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OBJECTIVES: This study investigated whether kidney transplant donors experience increased arterial stiffness compared with the general population and how arterial stiffness changes over time. MATERIALS AND METHODS: Our study included 59 kidney transplant donors and 27 healthy volunteers. All subjects underwent cardio-ankle vascular index measurements. We studied fibroblast growth factor23, klotho, monocyte chemoattractant protein-1, N-terminal pro-B-type natriuretic peptide, indoxyl sulfate, and p-cresyl sulfate levels. RESULTS: Cardio-ankle vascular index level was higher in donors 6 to 11 years after donation (8.02 ± 0.24 m/s) than in donors 2 to 6 years after donation (7.02 ± 0.27 m/s) and healthy volunteers (6.65 ± 0.22 m/s). Cardioankle vascular index level was positively correlated with age (r = 0.382, P < .001) and levels of triglyceride (r = 0.213, P = .049), blood urea nitrogen (r = 0.263, P = .014), creatinine (r = 0.354, P = .001), calcium (r = 0.228, P = .035), indoxyl sulfate (r = 0.219, P = .042), p-cresyl sulfate (r = 0.676, P ≤ .001), and monocyte chemoattractant protein-1 (r = 0.451, P ≤ .001) and negatively correlated with estimated glomerular filtration rate (r = -0.383, P < .001). Multiple linear regression analysis revealed that age (P = .026, B = 0.244), mean arterial blood pressure (P < .001, B = 0.446), blood urea nitrogen (P = .006, B = 0.302), creatinine (P = .032, B = 0.236), estimated glomerular filtration rate (P = .003, B = -0.323), fibroblast growth factor-23 (P = .007, B = 0.294), N-terminal pro-B-type natriuretic peptide (P = .005, B = 0.304), and monocyte chemoattractant protein-1 (P ≤ .001, B = 0.434) independently predicted cardio-ankle vascular index levels. CONCLUSIONS: Even without additional risk factors, kidney donors should be followed closely for arterial stiffness and cardiovascular disease, especially in the long-term (>5 years) after kidney transplant.
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Biomarcadores , Índice Vascular Cardio-Tobillo , Mediadores de Inflamación , Trasplante de Riñón , Valor Predictivo de las Pruebas , Calcificación Vascular , Rigidez Vascular , Humanos , Masculino , Femenino , Biomarcadores/sangre , Persona de Mediana Edad , Trasplante de Riñón/efectos adversos , Adulto , Estudios de Casos y Controles , Calcificación Vascular/sangre , Calcificación Vascular/fisiopatología , Calcificación Vascular/etiología , Calcificación Vascular/diagnóstico , Factores de Tiempo , Mediadores de Inflamación/sangre , Factores de Riesgo , Factores de Crecimiento de Fibroblastos/sangre , Factor-23 de Crecimiento de Fibroblastos , Quimiocina CCL2/sangre , Uremia/sangre , Uremia/diagnóstico , Uremia/fisiopatología , Indicán/sangre , Resultado del Tratamiento , Donadores VivosRESUMEN
BACKGROUND: Atherogenic index of plasma (AIP) index is an important marker of insulin resistance and a significant risk factor for cardiovascular disease. Abdominal aortic calcification (AAC) is significantly associated with subclinical atherosclerotic disease. However, there are no studies that have examined the relationship between AIP index and AAC, so we investigated the potential association between them in the general population. METHODS: This was a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES, 2013-2014). The association of AIP with AAC was estimated by multivariable regression analysis. RESULTS: After adjusting for confounders, the odds of extensive AAC doubled per unit increase in the AIP index (OR = 2.00, 95% CI: 1.05, 3.83; P = 0.035). The multivariable OR and 95% CI of the highest AIP index tertile compared with the lowest tertile was significantly different. (OR = 1.73, 95% CI: 1.05, 2.83; P = 0.031). The subgroup analyses indicated that the association was consistent irrespective of age, sex, hypertension, diabetes, smoking status, eGFR and hypercholesteremia. CONCLUSIONS: The AIP index was independently associated with the presence of extensive AAC in the study population. Further studies are required to confirm this relationship.
