RESUMEN
Cardiac allograft vasculopathy (CAV) is a leading cause of death after heart transplantation (HT). We evaluated donor-derived cell-free DNA (dd-cfDNA) as a noninvasive biomarker of CAV development after HT. The INSPIRE registry at the Intermountain Medical Center was queried for stored plasma samples from HT patients with and without CAV. At Stanford University, HT patients with CAV (cases) and without CAV (controls) were enrolled prospectively, and blood samples were collected. All the samples were analyzed for dd-cfDNA using the AlloSure assay (CareDx, Inc.). CAV was defined per the ISHLT 2010 standardized classification system. Univariate associations between patient demographics and clinical characteristics and their CAV grade were tested using chi-square and Wilcoxon rank sum tests. Associations between their dd-cfDNA levels and CAV grades were examined using a nonparametric Kruskal-Wallis test. A total of 69 pts were included, and 101 samples were analyzed for dd-cfDNA. The mean age at sample collection was 58.6 ± 13.7 years; 66.7% of the patients were male, and 81% were White. CAV 0, 1, 2, and 3 were present in 37.6%, 22.8%, 22.8%, and 16.8% of included samples, respectively. The median dd-cfDNA level was 0.13% (0.06, 0.33). The median dd-cfDNA level was not significantly different between CAV (-) and CAV (+): 0.09% (0.05%-0.32%) and 0.15% (0.07%-0.33%), respectively, p = 0.25 and with similar results across all CAV grades. In our study, dd-cfDNA levels did not correlate with the presence of CAV and did not differ across CAV grades. As such, dd-cfDNA does not appear to be a reliable noninvasive biomarker for CAV surveillance.
Asunto(s)
Biomarcadores , Ácidos Nucleicos Libres de Células , Trasplante de Corazón , Donantes de Tejidos , Humanos , Masculino , Femenino , Trasplante de Corazón/efectos adversos , Ácidos Nucleicos Libres de Células/sangre , Persona de Mediana Edad , Estudios de Seguimiento , Estudios Prospectivos , Biomarcadores/sangre , Pronóstico , Factores de Riesgo , Aloinjertos , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Estudios de Casos y Controles , Rechazo de Injerto/etiología , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/sangre , Supervivencia de Injerto , Enfermedades Vasculares/etiología , Enfermedades Vasculares/sangre , AdultoRESUMEN
The roles of lipoprotein(a) [Lp(a)] and related oxidized phospholipids (OxPLs) in the development and progression of coronary disease is known, but their influence on extracoronary vascular disease is not well-established. We sought to evaluate associations between Lp(a), OxPL apolipoprotein B (OxPL-apoB), and apolipoprotein(a) (OxPL-apo(a)) with angiographic extracoronary vascular disease and incident major adverse limb events (MALEs). Four hundred forty-six participants who underwent coronary and/or peripheral angiography were followed up for a median of 3.7 years. Lp(a) and OxPLs were measured before angiography. Elevated Lp(a) was defined as ≥150 nmol/L. Elevated OxPL-apoB and OxPL-apo(a) were defined as greater than or equal to the 75th percentile (OxPL-apoB ≥8.2 nmol/L and OxPL-apo(a) ≥35.8 nmol/L, respectively). Elevated Lp(a) had a stronger association with the presence of extracoronary vascular disease compared to OxPLs and was minimally improved with the addition of OxPLs in multivariable models. Compared to participants with normal Lp(a) and OxPL concentrations, participants with elevated Lp(a) levels were twice as likely to experience a MALE (odds ratio: 2.14, 95% confidence interval: 1.03, 4.44), and the strength of the association as well as the C statistic of 0.82 was largely unchanged with the addition of OxPL-apoB and OxPL-apo(a). Elevated Lp(a) and OxPLs are risk factors for progression and complications of extracoronary vascular disease. However, the addition of OxPLs to Lp(a) does not provide additional information about risk of extracoronary vascular disease. Therefore, Lp(a) alone captures the risk profile of Lp(a), OxPL-apoB, and OxPL-apo(a) in the development and progression of atherosclerotic plaque in peripheral arteries.
