RESUMEN
Immune, neuroendocrine, and autonomic nervous system dysregulation in anorexia nervosa lead to cardiovascular complications that can potentially result in increased morbidity and mortality. It is suggested that a complex non-invasive assessment of cardiovascular autonomic regulation-cardiac vagal control, sympathetic vascular activity, and cardiovascular reflex control-could represent a promising tool for early diagnosis, personalized therapy, and monitoring of therapeutic interventions in anorexia nervosa particularly at a vulnerable adolescent age. In this view, we recommend to consider in the diagnostic route, at least in the subset of patients with peripheral microvascular symptoms, a nailfold video-capillaroscopy as an easy not invasive tool for the early assessing of possible cardiovascular involvement.
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Anorexia Nerviosa/patología , Anomalías Cardiovasculares/patología , Enfermedades Vasculares Periféricas/patología , Anorexia Nerviosa/complicaciones , Anorexia Nerviosa/inmunología , Anorexia Nerviosa/metabolismo , Anomalías Cardiovasculares/complicaciones , Anomalías Cardiovasculares/inmunología , Anomalías Cardiovasculares/metabolismo , Frecuencia Cardíaca/fisiología , Humanos , Sistema Inmunológico/patología , Sistemas Neurosecretores/metabolismo , Sistemas Neurosecretores/patología , Enfermedades Vasculares Periféricas/complicaciones , Enfermedades Vasculares Periféricas/inmunología , Enfermedades Vasculares Periféricas/metabolismo , Nervio Vago/metabolismo , Nervio Vago/patologíaRESUMEN
OBJECTIVE: Inflammation is an early feature of acute limb ischaemia (ALI), hence the potential prognostic significance of inflammatory biomarkers. This study aimed to assess the value of pre-operative inflammatory biomarkers, specifically the neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR), for predicting an adverse outcome after revascularisation for ALI. METHODS: All patients submitted to lower limb revascularisation for Rutherford IIa or IIb ALI at the authors' institution between 2009 and 2019 were screened retrospectively. Pre-operative NLR and PLR were analysed, along with other known prognostic factors. Primary outcome was the composite endpoint of 30 day death or amputation. RESULTS: A total of 345 patients were included, 84 of whom suffered the primary outcome (24.3%). The median follow up was 23.1 months (3.1 - 52.2). Higher age (OR 1.05 per year increase, 95% CI 1.01 - 1.09), diabetes (OR 2.63, 95% CI 1.14 - 6.06), Rutherford grade IIb vs. IIa (OR 5.51, 95% CI 2.11 - 14.42), higher NLR (OR 1.28 per unit increase, 95% CI 1.12 - 1.47), and fasciotomy need (OR 3.44, 95% CI 1.14 - 10.34) were independently associated with 30 day death or amputation, whereas pre-operative statin or anticoagulant medication were associated with a risk reduction (OR 0.23, 95% CI 0.53 - 0.96 and OR 0.20, 95% CI 0.05 - 0.84, respectively). PLR did not show an independent effect on this population. Pre-operative NLR presented a good discriminative ability (AUC 0.86, 95% CI 0.82 - 0.90). A cut off NLR level ≥ 5.4 demonstrated a 90.5% sensitivity and 73.6% specificity for 30 day death or amputation. Kaplan-Meier analysis showed that patients with pre-operative NLR ≥ 5.4 had significantly lower 30 day, six month and one year amputation free survival when compared with those with NLR < 5.4 (64.8 ± 4.0%, 44.1 ± 4.1%, and 37.5 ± 4.1% vs. 98.5 ± 0.9%, 91.9 ± 2.0%, and 85.9 ± 2.5%, log rank p < .001). CONCLUSION: In this study, higher pre-operative NLR was associated with 30 day death or amputation following intervention for Rutherford grade IIa or IIb ALI. NLR potentially stands as a simple, widely available and inexpensive biomarker that can refine decision making and possibly contribute to ALI morbidity and mortality reduction.
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Isquemia/mortalidad , Linfocitos , Neutrófilos , Enfermedades Vasculares Periféricas/mortalidad , Procedimientos Quirúrgicos Vasculares/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Amputación Quirúrgica/estadística & datos numéricos , Anticoagulantes/uso terapéutico , Biomarcadores/sangre , Plaquetas , Toma de Decisiones Clínicas , Terapia Combinada/métodos , Terapia Combinada/estadística & datos numéricos , Extremidades/irrigación sanguínea , Extremidades/cirugía , Fasciotomía/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inflamación/diagnóstico , Inflamación/inmunología , Isquemia/sangre , Isquemia/inmunología , Isquemia/terapia , Estimación de Kaplan-Meier , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/sangre , Enfermedades Vasculares Periféricas/inmunología , Enfermedades Vasculares Periféricas/terapia , Recuento de Plaquetas , Periodo Preoperatorio , Pronóstico , Estudios Retrospectivos , Medición de Riesgo/estadística & datos numéricos , Resultado del TratamientoRESUMEN
OBJECTIVES: To analyze the correlation between the serum concentration of interleukin- (IL-) 23 and atherosclerotic changes, traditional atherosclerotic risk factors, the autoantibody profile, and involvement of selected organs in systemic lupus erythematosus (SLE) patients. PATIENTS AND METHODS: We studied 94 SLE patients and 27 controls. We analyzed the IL-23 serum concentration, autoantibodies, carotid intima-media thickness and atherosclerotic plaque, the ankle-brachial index, atherosclerotic risk factors, and organ manifestations. RESULTS: Concentrations of IL-23 significantly differed between SLE patients and the controls (p = 0.0015). On the basis of multivariate stepwise analysis, we revealed that high levels of IL-23 were associated with atherosclerotic plaque in common femoral arteries (OR = 12.67; 95% CI: 1.41-113.84), lupus nephritis (OR = 3.69; 95% CI: 1.16-12.22), and obesity (OR = 4.21; 95% CI: 1.40-12.67). Autoantibodies related to IL-23 were anti-phosphatidylethanolamine antibodies (OR = 11.06; 95% CI: 1.24-98.65) and anti-SS-B/La antibodies (OR = 15.43; 95% CI: 1.73-137.25). CONCLUSIONS: IL-23 may be involved in lupus nephritis pathogenesis. Through its association with obesity and selected antiphospholipid antibodies, IL-23 might promote a hypercoagulable state contributing to atherothrombosis development in SLE patients.