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Aorta Abdominal , Aterosclerosis , Encuestas Nutricionales , Calcificación Vascular , Humanos , Estudios Transversales , Masculino , Femenino , Persona de Mediana Edad , Aorta Abdominal/diagnóstico por imagen , Aorta Abdominal/patología , Calcificación Vascular/epidemiología , Calcificación Vascular/sangre , Aterosclerosis/epidemiología , Aterosclerosis/sangre , Adulto , Factores de Riesgo , Biomarcadores/sangre , Enfermedades de la Aorta/epidemiología , Enfermedades de la Aorta/sangre , AncianoRESUMEN
Background: Coronary artery disease (CAD) imposes a significant global health burden, necessitating a deeper comprehension of its genetic foundations to uncover innovative therapeutic targets. Employing a comprehensive Mendelian randomization (MR) approach, we aimed to explore the genetic associations between lipid profiles, immune cell phenotypes, and CAD risk. Methods: Utilizing data from recent large-scale genome-wide association studies (GWAS), we scrutinized 179 lipid and 731 immune cell phenotypes to delineate their genetic contributions to CAD pathogenesis, including coronary artery calcification (CAC). Moreover, specific immune cell phenotypes were examined as potential mediators of the lipid-CAD/CAC causal pathway. Results: Among the 162 lipid species with qualified instrumental variables (IVs) included in the analysis, we identified 36 lipids that exhibit a genetic causal relationship with CAD, with 29 being risk factors and 7 serving as protective factors. Phosphatidylethanolamine (18:0_20:4) with 8 IVs (OR, 95% CI, P-value: 1.04, 1.02-1.06, 1.50E-04) met the Bonferroni-corrected significance threshold (0.05/162 = 3.09E-04). Notably, all 18 shared lipids were determined to be risk factors for both CAD and CAC, including 16 triacylglycerol traits (15 of which had ≥ 3 IVs), with (50:1) exhibiting the highest risk [OR (95% CI) in CAC: 1.428 (1.129-1.807); OR (95% CI) in CAD: 1.119 (1.046-1.198)], and 2 diacylglycerol traits. Furthermore, we identified HLA DR+ natural killer cells (IVs = 3) as nominally significant with lipids and as potential mediators in the causal pathway between diacylglycerol (16:1_18:1) or various triacylglycerols and CAD (mediated effect: 0.007 to 0.013). Conclusions: This study provides preliminary insights into the genetic correlations between lipid metabolism, immune cell dynamics, and CAD susceptibility, highlighting the potential involvement of natural killer cells in the lipid-CAD/CAC causal pathway and suggesting new targets for therapy. Further evidence is necessary to substantiate our findings.
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Enfermedad de la Arteria Coronaria , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Células Asesinas Naturales , Análisis de la Aleatorización Mendeliana , Humanos , Enfermedad de la Arteria Coronaria/inmunología , Enfermedad de la Arteria Coronaria/genética , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Calcificación Vascular/inmunología , Calcificación Vascular/genética , Lípidos , Metabolismo de los Lípidos/genética , Factores de Riesgo , Fenotipo , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: The aim of this study (EPIDIAB) was to assess the relationship between epicardial adipose tissue (EAT) and the micro and macrovascular complications (MVC) of type 2 diabetes (T2D). METHODS: EPIDIAB is a post hoc analysis from the AngioSafe T2D study, which is a multicentric study aimed at determining the safety of antihyperglycemic drugs on retina and including patients with T2D screened for diabetic retinopathy (DR) (n = 7200) and deeply phenotyped for MVC. Patients included who had undergone cardiac CT for CAC (Coronary Artery Calcium) scoring after inclusion (n = 1253) were tested with a validated deep learning segmentation pipeline for EAT volume quantification. RESULTS: Median age of the study population was 61 [54;67], with a majority of men (57%) a median duration of the disease 11 years [5;18] and a mean HbA1c of7.8 ± 1.4%. EAT was significantly associated with all traditional CV risk factors. EAT volume significantly increased with chronic kidney disease (CKD vs no CKD: 87.8 [63.5;118.6] vs 82.7 mL [58.8;110.8], p = 0.008), coronary artery disease (CAD vs no CAD: 112.2 [82.7;133.3] vs 83.8 mL [59.4;112.1], p = 0.0004, peripheral arterial disease (PAD vs no PAD: 107 [76.2;141] vs 84.6 mL[59.2; 114], p = 0.0005 and elevated CAC score (> 100 vs < 100 AU: 96.8 mL [69.1;130] vs 77.9 mL [53.8;107.7], p < 0.0001). By contrast, EAT volume was neither associated with DR, nor with peripheral neuropathy. We further evidenced a subgroup of patients with high EAT volume and a null CAC score. Interestingly, this group were more likely to be composed of young women with a high BMI, a lower duration of T2D, a lower prevalence of microvascular complications, and a higher inflammatory profile. CONCLUSIONS: Fully-automated EAT volume quantification could provide useful information about the risk of both renal and macrovascular complications in T2D patients.