Asunto(s)
Lipoproteína(a) , Oxidación-Reducción , Fosfolípidos , Humanos , Lipoproteína(a)/sangre , Masculino , Femenino , Persona de Mediana Edad , Fosfolípidos/sangre , Fosfolípidos/metabolismo , Anciano , Enfermedades Vasculares/sangre , Enfermedades Vasculares/metabolismoRESUMEN
BACKGROUND: Systemic sclerosis (SSc) is a heterogeneous disease, characterized by variable tissue and vascular fibrosis in the context of autoimmune activation. CCL24 (or Eotaxin2) has been shown to promote microangiopathic, proinflammatory, and profibrotic processes in preclinical models of SSc. Here, we study serum CCL24 levels in a real-life cohort of patients with SSc, to determine its distribution across disease features and its value in predicting disease progression and related mortality. METHODS: Serum CCL24 was assessed in an observational cohort of consecutively enrolled patients with SSc. A high CCL24 cutoff was defined based on its distribution in a matched cohort of healthy controls. Disease progression and mortality were analyzed from the date of serum assessment. RESULTS: Two-hundred thirteen consecutively enrolled patients with SSc were included in this analysis. Median disease duration was six years (interquartile range 3-14), 28.6% of patients presented with interstitial lung disease (ILD), 46.9% had digital ulcers, and 25.3% showed high CCL24 serum concentration. High-CCL24 patients were more frequently male and positive for anti-scl-70, with a diagnosis of ILD and synovitis (P < 0.05 for all). Notably, high-CCL24 patients had lower diffusion of carbon monoxide and higher prevalence of digital ulcers, telangiectasias, and calcinosis (P < 0.05 for all). In a longitudinal setting, high CCL24 was associated with greater lung function decline and with higher disease-related mortality. CONCLUSION: Serum CCL24 is a biomarker of disease severity across fibrotic and vascular disease manifestations. These data support the development of therapies targeting CCL24 as a novel comprehensive therapeutic target in SSc.
Asunto(s)
Biomarcadores , Quimiocina CCL24 , Fibrosis , Esclerodermia Sistémica , Índice de Severidad de la Enfermedad , Humanos , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/diagnóstico , Esclerodermia Sistémica/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Biomarcadores/sangre , Quimiocina CCL24/sangre , Anciano , Fibrosis/sangre , Progresión de la Enfermedad , Adulto , Enfermedades Vasculares/sangre , Enfermedades Vasculares/diagnósticoRESUMEN
Inflammation plays an important role in the development of sepsis-acute respiratory distress syndrome (ARDS). Olink inflammation-related biomarker panels were used to analyze the levels of 92 inflammation-related proteins in plasma with sepsis-ARDS (n = 25) and healthy subjects (n = 25). There were significant differences in 64 inflammatory factors, including TNFRSF11B in sepsis-ARDS, which was significantly higher than that in controls. Functional analysis showed that TNFRSF11B was closely focused on signal transduction, immune response, and inflammatory response. The TNFRSF11B level in sepsis-ARDS plasma, LPS-induced mice, and LPS-stimulated HUVECs significantly increased. The highest plasma concentration of TNFRSF11B in patients with sepsis-ARDS was 10-20 ng/mL, and 10 ng/mL was selected to stimulate HUVECs. Western blot results demonstrated that the levels of syndecan-1, claudin-5, VE-cadherin, occludin, aquaporin-1, and caveolin-1 in TNFRSF11B-stimulated HUVECs decreased, whereas that of connexin-43 increased in TNFRSF11B-stimulated HUVECs. To the best of the authors' knowledge, this study was the first to reveal elevated TNFRSF11B in sepsis-ARDS associated with vascular endothelial dysfunction. In summary, TNFRSF11B may be a new potential predictive and diagnostic biomarker for vascular endothelium damage in sepsis-ARDS.
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Osteoprotegerina , Síndrome de Dificultad Respiratoria , Sepsis , Enfermedades Vasculares , Animales , Humanos , Ratones , Biomarcadores/sangre , Inflamación/metabolismo , Lipopolisacáridos/farmacología , Osteoprotegerina/sangre , Síndrome de Dificultad Respiratoria/sangre , Síndrome de Dificultad Respiratoria/complicaciones , Síndrome de Dificultad Respiratoria/diagnóstico , Sepsis/sangre , Sepsis/complicaciones , Sepsis/diagnóstico , Enfermedades Vasculares/sangre , Enfermedades Vasculares/complicaciones , Enfermedades Vasculares/diagnósticoRESUMEN
BACKGROUND: The vascular endothelium is markedly disrupted in sickle cell disease (SCD) and is the converging cascade of the complex pathophysiologic processes linked to sickle cell vasculopathy. Circulating endothelial activation and/or apoptotic markers may reflect this endothelial activation/damage that contributes to the pathophysiology of the SCD vascular complications. METHODS: Plasmatic levels of circulating endothelial cells (CECs), E-selectin, progenitor's endothelial cells (EPCs), and circulating extracellular vesicles (EVs) were evaluated in 50 SCD patients, 16 with vasculopathy. The association between these markers and the occurrence of disease-related microvascular injuries of the eye (retinopathy), kidney (nephropathy), and skin (chronic active ulcers) was explored. RESULTS: Among the endothelial activation markers studied, only higher plasma levels of E-selectin were found in SCD patients with vasculopathy (p = .015). Increased E-selectin levels were associated with retinopathy (p < .001) but not with nephropathy or leg ulcers. All patients, at steady state, with or without vasculopathy, did not display a high count of CEC and EPC, markers of endothelial injury and repair. We did not show any significant differences in EVs levels between vasculopathy and not vasculopathy SCD patients. CONCLUSIONS: Further studies will be required to determine whether the E-selectin could be used as an early biomarker of retinopathy sickle cell development.
