RESUMEN
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
Experimental studies support a link between activation of the renin-angiotensin-aldosterone system and cardiovascular disease (CVD). The relationship with subclinical atherosclerosis is uncertain. Among 1,699 individuals without prevalent CVD from the Multiethnic Study of Atherosclerosis, we measured plasma renin activity (PRA) and aldosterone. Using multivariable logistic regression with restricted cubic splines, we assessed continuous log-transformed PRA and aldosterone associations with the ankle-brachial index (ABI) and coronary artery calcium (CAC) scores (Agatston) with adjustment for cardiovascular disease (CVD) risk factors, kidney function, and inflammatory biomarkers. In fully adjusted models mutually adjusting for PRA and aldosterone, higher PRA was associated with an ABI <1.0 (p overall <0.001, p nonlinearâ¯=â¯0.02) and CAC Agatston score >300 (p overallâ¯=â¯0.02, p nonlinearâ¯=â¯0.22), while aldosterone was not associated with either outcome. For example, compared to the 10th percentile (0.16 ng/ml/hr) of PRA, the 90th percentile (2.68 ng/ml/hr) had 3.6 times (OR 3.62; 95% CI: 2.13 to 6.13) and 1.7 times higher odds (odds ratio 1.67; 95% confidence interval: 1.13 to 2.48) of ABI <1.0 and CAC >300, respectively. These associations persisted after adjustment for levels of C-reactive protein, Interleukin-6, and Tumor Necrosis Factor-alpha. There were no significant differences in these associations by race/ethnicity or antihypertensive medication status. In conclusion, in a multiethnic cohort of community-living adults without prevalent clinical CVD, PRA was associated with greater burden of subclinical peripheral artery and coronary artery disease. These findings provide additional evidence that PRA may have deleterious effects on cardiovascular health through an atherosclerotic pathway.
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Aterosclerosis/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedades Vasculares Periféricas/sangre , Renina/sangre , Aldosterona/sangre , Índice Tobillo Braquial , Biomarcadores/sangre , Femenino , Humanos , Inflamación/sangre , Pruebas de Función Renal , Masculino , Factores de Riesgo , Calcificación Vascular/sangreAsunto(s)
Isquemia/mortalidad , Extremidad Inferior/irrigación sanguínea , Linfocitos , Neutrófilos , Enfermedades Vasculares Periféricas/complicaciones , Enfermedad Aguda/mortalidad , Anciano , Amputación Quirúrgica/estadística & datos numéricos , Biomarcadores , Femenino , Estudios de Seguimiento , Humanos , Isquemia/sangre , Isquemia/etiología , Isquemia/cirugía , Recuento de Leucocitos , Extremidad Inferior/cirugía , Masculino , Enfermedades Vasculares Periféricas/sangre , Enfermedades Vasculares Periféricas/mortalidad , Enfermedades Vasculares Periféricas/cirugía , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
: Chronic Kidney Disease (CKD) represents a risk factor for fatal and nonfatal cardiovascular (CV) events, including peripheral vascular disease (PVD). This occurs because CKD encompasses several factors that lead to poor prognoses, mainly due to a reduction of the estimated glomerular filtration rate (eGFR), the presence of proteinuria, and the uremic inflammatory milieu. The matrix metalloproteinases (MMPs) are a group of zinc-containing endopeptidases implicated in extracellular matrix (ECM) remodeling, a systemic process in tissue homeostasis. MMPs play an important role in cell differentiation, angiogenesis, inflammation, and vascular damage. Our aim was to review the published evidence regarding the association between MMPs, PVD, and CKD to find possible common pathophysiological mechanisms. MMPs favor ECM deposition through the glomeruli, and start the shedding of cellular junctions and epithelial-mesenchymal transition in the renal tubules. MMP-2 and -9 have also been associated with the presence of systemic vascular damage, since they exert a pro-inflammatory and proatherosclerotic actions. An imbalance of MMPs was found in the context of PVD, where MMPs are predictors of poor prognoses in patients who underwent lower extremity revascularization. MMP circulating levels are increased in both conditions, i.e., that of CKD and PVD. A possible pathogenic link between these conditions is represented by the enhanced production of transforming growth factor-ß that worsens vascular calcifications and atherosclerosis and the development of proteinuria in patients with increased levels of MMPs. Proteinuria has been recognized as a marker of systemic vascular damage, and this may explain in part the increase in CV risk that is manifest in patients with CKD and PVD. In conclusion, MMPs can be considered a useful tool by which to stratify CV risk in patients with CKD and PVD. Further studies are needed to investigate the causal-relationships between MMPs, CKD, and PVD, and to optimize their prognostic and predictive (in response to treatments) roles.