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Tejido Adiposo , Automatización , Enfermedad de la Arteria Coronaria , Aprendizaje Profundo , Diabetes Mellitus Tipo 2 , Pericardio , Valor Predictivo de las Pruebas , Calcificación Vascular , Humanos , Masculino , Femenino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Pericardio/diagnóstico por imagen , Persona de Mediana Edad , Tejido Adiposo/diagnóstico por imagen , Anciano , Calcificación Vascular/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Angiopatías Diabéticas/diagnóstico por imagen , Angiopatías Diabéticas/etiología , Angiopatías Diabéticas/diagnóstico , Medición de Riesgo , Interpretación de Imagen Radiográfica Asistida por Computador , Angiografía por Tomografía Computarizada , Adiposidad , Angiografía Coronaria , Factores de Riesgo , Reproducibilidad de los Resultados , Pronóstico , Tejido Adiposo EpicárdicoRESUMEN
BACKGROUND: The prevalence of vascular calcification (VC) in chronic kidney disease (CKD) patients remains substantial, but currently, there are no effective pharmaceutical therapies available. BRCA1/BRCA2-containing complex subunit 36 (BRCC36) has been implicated in osteoblast osteogenic conversion; however, its specific role in VC remains to be fully elucidated. The aim of this study was to investigate the role and underlying mechanisms of BRCC36 in VC. METHODS: The association between BRCC36 expression and VC was examined in radial arteries from patients with CKD, high-adenine-induced CKD mice, and vascular smooth muscle cells (VSMCs). Western blotting, real-time polymerase chain reaction, immunofluorescence, and immunohistochemistry were used to analyse gene expression. Gain- and loss-of-function experiments were performed to comprehensively investigate the effects of BRCC36 on VC. Coimmunoprecipitation and TOPFlash luciferase assays were utilized to further investigate the regulatory effects of BRCC36 on the Wnt/ß-catenin pathway. RESULTS: BRCC36 expression was downregulated in human calcified radial arteries, calcified aortas from CKD mice, and calcified VSMCs. VSMC-specific BRCC36 overexpression alleviated calcium deposition in the vasculature, whereas BRCC36 depletion aggravated VC progression. Furthermore, BRCC36 inhibited the osteogenic differentiation of VSMCs in vitro. Rescue experiments revealed that BRCC36 exerts the protective effects on VC partly by regulating the Wnt/ß-catenin signalling pathway. Mechanistically, BRCC36 inhibited the Wnt/ß-catenin pathway by decreasing the K63-linked ubiquitination of ß-catenin. Additionally, pioglitazone attenuated VC partly through upregulating BRCC36 expression. CONCLUSIONS: Our research results emphasize the critical role of the BRCC36-ß-catenin axis in VC, suggesting that BRCC36 or ß-catenin may be promising therapeutic targets to prevent the progression of VC in CKD patients.
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Ratones Endogámicos C57BL , Insuficiencia Renal Crónica , Ubiquitinación , Calcificación Vascular , Vía de Señalización Wnt , beta Catenina , Calcificación Vascular/metabolismo , Calcificación Vascular/patología , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/complicaciones , Animales , beta Catenina/metabolismo , Humanos , Masculino , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Ratones , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Osteogénesis , Persona de Mediana Edad , Diferenciación CelularRESUMEN
BACKGROUND: Patients with osteoporosis demonstrate increased vascular calcification but the effect of osteoporosis treatments on vascular calcification remains unclear. The present study aimed to examine whether coronary or aortic calcification are influenced by denosumab and alendronic acid treatment. METHODS AND RESULTS: In a double-blind randomized controlled SALTIRE2 (Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis) trial, patients with aortic stenosis were randomized 2:1:2:1 to denosumab, placebo injection, alendronic acid, or placebo capsule. Participants underwent serial imaging with computed tomography and 18F-sodium fluoride positron emission tomography for the assessment of vascular calcium burden and calcification activity, respectively. We report the prespecified secondary analyses of 24-month change in coronary calcium score, and 12-month changes in thoracic aorta calcium score, coronary and aortic 18F-sodium fluoride activity. One hundred fifty patients with aortic stenosis (72±8 years; 21% female) were randomized to denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25). There were no differences in change in coronary calcium scores between placebo (16 [-64 to 148] Agatston units) and either denosumab (94 [0-212] Agatston units, P=0.24) or alendronic acid (34 [-62 to 134], P=0.99). There were no differences in change in thoracic aorta calcium scores between placebo (132 [22-512] Agatston units) and either denosumab (118 [11-340], P=0.75) or alendronic acid (116 [26-498] Agatston units, P=0.62). There were no differences in changes in coronary or aortic 18F-sodium fluoride activity between treatment groups. CONCLUSIONS: Neither alendronic acid nor denosumab are associated with changes in the activity or progression of coronary or aortic calcification. Osteoporosis treatments do not appear to have major impact on vascular calcification of atherosclerosis. REGISTRATION: https://www.clinicaltrials.gov; Unique identifier: NCT02132026.
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Alendronato , Conservadores de la Densidad Ósea , Denosumab , Calcificación Vascular , Humanos , Femenino , Masculino , Denosumab/uso terapéutico , Anciano , Método Doble Ciego , Calcificación Vascular/diagnóstico por imagen , Alendronato/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Resultado del Tratamiento , Estenosis de la Válvula Aórtica/tratamiento farmacológico , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Osteoporosis/tratamiento farmacológico , Osteoporosis/diagnóstico por imagen , Persona de Mediana Edad , Anciano de 80 o más Años , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnóstico , Tomografía de Emisión de Positrones , Factores de TiempoRESUMEN
OBJECTIVES: This study attempts to compare the predictive effects of several prediction models on obstructive coronary artery disease (OCAD) in young patients (30-50 years old), with a view to providing a new evaluation tool for the prediction of premature coronary artery disease (PCAD). METHODS: A total of 532 hospitalized patients aged 30-50 were included in the study.All of them underwent coronary computed tomography angiography (CCTA) for suspected symptoms of coronary heart disease.Coronary artery calcium score (CACS) combined with traditional risk factors and pre-test probability models are the prediction models to be compared in this study.The PTP model was selected from the upgraded Diamond-Forrester model (UDFM) and the Duke clinical score (DCS). RESULTS: All patients included in the study were aged 30-50 years. Among them, women accounted for 24.4%, and 355 patients (66.7%) had a CACS of 0. OCAD was diagnosed in 43 patients (8.1%). The CACS combined with traditional risk factors to predict the OCAD area under the curve of receiver operating characteristic (ROC) (AUC = 0.794,p < 0.001) was greater than the PTP models (AUCUDFM=0.6977,p < 0.001;AUCDCS=0.6214,p < 0.001). By calculating the net reclassification index (NRI) and the integrated discrimination index (IDI), the ability to predict the risk of OCAD using the CACS combined with traditional risk factors was improved compared with the PTP models (NRI&IDI > 0,p < 0.05). CONCLUSION: The predictive value of CACS combined with traditional risk factors for OCAD in young patients is better than the PTP models.