Asunto(s)
Anemia de Células Falciformes , Selectina E , Enfermedades de la Retina , Enfermedades Vasculares , Humanos , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/diagnóstico , Selectina E/sangre , Células Endoteliales/patología , Enfermedades de la Retina/sangre , Enfermedades de la Retina/etiología , Enfermedades Vasculares/sangre , Enfermedades Vasculares/etiologíaRESUMEN
Objective: To determine if the number of vaso-occlusive events in SCD relates to plasma concentration of fucosyltransferase 7 (FUT7), which catalyses the synthesis of selectin ligands. Design: A prospective, analytical study. Setting: Haematology and Chemical Pathology Departments of tertiary healthcare centres. Participants: Steady state HbSS individuals aged 13-45 years, 20 had 3 or more vaso-occlusive crises that required hospital admission in the previous year (with or without complications of SCD); 17 other HbSS persons had 0-1 vaso-occlusive crisis that required hospital admission in the previous year and no disease complications. Intervention: Steady-state plasma concentrations of FUT7 measured by ELISA were compared between SCD patients who had one vaso-occlusive crisis requiring hospital treatment in the previous year but no disease complications and those who had >3 crises with or without complications. Main Outcome Measures: Plasma level of FUT7and the number of vaso-occlusive events in each HbSS patient. Results: Mean + standard deviation plasma concentration of FUT7 was 8.6 + 2.7 ng/ml in patients with >3 vasoocclusive crises in the previous year and 7.3 + 1.7 ng/ml in those with 0-1 crisis and no complications; independent sample t-test, p > 0.05, not significantly different. Conclusion: Plasma concentration of fucosyltransferase7 is not associated with the number of vaso-occlusive events in sickle cell disease. Funding: None declared.
Asunto(s)
Anemia de Células Falciformes , Fucosiltransferasas , Humanos , Fucosiltransferasas/sangre , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/complicaciones , Adulto , Femenino , Masculino , Estudios Prospectivos , Adolescente , Adulto Joven , Persona de Mediana Edad , Enfermedades Vasculares/sangre , Enfermedades Vasculares/etiología , Ensayo de Inmunoadsorción Enzimática , Biomarcadores/sangreRESUMEN
BACKGROUND: Haemophilic arthropathy (HA) is a major complication in haemophilia. Collagens IV, XV and XVIII are responsible for maintaining the integrity of the vessel wall in the joint. Following joint remodelling and damage, the short isoform of collagen type XVIII (COL-18N) is degraded, releasing measurable fragments. Our goal was to quantify the specific isoform COL-18N in haemophilia A patients and to assess its relation to the clinical and radiological data as well as haemophilia joint health score (HJHS), functional independence score for haemophilia (FISH), and haemophilia quality of life (Haemo-Qol). METHODS: This cross-sectional study included 50 haemophilia A patients recruited from the Paediatric Haematology and Oncology unit, Ain Shams University, Cairo, Egypt. Quantification of COL-18N was done by ELISA. Assessment of joint state clinically using FISH and HJH scores and radiologically by X-rays and ultrasound. RESULTS: Haemophilia A patients had significantly higher median COL-18N levels compared to the control group. Inhibitor positive and negative haemophilia A patients as well as those on non-steroidal anti-inflammatory drug and those not had comparable COL-18N levels. Patients with ≥2 target joints had significantly higher COL-18N level compared to those with one or those without target joints. There were significant positive correlations between COL-18N level and the total HJHS, Haemo-Qol, the HEAD-US score and annual bleeding rate. CONCLUSION: Our results demonstrated a high level of COL-18N in haemophilia A patients and argued its benefit as a potential marker for monitoring the development of haemophilic arthropathy and tailoring the optimal treatment to prevent further joint damage.
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Colágeno Tipo XVIII , Hemartrosis , Hemofilia A , Enfermedades Vasculares , Adolescente , Vasos Sanguíneos/fisiopatología , Niño , Colágeno Tipo XVIII/sangre , Estudios Transversales , Femenino , Hemartrosis/sangre , Hemartrosis/etiología , Hemofilia A/sangre , Hemofilia A/complicaciones , Humanos , Masculino , Isoformas de Proteínas/sangre , Calidad de Vida , Enfermedades Vasculares/sangre , Enfermedades Vasculares/etiologíaRESUMEN
Various clinically applicable scores and indices are available to help identify the state of a microcirculatory disorder in a patient. Several of these methods, however, leave room for interpretation and only provide clues for diagnosis. Thus, a measurement method that allows a reliable detection of impending or manifest circulatory malfunctions would be of great value. In this context, the optical and non-invasive method of shifted position-diffuse reflectance imaging (SP-DRI) was developed. It allows to determine the capillary diameter and thus to assess the state of the microcirculation. The aim of the present study is to investigate how the quantification of capillary diameters by SP-DRI behaves in different individuals, i.e. for a wide range of optical properties. For this, within Monte-Carlo simulations all optical properties (seven skin layers, hemoglobin) were randomly varied following a Gaussian distribution. An important finding from the present investigation is that SP-DRI works when the optical properties are chosen randomly. Furthermore, it is shown that appropriate data analysis allows calibration-free absolute quantification of the capillary diameter across individuals using SP-DRI. This underpins the potential of SP-DRI to serve as an early alert system for the onset of microcirculatory associated diseases.