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Metaloproteinasas de la Matriz/metabolismo , Enfermedades Vasculares Periféricas/metabolismo , Insuficiencia Renal Crónica/metabolismo , Animales , Humanos , Riñón/metabolismo , Riñón/fisiopatología , Metaloproteinasas de la Matriz/análisis , Metaloproteinasas de la Matriz/sangre , Enfermedades Vasculares Periféricas/sangre , Enfermedades Vasculares Periféricas/fisiopatología , Proteinuria/sangre , Proteinuria/metabolismo , Proteinuria/fisiopatología , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/fisiopatología , Calcificación Vascular/sangre , Calcificación Vascular/metabolismo , Calcificación Vascular/fisiopatologíaAsunto(s)
Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/mortalidad , LDL-Colesterol/sangre , Enfermedades Vasculares Periféricas/sangre , Enfermedades Vasculares Periféricas/mortalidad , Adulto , Anciano , Causas de Muerte , Femenino , Humanos , Hipolipemiantes , Incidencia , Masculino , Persona de Mediana Edad , Factores de Riesgo , España/epidemiologíaRESUMEN
OBJECTIVE: Metabolic changes in type 1 diabetes mellitus (T1DM) impair vasodilation, and this leads to tissue hypoxia and microvascular pathology. Hyperbaric oxygen therapy (HBOT) can significantly improve the outcome of ischemic conditions in T1DM patients and reduce vascular complications. The aim of our study was to assess the effects of HBOT on plasma fatty acid (FA) composition, and expression of insulin-like growth factor binding protein 1 (IGFBP-1) in T1DM patients. METHODS: Our study included 24 adult T1DM patients diagnosed with peripheral vascular complications. The patients were exposed to 10 sessions of 100% oxygen inhalation at 2.4 atmosphere absolute for 1 hour. Blood samples were collected at admission and after HBOT for measurement of metabolic parameters, FA composition and IGFBP-1. Measurement of plasma FA composition was determined by gas chromatography. Expression of IGFBP-1 in the serum was estimated by Western blot analysis. RESULTS: HBOT decreased blood levels of total cholesterol (p<0.05), triglycerides (p<0.05) and low-density lipoprotein (p<0.05). HBOT increased plasma levels of individual FAs: palmitic acid (p<0.05), palmitoleic acid (p<0.05), docosapentaenoic acid (p<0.05) and docosahexaenoic acid (p<0.01), and decreased levels of stearic acid (p<0.05), alpha linolenic acid (p<0.05) and linoleic acid (p<0.01). Expression of IGFBP-1 (p<0.01) was increased, whereas the level of insulin (p<0.001) was decreased in the serum after HBOT. CONCLUSIONS: Our results indicate that HBOT exerts beneficial effects in T1DM patients by improving the lipid profile and altering FA composition.
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Biomarcadores/sangre , Complicaciones de la Diabetes/sangre , Diabetes Mellitus Tipo 1/sangre , Ácidos Grasos/sangre , Oxigenoterapia Hiperbárica/métodos , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Enfermedades Vasculares Periféricas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Complicaciones de la Diabetes/etiología , Complicaciones de la Diabetes/terapia , Diabetes Mellitus Tipo 1/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/etiología , Enfermedades Vasculares Periféricas/terapia , Proyectos Piloto , Pronóstico , Estudios ProspectivosAsunto(s)
Úlcera de la Pierna , Enfermedades Vasculares Periféricas , Plasma/metabolismo , Vitamina K , Administración Intravenosa , Humanos , Úlcera de la Pierna/sangre , Úlcera de la Pierna/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/sangre , Enfermedades Vasculares Periféricas/tratamiento farmacológico , Vitamina K/administración & dosificación , Vitamina K/efectos adversosRESUMEN
Microparticles are a distinctive group of small vesicles, without nucleus, which are involved as significant modulators in several physiological and pathophysiological mechanisms. Plasma microparticles from various cellular lines have been subject of research. Data suggest that they are key players in development and manifestation of cardiovascular diseases and their presence, in high levels, is associated with chronic inflammation, endothelial damage and thrombosis. The strong correlation of microparticle levels with several outcomes in cardiovascular diseases has led to their utilization as biomarkers. Despite the limited clinical application at present, their significance emerges, mainly because their detection and enumeration methods are improving. This review article summarizes the evidence derived from research, related with the genesis and the function of microparticles in the presence of various cardiovascular risk factors and conditions. The current data provide a substrate for several theories of how microparticles influence various cellular mechanisms by transferring biological information.