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Angiografía por Tomografía Computarizada , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Factores de Riesgo de Enfermedad Cardiaca , Valor Predictivo de las Pruebas , Calcificación Vascular , Humanos , Femenino , Masculino , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/epidemiología , Persona de Mediana Edad , Medición de Riesgo , Adulto , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/diagnóstico , Factores de Edad , Pronóstico , Técnicas de Apoyo para la Decisión , Factores de RiesgoRESUMEN
OBJECTIVE: This study aimed to investigate the effect of the soluble Klotho (sKlotho)/Wnt/ß-catenin signaling pathway on vascular calcification in rat models of chronic kidney disease (CKD) and the intervention effect of Shenyuan granules. METHODS: Rats with 5/6 nephrectomy and high phosphorus feeding were used to establish the vascular calcification model. The rats were given gradient doses of Shenyuan granules aqueous solution and calcitriol solution by gavage for 8 weeks, which were divided into experimental group and positive control group. RESULTS: The 5/6 nephrectomy combined with high phosphorus feeding induced thoracic aortic calcification in rats. Shenyuan granules intervention increased the serum sKlotho level, inhibited the mRNA and protein expression of Wnt1, ß-catenin, and Runx2 in the thoracic aorta, and alleviated thoracic aortic media calcification in rats. CONCLUSION: Shenyuan granules may partially regulate the Wnt/ß-catenin signaling pathway via serum sKl to interfere with the expression of Runx2, thereby improving vascular calcification in CKD.
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Medicamentos Herbarios Chinos , Glucuronidasa , Proteínas Klotho , Insuficiencia Renal Crónica , Calcificación Vascular , Vía de Señalización Wnt , beta Catenina , Animales , Masculino , Ratas , Aorta Torácica/metabolismo , Aorta Torácica/patología , beta Catenina/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Glucuronidasa/metabolismo , Glucuronidasa/genética , Proteínas Klotho/metabolismo , Nefrectomía , Ratas Sprague-Dawley , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/complicaciones , Calcificación Vascular/metabolismo , Calcificación Vascular/etiología , Calcificación Vascular/patología , Vía de Señalización Wnt/efectos de los fármacos , Proteína Wnt1/metabolismo , Proteína Wnt1/genéticaRESUMEN
Previous studies have reported correlations between metabolic factors and abdominal aortic calcification (AAC). However, the causal relationship between blood metabolites and AAC remains to be fully explored. We employed bidirectional two-sample Mendelian randomization (MR) to investigate the potential causal relationships between 486 blood metabolites and AAC. The inverse variance weighted method was primarily utilized for MR analysis, and the MR-Egger, weighted median, and Robust Adjusted Profile Score methods were used for supplementary analysis. Sensitivity analyses were conducted using Radial MR, MR-PRESSO, Cochran Q test, MR-Egger intercept, and leave-one-out analysis to evaluate the heterogeneity and pleiotropy. Furthermore, the Steiger test and linkage disequilibrium score regression were used to assess genetic correlation and directionality. Multivariable MR analysis was performed to evaluate the direct effect of metabolites on AAC. Through rigorous screening, we identified 6 metabolites with presumed causal effects on AAC: 4-methyl-2-oxopentanoate (effect size [ES] 0.46, 95% confidence interval [CI]: 0.10-0.82), erythrose (ES -0.35, 95% CI: -0.59 to -0.11), 10-undecenoate (11:1n1) (ES 0.14, 95% CI: 0.03-0.25), 1-myristoylglycerophosphocholine (ES 0.31, 95% CI: 0.11-0.50), glycerol 2-phosphate (ES 0.20, 95% CI: 0.04-0.37), and the unidentified metabolite X-11469 (ES 0.19, 95% CI: 0.08-0.30). Multivariable MR analysis revealed that genetically predicted erythrose, 10-undecenoate, 1-myristoylglycerophosphocholine, and X-11469 could directly affect AAC independent of other metabolites. Reverse MR analysis revealed an alteration in 12 blood metabolites due to AAC, including caffeine, 1,7-dimethylurate, arachidonic acid, and 1-arachidonoylglycerophosphocholine. This study provides evidence supporting a causal relationship between metabolites and AAC. These findings help elucidate the underlying biological mechanisms of AAC and may offer insights into screening, prevention, and treatment approaches.