Asunto(s)
Capilares/diagnóstico por imagen , Microcirculación , Imagen Óptica , Piel/irrigación sanguínea , Enfermedades Vasculares/diagnóstico por imagen , Algoritmos , Capilares/fisiopatología , Simulación por Computador , Humanos , Modelos Cardiovasculares , Método de Montecarlo , Oxihemoglobinas/metabolismo , Enfermedades Vasculares/sangre , Enfermedades Vasculares/fisiopatologíaRESUMEN
OBJECTIVE: The association between neutrophil-to-lymphocyte ratio (NLR) with subclinical macrovascular and microvascular diseases has been less investigated. We sought to examine the association between NLR and new-onset subclinical macrovascular and microvascular abnormalities in the Chinese population. METHODS: From a community cohort, we included 6,430 adults aged ≥ 40 years without subclinical macrovascular and microvascular diseases at baseline. We measured subclinical macrovascular and microvascular abnormalities separately using the ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and albuminuria. RESULTS: During a mean follow-up of 4.3 years, 110 participants developed incident abnormal ABI, 746 participants developed incident elevated baPWV, and 503 participants developed incident albuminuria. Poisson regression analysis indicated that NLR was significantly associated with an increased risk of new-onset abnormal ABI, elevated baPWV, and albuminuria. Compared to overweight/obese participants, we found a much stronger association between NLR and subclinical vascular abnormalities in participants with normal weight. Furthermore, we found an interaction between the NLR and body mass index (BMI) on the risk of new-onset abnormal ABI ( P for interaction: 0.01). CONCLUSION: NLR was associated with subclinical macrovascular and microvascular diseases in the Chinese population. Furthermore, in participants with normal weight, the association between NLR and subclinical vascular abnormalities was much stronger.
Asunto(s)
Linfocitos/citología , Neutrófilos/citología , Enfermedades Vasculares/etiología , Adulto , Anciano , Índice Tobillo Braquial , Índice de Masa Corporal , China/epidemiología , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Distribución de Poisson , Estudios Prospectivos , Enfermedades Vasculares/sangre , Enfermedades Vasculares/epidemiologíaRESUMEN
BACKGROUND: The Canadian Cardiovascular Society 2016 guidelines recommend pre-operative measurement of brain natriuretic peptide (BNP) to risk-stratify patients for a 30-day composite outcome of death, myocardial infarction, or asymptomatic myocardial injury after noncardiac surgery (MINS). Whether this practice affects outcomes is unclear. The aim of this study was to examine the clinical utility of brain natriuretic peptide and myocardial injury after noncardiac surgery. METHODS: Analysis of a prospectively maintained database identified all elective open vascular surgery cases at an academic teaching hospital from January 2015 to December 2018. Pre-operative BNP values were available from June 2018 onward after becoming institutionally mandated. Co-morbidities were also collected to stratify patients using the Revised Cardiac Risk Index. The composite outcome of 30-day mortality, myocardial infarction, or MINS was determined. RESULTS: Prior to BNP becoming an institutionally required test, data was available from 1176 open cases. The 30-day mortality was 1.3% (15/1176) and post-operative myocardial infarction rate was 2.3% (27/1176). BNP measurements were collected in 91 consecutive patients. Ten patients (11%) experienced the composite outcome of mortality, myocardial infarction, or MINS. Elevated BNP was associated with increased odds of the composite outcome (P = 0.04), but not with mortality or myocardial infarction. Revised Cardiac Risk Index score was not predictive of outcomes. The majority of patients who qualified for the composite outcome experienced only an asymptomatic troponin rise (80%). Two patients met the universal definition of myocardial infarction, one of whom died. No other deaths occurred within 30 days. Detection of MINS did not result in any significant changes to patient management. CONCLUSIONS: Elevated BNP correlates with increased MINS. An asymptomatic troponin rise is the most commonly observed event, with unclear clinical implications. BNP may over-estimate surgical risk. Further studies on the long-term outcomes of patients with elevated BNP and MINS are required before widely adopting this strategy in vascular surgery patients.