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Enfermedades Cardiovasculares/fisiopatología , Micropartículas Derivadas de Células/fisiología , Insuficiencia Cardíaca/fisiopatología , Síndrome Coronario Agudo/sangre , Apoptosis/fisiología , Aterosclerosis/sangre , Fibrilación Atrial/sangre , Biomarcadores/sangre , Coagulación Sanguínea/fisiología , Vasos Sanguíneos/fisiopatología , Enfermedades Cardiovasculares/sangre , Diabetes Mellitus/sangre , Dislipidemias/sangre , Endotelio Vascular/patología , Hipertensión Esencial/sangre , Insuficiencia Cardíaca/sangre , Humanos , Hipertensión Pulmonar/sangre , Inflamación/sangre , Neovascularización Patológica/sangre , Estrés Oxidativo/fisiología , Enfermedades Vasculares Periféricas/sangre , Pronóstico , Factores de Riesgo , Fumar/sangre , Accidente Cerebrovascular/sangre , Trombosis/sangreRESUMEN
Peripheral disease affects both arteries and veins and encompasses pathophysiologic conditions that affect arterial, venous, and lymphatic circulations. This article discusses disorders of peripheral vascular disease (PVD) that affect the lower extremity. PVD is an obstruction in the arteries known as arteriosclerosis obliterans, a condition that manifests from insufficient tissue perfusion that results in hardening of the arteries. Peripheral artery disease leads to an inflammatory condition called atherosclerosis. People at greatest risk include smokers, diabetics, those with high blood pressure, and those with elevated cholesterol levels.
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Alta del Paciente , Educación del Paciente como Asunto , Enfermedades Vasculares Periféricas/terapia , Adulto , Arterias , Diabetes Mellitus , Femenino , Humanos , Hipertensión , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/sangre , Enfermedades Vasculares Periféricas/epidemiología , Conducta de Reducción del Riesgo , Fumadores , VenasRESUMEN
BACKGROUND AND OBJECTIVE: In patients with peripheral artery disease requiring surgery, anaemia has been found to independently predict short and medium term higher morbidity and mortality. PATIENTS AND METHODS: We retrospectively studied all patients undergoing surgery, consecutively during 2months in 12 vascular surgery units. We analysed cardiovascular risk factors and preoperative haemoglobin. Statistical analysis was done with Kaplan-Meier for survival and logistic regression modelling to identify predictors of mortality. RESULTS: 518 patients were consecutively operated on in our vascular units, the mortality rate was 21% the first year and 34% for cardiovascular events. Preoperative anaemia was present in 63% of the ischemic patients and in 23% of the patients requiring aneurysm repair, one year after surgery it increased to 68% and 50% respectively. When preoperative anaemia was superior to 10mg/dl, one year survival increased (96% vs. 90%), fewer cardiovascular events occurred and there were fewer amputations (24% vs. 68%). CONCLUSIONS: On multivariable analysis: age, renal failure, chronic lung disease, coronary artery disease, postoperative complications and previous cardiovascular events were associated with an increased risk mortality rate. Preoperative haemoglobin influenced proportionally such that for every 1mg /dl increase, the probability of mortality decreases by 0.81. Preoperative anaemia, especially when haemoglobin is inferior to 10mg/dl, is associated with an increased risk of death and amputation.