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Aorta Abdominal , Análisis de la Aleatorización Mendeliana , Calcificación Vascular , Humanos , Aorta Abdominal/metabolismo , Aorta Abdominal/patología , Calcificación Vascular/sangre , Calcificación Vascular/genética , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/sangreRESUMEN
The present study aimed to explore the effect of swimming exercise on vascular calcification in type 2 diabetic rats and its related molecular mechanism. Male Sprague Dawley (SD) rats were randomly divided into normal control (NC), diabetes control (DC) and diabetes+exercise (DE) groups. The DC and DE groups were intraperitoneally injected with streptozotocin (STZ) and fed with high-fat diet to establish type 2 diabetes mellitus model. The NC and DC groups did not exercise, and the DE group performed swimming exercise for 8 weeks. ELISA was used to detect the serum glycated hemoglobin A1c (HbA1c) level. The aortas of rats were taken as sample. Assay kits were used to detect vascular calcium content and alkaline phosphatase (ALP) activity. Von Kossa staining was used to detect calcium deposition. qRT-PCR was used detect the expression of microRNA-145 (miR-145). Western blot was used to detect the protein expression levels of smooth muscle contraction markers, calcification marker and related proteins. The results showed that, compared with the NC group, the blood glucose, serum HbA1c level, vascular calcium content and ALP activity in the DC group were significantly increased, the protein expression levels of smooth muscle contraction markers smooth muscle protein 22α (SM22α) and α-smooth muscle actin (α-SMA) were significantly down-regulated, and the protein expression level of calcification marker osteopontin (OPN) was significantly up-regulated; Compared with the DC group, the serum HbA1c level, vascular calcium content and ALP activity in the DE group were significantly decreased, the protein expression levels of SM22α and α-SMA were significantly up-regulated, and the protein expression level of OPN was significantly down-regulated; Compared with the NC group, the expression of miR-145-5p in the DC group was significantly down-regulated, and the protein expression levels of transforming growth factor-ß (TGF-ß), SMAD2, ERK1/2 and p-ERK1/2 were significantly up-regulated; Compared with the DC group, the expression of miR-145-5p was significantly up-regulated in the DE group, while the expressions of TGF-ß, ERK1/2 and p-ERK1/2 were significantly down-regulated. These results suggest that miR-145/TGF-ß signaling is involved in the improving effects of 8-week swimming exercise on glucose metabolism disorder, vascular smooth muscle cell phenotype switching and vascular calcification in type 2 diabetes mellitus.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , MicroARNs , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Natación , Calcificación Vascular , Animales , Masculino , Ratas , MicroARNs/metabolismo , MicroARNs/genética , Calcificación Vascular/metabolismo , Calcificación Vascular/etiología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Experimental/metabolismo , Natación/fisiología , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
BACKGROUND: Menopausal vasomotor symptoms (VMS) are increasingly emphasized as a potentially important cardiovascular risk factor, but their role is still unclear. We assessed the association between VMS and subclinical atherosclerotic cardiovascular disease in peri- and postmenopausal women. METHODS AND RESULTS: Using a cross-sectional study design, questionnaire data were collected from a population-based sample of women aged 50 to 64. The questionnaire asked whether menopause was/is associated with bothersome VMS. A 4-point severity scale was used: (1) never, (2) mild, (3) moderate, and (4) severe. The VMS duration and time of onset were also assessed. Associations with subclinical atherosclerotic cardiovascular disease, detected via coronary computed tomography angiography, coronary artery calcium score, and carotid ultrasound were assessed using the outcome variables "any coronary atherosclerosis," "segmental involvement score >3," "coronary artery calcium score >100," and "any carotid plaque," using logistic regression. Covariate adjustments included socioeconomic, lifestyle, and clinical factors. Of 2995 women, 14.2% reported ever severe, 18.1% ever moderate, and 67.7% ever mild/never VMS. Using the latter as reference, ever severe VMS were significantly associated with coronary computed tomography angiography-detected coronary atherosclerosis (multivariable adjusted odds ratio, 1.33 [95% CI, 1.02-1.72]). Corresponding results for ever severe VMS persisting >5 years or beginning before the final menstrual period were 1.50 (95% CI, 1.07-2.11) and 1.66 (95% CI, 1.10-2.50), respectively. No significant association was observed with segmental involvement score >3, coronary artery calcium score >100, or with any carotid plaque. CONCLUSIONS: Ever occurring severe, but not moderate, VMS were significantly associated with subclinical coronary computed tomography angiography-detected atherosclerosis, independent of a broad range of cardiovascular risk factors and especially in case of long durations or early onset.
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Enfermedades de las Arterias Carótidas , Angiografía por Tomografía Computarizada , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Sofocos , Humanos , Femenino , Persona de Mediana Edad , Estudios Transversales , Sofocos/epidemiología , Sofocos/fisiopatología , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedades de las Arterias Carótidas/epidemiología , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/fisiopatología , Menopausia , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Factores de Riesgo , Enfermedades Asintomáticas , Sistema Vasomotor/fisiopatología , Placa Aterosclerótica/epidemiología , Calcificación Vascular/epidemiología , Calcificación Vascular/diagnóstico por imagen , Modelos LogísticosRESUMEN
OBJECTIVE: To address the relationship between tissue accumulation of advanced glycation end-products, assessed by skin autofluorescence (SAF), and subclinical atherosclerosis quantified with coronary artery calcium score (CACS) in the general Dutch population. METHODS: A total of 3,839 participants of the LifeLines Cohort Study without diabetes or cardiovascular disease were included in this cross-sectional evaluation. They underwent SAF measurement and cardiac computed tomography to measure CACS. Associations between SAF and CACS was assessed using regression models. Participants at elevated risk for cardiovascular disease were selected by either CACS≥100, or SAF value in the top 15%; overlap and cardiovascular risk profile of these participants were compared. RESULTS: In univariate analysis, every 1 arbitrary unit (AU) increase in SAF resulted in an odds ratio of 2.91 (95% confidence interval 2.44-3.48, p<0.001) for coronary calcification. After adjustment for cardiovascular risk factors, there was still 20% higher odds of coronary calcification with 1 AU increase in SAF, but significance was lost. In total, 1025 (27%) participants either had high SAF and/or high CACS, of these 441 (12%) had only high SAF, 450 (12%) had only high CACS and 134 (3%) participants had high SAF and high CACS. CONCLUSION: In a population-based Dutch cohort, SAF was associated with the degree of coronary calcification. This association was largely explained by classical cardiovascular risk factors. Limited overlap was found in subgroups with high SAF or high CACS, indicating that SAF and CACS may have complementary role in identifying individuals at elevated cardiovascular risk.