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Interleucina-23/sangre , Lupus Eritematoso Sistémico/inmunología , Nefritis Lúpica/etiología , Obesidad/etiología , Enfermedades Vasculares Periféricas/etiología , Adulto , Autoanticuerpos/sangre , Femenino , Humanos , Nefritis Lúpica/inmunología , Masculino , Persona de Mediana Edad , Obesidad/inmunología , Enfermedades Vasculares Periféricas/inmunología , Placa Aterosclerótica/etiologíaRESUMEN
Cancer produces a variety of collateral effects in patients beyond the malignancy itself, including threats to distal organ functions. However, the basis for such effects, associated with either primary or metastatic tumors, are generally poorly understood. In this study, we show how heart and kidney vascular function is impaired by neutrophils that accumulate in those tissues as a result of tumor formation in two different transgenic mouse models of cancer (RIP1-Tag2 model of insulinoma and MMTV-PyMT model of breast cancer). Neutrophil depletion by systemic administration of an anti-Gr1 antibody improved vascular perfusion and prevented vascular leakage in kidney vessels. We also observed the accumulation of platelet-neutrophil complexes, a signature of neutrophil extracellular traps (NET), in the kidneys of tumor-bearing mice that were completely absent from healthy nontumor-bearing littermates. NET accumulation in the vasculature was associated with upregulation of the proinflammatory adhesion molecules ICAM-1, VCAM-1, and E-selectin, as well as the proinflammatory cytokines IL1ß, IL6, and the chemokine CXCL1. Administering DNase I to dissolve NETs, which have a high DNA content, restored perfusion in the kidney and heart to levels seen in nontumor-bearing mice, and also prevented vessel leakage in the blood vasculature of these organs. Taken together, our findings strongly suggest that NETs mediate the negative collateral effects of tumors on distal organs, acting to impair vascular function, and to heighten inflammation at these sites.
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Trampas Extracelulares/inmunología , Neoplasias Mamarias Experimentales/inmunología , Neutrófilos/inmunología , Neoplasias Pancreáticas/inmunología , Enfermedades Vasculares Periféricas/inmunología , Animales , Citocinas/biosíntesis , Citocinas/inmunología , Femenino , Riñón/irrigación sanguínea , Riñón/inmunología , Riñón/patología , Neoplasias Mamarias Experimentales/patología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Neutrófilos/patología , Neoplasias Pancreáticas/patología , Enfermedades Vasculares Periféricas/patologíaRESUMEN
Vascular disease is a hallmark of systemic sclerosis (SSc). It is present in every patient, being responsible both for the earliest clinical manifestations and the major life-threatening complications of the disease, and thus determining important morbidity and mortality. In SSc, progressive vascular injury leads to vascular tone dysfunction and reduced capillary blood flow, with consequent tissue ischemia and chronic hypoxia. These phenomena are often accompanied by abnormal levels of vascular factors. Microangiopathy in SSc may be easily assessed by nailfold videocapillaroscopy. The variety of derangements detected in the nailfold capillaries is accompanied by abnormal levels of different vascular mediators and appears to be the best evaluable predictor of the development of peripheral vascular complications, such as digital ulcers. The purpose of this review is to summarize in SSc the most relevant vascular biomarkers and the main associations between vascular biomarkers and capillaroscopic parameters and/or the presence of digital ulcers. Vascular biomarkers could become useful predictive factors of vascular damage in SSc, allowing an earlier management of vascular complications.