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Amputación Quirúrgica/estadística & datos numéricos , Anemia/complicaciones , Enfermedades Vasculares Periféricas/cirugía , Complicaciones Posoperatorias/mortalidad , Procedimientos Quirúrgicos Vasculares/mortalidad , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Anemia/sangre , Anemia/epidemiología , Aneurisma/sangre , Aneurisma/cirugía , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/mortalidad , Causas de Muerte , Femenino , Hemoglobina A/análisis , Humanos , Isquemia/sangre , Isquemia/cirugía , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/sangre , Enfermedades Vasculares Periféricas/mortalidad , Complicaciones Posoperatorias/sangre , Prevalencia , Pronóstico , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Procedimientos Quirúrgicos Vasculares/efectos adversosRESUMEN
OBJECTIVES: To examine the influence of serum magnesium on 30-day mortality and cardiac and noncardiac morbidity. DESIGN: Retrospective cross-sectional observational study of routinely collected prospective data. SETTING: Single-center tertiary vascular center in the United Kingdom. PARTICIPANTS: All patients undergoing arterial peripheral vascular surgery during an unplanned admission. INTERVENTIONS: Observational, no interventions implemented. MEASUREMENTS AND MAIN RESULTS: In the study, nâ¯=â¯197. One hundred thirty-eight were male (70.1%). Median age at procedure was 70.0 years (interquartile range 20.0). Of those with a documented history, 37.9% had diabetes, 81.7% had a smoking history, 63.7% had hypertension, and 26.5% had known ischemic heart disease or heart failure. There was a significant perioperative change in magnesium (p < 0.001), calcium (p < 0.001), and creatinine (pâ¯=â¯0.004), with no significant alteration in potassium (pâ¯=â¯0.096). Thirty-day mortality was 4.6%. Thirty-day cardiac morbidity was 4.1%. Thirty-day noncardiac morbidity was 32.3%. Postoperative magnesium was independently predictive for 30-day mortality (pâ¯=â¯0.02, odds ratio [OR] 0.96, 95% confidence interval [CI] 0.94-0.99) and cardiac morbidity (pâ¯=â¯0.03, OR 0.97, 95% CI 0.95-1.00). Only a previous smoking history was independently predictive of noncardiac morbidity (pâ¯=â¯0.03, OR 9.67, 95% CI 1.20-78.15). CONCLUSION: Perioperative changes in serum magnesium may have an influence on short-term mortality and cardiac complications. This should be considered in the management of patients undergoing unplanned peripheral vascular surgery; however, further research is needed to examine the benefit of supplementation perioperatively and to explore the exact mechanisms.
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Urgencias Médicas , Cardiopatías/epidemiología , Magnesio/sangre , Enfermedades Vasculares Periféricas/cirugía , Complicaciones Posoperatorias/epidemiología , Procedimientos Quirúrgicos Vasculares/efectos adversos , Anciano , Biomarcadores/sangre , Estudios Transversales , Femenino , Cardiopatías/sangre , Cardiopatías/etiología , Humanos , Masculino , Morbilidad/tendencias , Periodo Perioperatorio , Enfermedades Vasculares Periféricas/sangre , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Reino Unido/epidemiologíaRESUMEN
BACKGROUND AND AIMS: The lysosomal cysteine proteases cathepsin B and S have been implicated in the atherosclerotic process. The present paper investigates the association between serum levels of cathepsin B and S and cardiovascular events and mortality in patients with stable coronary heart disease. METHODS: The CLARICOR trial is a randomised, placebo-controlled trial investigating the effect of clarithromycin versus placebo in patients with stable coronary heart disease. The outcome was time to either a cardiovascular event or all-cause mortality. The placebo group was used as discovery sample and the clarithromycin group as replication sample: nâ¯=â¯1998, nâ¯=â¯1979; mean age (years) 65, 65; 31%, 30% women; follow-up for 10 years; number of composite outcomes nâ¯=â¯1204, nâ¯=â¯1220; respectively. We used a pre-defined multivariable Cox regression model adjusting for inflammation, established cardiovascular risk factors, kidney function, and use of cardiovascular drugs. RESULTS: Cathepsin B was associated with an increased risk of the composite outcome in both samples after multivariable adjustment (discovery: multivariable ratio (HR) per standard deviation increase 1.12, 95% confidence interval (CI) 1.05-1.19, pâ¯<â¯0.001, replication; HR 1.14, 95% CI 1.07-1.21, pâ¯<â¯0.001). There was no significant association between cathepsin S and the composite outcome in either the discovery or replication sample after multivariable adjustment (p>0.45). Secondary analyses suggest that cathepsin B was predominantly associated with mortality rather than specific cardiovascular events. CONCLUSIONS: Cathepsin B, but not serum cathepsin S, was associated with an increased risk of cardiovascular events in patients with stable coronary heart disease. The clinical implications of our findings remain to be established.