Asunto(s)
Lesiones Cardíacas/etiología , Infarto del Miocardio/etiología , Péptido Natriurético Encefálico/sangre , Enfermedades Vasculares/cirugía , Procedimientos Quirúrgicos Vasculares/efectos adversos , Anciano , Biomarcadores/sangre , Femenino , Lesiones Cardíacas/sangre , Lesiones Cardíacas/diagnóstico , Lesiones Cardíacas/mortalidad , Humanos , Masculino , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/mortalidad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Troponina/sangre , Enfermedades Vasculares/sangre , Enfermedades Vasculares/diagnóstico , Enfermedades Vasculares/mortalidad , Procedimientos Quirúrgicos Vasculares/mortalidadRESUMEN
OBJECTIVE: Thromboelastography (TEG) is diagnostic modality that analyzes real-time blood coagulation parameters. Clinically, TEG primarily allows for directed blood component resuscitation among patients with acute blood loss and coagulopathy. The utilization of TEG has been widely adopted in among other surgical specialties; however, its use in vascular surgery is less prominent. We aimed to provide an up-to-date review of TEG utilization in vascular and endovascular surgery. METHODS: Using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a literature review with the Medical Subject Headings (MeSH) terms "TEG and arterial events", "TEG and vascular surgery", "TEG and vascular", "TEG and endovascular surgery", "TEG and endovascular", "TEG and peripheral artery disease", "TEG and prediction of arterial events", "TEG and prediction of complications ", "TEG and prediction of thrombosis", "TEG and prediction of amputation", and "TEG and amputation" was performed in Cochrane and PubMed databases to identify all peer-reviewed studies of TEG utilization in vascular surgery, written between 2000 and 2021 in the English language. The free-text and MeSH subheadings search terms included diagnosis, complications, physiopathology, surgery, mortality, and therapy to further restrict the articles. Studies were excluded if they were not in humans or pertaining to vascular or endovascular surgery. Additionally, case reports and studies with limited information regarding TEG utilization were excluded. Each study was independently reviewed by two researchers to assess for eligibility. RESULTS: Of the 262 studies identified through the MeSH strategy, 15 studies met inclusion criteria and were reviewed and summarized. Literature on TEG utilization in vascular surgery spanned cerebrovascular disease (n = 3), peripheral arterial disease (n = 3), arteriovenous malformations (n = 1), venous thromboembolic events (n = 7), and perioperative bleeding and transfusion (n = 1). In cerebrovascular disease, TEG may predict the presence and stability of carotid plaques, analyze platelet function before carotid stenting, and compare efficacy of antiplatelet therapy after stent deployment. In peripheral arterial disease, TEG has been used to predict disease severity and analyze the impact of contrast on coagulation parameters. In venous disease, TEG may predict hypercoagulability and thromboembolic events among various patient populations. Finally, TEG can be utilized in the postoperative setting to predict hemorrhage and transfusion requirements. CONCLUSIONS: This systematic review provides an up-to-date summarization of TEG utilization in multiple facets of vascular and endovascular surgery.
Asunto(s)
Coagulación Sanguínea , Procedimientos Endovasculares , Monitoreo Intraoperatorio , Tromboelastografía , Enfermedades Vasculares/cirugía , Procedimientos Quirúrgicos Vasculares , Pérdida de Sangre Quirúrgica , Transfusión Sanguínea , Procedimientos Endovasculares/efectos adversos , Humanos , Hemorragia Posoperatoria/sangre , Hemorragia Posoperatoria/diagnóstico , Hemorragia Posoperatoria/terapia , Valor Predictivo de las Pruebas , Resultado del Tratamiento , Enfermedades Vasculares/sangre , Enfermedades Vasculares/diagnóstico , Procedimientos Quirúrgicos Vasculares/efectos adversosRESUMEN
Moyamoya arteriopathy (MA) is a rare cerebrovascular disorder characterized by ischemic/hemorrhagic strokes. The pathophysiology is unknown. A deregulation of vasculogenic/angiogenic/inflammatory pathways has been hypothesized as a possible pathophysiological mechanism. Since lipids are implicated in modulating neo-vascularization/angiogenesis and inflammation, their deregulation is potentially involved in MA. Our aim is to evaluate angiogenic/vasculogenic/inflammatory proteins and lipid profile in plasma of MA patients and control subjects (healthy donors HD or subjects with atherosclerotic cerebrovascular disease ACVD). Angiogenic and inflammatory protein levels were measured by ELISA and a complete lipidomic analysis was performed on plasma by mass spectrometry. ELISA showed a significant decrease for MMP-9 released in plasma of MA. The untargeted lipidomic analysis showed a cumulative depletion of lipid asset in plasma of MA as compared to HD. Specifically, a decrease in membrane complex glycosphingolipids peripherally circulating in MA plasma with respect to HD was observed, likely suggestive of cerebral cellular recruitment. The quantitative targeted approach demonstrated an increase in free sphingoid bases, likely associated with a deregulated angiogenesis. Our findings indicate that lipid signature could play a central role in MA and that a detailed biomarker profile may contribute to untangle the complex, and still obscure, pathogenesis of MA.