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Proteínas Angiostáticas/análisis , Moléculas de Adhesión Celular/análisis , Quimiocinas/análisis , Enfermedades Vasculares Periféricas/patología , Esclerodermia Sistémica/inmunología , Esclerodermia Sistémica/patología , Autoinmunidad , Biomarcadores/análisis , Quimiocinas/inmunología , Humanos , Angioscopía Microscópica , Enfermedades Vasculares Periféricas/inmunología , Esclerodermia Sistémica/fisiopatología , Úlcera Cutánea/inmunología , Úlcera Cutánea/patologíaRESUMEN
The inflammatory response to healing in venous thrombosis might cause vein damage and post-thrombotic syndrome. Inflammation may also be involved in venous insufficiency apart from deep-vein thrombosis. We studied the association of inflammation markers with venous insufficiency in a general population sample. We characterised 2,404 men and women in a general population cohort for peripheral venous disease and its severity using physical exam, symptom assessment, and venous ultrasound. Inflammation markers, C-reactive protein (CRP), fibrinogen, interleukin 1-beta (IL-1-beta), IL-8, IL-10, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, monocyte chemoattractant-1 (MCP-1) and vascular endothelial cell growth factor (VEGF) were compared in 352 case participants with peripheral venous disease and 352 controls with no venous abnormalities frequency matched to cases by age, sex and race. Associations were also evaluated including a subset of 108 cases of severe venous disease, as previously defined. Odds ratios (95% CI), for peripheral venous disease for biomarkers in the top quartile (adjusting for age, race, sex, body mass index and history of venous thrombosis) were 1.8 (1.1-3.0), 1.6 (1.0-2.5) and 1.5 (0.9-2.3) for CRP, fibrinogen and IL-10, respectively. Associations were larger considering cases of severe venous disease, with odds ratios for these three analytes of 2.6 (1.2-5.9), 3.1 (1.3-7.3) and 2.2 (1.1-4.4), and for IL-8: 2.4 (1.1-5.2). There was no association of IL-1-beta, ICAM-1, VCAM-1, E-selectin, MCP-1 or VEGF with overall cases or severe venous disease. In conclusion, a subset of inflammation markers were associated with increased risk of peripheral venous disease, suggesting potential therapeutic targets for treatment.
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Proteína C-Reactiva/metabolismo , Citocinas/metabolismo , Fibrinógeno/metabolismo , Enfermedades Vasculares Periféricas/diagnóstico , Venas/metabolismo , Anciano , Biomarcadores/metabolismo , California , Quimiocina CCL2/metabolismo , Progresión de la Enfermedad , Selectina E/metabolismo , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/inmunología , Grupos de Población , Molécula 1 de Adhesión Celular Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Venas/patologíaRESUMEN
When food is heated to high temperatures, the characteristic "browning" generates advanced glycation end products (AGEs). AGEs are associated with an increased risk of cardiovascular disease, diabetes, and other adverse outcomes. Whether dietary AGEs are absorbed and are harmful to human health remains highly controversial. The objective of this study was to compare the effects of a diet high or low in AGEs on endothelial function, circulating AGEs, inflammatory mediators, and circulating receptors for AGEs in healthy adults. A randomized, parallel-arm, controlled dietary intervention was conducted for 6 wk with 24 healthy adults, aged 50-69 y, that compared isocaloric, food-equivalent diets that were prepared at either high or mild temperatures. Peripheral arterial tonometry, serum and urine carboxymethyl-lysine (CML), inflammatory mediators (interleukin-6, C-reactive protein, vascular adhesion molecule-1, and tumor necrosis factor-α receptors I and II), soluble receptor for AGEs, and endogenous secretory receptor for AGEs were measured at baseline and after 6 wk of dietary intervention. In the low-AGE diet group, the following changed from baseline to 6 wk (mean ± SE): serum CML from 763 ± 24 to 679 ± 29 ng/mL (P = 0.03) and urine CML from 1.37 ± 1.47 to 0.77 ± 2.01 µg/mL creatinine (P = 0.02). There were no significant changes in serum and urinary CML concentrations from baseline to follow-up in the high-AGE diet group. A high- or low-AGE diet had no significant impact on peripheral arterial tonometry or any inflammatory mediators after 6 wk of dietary intervention. In healthy middle-aged to older adults, consumption of a diet high or low in AGEs for 6 wk had no impact on endothelial function and inflammatory mediators, 2 precursors of cardiovascular disease.
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Proteínas en la Dieta/efectos adversos , Endotelio Vascular/fisiopatología , Productos Finales de Glicación Avanzada/efectos adversos , Enfermedades Vasculares Periféricas/etiología , Receptores Inmunológicos/sangre , Vasculitis/etiología , Anciano , Biomarcadores/sangre , Biomarcadores/orina , Proteínas en la Dieta/metabolismo , Endotelio Vascular/inmunología , Femenino , Estudios de Seguimiento , Productos Finales de Glicación Avanzada/sangre , Humanos , Hiperemia/epidemiología , Hiperemia/etiología , Hiperemia/inmunología , Hiperemia/fisiopatología , Mediadores de Inflamación/sangre , Lisina/análogos & derivados , Lisina/sangre , Lisina/orina , Reacción de Maillard , Masculino , Maryland/epidemiología , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/epidemiología , Enfermedades Vasculares Periféricas/inmunología , Enfermedades Vasculares Periféricas/fisiopatología , Receptor para Productos Finales de Glicación Avanzada , Receptores Inmunológicos/química , Riesgo , Índice de Severidad de la Enfermedad , Solubilidad , Resistencia Vascular , Vasculitis/epidemiología , Vasculitis/inmunología , Vasculitis/fisiopatologíaAsunto(s)
Enfermedades Vasculares Periféricas/inmunología , Enfermedades de la Piel/inmunología , Trombofilia/complicaciones , Biomarcadores/análisis , Complemento C3/análisis , Técnica del Anticuerpo Fluorescente , Humanos , Inmunoglobulina M/análisis , Enfermedades Vasculares Periféricas/patología , Enfermedades de la Piel/patologíaRESUMEN
BACKGROUND: Much has been made of obesity's health impact, largely founded on data regarding patient weight and circulating adipose-derived mediator levels. Paradoxically, a "healthy obese" state exists, but substantial knowledge gaps also exist regarding human adipose-phenotype determinants. Surgical major amputation (AMP) patients are the "sickest-of-the-sick." Conversely, elective knee replacement (TKR) is reserved for patients who expect continued health and longevity. To delineate human adipose biology variability and clinical determinants, we studied fresh subcutaneous adipose from AMP patients, using TKR patients as controls. We hypothesized that AMP patients would display a pro-inflammatory adipokine signature, and that certain clinical conditions (diabetes, hypertension, hyperlipidemia, high BMI, uremia) would independently drive elevated adipose inflammation. METHODS: AMP (n = 29) and TKR (n = 20) adipose tissue samples and clinical data were collected prospectively, and protein was isolated and analyzed for 8 adipose-related mediators. Statistical analyses included Wilcoxon's rank sum test, Fisher's exact test, and multiple linear regression modeling of clinical parameter predictors of mediator expression. RESULTS: Interleukin-(IL)-6, IL-8, leptin, resistin, and PAI-1 were differentially expressed (up to 200-fold) between AMP/TKR cohorts. Key clinical parameters that associated with protein levels of adipose phenotype included age, gender, hypertension, hyperlipidemia, congestive heart failure, cerebrovascular disease, renal disease, and warfarin, statin, and insulin use. BMI failed to be predictive. CONCLUSIONS: AMP patients display adiposopathy with a pro-inflammatory adipose phenotypic signature compared with TKR controls. BMI fails to predict phenotype, yet other clinical conditions, such as age, hyperlipidemia, and renal insufficiency, do drive adipokine expression. Understanding human adipose phenotypic determinants stands as a fundamental priority when future studies dissect the interplay between adipose biology and surgical diseases/outcomes.