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Aterosclerosis/sangre , Enfermedades Cardiovasculares/epidemiología , Catepsina B/sangre , Catepsinas/sangre , Enfermedad Coronaria/sangre , Anciano , Angina Inestable/sangre , Aterosclerosis/tratamiento farmacológico , Trastornos Cerebrovasculares/sangre , Claritromicina/uso terapéutico , Enfermedad Coronaria/tratamiento farmacológico , Dinamarca , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Lisosomas/metabolismo , Masculino , Persona de Mediana Edad , Mortalidad , Infarto del Miocardio/sangre , Enfermedades Vasculares Periféricas/sangre , Modelos de Riesgos Proporcionales , Sistema de Registros , Factores de Riesgo , Resultado del TratamientoRESUMEN
It has long been known that chronic metabolic disease is associated with a parallel increase in the risk for developing peripheral vascular disease. Although more clinically relevant, our understanding about reversing established vasculopathy is limited compared with our understanding of the mechanisms and development of impaired vascular structure/function under these conditions. Using the 13-wk-old obese Zucker rat (OZR) model of metabolic syndrome, where microvascular dysfunction is sufficiently established to contribute to impaired skeletal muscle function, we imposed a 7-wk intervention of chronic atorvastatin treatment, chronic treadmill exercise, or both. By 20 wk of age, untreated OZRs manifested a diverse vasculopathy that was a central contributor to poor muscle performance, perfusion, and impaired O2 exchange. Atorvastatin or exercise, with the combination being most effective, improved skeletal muscle vascular metabolite profiles (i.e., nitric oxide, PGI2, and thromboxane A2 bioavailability), reactivity, and perfusion distribution at both individual bifurcations and within the entire microvascular network versus responses in untreated OZRs. However, improvements to microvascular structure (i.e., wall mechanics and microvascular density) were less robust. The combination of the above improvements to vascular function with interventions resulted in an improved muscle performance and O2 transport and exchange versus untreated OZRs, especially at moderate metabolic rates (3-Hz twitch contraction). These results suggest that specific interventions can improve specific indexes of function from established vasculopathy, but either this process was incomplete after 7-wk duration or measures of vascular structure are either resistant to reversal or require better-targeted interventions. NEW & NOTEWORTHY We used atorvastatin and/or chronic exercise to reverse established microvasculopathy in skeletal muscle of rats with metabolic syndrome. With established vasculopathy, atorvastatin and exercise had moderate abilities to reverse dysfunction, and the combined application of both was more effective at restoring function. However, increased vascular wall stiffness and reduced microvessel density were more resistant to reversal. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/reversal-of-microvascular-dysfunction/ .
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Atorvastatina/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Síndrome Metabólico/terapia , Microcirculación/efectos de los fármacos , Microvasos/efectos de los fármacos , Músculo Esquelético/irrigación sanguínea , Enfermedades Vasculares Periféricas/terapia , Condicionamiento Físico Animal/métodos , Esfuerzo Físico , Animales , Biomarcadores/sangre , Modelos Animales de Enfermedad , Epoprostenol/sangre , Hemodinámica/efectos de los fármacos , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/patología , Síndrome Metabólico/fisiopatología , Microvasos/patología , Microvasos/fisiopatología , Modelos Cardiovasculares , Músculo Esquelético/metabolismo , Óxido Nítrico/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Enfermedades Vasculares Periféricas/sangre , Enfermedades Vasculares Periféricas/patología , Enfermedades Vasculares Periféricas/fisiopatología , Ratas Zucker , Flujo Sanguíneo Regional , Carrera , Tromboxano A2/sangre , Factores de TiempoRESUMEN
The pathophysiology of sporadic Alzheimer's disease (AD) remains uncertain. Along with brain amyloid-ß (Aß) deposits and neurofibrillary tangles, cerebrovascular dysfunction is increasingly recognized as fundamental to the pathogenesis of AD. Using an experimental model of limb ischemia in transgenic APPPS1 mice, a model of AD (AD mice), we showed that microvascular impairment also extends to the peripheral vasculature in AD. At D70 following femoral ligation, we evidenced a significant decrease in cutaneous blood flow (- 29%, P < 0.001), collateral recruitment (- 24%, P < 0.001), capillary density (- 22%; P < 0.01) and arteriole density (- 28%; P < 0.05) in hind limbs of AD mice compared to control WT littermates. The reactivity of large arteries was not affected in AD mice, as confirmed by unaltered size, and vasoactive responses to pharmacological stimuli of the femoral artery. We identified blood as the only source of Aß in the hind limb; thus, circulating Aß is likely responsible for the impairment of peripheral vasculature repair mechanisms. The levels of the majority of pro-angiogenic mediators were not significantly modified in AD mice compared to WT mice, except for TGF-ß1 and PlGF-2, both of which are involved in vessel stabilization and decreased in AD mice (P = 0.025 and 0.019, respectively). Importantly, endothelin-1 levels were significantly increased, while those of nitric oxide were decreased in the hind limb of AD mice (P < 0.05). Our results suggest that vascular dysfunction is a systemic disorder in AD mice. Assessment of peripheral vascular function may therefore provide additional tools for early diagnosis and management of AD.
