-perceived health. One single case, a 32-year-old male, smoker, sedentary individual with a family history of cardiovascular disease, presented coronary calcification (0.6%). His HDL-cholesterol was reduced by 43.4%, with levels of less than 25 mg/dL at the time of coronary calcium scoring. Our findings may prompt broader studies of populations under 35 years with HDL-C levels below 25 mg/dL and family histories of cardiovascular disease, associated with obesity, sedentary lifestyle and smoking.

Personalized Management of Bone and Mineral Disorders and Precision Medicine in End-Stage Kidney Disease.

Chronic kidney disease mineral bone disorder (CKD-MBD) is common in end-stage renal disease and is associated with an increased risk of cardiovascular morbidity and mortality. Mainstays of treatment include decreasing serum phosphorus level toward the normal range with dietary interventions and phosphate binders and treating increased parathyroid hormone levels with activated vitamin D and/or calcimimetics. There is significant variation in serum levels of mineral metabolism markers, intestinal absorption of phosphorus, and therapeutic response among individual patients and subgroups of patients with end-stage renal disease. This variation may be partly explained by polymorphisms in genes associated with calcium and phosphorus homeostasis such as the calcium-sensing receptor gene, the vitamin D-binding receptor gene, and genes associated with vascular calcification. In this review, we discuss how personalized medicine may be used for the management of CKD-MBD and how it ultimately may lead to improved clinical outcomes. Although genetic variants may seem attractive targets to tailor CKD-MBD therapy, complete understanding of how these polymorphisms function and their clinical utility and applicability to personalized medicine need to be determined.

Effect of cross-linked chitosan iron (III) on vascular calcification in uremic rats.

Cross-linked chitosan iron (III) is a chitin-derived polymer with a chelating effect on phosphorus, but it is untested in vascular calcification. We evaluated this compound's ability to reduce hyperphosphatemia and its effect on vascular calcification in uremic rats using an adenine-based, phosphorus-rich diet for seven weeks. We used a control group to characterize the uremia. Uremic rats were divided according the treatment into chronic kidney disease, CKD-Ch-Fe(III)CL (CKD-Ch), CKD-calcium carbonate, or CKD-sevelamer groups. We measured creatinine, phosphorus, calcium, alkaline phosphatase, phosphorus excretion fraction, parathyroid hormone, and fibroblast growth factor 23. Vascular calcification was assessed using the aortic calcium content, and a semi-quantitative analysis was performed using Von Kossa and hematoxylin-eosin staining. At week seven, rats in the chronic kidney disease group had higher creatinine, phosphorus, phosphorus excretion fraction, calcium, alkaline phosphatase, fibroblast growth factor 23, and aortic calcium content than those in the Control group. Treatments with cross-linked chitosan iron (III) and calcium carbonate prevented phosphorus increase (20%-30% reduction). The aortic calcium content was lowered by 88% and 85% in the CKD-Ch and CKD-sevelamer groups, respectively. The prevalence of vascular changes was higher in the chronic kidney disease and CKD-calcium carbonate (62.5%) groups than in the CKD-Ch group (37.5%). In conclusion, cross-linked chitosan iron (III) had a phosphorus chelating effect similar to calcium carbonate already available for clinical use, and prevented calcium accumulation in the aorta. Impact statement Vascular calcification (VC) is a common complication due to CKD-related bone and mineral disorder (BMD) and is characterized by deposition of calcium in vessels. Effective therapies are not yet available but new phosphorus chelators can prevent complications from CV. We tested the effect of chitosan, a new phosphorus chelator, on the VC of uremic animals. It has recently been proposed that chitosan treatment may be effective in the treatment of hyperphosphataemia. However, its action on vascular calcification has not been investigated yet. In this study, we demonstrated that chitosan reduced the calcium content in the aorta, suggesting that this may be a therapeutic approach in the treatment of hyperphosphatemia by preventing CV.

Association between Dietary Intake and Coronary Artery Calcification in Non-Dialysis Chronic Kidney Disease: The PROGREDIR Study.

Coronary artery calcification (CAC) is a widespread condition in chronic kidney disease (CKD). Diet may play an important role in CAC, but this role is not clear. This study evaluated the association between macro-and micronutrient intakes and CAC in non-dialysis CKD patients. We analyzed the baseline data from 454 participants of the PROGREDIR study. Dietary intake was evaluated by a food frequency questionnaire. CAC was measured by computed tomography. After exclusion of participants with a coronary stent, 373 people remained for the analyses. The highest tertile of CAC was directly associated with the intake of phosphorus, calcium and magnesium. There was a higher intake of pantothenic acid and potassium in the second tertile. After adjustments for confounding variables, the intake of pantothenic acid, phosphorus, calcium and potassium remained associated with CAC in the generalized linear mixed models. In order to handle the collinearity between these nutrients, we used the LASSO (least absolute shrinkage and selection operator) regression to evaluate the nutrients associated with CAC variability. In this approach, the nutrients that most explained the variance of CAC were phosphorus, calcium and potassium. Prospective studies are needed to confirm these findings and assess the role of interventions regarding these micronutrients on CAC prevention and progression.