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Amputación Quirúrgica , Citocinas/análisis , Mediadores de Inflamación/análisis , Inflamación/inmunología , Enfermedades Vasculares Periféricas/cirugía , Grasa Subcutánea/inmunología , Factores de Edad , Anciano , Artroplastia de Reemplazo de Rodilla , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/inmunología , Estudios de Casos y Controles , Enfermedad Crónica , Comorbilidad , Diabetes Mellitus/epidemiología , Diabetes Mellitus/inmunología , Procedimientos Quirúrgicos Electivos , Femenino , Humanos , Inflamación/epidemiología , Interleucina-6/análisis , Interleucina-8/análisis , Leptina/análisis , Modelos Lineales , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Obesidad/inmunología , Enfermedades Vasculares Periféricas/epidemiología , Enfermedades Vasculares Periféricas/inmunología , Fenotipo , Inhibidor 1 de Activador Plasminogénico/análisis , Polifarmacia , Estudios Prospectivos , Resistina/análisis , Factores SexualesRESUMEN
PURPOSE: Sulodexide is a mixture of heparin and dermatan sulphate which has an antithrombotic action. It was shown that it has also direct effect on the endothelial cells. We tested the effect of sulodexide on the intravascular homeostasis in patients with peripheral vascular disease. METHODS: Sulodexide was infused iv. at a dose of 1200 Lipoprotein Lipase Releasing Units (LRU) in 10 patients with peripheral vascular disease. Blood samples were collected before the infusion and 1, 6 and 24 hours after the infusion. Inflammatory and fibrinolytic parameters were studied in the collected serum samples. Additionally, ex-vivo effect of the serum samples on in vitro function of the endothelial cells was studied. RESULTS: Infusion of sulodexide caused acute and transient peak of the Hepatocyte Growth Factor (HGF) concentration in blood and decrease of the Vascular Endothelial Growth Factor (VEGF) level, what, as we found in in vitro experiments, was due to adsorption of VEGF to endothelium. We found that HGF enhanced in vitro stimulating effect of VEGF on proliferation of the endothelial cells. Serum level of interleukin-6 was gradually decreased, whereas fibrinolytic activity of serum, reflected by t-PA/PAI-1 ratio, increased. Serum samples obtained from the studied patients suppressed oxidative stress and release of interleukin-6 in endothelial cells maintained in in vitro culture. CONCLUSION: Sulodexide reduces intravascular inflammation and suppresses inflammatory reaction in the endothelial cells; both effects are desirable in patients with peripheral vascular disease.