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Enfermedad de Alzheimer/fisiopatología , Miembro Posterior/fisiopatología , Isquemia/fisiopatología , Enfermedades Vasculares Periféricas/fisiopatología , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Arteriolas/metabolismo , Arteriolas/fisiopatología , Capilares/metabolismo , Capilares/fisiopatología , Modelos Animales de Enfermedad , Endotelina-1/sangre , Arteria Femoral/metabolismo , Arteria Femoral/fisiopatología , Miembro Posterior/irrigación sanguínea , Humanos , Isquemia/genética , Ratones , Ratones Transgénicos , Microcirculación/genética , Óxido Nítrico/sangre , Enfermedades Vasculares Periféricas/sangre , Enfermedades Vasculares Periféricas/genética , Factor de Crecimiento Placentario/sangre , Factor de Crecimiento Transformador beta1/sangreRESUMEN
BACKGROUND: A number of studies suggest that bivalirudin (BIV) is associated with similar efficacy but reduced bleeding when compared with unfractionated heparin (UFH) in patients undergoing peripheral vascular interventions (PVI). METHODS: A comprehensive literature search was conducted with the electronic databases MEDLINE, EMBASE and CENTRAL. These were queried to identify studies comparing BIV with UFH in PVI. Study endpoints included total bleeding events, major and minor bleeding events and procedural success. Random-effects meta-analysis method was used to pool endpoint odds ratios (OR) for both UFH and BIV with 95% confidence intervals (CI). RESULTS: A total of 12,335 patients (70.6â¯years; 59.7% male) were included from seven observational cohort studies (two prospective and five retrospective) comparing outcomes between BIV and UFH during PVI between January 2000 and May 2017. Compared with BIV, UFH was associated with significantly higher total bleeding, (OR 1.52 with 95% CI 1.11 to 2.09, pâ¯=â¯0.009), major bleeding (OR 1.38 with 95% CI 1.13 to 1.68, pâ¯=â¯0.002), and minor bleeding (OR 1.51 with 95% CI 1.09 to 2.08, pâ¯=â¯0.01). Procedural success rates were not different between the two groups (BIV vs HEP: OR 0.90 with 95% CI 0.49 to 1.64, pâ¯=â¯0.72) CONCLUSION: Compared with BIV, UFH was associated with more bleeding when used during PVI. There was no significant difference in procedural success between the two anticoagulation strategies.
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Anticoagulantes/uso terapéutico , Antitrombinas/uso terapéutico , Procedimientos Endovasculares , Heparina/uso terapéutico , Fragmentos de Péptidos/uso terapéutico , Enfermedades Vasculares Periféricas/terapia , Anciano , Anticoagulantes/efectos adversos , Antitrombinas/efectos adversos , Procedimientos Endovasculares/efectos adversos , Femenino , Hemorragia/inducido químicamente , Heparina/efectos adversos , Hirudinas/efectos adversos , Humanos , Masculino , Estudios Observacionales como Asunto , Fragmentos de Péptidos/efectos adversos , Enfermedades Vasculares Periféricas/sangre , Enfermedades Vasculares Periféricas/diagnóstico , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Medición de Riesgo , Factores de Riesgo , Resultado del TratamientoRESUMEN
The mechanisms underlying endothelial cell injury and defective vascular repair in systemic sclerosis (SSc) remain unclear. Since the recently discovered angiogenic T cells (Tang) may have an important role in the repair of damaged endothelium, this study aimed to analyze the Tang population in relation to disease-related peripheral vascular features in SSc patients. Tang (CD3+CD31+CXCR4+) were quantified by flow cytometry in peripheral blood samples from 39 SSc patients and 18 healthy controls (HC). Circulating levels of the CXCR4 ligand stromal cell-derived factor (SDF)-1α and proangiogenic factors were assessed in paired serum samples by immunoassay. Serial skin sections from SSc patients and HC were subjected to CD3/CD31 and CD3/CXCR4 double immunofluorescence. Circulating Tang were significantly increased in SSc patients with digital ulcers (DU) compared either with SSc patients without DU or with HC. Tang levels were significantly higher in SSc patients with late nailfold videocapillaroscopy (NVC) pattern than in those with early/active NVC patterns and in HC. No difference in circulating Tang was found when comparing either SSc patients without DU or patients with early/active NVC patterns and HC. In SSc peripheral blood, Tang percentage was inversely correlated to levels of SDF-1α and CD34+CD133+VEGFR-2+ endothelial progenitor cells (EPC), and positively correlated to levels of vascular endothelial growth factor and matrix metalloproteinase-9. Tang were frequently detected in SSc dermal perivascular inflammatory infiltrates. In summary, our findings demonstrate for the first time that Tang cells are selectively expanded in the circulation of SSc patients displaying severe peripheral vascular complications like DU. In SSc, Tang may represent a potentially useful biomarker reflecting peripheral vascular damage severity. Tang expansion may be an ineffective attempt to compensate the need for increased angiogenesis and EPC function. Further studies are required to clarify the function of Tang cells and investigate the mechanisms responsible for their change in SSc.