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Enfermedad de la Arteria Coronaria , Piel , Calcificación Vascular , Humanos , Masculino , Femenino , Persona de Mediana Edad , Piel/metabolismo , Piel/diagnóstico por imagen , Piel/patología , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estudios Transversales , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/epidemiología , Anciano , Adulto , Países Bajos/epidemiología , Productos Finales de Glicación Avanzada/metabolismo , Productos Finales de Glicación Avanzada/análisis , Imagen Óptica , Factores de Riesgo , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/metabolismo , Vasos Coronarios/patologíaRESUMEN
BACKGROUND: Vascular calcification is a common vascular lesion associated with high morbidity and mortality from cardiovascular events. Antibiotics can disrupt the gut microbiota (GM) and have been shown to exacerbate or attenuate several human diseases. However, whether antibiotic-induced GM disruption affects vascular calcification remains unclear. METHODS: Antibiotic cocktail (ABX) treatment was utilized to test the potential effects of antibiotics on vascular calcification. The effects of antibiotics on GM and serum short-chain fatty acids (SCFAs) in vascular calcification mice were analyzed using 16 S rRNA gene sequencing and targeted metabolomics, respectively. Further, the effects of acetate, propionate and butyrate on vascular calcification were evaluated. Finally, the potential mechanism by which acetate inhibits osteogenic transformation of VSMCs was explored by proteomics. RESULTS: ABX and vancomycin exacerbated vascular calcification. 16 S rRNA gene sequencing and targeted metabolomics analyses showed that ABX and vancomycin treatments resulted in decreased abundance of Bacteroidetes in the fecal microbiota of the mice and decreased serum levels of SCFAs. In addition, supplementation with acetate was found to reduce calcium salt deposition in the aorta of mice and inhibit osteogenic transformation in VSMCs. Finally, using proteomics, we found that the inhibition of osteogenic transformation of VSMCs by acetate may be related to glutathione metabolism and ubiquitin-mediated proteolysis. After adding the glutathione inhibitor Buthionine sulfoximine (BSO) and the ubiquitination inhibitor MG132, we found that the inhibitory effect of acetate on VSMC osteogenic differentiation was weakened by the intervention of BSO, but MG132 had no effect. CONCLUSION: ABX exacerbates vascular calcification, possibly by depleting the abundance of Bacteroidetes and SCFAs in the intestine. Supplementation with acetate has the potential to alleviate vascular calcification, which may be an important target for future treatment of vascular calcification.
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Acetatos , Antibacterianos , Ácidos Grasos Volátiles , Microbioma Gastrointestinal , Calcificación Vascular , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Calcificación Vascular/metabolismo , Calcificación Vascular/etiología , Calcificación Vascular/tratamiento farmacológico , Ratones , Ácidos Grasos Volátiles/metabolismo , Acetatos/farmacología , Antibacterianos/efectos adversos , Antibacterianos/farmacología , Masculino , Osteogénesis/efectos de los fármacos , ARN Ribosómico 16S/genética , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Vancomicina/efectos adversos , Vancomicina/farmacología , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efectos de los fármacosRESUMEN
BACKGROUND: As the burden and distribution of calcification within chronic total occlusion (CTO) lesions can be diverse, its effect on CTO recanalization using multiple devices and techniques is debatable. This study investigated the role of calcification in wiring-based intraplaque tracking techniques for CTO recanalization. METHODS: A modified J-CTO score without counting calcification was used to analyze the procedures of 458 consecutive patients who underwent CTO interventions. Failed guidewire crossing and intraplaque tracking were considered procedural failures. Recanalization time details were analyzed for successful procedures. RESULTS: In patients with calcified CTO, the rate of procedural success only significantly declined to be lower than that of noncalcified CTO when the modified J-CTO score was ≥3 (77% vs. 94%, p = 0.008). In 422 patients with successful procedures, the presence of calcification was irrelevant to guidewire crossing time, but was accompanied with longer time from guidewire cross to final angiogram when the modified J-CTO score was 1-2 (53 ± 35 vs. 35 ± 17 [noncalcified] min, p < 0.001). Multivariate analyses showed that calcification was independently associated with procedural failure (odds ratio [OR] = 5.1, 95% confidence interval [CI] = 1.4-18.3) in lesions with modified J-CTO ≥3, and prolonged angioplasty/stenting procedures >60 min (OR = 4.8, 95% CI = 2.2-10.2) in successfully recanalized lesions with modified J-CTO score 1-2. CONCLUSIONS: Using intraplaque guidewire tracking, calcification was unfavorable for very difficult CTO lesions, and caused prolongation of angioplasty time for lesions with moderate complexity. This suggested that the role of calcification in the J-CTO score could be altered when different recanalization techniques were applied for CTO interventions.