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Anticoagulantes/administración & dosificación , Endotelio Vascular/efectos de los fármacos , Glicosaminoglicanos/administración & dosificación , Homeostasis/efectos de los fármacos , Enfermedades Vasculares Periféricas/tratamiento farmacológico , Vasculitis/tratamiento farmacológico , Anticoagulantes/farmacología , Biomarcadores/sangre , Biomarcadores/metabolismo , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Endoteliales/efectos de los fármacos , Células Endoteliales/inmunología , Células Endoteliales/metabolismo , Endotelio Vascular/inmunología , Endotelio Vascular/metabolismo , Glicosaminoglicanos/farmacología , Factor de Crecimiento de Hepatocito/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Inyecciones Intravenosas , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/inmunología , Enfermedades Vasculares Periféricas/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Vasculitis/inmunología , Vasculitis/metabolismoRESUMEN
BACKGROUND: Statin therapy is used in the medical management of patients with peripheral vascular disease (PVD) and abdominal aortic aneurysm (AAA) for the pleiotropic and anti-inflammatory benefits. We hypothesize that the inflammatory mechanisms of monocyte-endothelial cell interactions in endothelial barrier dysfunction are more significant in patients with PVD compared with those with AAA. The purpose of this study was to assess patient peripheral blood monocyte adhesion molecules by flow cytometry and monocyte-induced endothelial barrier dysfunction by using an in vitro endothelial cell layer and electric cell-substrate impedance sensing (ECIS) system. METHODS: Peripheral blood was collected from patients with either PVD (ankle-brachial index <0.9, toe-arm index <0.8, or required lower extremity vascular intervention) or AAA (aortic diameter >3.0 cm). Monocytes were isolated from fresh whole blood using an accuspin-histopaque technique. The separated monocytes underwent flow cytometry analysis to evaluate the expression levels of the cell membrane adhesion molecules: CD18, CD11a/b/c, and very late antigen-4. Endothelial cell function was assessed by adding monocytes to an endothelial monolayer on ECIS arrays and coculturing overnight. Peak changes in transendothelial electrical resistance were measured and compared between patient groups. RESULTS: Twenty-eight monocyte samples were analyzed for adhesion molecules (PVD, 19 and AAA, 9) via flow cytometry, and 11 patients were evaluated for endothelial dysfunction (PVD, 7 and AAA, 4) via ECIS. There was no significant difference between risk factors among PVD and AAA patients except for age, where AAA patients were significantly older than PVD patients in both flow cytometry and ECIS groups (P=0.02 and 0.01, respectively). There were significantly higher levels of adhesion molecules CD11a, CD18, and CD11c (averaged mean fluorescent intensity P values: 0.047, 0.038, and 0.014, respectively) in PVD patients compared with AAA patients. No significant difference was found for CD11b and very late antigen-4 expression (P=0.21 and 0.15, respectively). There was significantly more monocyte-endothelial cell dysfunction in patients with PVD versus patients with AAA, with a maximal effect seen at 15h after monocyte addition (P=0.032). CONCLUSIONS: Patients with PVD have increased expression levels of certain monocyte adhesion molecules and greater monocyte-induced endothelial layer dysfunction compared with those with AAA. This may lead to other methods of targeted therapy to improve outcomes of these vascular patients.
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Aneurisma de la Aorta Abdominal/metabolismo , Moléculas de Adhesión Celular/metabolismo , Endotelio Vascular/fisiopatología , Monocitos/metabolismo , Enfermedades Vasculares Periféricas/metabolismo , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/inmunología , Células Endoteliales/fisiología , Femenino , Citometría de Flujo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/inmunologíaRESUMEN
OBJECTIVE: Decidual vasculopathy (DV) describes pathological findings seen in the spiral arteries in preeclampsia (PE). Morphologically, DV is characterized by fibrinoid necrosis and foamy macrophages within the vessel walls. The impact of the lesions on clinical outcome and placental pathology is unclear. We compared cases with DV to cases without these lesions on clinical outcome and placental histology in PE. STUDY DESIGN: Placental sections from 107 patients admitted with PE at the Radboud University Nijmegen Medical Centre, during the years 1995-2000, were analyzed. 25 cases were excluded due to incomplete records or multiple pregnancy. Cases with DV (n = 41) and without DV (n = 41) were compared for various clinical and placental histological parameters, using Mann-Whitney test. P-value < 0.05 was considered significant. RESULTS: Clinically, DV related to higher diastolic blood pressure, shorter gestational age, lower birth weight and lower umbilical artery pH. Histologically, DV related to more accelerated villous maturity and perivascular inflammatory cell infiltration. No differences were found in maternal biochemical variables (protein-to-creatinine ratio, constituents of HELLP syndrome), fetal-maternal interface parameters (placenta weight, infarctions, hematoma, calcifications), or neonatal outcome measures (birth weight centile, APGAR scores, and perinatal death). CONCLUSIONS: In PE, the presence of DV related to placental accelerated villous maturity, perivascular inflammatory cell infiltration, and adverse maternal and fetal outcome without affecting neonatal survival. Whether or not DV results from or raises the risk on severe preeclampsia remains to be elucidated.
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Decidua/irrigación sanguínea , Enfermedades Vasculares Periféricas/patología , Enfermedades Placentarias/patología , Circulación Placentaria , Preeclampsia/fisiopatología , Centros Médicos Académicos , Adulto , Decidua/inmunología , Decidua/patología , Femenino , Células Espumosas/inmunología , Células Espumosas/patología , Humanos , Recién Nacido , Masculino , Necrosis , Países Bajos/epidemiología , Infiltración Neutrófila , Enfermedades Vasculares Periféricas/epidemiología , Enfermedades Vasculares Periféricas/etiología , Enfermedades Vasculares Periféricas/inmunología , Enfermedades Placentarias/epidemiología , Enfermedades Placentarias/etiología , Enfermedades Placentarias/inmunología , Placentación , Preeclampsia/etiología , Preeclampsia/inmunología , Preeclampsia/patología , Embarazo , Prevalencia , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND AND OBJECTIVES: The objective of this study was to determine the clinical significance of renal vascular lesions in lupus nephritis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Renal vascular lesions defined as thrombotic microangiopathy, lupus vasculopathy, uncomplicated vascular immune deposits, and arterial sclerosis were evaluated in relation to renal and vascular morbidity and overall mortality. RESULTS: Biopsies from 161 patients revealed thrombotic microangiopathy (13), lupus vasculopathy (5), and arterial sclerosis (93). No renal vascular lesions were found in 24.8% of patients. At the time of biopsy, arterial sclerosis or lupus vasculopathy patients were older (arterial sclerosis=37.9±13.0 and lupus vasculopathy=44.4±8.9 versus controls=33.1±8.9 years, P<0.05), and the mean arterial pressure was higher in all groups compared with controls. Nephritis subtype, activity indices, and proteinuria were similar between groups, estimated GFR was lower in arterial sclerosis (70.5±33.3 versus 84.5±26.6 ml/min per 1.73 m(2), P=0.03), and chronicity index (thrombotic microangiopathy=3.5, lupus vasculopathy=4.5, and arterial sclerosis=2.5) was higher in all renal vascular lesions subgroups versus controls (1.0, P<0.05). In 133 patients with similar follow-up, the association between renal vascular lesions and vascular events was significant (Fisher exact test, P=0.002) and remained so after multivariate analysis (exact conditional scores test, P=0.04), where the difference between arterial sclerosis and uncomplicated vascular immune deposits was most noticeable (odds ratio [95% confidence interval]=8.35[0.98, 83.12], P=0.05). The associations between renal vascular lesions, renal outcomes, and death were not significant, likely because of insufficient power. CONCLUSIONS: Renal vascular lesions are common in SLE patients with nephritis and may be associated with arterial vascular events.