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Enfermedades Vasculares Periféricas/etiología , Enfermedades Vasculares Periféricas/patología , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/patología , Linfocitos T/patología , Adulto , Anciano , Complejo CD3/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neovascularización Patológica/sangre , Neovascularización Patológica/patología , Enfermedades Vasculares Periféricas/sangre , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/análisis , Receptores CXCR4/análisis , Esclerodermia Sistémica/sangreRESUMEN
Importance: The etiologic factors of late-life depression are still poorly understood. Recent evidence suggests that microvascular dysfunction is associated with depression, which may have implications for prevention and treatment. However, this association has not been systematically reviewed. Objective: To examine the associations of peripheral and cerebral microvascular dysfunction with late-life depression. Data Sources: A systematic literature search was conducted in MEDLINE and EMBASE for and longitudinal studies published since inception to October 16, 2016, that assessed the associations between microvascular dysfunction and depression. Study Selection: Three independent researchers performed the study selection based on consensus. Inclusion criteria were a study population 40 years of age or older, a validated method of detecting depression, and validated measures of microvascular function. Data Extraction and Synthesis: This systematic review and meta-analysis has been registered at PROSPERO (CRD42016049158) and is reported in accordance with the PRISMA and MOOSE guidelines. Data extraction was performed by an independent researcher. Main Outcomes and Measures: The following 5 estimates of microvascular dysfunction were considered in participants with or without depression: plasma markers of endothelial function, albuminuria, measurements of skin and muscle microcirculation, retinal arteriolar and venular diameter, and markers for cerebral small vessel disease. Data are reported as pooled odds ratios (ORs) by use of the generic inverse variance method with the use of random-effects models. Results: A total of 712 studies were identified; 48 were included in the meta-analysis, of which 8 described longitudinal data. Data from 43â¯600 participants, 9203 individuals with depression, and 72â¯441 person-years (mean follow-up, 3.7 years) were available. Higher levels of plasma endothelial biomarkers (soluble intercellular adhesion molecule-1: OR, 1.58; 95% CI, 1.28-1.96), white matter hyperintensities (OR, 1.29; 95% CI, 1.19-1.39), cerebral microbleeds (OR, 1.18; 95% CI, 1.03-1.34), and cerebral (micro)infarctions (OR, 1.30; 95% CI, 1.21-1.39) were associated with depression. Among the studies available, no significant associations of albuminuria and retinal vessel diameters with depression were reported. Longitudinal data showed a significant association of white matter hyperintensities with incident depression (OR, 1.19; 95% CI, 1.09-1.30). Conclusions and Relevance: This meta-analysis shows that both the peripheral and cerebral forms of microvascular dysfunction are associated with higher odds of (incident) late-life depression. This finding may have clinical implications because microvascular dysfunction might provide a potential target for the prevention and treatment of depression.
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Enfermedades de los Pequeños Vasos Cerebrales/epidemiología , Comorbilidad , Trastorno Depresivo/epidemiología , Microvasos/fisiopatología , Enfermedades Vasculares Periféricas/epidemiología , Anciano , Enfermedades de los Pequeños Vasos Cerebrales/sangre , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Trastorno Depresivo/sangre , Trastorno Depresivo/diagnóstico por imagen , Humanos , Microvasos/diagnóstico por imagen , Enfermedades Vasculares Periféricas/sangre , Enfermedades Vasculares Periféricas/diagnóstico por imagenRESUMEN
BACKGROUND: Hyperspectral imaging technology is a novel method of using transcutaneous measurement of oxyhemoglobin (HT-Oxy) and deoxyhemoglobin (HT-Deoxy) concentrations to create a two-dimensional, color-coded "oxygen map." The aims of this study were to compare the use of a hyperspectral imaging device with the transcutaneous oxygen measurement (TCOM), ankle-brachial index (ABI), and severity of peripheral vascular disease (PVD) and to assess their correlations. METHODS: This prospective study recruited 294 participants divided into three distinct groups composed of healthy volunteers and patients with PVD. Patients underwent measurements of lower limbs at a standardized point over the head of the first metatarsal on the plantar aspect using the hyperspectral imaging device, generating four outputs including HT-Oxy, HT-Deoxy, oxygen saturation (HT-Sat), and skin temperature, and the TCOM system, generating transcutaneous partial pressure of oxygen (TcpO2) and carbon dioxide (TcpCO2). Demographic data, severity of PVD, ABI, and other pertinent information were obtained from both the participants and medical records. RESULTS: Interoperator reliability ranged from 86% to 94% across the four hyperspectral imaging device outputs, whereas intraoperator reliability ranged from 92% to 94%. The HT-Oxy, HT-Sat, TcpCO2, and ABI of the diseased limb correlated significantly with the severity of PVD. HT-Sat significantly correlated with TcpO2 (R = 0.19), TcpCO2 (R = -0.26), ABI (R = 0.42), and skin temperature (R = 0.56). HT-Deoxy also correlated with TcpCO2 (R = 0.27). CONCLUSIONS: This study demonstrates the reliability of hyperspectral imaging in comparison to TCOM, ABI, skin temperature, and severity of PVD in a series of patients. Its correlation to other established modalities and low interoperator and intraoperator variability could enable this modality to be a useful screening tool in PVD.