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Lípidos/sangre , Enfermedad de Moyamoya/sangre , Enfermedades Vasculares/sangre , Biomarcadores/sangre , Femenino , Humanos , Inflamación/sangre , Arteriosclerosis Intracraneal/sangre , Lipidómica/métodos , Masculino , Persona de Mediana Edad , Neovascularización Patológica/sangreRESUMEN
BACKGROUND: Very few studies have reported on association of postprandial lipids and endothelial dysfunction among patients with diabetes. Whether endothelial dysfunction particularly postprandial FMD is worse in patients with T2DM with macrovascular disease compared to those without and whether this difference is related to postprandial hypertriglyceridemia (PPHTg) is unclear. Therefore, present study was aimed to assess the relationship between PPHTg and endothelial function in patients with T2DM with and without macrovascular disease. METHOD: Endothelial dysfunction by FMD and CIMT were compared in patients with T2DM with and without macrovascular disease (n = 13 each group) and 13 age, sex and BMI matched healthy individuals after an oral fat challenge. RESULTS: There was significant postprandial deterioration of FMD 4-hr after fat challenge in patients with diabetes (P < 0.001) as well as healthy individuals (P = 0.004). Patients with diabetes with macrovascular disease had significantly lower fasting (5.7 ± 6.1% vs. 22.7 ± 10.0% and vs. 24.7 ± 5.3%) as well as postprandial (4-hr) (3.1 ± 5.0% vs. 15.3 ± 8.1% and vs. 15.4 ± 5.7%) FMD compared to other two groups. Fasting, postprandial as well as change in FMD and CIMT in patients with diabetes correlated significantly with fasting as well as postprandial triglycerides with stronger correlation in those with macrovascular disease. CONCLUSION: Study found significant endothelial dysfunction by FMD that shows substantial further deterioration postprandially following high fat meal in patients with diabetes with macrovascular disease compared to patients with diabetes without macrovascular disease and healthy individuals. Study also indicates that PPHTg is a contributor to endothelial dysfunction. However, more studies are required to corroborate these findings.
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Grosor Intima-Media Carotídeo , Diabetes Mellitus Tipo 2/sangre , Grasas de la Dieta/administración & dosificación , Endotelio Vascular/metabolismo , Periodo Posprandial/fisiología , Enfermedades Vasculares/sangre , Administración Oral , Adulto , Grosor Intima-Media Carotídeo/tendencias , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/fisiopatología , Endotelio Vascular/fisiopatología , Femenino , Humanos , Hipertrigliceridemia/sangre , Hipertrigliceridemia/epidemiología , Hipertrigliceridemia/fisiopatología , Masculino , Persona de Mediana Edad , Enfermedades Vasculares/epidemiología , Enfermedades Vasculares/fisiopatologíaRESUMEN
The severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) keeps on destroying normal social integrity worldwide, bringing about extraordinary medical services, cultural and financial interruption. Individuals with diabetes have been demonstrated to be at higher risk of complications and even death when exposed to SARS-CoV-2. Regardless of pandemic scale infection, there is presently limited comprehension on the potential impact of SARS-CoV-2 on individuals with diabetes. Human serum albumin (HSA) is the most abundant circulating plasma protein in human serum and attracted more interest from researchers because most susceptible to non-enzymatic glycation reactions. Albumin down-regulates the expression of ACE2 that is the target receptor of COVID-19. Hypoalbuminemia, coagulopathy, and vascular disease have been connected in COVID-19 and appear to predict outcomes independent of age and morbidity. This review discusses the most recent evidence that the ACE/ACE2 ratio could influence by human serum albumin both the susceptibility of individuals to SARS-CoV-2 infection and the outcome of the COVID-19 disease.
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Enzima Convertidora de Angiotensina 2/sangre , COVID-19 , SARS-CoV-2/metabolismo , Albúmina Sérica Humana/metabolismo , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/diagnóstico , Trastornos de la Coagulación Sanguínea/terapia , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/terapia , Susceptibilidad a Enfermedades , Humanos , Enfermedades Vasculares/sangre , Enfermedades Vasculares/diagnóstico , Enfermedades Vasculares/terapiaRESUMEN
BACKGROUND: Hypercoagulability is a risk factor of thromboembolic events in COVID-19. Anti-phospholipid (aPL) antibodies have been hypothesized to be involved. Typical COVID-19 dermatological manifestations of livedo reticularis and digital ischemia may resemble cutaneous manifestations of anti-phospholipid syndrome (APS). OBJECTIVES: To investigate the association between aPL antibodies and thromboembolic events, COVID-19 severity, mortality, and cutaneous manifestations in patients with COVID-19. METHODS: aPL antibodies [anti-beta2-glycoprotein-1 (B2GP1) and anti-cardiolipin (aCL) antibodies] were titered in frozen serum samples from hospitalized COVID-19 patients and the patients' clinical records were retrospectively analyzed. RESULTS: 173 patients were enrolled. aPL antibodies were detected in 34.7% of patients, anti-B2GP1 antibodies in 30.1%, and aCL antibodies in 10.4%. Double positivity was observed in 5.2% of patients. Thromboembolic events occurred in 9.8% of patients, including 11 pulmonary embolisms, 1 case of celiac tripod thrombosis, and six arterial ischemic events affecting the cerebral, celiac, splenic, or femoral-popliteal arteries or the aorta. aPL antibodies were found in 52.9% of patients with vascular events, but thromboembolic events were not correlated to aPL antibodies (adjusted OR = 1.69, p = 0.502). Ten patients (5.8%) had cutaneous signs of vasculopathy: nine livedo reticularis and one acrocyanosis. No significant association was observed between the presence of cutaneous vasculopathy and aPL antibodies (p = 0.692). CONCLUSIONS: Anti-phospholipid antibodies cannot be considered responsible for hypercoagulability and thrombotic events in COVID-19 patients. In COVID-19 patients, livedo reticularis and acrocyanosis do not appear to be cutaneous manifestations of APS.