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Vasos Sanguíneos/patología , Riñón/irrigación sanguínea , Nefritis Lúpica/complicaciones , Nefritis Lúpica/patología , Enfermedades Vasculares Periféricas/patología , Microangiopatías Trombóticas/patología , Adulto , Presión Sanguínea , Intervalos de Confianza , Progresión de la Enfermedad , Tasa de Filtración Glomerular , Humanos , Nefritis Lúpica/fisiopatología , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Enfermedades Vasculares Periféricas/complicaciones , Enfermedades Vasculares Periféricas/inmunología , Estudios Prospectivos , Proteinuria/orina , Insuficiencia Renal Crónica/etiología , Esclerosis , Índice de Severidad de la Enfermedad , Microangiopatías Trombóticas/complicaciones , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Many markers of platelet activation have been described but their reproducibility and comparability in patient populations are poorly defined. OBJECTIVES: We sought to compare markers of platelet and monocyte activation with platelet-monocyte aggregates, a proposed gold standard of in vivo platelet activation, and assess their reproducibility in patients with peripheral arterial disease: a population with substantial platelet activation, inflammation and risk of thrombotic events. PATIENTS/METHODS: Thirty patients with peripheral vascular disease attended on two occasions to permit within-day and between-day comparisons. In vivo platelet and monocyte activation were determined by flow-cytometric quantification of platelet-monocyte aggregation, platelet surface expression of P-selectin and CD40L, platelet-derived microparticles, and monocyte surface expression of CD40 and CD11b. Plasma concentrations of platelet-derived microparticles, soluble P-selectin and CD40L were measured by enzyme-linked immunosorbant assays. RESULTS: Platelet-monocyte aggregation (36.7±7.86%), and platelet surface expression of P-selectin (5.8±1.65%) and CD40L (3.3±1.45%) demonstrated comparable within-day (mean difference±co-efficient of reproducibility; 0.9±15.4%, 0.21±1.65% and 0.2±2.8% respectively) and between-day reproducibility (2.0±12.4%, 0.10±2.25% and 0.9±6.4% respectively). Platelet-monocyte aggregates correlated well with other platelet (r=0.30-0.50, P<0.02) and monocyte (r=0.27-0.47, P<0.03) activation markers. Flow cytometric and assay quantified platelet-derived microparticles showed poorer reproducibility (co-efficient of reproducibility >40). CONCLUSIONS: In patients with peripheral arterial disease, measurements of platelet-monocyte aggregates have good reproducibility and consistently reflect other markers of platelet and monocyte activation.
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Biomarcadores/sangre , Enfermedades Vasculares Periféricas/sangre , Activación Plaquetaria , Pruebas de Función Plaquetaria , Antígeno CD11b/sangre , Antígenos CD40/sangre , Ligando de CD40/sangre , Micropartículas Derivadas de Células/metabolismo , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Monocitos/inmunología , Monocitos/metabolismo , Variaciones Dependientes del Observador , Selectina-P/sangre , Enfermedades Vasculares Periféricas/diagnóstico , Enfermedades Vasculares Periféricas/inmunología , Adhesividad Plaquetaria , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , EscociaRESUMEN
BACKGROUND: Peripheral artery disease (PAD) is a common complication in patients receiving hemodialysis (HD). Cilostazol is used for the treatment of ischemic symptoms in patients with PAD, based on its antiplatelet and vasodilating effects. In addition to these beneficial effects on clinical symptoms in PAD patients, cilostazol has been proposed to have additional effects on clinical symptoms in patients with restless legs syndrome (RLS) via the upregulation of dopamine. We performed an observational, prospective study to evaluate the effect of cilostazol on several clinical and biochemical parameters in HD patients with PAD and RLS. METHODS: All the study patients received cilostazol treatment for 12 months. During the study period, several biochemical parameters, such as high-sensitivity CRP, von Willebrand antigen (VW-Ag), triglyceride (TG), high-density lipoprotein (HDL) and malondialdehyde-modified low-density lipoprotein, were monitored. A questionnaire on the physical status of PAD and RLS was also completed. 45 HD patients who received cilostazol were compared with a control group of 22 patients. RESULTS: The patients who continued cilostazol treatment exhibited a improvement in their serum inflammatory and biochemical parameters (VW-Ag, TG, HDL). Although PAD and RLS scores were not improved by multivariate analysis, several patients showed improvement of signs and symptoms which were included in the PAD or RLS scores. CONCLUSION: The treatment of HD patients with cilostazol improved some of the lipid-related and endovascular inflammatory biochemical parameters associated with PAD, and relieved the clinical symptoms and physical status of PAD in some cases.