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Monitoreo de Gas Sanguíneo Transcutáneo/métodos , Interpretación de Imagen Asistida por Computador , Extremidad Inferior/irrigación sanguínea , Enfermedades Vasculares Periféricas/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Índice Tobillo Braquial , Biomarcadores/sangre , Femenino , Hemoglobinas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Nueva Zelanda , Variaciones Dependientes del Observador , Oxihemoglobinas/metabolismo , Enfermedades Vasculares Periféricas/sangre , Enfermedades Vasculares Periféricas/fisiopatología , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
Inflammation plays a pivotal role in peripheral artery disease (PAD). Cellular adhesion proteins mediate the interaction of leukocytes with endothelial cells during inflammation. To determine the association of cellular adhesion molecules with ankle-brachial index (ABI) and ABI category (≤1.0 vs >1.0) in a diverse population, 15 adhesion proteins were measured in the Multi-Ethnic Study of Atherosclerosis (MESA). To assess multivariable associations of each protein with ABI and ABI category, linear and logistic regression was used, respectively. Among 2364 participants, 23 presented with poorly compressible arteries (ABI > 1.4) and were excluded and 261 had ABI ≤ 1.0. Adjusting for traditional risk factors, elevated levels of soluble P-selectin, hepatocyte growth factor, and secretory leukocyte protease inhibitor were associated with lower ABI ( P = .0004, .001, and .002, respectively). Per each standard deviation of protein, we found 26%, 20%, and 19% greater odds of lower ABI category ( P = .001, .01, and .02, respectively). Further investigation into the adhesion pathway may shed new light on biological mechanisms implicated in PAD.
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Índice Tobillo Braquial , Aterosclerosis/sangre , Moléculas de Adhesión Celular/sangre , Enfermedades Vasculares Periféricas/sangre , Anciano , Aterosclerosis/etnología , Biomarcadores/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inflamación/sangre , Inflamación/etnología , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/etnología , Factores de RiesgoRESUMEN
BACKGROUND AND OBJECTIVES: Patients receiving hemodialysis are at risk of cardiovascular events. A novel blood test (T50 test) determines the individual calcification propensity of blood. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: T50 was determined in 2785 baseline serum samples of patients receiving hemodialysis enrolled in the Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE) trial and the T50 results were related to patient outcomes. RESULTS: Serum albumin, bicarbonate, HDL cholesterol, and creatinine were the main factors positively/directly and phosphate was the main factor negatively/inversely associated with T50. The primary composite end point (all-cause mortality, myocardial infarction [MI], hospitalization for unstable angina, heart failure, or peripheral vascular event [PVE]) was reached in 1350 patients after a median follow-up time of 619 days. After adjustments for confounding, a lower T50 was independently associated with a higher risk of the primary composite end point as a continuous measure (hazard ratio [HR] per 1 SD lower T50, 1.15; 95% confidence interval [95% CI], 1.08 to 1.22; P<0.001). Furthermore, lower T50 was associated with a higher risk in all-cause mortality (HR per 1 SD lower T50, 1.10; 95% CI, 1.02 to 1.17; P=0.001), MI (HR per 1 SD lower T50, 1.38; 95% CI, 1.19 to 1.60; P<0.001), and PVE (HR per 1 SD lower T50, 1.22; 95% CI, 1.05 to 1.42; P=0.01). T50 improved risk prediction (integrated discrimination improvement and net reclassification improvement, P<0.001 and P=0.001) of the primary composite end point. CONCLUSIONS: Blood calcification propensity was independently associated with the primary composite end point, all-cause mortality, MI, and PVE in the EVOLVE study and improved risk prediction. Prospective trials should clarify whether T50-guided therapies improve outcomes.