RESUMEN
BACKGROUND The role of nicotinic acetylcholine receptor alpha7 subunit (a7nAchR) in the treatment of acute cerebral ischemia by VNS has not been thoroughly clarified to date. Therefore, this study aimed to investigate the specific role of a7nAchR and explore whether this process is involved in the mechanisms of VNS-induced neuroprotection in rats undergoing permanent middle cerebral artery occlusion (PMCAO) surgery. MATERIAL AND METHODS Rats received a7nAChR antagonist (A) or antagonist placebo injection for control (AC), followed by PMCAO and VNS treatment, whereas the a7nAChR agonist (P) was utilized singly without VNS treatment but only with PMCAO pretreatment. The rats were randomly divided into 6 groups: sham PMCAO, PMCAO, PMCAO+VNS, PMCAO+VNS+A, PMCAO+VNS+AC, and PMCAO+P. Neurological function and cerebral infarct volume were measured to evaluate the level of brain injury at 24 h after PMCAO or PMCAO-sham. Moreover, the related proteins levels of a7nAChR, p-JAK2, and p-STAT3 in the ischemic penumbra were assessed by Western blot analysis. RESULTS Rats pretreated with VNS had significantly improved neurological function and reduced cerebral infarct volume after PMCAO injury (p<0.05). In addition, VNS enhanced the levels of a7nAchR, p-JAK2, and p-STAT3 in the ischemic penumbra (p<0.05). However, inhibition of a7nAchR not only attenuated the beneficial neuroprotective effects induced by VNS, but also decreased levels of p-JAK2 and p-STAT3. Strikingly, pharmacological activation of a7nAchR can partially substitute for VNS-induced beneficial neurological protection. CONCLUSIONS These results suggest that a7nAchR is a pivotal mediator of VNS-induced neuroprotective effects on PMCAO injury, which may be related to suppressed inflammation via activation of the a7nAchR/JAK2 anti-inflammatory pathway.
Asunto(s)
Isquemia Encefálica/terapia , Janus Quinasa 2/metabolismo , Estimulación del Nervio Vago/métodos , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Animales , Lesiones Encefálicas/tratamiento farmacológico , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/cirugía , Inflamación/tratamiento farmacológico , Masculino , Fármacos Neuroprotectores/uso terapéutico , Ratas , Ratas Sprague-Dawley , Factor de Transcripción STAT3/metabolismo , Nervio Vago/metabolismo , Receptor Nicotínico de Acetilcolina alfa 7/agonistas , Receptor Nicotínico de Acetilcolina alfa 7/antagonistas & inhibidoresRESUMEN
Large-scale randomized controlled trials (RCTs) have well demonstrated the beneficial effects of cholesterol-lowering treatment with statins in patients at high risk of vascular disease. However, large statin RCTs were usually restricted to the typical 5-6 years. Moreover, non-cardiovascular events, especially the risk of cancer, probably failed to emerge within a restricted period of 6 years. The aim of this study was to evaluate the long-term efficacy and safety of statin treatment by performing a meta-analysis of statin RCTs with extended follow-up beyond 6 years. Six RCTs with post-trial follow-up were eligible for inclusion, involving 47,296 patients with total follow-up ranging from 6.7 to 14.7 years. During the post-trial period, all the surviving participants were advised to take a statin and the cholesterol level were almost identical between the original statin group and the original placebo group. Over the entire 6.7-14.7 years of follow-up, a significant reduction in the rates of all-cause mortality (relative risk 0.90, 95% confidence interval 0.85-0.96; P=0.0009), cardiovascular mortality (0.87, 0.81-0.93; P<0.0001) and major coronary events (0.79, 0.72-0.86; P<0.00001) was observed in favour of the original statin group. During 2-year post-trial period, further reduction in all-cause mortality (0.83, 0.74-0.93; P=0.001), cardiovascular mortality (0.81, 0.69-0.95; P=0.01) and major coronary events (0.77, 0.63-0.95; P=0.01) was observed among initially statin-treated patients. Over the entire follow-up period, statin treatment did not increase the incidence of cancers (0.99, 0.95-1.04; P=0.79), deaths from cancers (1.00, 0.93-1.07; P=0.98) and non-cardiovascular mortality (0.95, 0.90-1.00; P=0.07). In conclusion, statin treatment beyond 6 years is effective and safe in patients at high risk of vascular events. Moreover, earlier treatment with statin may not only preserve the initial benefit but also have further survival benefit for additional 2 years. Further studies are called for to explore the underlying mechanisms.
Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Neoplasias/epidemiología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Hipercolesterolemia/epidemiología , Incidencia , Mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND: Uncertainties exist with regard to the efficacy of drug-eluting stent (DES) versus bare-metal stent (BMS) in large coronary arteries. OBJECTIVE AND METHODS: The aim of this study was to investigate the efficacy of BMS versus DES in terms of clinical events in large coronary vessels (≥3.0 mm) by performing a meta-analysis of all relevant randomized controlled trials (RCTs). RESULTS: Six RCTs with 4,399 patients were included in this study. Overall, there were no significant between-group differences in the risks of the composite of cardiac death and nonfatal myocardial infarction (cardiac death/MI), cardiac death, myocardial infarction, and stent thrombosis, however, DES was associated with significant reduction in the risk of target vessel revascularization (TVR) compared with BMS [0.48 (0.33, 0.70)] with consistent benefits among patients with reference vessel diameter ≥ 3.5 mm, reference vessel diameter ≥ 4.0 mm, stent length ≤ 15 mm, first-generation DES or second-generation DES. In patients with ≥ 3-year follow-up, there were no significant between-group differences in the risk of cardiac death/MI, TVR, cardiac death, myocardial infarction or stent thrombosis. CONCLUSIONS: This meta-analysis suggests that DES is superior to BMS in terms of adverse cardiac events in large coronary arteries at the mid-term follow-up. The long-term efficacy of newer-generation DES versus BMS in larger coronary arteries is still worth further evaluation.