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Mediadores de Inflamación/sangre , Inhibidores de Agregación Plaquetaria/uso terapéutico , Diálisis Renal/efectos adversos , Síndrome de las Piernas Inquietas/tratamiento farmacológico , Tetrazoles/uso terapéutico , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Cilostazol , Femenino , Humanos , Japón , Lípidos/sangre , Masculino , Persona de Mediana Edad , Análisis Multivariante , Enfermedades Vasculares Periféricas/tratamiento farmacológico , Enfermedades Vasculares Periféricas/etiología , Enfermedades Vasculares Periféricas/inmunología , Inhibidores de Agregación Plaquetaria/efectos adversos , Estudios Prospectivos , Síndrome de las Piernas Inquietas/etiología , Síndrome de las Piernas Inquietas/inmunología , Encuestas y Cuestionarios , Tetrazoles/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: Neutrophils play a key role in the immune response but can undesirably exacerbate inflammation. High-density lipoproteins (HDL) are antiinflammatory particles, exerting beneficial cardiovascular influences. We determined whether HDL exerts antiinflammatory effects on neutrophils and explored the mechanisms by which these occur. METHODS AND RESULTS: CD11b on activated human neutrophils was significantly attenuated by apolipoprotein A-I (apoA-I) and HDL. The effects of apoA-I were mediated via ABCA1, whereas the effects of HDL were via scavenger receptor BI. Both were associated with a reduction in the abundance of lipid rafts, and a strong correlation between raft abundance and CD11b activation was observed. ApoA-I and HDL reduced neutrophil adhesion to a platelet monolayer under shear flow, as well as neutrophil spreading and migration. ApoA-I also inhibited leukocyte recruitment to the endothelium in an acute in vivo model of inflammation. Finally, infusion of reconstituted HDL in patients with peripheral vascular disease was demonstrated to significantly attenuate neutrophil activation. CONCLUSION: We describe here a novel role for HDL and apoA-I in regulating neutrophil activation using in vitro, in vivo, and clinical approaches. We also show that these effects of HDL and apoA-I involve a mechanism requiring changes in membrane domain content rather than in cholesterol efflux per se.
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Apolipoproteína A-I/fisiología , Inflamación/inmunología , Lipoproteínas HDL/fisiología , Activación Neutrófila , Animales , Antígeno CD11b/análisis , Adhesión Celular , Movimiento Celular , Colesterol/metabolismo , Humanos , Inflamación/prevención & control , Masculino , Microdominios de Membrana/fisiología , Ratones , Ratones Endogámicos C57BL , Enfermedades Vasculares Periféricas/inmunología , Receptores Depuradores de Clase B , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
BACKGROUND: The systemic nature of atherosclerosis compromises medium-term survival following major vascular surgery. Neutrophil-lymphocyte ratio (NLR) is a simple index of systemic inflammatory burden which correlates with survival following percutaneous coronary intervention. METHODS: Patients undergoing elective major vascular surgery in 2 tertiary vascular units were identified from prospectively maintained databases. Factors associated with 2-year mortality were assessed by univariate and multivariate analyses. RESULTS: Over a 4-year period, 1021 patients underwent elective major vascular surgery (carotid endarterectomy, abdominal aortic aneurysm repair, lower limb revascularization). Two-year mortality was 11.2%. In multivariate analysis, preoperative NLR > 5 was independently associated with 2-year mortality (multivariate odds ratio [OR] 2.21; 95% confidence interval [CI] 1.22-4.01). CONCLUSION: Preoperative NLR identifies patients at increased risk of death within 2 years of major vascular surgery. This simple index may facilitate targeted preventive measures for high-risk patients.
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Linfocitos/inmunología , Neutrófilos/inmunología , Enfermedades Vasculares Periféricas/cirugía , Procedimientos Quirúrgicos Vasculares/mortalidad , Anciano , Anciano de 80 o más Años , Estudios Transversales , Procedimientos Quirúrgicos Electivos/mortalidad , Endarterectomía Carotidea/mortalidad , Procedimientos Endovasculares/mortalidad , Inglaterra , Femenino , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Enfermedades Vasculares Periféricas/inmunología , Enfermedades Vasculares Periféricas/mortalidad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Tasa de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
Matrix metalloproteinases are responsible for degradation and remodelling of extracellular matrix and exert important roles in initiation and progression of inflammatory diseases. We aimed to examine the role of Matrix metalloproteinases (MMPs) and their regulators in degenerative arterial diseases. Serum samples were collected from patients with arterial disease (n = 126), who underwent surgery because of symptomatic aorto-occlusive disease (AOD, n = 18), carotid artery stenosis (n = 67) or abdominal arotic aneurysm (n = 41). Serum MMP-1, MMP-8, MMP-13, TIMP-1, myeloperoxidase (MPO) and neutrophil elastase (HNE) concentrations were determined by ELISA, and the molar ratio of MMP-8 and TIMP-1 was calculated. To get reference values, the determinations were done on samples of healthy blood donors (n = 100). In univariate analyses, the patients had higher MMP-8 (P < 0.001), TIMP-1 (P = 0.045), and MMP-8/TIMP-1 (P < 0.001), and lower MPO (P < 0.001) when compared with the blood donors. All three subgroups had higher MMP-8 (P < 0.001) and MMP-8/TIMP-1 (P < 0.001), and lower MPO (P < 0.01, except AOD) levels when compared with the references. In multiple logistic regression analyses, the male gender (P < 0.01), age (P < 0.001), elevated MMP-8 (P < 0.001) and decreased MPO (P < 0.001) concentrations associated significantly with the risk for arterial disease, and provided an area under curve (AUC) of 0.97 in the Receiver operating characteristics analyses. In multiple linear regression analyses, HNE correlated with both MMP-8 (P < 0.001) and MPO (P = 0.008) concentrations. Combination of high MMP-8 and low MPO level in serum eventually reflecting selectively modified neutrophil degranulation may indicate increased risk for arterial disease.