Prevalencia y extensión de la calcificación arterial coronaria en población mexicana asintomática cardiovascular: estudio Genética de la Enfermedad Aterosclerosa / Prevalence and extent of coronary artery calcification in an asymptomatic cardiovascular Mexican population: Genetics of Atherosclerotic Disease study

Resumen: Objetivo: La prevalencia de calcificación arterial coronaria (CAC), marcador específico de aterosclerosis, no es conocida en México. Nuestro objetivo fue investigar la prevalencia y extensión de CAC y su asociación con factores de riesgo cardiovascular en población mexicana. Métodos: La CAC fue medida por tomografía computarizada multidetector en individuos asintomáticos que participaron en el estudio Genética de la Enfermedad Aterosclerosa. Los factores de riesgo cardiovascular y los medicamentos fueron registrados. Resultados: La muestra incluyó 1,423 individuos (49.5% hombres), con una edad de 53.7 ± 8.4 años. Los portadores de CAC mostraron prevalencias más altas de dislipidemia, diabetes, hipertensión y otros factores de riesgo. La prevalencia de CAC > 0 unidades Agatston fue de 27%, significativamente más alta en hombres (40%) que en mujeres (13%). Los valores medios del puntaje de CAC aumentaron consistentemente con la edad y fueron más altos en hombres que en mujeres en todos los grupos etarios. La edad y el c-LDL elevado se asociaron de manera independiente con la prevalencia de CAC > 0 en hombres y mujeres, mientras que la presión arterial sistólica en las mujeres, y el incremento de la edad en ambos géneros mostró una asociación independiente con la severidad de CAC. Conclusiones: En población mexicana la prevalencia y la extensión de CAC fueron mucho más altas en hombres que en mujeres y aumentaron consistentemente con la edad. Los predictores independientes de la prevalencia de CAC fueron la edad y el c-LDL.

Abstract: Objective: The prevalence of coronary artery calcification (CAC), a specific marker of atherosclerosis, is unknown in Mexico. Our aim was to investigate the prevalence and quantity of CAC and their association with cardiovascular risk factors in a Mexican population. Methods: CAC was measured by multidetector computed tomography in asymptomatic subjects who participated in the Genetics of Atherosclerotic Disease study. Cardiovascular risk factors and medication were recorded. Results: The sample included 1,423 individuals (49.5% men), aged 53.7 ± 8.4 years. Those with CAC showed a higher prevalence of dyslipidaemia, diabetes, hypertension, and other risk factors. The prevalence of CAC > 0 Agatston units was significantly higher among men (40%) than among women (13%). Mean values of CAC score increased consistently with increasing age and were higher in men than women in each age group. Age and high low density lipoprotein cholesterol were independently associated with prevalence of CAC > 0 in men and women, while increasing systolic blood pressure in women and age in both genders showed an independent association with CAC extension. Conclusions: In the Mexican population the prevalence and extent of CAC were much higher in men than in women, and strongly increased with age. Independent predictors of CAC prevalence were age and low density lipoprotein cholesterol (LDL-C).

Osteoprotegerin Is the Strongest Predictor for Progression of Arterial Calcification in Peritoneal Dialysis Patients.

BACKGROUND: Arterial calcification (AC) is frequent in patients with end stage renal disease and is also considered a risk factor for later morbidity and mortality. However, long-term factors associated with the process are not well known. We analyzed the trends over time of biomarkers related with development and progression of AC in incident patients on peritoneal dialysis (PD). METHODS: We performed a prospective study with 186 patients on PD followed up for 1 year. We analyzed the progression of AC in the abdominal aorta and pelvic vessels by calcification score (CaSc), using16-cut computerized multidetector tomography at baseline and 1 year. Variables related with PD treatment, inflammation, and mineral metabolism were measured at baseline, 6, and 12 months of follow-up. Changes in biochemical variables were analyzed for their relationship with changes in AC. RESULTS: Over 1 year, the number of patients with AC increased from 47 to 56%, and CaSc from 355 (interquartile range [IQR] 75-792) to 529 (IQR 185-1632). A total of 43.5% of patients remained free of calcification, 11.7% had new calcifications, and 44.8% had progression of calcification. Older age, diabetes, high systolic blood pressure, body mass index, cholesterol, and osteoprotegerin (OPG), as well as lower levels of albumin, serum creatinine, and osteocalcin, were associated with development of new, and rapid progression of, calcification. In multivariate logistic analysis, OPG remained the most significant (OR 1.27, 95% CI 1.11-1.47, p < 0.001). CONCLUSION: OPG was the strongest risk factor associated with new development and rapid progression of AC in incident PD patients.

Prevalence of factors related to vascular calcifications in patients with chronic kidney disease on dialysis.

The main aim of the study was to determine the prevalence of vascular calcifications in patients with chronic kidney disease on dialysis in our population assessed by X-ray. The secondary objectives were to determine the cardiovascular risk factors associated with the presence of vascular calcifications and to evaluate the complementary use of the echocardiogram in a cross-sectional, observational, multicentric study. We included patients with chronic kidney disease on dialysis, age =18 years with at least 3 months of renal replacement therapy in 8 dialysis centres in Argentina. The degree of vascular calcification was determined using Adragao and Kauppila scores. The presence of valvular calcifications was established through a trans-thoracic doppler echocardiogram. Univariate and multivariate analysis were undertaken, considering the degree of vascular calcification as the dependent variable; 443 adult patients were evaluated at 8 centres across 5 provinces in Argentina. The prevalence of vascular calcifications by the X-rays was 63%, while 73% presented calcifications in hands and pelvis, with an Adragao score > 3, and 60% presented calcifications in the abdominal aorta with a Kauppila score > 4. The prevalence of valvular calcifications: 28%. We have shown a higher rate of vascular calcifications with the use of plain X-rays when compared to the prevalence of valvular calcifications obtained with echocardiograms. In this regard, valvular calcifications were present particularly in those patients with a severe level of radiological vascular calcification.