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Anticuerpos Antifosfolípidos/sangre , COVID-19/complicaciones , SARS-CoV-2 , Enfermedades de la Piel/sangre , Enfermedades Vasculares/sangre , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Anticardiolipina/sangre , COVID-19/sangre , COVID-19/inmunología , COVID-19/mortalidad , Femenino , Hospitalización , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estudios Seroepidemiológicos , Enfermedades de la Piel/inmunología , Enfermedades de la Piel/mortalidad , Enfermedades Vasculares/inmunología , Enfermedades Vasculares/mortalidad , beta 2 Glicoproteína I/inmunologíaRESUMEN
Galectin-3, which is a novel biomarker of cardiovascular stress and related to inflammation, could predict adverse cardiovascular events. However, its relationship with endothelial function in patients with chronic kidney disease (CKD) remains inconclusive. This study aimed to investigate the association between serum galectin-3 levels and endothelial function in patients with stages 3-5 CKD. Fasting blood samples were obtained from 130 patients. Serum galectin-3 levels were determined using the enzyme-linked immunosorbent assay. The endothelial function, demonstrated as a vascular reactivity index (VRI), was measured noninvasively through digital thermal monitoring test. Then, we sorted the patients into poor, intermediate, and good vascular reactivity (VRI < 1.0, 1.0 ≤ VRI < 2.0, and VRI ≥ 2.0), accounting for 24 (18.5%), 44 (33.8%), and 62 (47.7%) patients, respectively. As the VRI decreased, the serum galectin-3 and C-reactive protein (CRP) levels significantly increased. The galectin-3 value positively correlated with the CRP value but negatively correlated with estimated glomerular filtration rate. In multivariable stepwise linear regression analysis, serum log-transformed galectin-3 level and log-transformed CRP were significantly negatively associated with VRI values. Therefore, galectin-3 together with CRP is associated with VRI values and is a potential endothelial function modulator and a valuable biomarker of endothelial dysfunction in patients with CKD.
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Galectinas/sangre , Insuficiencia Renal Crónica/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Proteínas Sanguíneas , Proteína C-Reactiva/análisis , Endotelio Vascular/fisiopatología , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/fisiopatología , Enfermedades Vasculares/sangre , Enfermedades Vasculares/fisiopatologíaRESUMEN
Rapidly growing interest in the study of extracellular vesicles (EVs) has led to the accumulation of evidence on their critical roles in various pathologies, as well as opportunities to design novel therapeutic EV-based applications. Efficiently exploiting the constantly expanding knowledge of the biology and function of EVs requires a deep understanding of the various possible strategies of using EVs for therapeutic purposes. Accordingly, in the present work, we have narrowed the broad therapeutic potential of EVs and consider the similarities and differences of various strategies as we articulate three major aspects (i.e., a triad) of their therapeutic uses: (i) EVs as drug targets, whereby we discuss therapeutic targeting of disease-promoting EVs; (ii) EVs as drugs, whereby we consider the natural medicinal properties of EVs and the available options for their optimization; and (iii) EVs as drug carriers, whereby we highlight the advantages of EVs as vehicles for efficacious drug delivery of natural compounds. Finally, after conducting a comprehensive review of the latest literature on each of these aspects, we outline opportunities, limitations, and potential solutions.
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Factores Biológicos/metabolismo , Portadores de Fármacos/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Vesículas Extracelulares/metabolismo , Animales , Factores Biológicos/administración & dosificación , Portadores de Fármacos/administración & dosificación , Exosomas/metabolismo , Humanos , Enfermedades Vasculares/sangre , Enfermedades Vasculares/tratamiento farmacológicoRESUMEN
Maintaining hemodynamic stability during the induction and maintenance of anesthesia is one of the challenges of the anesthesiologist. Patients with vascular disease are at increased risk of instability due to imbalance between the sympathetic and parasympathetic parts of the autonomic nervous system, a balance accessible by serum cholinesterase activity. We aim to characterize the dynamics of cholinesterase activity in patients undergoing general anesthesia (GA) and surgery. This was a prospective study of 57 patients undergoing ambulatory or vascular surgery under GA. Cholinesterase activity was measured before the induction of anesthesia, after 15 min and at the end of surgery by calculating the capacity of serum acetylcholinesterase (AChE) and butyrylcholinesterase to hydrolyze AcetylThioCholine. Data on atherosclerotic disease, anesthesia management were analyzed. Both AChE and total cholinergic status (CS) decreased significantly after GA induction at 15 min and even more so by the end of surgery. Vascular surgery patients had lower baseline cholinesterase activity compared to ambulatory surgery patients. Patients requiring intraoperative administration of phenylephrine for hemodynamic support (21.1%) had a significantly lower level of AChE and CS compared to untreated patients. Our findings serve as a mirror to the sympathetic/parasympathetic imbalance during GA, with a marked decrease in the parasympathetic tone. The data of a subgroup analysis show a correlation between low cholinesterase activity and an increase in the need for hemodynamic support.