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Aneurisma de la Aorta Abdominal/enzimología , Metaloproteinasa 8 de la Matriz/sangre , Enfermedades Vasculares Periféricas/enzimología , Peroxidasa/sangre , Factores de Edad , Anciano , Aneurisma de la Aorta Abdominal/sangre , Aneurisma de la Aorta Abdominal/inmunología , Femenino , Humanos , Modelos Lineales , Masculino , Metaloproteinasa 8 de la Matriz/inmunología , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/sangre , Enfermedades Vasculares Periféricas/inmunología , Peroxidasa/inmunología , Curva ROC , Factores Sexuales , Inhibidor Tisular de Metaloproteinasa-1/sangre , Inhibidor Tisular de Metaloproteinasa-1/inmunologíaRESUMEN
PURPOSE: Endovascular therapy (EVT) has been widely performed for peripheral artery disease. However, the high restenosis rate after EVT remains a major problem in patients on hemodialysis. Recent studies suggest that C-reactive protein (CRP) reflects vascular wall inflammation and can predict adverse events. We evaluated the possible prognostic values of CRP on outcomes in hemodialysis patients undergoing EVT. METHODS: A total of 234 hemodialysis patients undergoing EVT for peripheral artery disease were enrolled and followed-up for up to 5 years. They were divided into tertiles according to serum CRP levels (lowest tertile, < 1.4 mg/L; middle tertile, 1.4-6.0 mg/L; highest tertile, ≥ 6.0 mg/L). We analyzed the incidence of any reintervention or above-ankle amputation of the limb index (RAO) and any-cause death. RESULTS: Kaplan-Meier analysis showed that the event-free rate from the composite end point of RAO and any-cause death for 5 years was 60.2% in the lowest tertile, 50.0% in the middle tertile, and 25.1% in the highest tertile (P < .0001). The survival rate from any-cause death for 5 years was 81.5% in the lowest tertile, 65.2% in the middle tertile, and 59.3% in the highest tertile (P = .0078). Even after adjusting for other risk factors at baseline, preprocedural CRP levels were a significant predictive factor for RAO and any-cause death after EVT in a multivariable Cox analysis. CONCLUSIONS: Elevated preprocedural serum CRP levels were associated with RAO and any-cause death after EVT in hemodialysis patients with peripheral artery disease.
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Angioplastia de Balón , Proteína C-Reactiva/análisis , Mediadores de Inflamación/sangre , Enfermedades Vasculares Periféricas/terapia , Diálisis Renal , Anciano , Amputación Quirúrgica , Angioplastia de Balón/efectos adversos , Angioplastia de Balón/instrumentación , Angioplastia de Balón/mortalidad , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Supervivencia sin Enfermedad , Femenino , Humanos , Japón , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/diagnóstico , Enfermedades Vasculares Periféricas/inmunología , Enfermedades Vasculares Periféricas/mortalidad , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Recurrencia , Diálisis Renal/efectos adversos , Diálisis Renal/mortalidad , Medición de Riesgo , Factores de Riesgo , Stents , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía Doppler , Regulación hacia ArribaRESUMEN
OBJECTIVE: To determine whether or not elevated titers of antinuclear antibodies (ANA) and/or rheumatoid factor (RF) are associated with patients with advanced peripheral arterial disease (PAD). SUBJECTS AND METHODS: A cross-sectional study was done between September 2005 and December 2006. Fifty-eight patients with clinical and angiographic evidence of PAD and 41 controls were studied. Controls had no documented history of peripheral, coronary or cerebral vascular disease. All subjects were screened for metabolic syndrome and C-reactive protein (CRP) as risk factors for peripheral vascular disease. Additionally, all were tested for anti-mitochondrial, anti-neutrophil cytoplasmic and anti-smooth muscle antibodies; those with positive results were excluded. ANA and RF were measured in sera from cases and controls. RESULTS: One case and 3 controls had positive anti-smooth muscle antibodies and were therefore excluded from statistical analysis. Metabolic syndrome was significantly more prevalent in patients than controls (p<0.05). Mean CRP level was 4.78+/-7.70 and 2.65+/-3.86 mg/dl in cases and controls, respectively (p=0.021). ANA were detected at a titer of >or=1:40 in 6 (10.5%) of the advanced PAD patients but none of the controls; the difference was not statistically significant. RF was less prevalent in cases than controls (p<0.05). CONCLUSION: RF and ANA do not appear to be associated with PAD in a Kuwaiti population.