Since several commonly used scoring systems for grading the difficulty of CTO-PCI are derived from multiple recanalization techniques and devices, their application should be fundamental. However, most CTO interventionists usually have their own favored recanalization techniques in the real-world. As one of the parameters of J-CTO score, the findings of the study suggest that the interpretation of calcification during CTO-PCI could be altered and should be cautious if different recanalization technique was used.
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Oclusión Coronaria , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Oclusión Coronaria/diagnóstico por imagen , Oclusión Coronaria/cirugía , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Intervención Coronaria Percutánea/instrumentación , Calcificación Vascular/diagnóstico por imagen , Angiografía Coronaria/métodos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Calcinosis/diagnóstico por imagen , Enfermedad Crónica , Resultado del TratamientoRESUMEN
OBJECTIVE: To assess the role of the systolic blood pressure polygenic risk score (SBP-PRS) in antihypertensive treatment initiation and its comparative efficacy with coronary artery calcium (CAC) scores. PATIENTS AND METHODS: This retrospective cohort study included participants with whole genome sequencing data who underwent CAC scanning between 1971 and 2008, were free of prevalent cardiovascular disease (CVD), and were not taking antihypertensive medications. The cohort was stratified by blood pressure (BP) treatment group and SBP-PRS (low/intermediate, first and second tertiles; high, third tertile) and CAC score (0 vs >0) subgroups. The primary outcome was the first occurence of adjudicated coronary heart disease, heart failure, or stroke during 10-year follow-up. The 10-year number needed to treat (NNT) to prevent 1 event of the primary outcome was estimated. A relative risk reduction of 25% for the primary outcome based on the treatment effect of intensive control (SBP <120 mm Hg) of hypertension in SPRINT (Systolic Blood Pressure Intervention Trial) was used for estimating the NNT. RESULTS: Among the 5267 study participants, the median age was 59 years (interquartile range, 51-68 years); 2817 (53.5%) were women and 2880 (54.7%) were non-White individuals. Among 1317 individuals with elevated BP/low-risk stage 1 hypertension not recommended treatment, the 10-year incidence rate of the primary outcome was 5.6% for low/intermediate SBP-PRS and 6.3% for high SBP-PRS with NNTs of 63 and 59, respectively. Similarly, the 10-year incidence rate of the primary outcome was 2.9% for CAC score 0 and 9.7% for CAC score greater than 0, with NNTs of 117 and 37, respectively. CONCLUSION: Including genetic information in risk estimation of individuals with elevated BP/low-risk stage 1 hypertension has modest value in the initiation of antihypertensive therapy. Genetic risk and CAC both have efficacy in personalizing antihypertensive therapy.
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Antihipertensivos , Enfermedad de la Arteria Coronaria , Hipertensión , Humanos , Femenino , Persona de Mediana Edad , Masculino , Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipertensión/genética , Hipertensión/epidemiología , Estudios Retrospectivos , Anciano , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Medicina de Precisión/métodos , Calcificación Vascular/genética , Calcificación Vascular/epidemiología , Medición de Riesgo , Presión Sanguínea/efectos de los fármacos , Factores de Riesgo , Predisposición Genética a la Enfermedad , Vasos Coronarios/diagnóstico por imagen , Estudios de CohortesAsunto(s)
Aterosclerosis , Mamografía , Humanos , Mamografía/métodos , Femenino , Aterosclerosis/diagnóstico por imagen , Calcificación Vascular/diagnóstico por imagen , Mama/diagnóstico por imagen , Mama/irrigación sanguínea , Medición de Riesgo , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y Especificidad , Enfermedades de la Mama/diagnóstico por imagen , Persona de Mediana EdadRESUMEN
BACKGROUND: Carotid siphon calcification (CSC) serves as a marker of atherosclerosis and therefore may influence the outcome after subarachnoid hemorrhage (aSAH). We aimed to analyze the impact of CSC on neurological outcomes, ischemia, and vasospasm. METHODS: A total of 716 patients with aSAH were treated between December 2004 and June 2016 in our central European tertiary neurovascular care center in Essen, Germany. CSC was recorded using the Woodcock scale (grades 0-3) on a computed tomography scan. Study end points included an unfavorable outcome at 6 months post-aSAH (modified Rankin Scale score ≥4), vasospasm, and early cerebral ischemia (72 hours) and delayed cerebral ischemia (delayed cerebral ischemia; >72 hours) in the follow-up computed tomography scans. The associations were adjusted for patients' baseline characteristics and secondary complications. Finally, within a subgroup analysis, patients with and without daily aspirin intake after endovascular aneurysm occlusion were compared. RESULTS: Increasing grades of CSC were associated with lower rates of vasospasm in the anterior circulation. Severe CSC (grade 3) was independently related to the risk of an unfavorable outcome (adjusted odds ratio [aOR], 4.06 [95% CI, 1.98-8.33]; P<0.001) and early cerebral ischemia (aOR, 1.58 [95% CI, 1.03-2.43]; P=0.035) but not delayed cerebral ischemia (aOR, 1.08 [95% CI, 0.67-1.73]; P=0.763). In the aspirin subgroup analysis, the negative effect of severe CSC on functional outcome remained significant only in aSAH cases without aspirin (aOR, 5.47 [95% CI, 2.38-12.54]; P<0.001). In contrast, there was no association between severe CSC and unfavorable outcomes among individuals with daily aspirin intake (aOR, 0.84 [95% CI, 0.59-4.21]; P=0.603). CONCLUSIONS: Our data suggest CSC as a cerebrovascular risk factor resulting in higher rates of early cerebral ischemia and unfavorable outcomes after aSAH. However, by increasing arterial stiffness, CSC might lower the probability of vasospasm, which could explain the missing link between CSC and delayed cerebral ischemia. Additionally, aspirin intake seems to potentially mitigate the negative impact of CSC on aSAH outcome. Further investigations are needed to confirm the observations from the present study.