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Acetilcolinesterasa/sangre , Anestesia General , Butirilcolinesterasa/sangre , Enfermedades Vasculares/cirugía , Adulto , Anciano , Femenino , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Vasculares/sangreRESUMEN
Fontan palliation has improved survival for single ventricle patients, but long-term complications persist including cardiovascular dysfunction, neurohormonal abnormalities, and protein-losing enteropathy (PLE). Although chronic inflammation contributes to morbidity, an association between inflammation and vascular dysfunction has not been studied. We assessed inflammation and vascular function in 31 Fontan-palliated patients (52% male, median age 14.3 years), including 10 PLE+. Fontan circulation was associated with altered inflammatory cytokines (TNF-α: mean 2.5 ± 1.4 vs. 0.7 ± 0.2 pg/ml, p < 0.0001; sTNFR2: 371 ± 108 vs. 2694 ± 884 pg/ml, p < 0.0001) and vascular dysfunction [log-transformed reactive hyperemia index (lnRHI) 0.28 ± 0.19 vs. 0.47 ± 0.26, p < 0.01; augmentation index (AI) -2.9 ± 13.8 vs. -16.3 ± 12.0, pâ¯=â¯0.001; circulating endothelial progenitor cells (cEPCs) 5.0 ± 8.1 vs. 22.8 ± 15.9, pâ¯=â¯0.0002)]. Furthermore, PLE+ patients showed greater inflammation (IFN-γ 6.3 ± 2.2 vs. 11.5 ± 7.9 pg/ml, pâ¯=â¯0.01; sTNFR1: 1181 ± 420 vs. 771 ± 350 pg/ml, pâ¯=â¯0.01) and decreased arterial compliance (AI: 5.4 ± 17.1 vs. -6.8 ± 10.2, pâ¯=â¯0.02) than PLE- patients. Circulating EPCs, but not inflammatory cytokines, were inversely associated with arterial stiffness in Fontan patients. In conclusion, chronic inflammation and vascular dysfunction are observed after Fontan operation, with greater inflammation and arterial stiffness in Fontan patients with active PLE. However, there is no clear association between inflammatory cytokines and vascular dysfunction, suggesting these pathophysiologic processes are not mechanistically linked.
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Biomarcadores/sangre , Procedimiento de Fontan/efectos adversos , Cardiopatías Congénitas/cirugía , Complicaciones Posoperatorias/sangre , Enteropatías Perdedoras de Proteínas/sangre , Enfermedades Vasculares/sangre , Resistencia Vascular/fisiología , Adolescente , Adulto , Niño , Femenino , Estudios de Seguimiento , Cardiopatías Congénitas/sangre , Humanos , Inflamación/sangre , Inflamación/etiología , Masculino , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Enteropatías Perdedoras de Proteínas/etiología , Enfermedades Vasculares/etiología , Enfermedades Vasculares/fisiopatología , Adulto JovenRESUMEN
Background Recent evidence suggests cardiac troponin levels to be a marker of increased vascular risk. We aimed to assess whether levels of high-sensitivity cardiac troponin T (hs-cTnT) are associated with recurrent vascular events and death in patients with first-ever, mild to moderate ischemic stroke. Methods and Results We used data from the PROSCIS-B (Prospective Cohort With Incident Stroke Berlin) study. We computed Cox proportional hazards regression analyses to assess the association between hs-cTnT levels upon study entry (Roche Elecsys, upper reference limit, 14 ng/L) and the primary outcome (composite of recurrent stroke, myocardial infarction, and all-cause death). A total of 562 patients were analyzed (mean age, 67 years [SD 13]; 38.6% women; median National Institutes of Health Stroke Scale=2; hs-cTnT above upper reference limit, 39.2%). During a mean follow-up of 3 years, the primary outcome occurred in 89 patients (15.8%), including 40 (7.1%) recurrent strokes, 4 (0.7%) myocardial infarctions, and 51 (9.1%) events of all-cause death. The primary outcome occurred more often in patients with hs-cTnT above the upper reference limit (27.3% versus 10.2%; adjusted hazard ratio, 2.0; 95% CI, 1.3-3.3), with a dose-response relationship when the highest and lowest hs-cTnT quartiles were compared (15.2 versus 1.8 events per 100 person-years; adjusted hazard ratio, 4.8; 95% CI, 1.9-11.8). This association remained consistent in sensitivity analyses, which included age matching and stratification for sex. Conclusions Hs-cTnT is dose-dependently associated with an increased risk of recurrent vascular events and death within 3 years after first-ever, mild to moderate ischemic stroke. These findings support further studies of the utility of hs-cTnT for individualized risk stratification after stroke. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01363856.