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Hemorragia Subaracnoidea , Vasoespasmo Intracraneal , Humanos , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Anciano , Vasoespasmo Intracraneal/diagnóstico por imagen , Vasoespasmo Intracraneal/etiología , Isquemia Encefálica/diagnóstico por imagen , Adulto , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/complicaciones , Resultado del Tratamiento , Arteria Carótida Interna/diagnóstico por imagen , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/complicaciones , Procedimientos Endovasculares/métodos , Aspirina/uso terapéutico , Calcinosis/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
OBJECTIVE: This study was to investigate the role of serum Klotho, fetuin-A, and Matrix Gla Protein (MGP) in Coronary Artery Calcification (CAC) in patients with Maintenance Hemodialysis (MHD) and their predictive value for CAC. METHODS: 100 patients receiving MHD were selected. Serum Klotho, fetuin-A, and MGP levels were detected by ELISA. CAC scores were assessed by coronary CT scan. Multifactor analysis was used to evaluate the risk factors affecting CAC. The ability of serum Klotho, fetuin-A, and MGP levels to diagnose CAC was evaluated by receiver operating characteristic curves. RESULTS: Serum Klotho, fetuin-A, and MGP were independent risk factors for CAC. Serum Klotho, fetuin-A, and MGP were valuable in the diagnosis of CAC in MHD patients. CONCLUSION: There is a close relationship between Klotho, fetuin-A, and MGP levels in MHD patients and CAC.
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Biomarcadores , Proteínas de Unión al Calcio , Enfermedad de la Arteria Coronaria , Proteínas de la Matriz Extracelular , Glucuronidasa , Proteínas Klotho , Proteína Gla de la Matriz , Diálisis Renal , Calcificación Vascular , alfa-2-Glicoproteína-HS , Humanos , Diálisis Renal/efectos adversos , Masculino , Femenino , Proteínas de Unión al Calcio/sangre , Persona de Mediana Edad , alfa-2-Glicoproteína-HS/análisis , alfa-2-Glicoproteína-HS/metabolismo , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Glucuronidasa/sangre , Proteínas de la Matriz Extracelular/sangre , Biomarcadores/sangre , Calcificación Vascular/sangre , Calcificación Vascular/diagnóstico por imagen , Anciano , Factores de Riesgo , Ensayo de Inmunoadsorción Enzimática , Adulto , Curva ROC , Calcinosis/sangre , Calcinosis/diagnóstico por imagen , Calcinosis/etiología , Valor Predictivo de las PruebasRESUMEN
Although the adverse effects of long-term use of vitamin K oral anticoagulant (OAC), warfarin, on the coronary vasculature are well-established, it remains unknown whether nonvitamin K oral anticoagulants play a role in the attenuation of plaque progression and coronary calcification. This study aimed to compare the changes in atherosclerotic plaques and calcification of the coronary arteries in patients with atrial fibrillation (AF) treated with edoxaban and warfarin. A total of 150 OAC-naïve patients with AF and atherosclerotic lesions on coronary computed tomography angiography (CCTA) were enrolled and randomly assigned to the edoxaban or warfarin treatment groups. All enrolled patients received rosuvastatin 10 mg and 119 patients completed the entire study protocol. A total of 12 months after the assigned OAC treatment, follow-up CCTA was performed and changes in plaque and calcium volumes of the coronary arteries were analyzed. The baseline characteristics of the 2 groups were well-balanced. The percentage of time in therapeutic range in the warfarin group was 61.1%. Compared with the baseline CCTA, there was a significant reduction in plaque volume after 12 months of OAC and rosuvastatin administration in both groups, and the extent of regression did not differ significantly between the groups. The increase in calcium volume was greater in the warfarin group than in the edoxaban group; however, the difference was not significant. In OAC-naïve patients with AF and atherosclerotic coronary lesions who were treated with moderate-intensity statin, edoxaban use did not have a positive effect on atherosclerotic plaques and coronary calcification compared with warfarin use over a 12-month follow-up period.