Asunto(s)
Enfermedad de la Arteria Coronaria/terapia , Stents Liberadores de Fármacos , Metales , Intervención Coronaria Percutánea/instrumentación , Stents , Anciano , Distribución de Chi-Cuadrado , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/mortalidad , Reestenosis Coronaria/etiología , Reestenosis Coronaria/mortalidad , Trombosis Coronaria/etiología , Trombosis Coronaria/mortalidad , Medicina Basada en la Evidencia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Infarto del Miocardio/mortalidad , Oportunidad Relativa , Selección de Paciente , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Diseño de Prótesis , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Uncertainties still remain in terms of what kinds of patients benefit most from cilostazol-based triple antiplatelet therapy (TAT) after coronary stenting. METHODS: We performed a meta-analysis of all relevant randomized controlled trials (RCTs) to investigate the effect of TAT versus dual antiplatelet therapy (DAT) in terms of major adverse cardiovascular events (MACEs) in patients undergoing coronary stenting. RESULTS: Fourteen RCTs with 5,821 patients were included in this study. TAT was associated with a significant reduction in the risk of MACEs compared to DAT [9.2 vs. 13.4%; odds ratio 0.59 (0.46, 0.76)] with consistent benefits among patients with diabetes, long lesions and small vessels. There were no significant between-group differences in the risk of cardiac death, myocardial infarction, stent thrombosis and bleeding events; however, the risk of target lesion revascularization was significantly lower in the TAT group. TAT resulted in borderline significant reduction in the risk of cardiovascular thrombotic events in unselected patients and significant decrease in patients with acute coronary syndrome [odds ratio 0.51 (0.27, 0.94)]. CONCLUSION: Under the treatment of standard DAT, the addition of cilostazol is an effective and relatively safe strategy in preventing MACEs after coronary stenting, especially for patients at high risk of restenosis or clinical events.
Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Reestenosis Coronaria/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico , Stents , Tetrazoles/uso terapéutico , Aspirina/uso terapéutico , Prótesis Vascular , Implantación de Prótesis Vascular/métodos , Cilostazol , Clopidogrel , Quimioterapia Combinada , Hemorragia/inducido químicamente , Humanos , Infarto del Miocardio/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Accidente Cerebrovascular/prevención & control , Ticlopidina/análogos & derivados , Ticlopidina/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Ginsenoside Rb1, a major bioactive component of Panax ginseng, bears various beneficial effects on the cardiovascular system. This study investigated whether ginsenoside Rb1 preconditioning has protective effects on myocardial ischemia-reperfusion injury and its potential mechanism. METHODS: Rats subjected to 45 min of myocardial ischemia followed by 120 min of reperfusion were assigned to the following groups: sham-operated, ischemia-reperfusion (I/R), ginsenoside Rb1+I/R, wortmannin(a specific PI3K inhibitor)+I/R, wortmannin drug vehicle (dimethyl sulfoxide, DMSO), wortmannin+sham, ginsenoside Rb1+ wortmannin +I/R. Infarct size was assessed by triphenyltetrazolium chloride staining. Plasma creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB), lactate dehydrogenase (LDH), and troponin T levels were also measured. Akt phosphorylation expression was assessed by immunoblotting. RESULTS: Ginsenoside Rb1 preconditioning reduced infarct size compared with that in the I/R group: 30 +/- 2.6% versus 51 +/- 2.7% (p < 0.01). Ginsenoside Rb1 preconditioning also markedly reduced the plasma CK, CK-MB, LDH and troponin T levels in blood. Akt phosphorylation expression increased after ginsenoside Rb1 preconditioning. These effects of ginsenoside Rb1 preconditioning were significantly inhibited by wortmannin. CONCLUSION: This is the first study to demonstrate that ginsenoside Rb1 preconditioning has protective effects on myocardial ischemia and reperfusion injury, partly by mediating the activation of the PI3K pathway and phosphorylation of Akt.
Asunto(s)
Ginsenósidos/uso terapéutico , Precondicionamiento Isquémico Miocárdico/métodos , Infarto del Miocardio/tratamiento farmacológico , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Androstadienos/farmacología , Androstadienos/uso terapéutico , Animales , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Western Blotting/métodos , Creatina Quinasa/antagonistas & inhibidores , Creatina Quinasa/sangre , Creatina Quinasa/inmunología , Forma MB de la Creatina-Quinasa/antagonistas & inhibidores , Forma MB de la Creatina-Quinasa/sangre , Forma MB de la Creatina-Quinasa/inmunología , Dimetilsulfóxido/administración & dosificación , Dimetilsulfóxido/química , Esquema de Medicación , Quimioterapia Combinada , Ginsenósidos/antagonistas & inhibidores , Ginsenósidos/química , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Inyecciones Intravenosas , L-Lactato Deshidrogenasa/antagonistas & inhibidores , L-Lactato Deshidrogenasa/sangre , L-Lactato Deshidrogenasa/inmunología , Masculino , Estructura Molecular , Infarto del Miocardio/complicaciones , Daño por Reperfusión Miocárdica/complicaciones , Panax/química , Vehículos Farmacéuticos/química , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/farmacología , Fosforilación/efectos de los fármacos , Placebos/administración & dosificación , Ratas , Ratas Sprague-Dawley , Sales de Tetrazolio , Troponina T/antagonistas & inhibidores , Troponina T/sangre , Troponina T/inmunología , WortmaninaRESUMEN
BACKGROUND: Percutaneous coronary intervention has been widely used in the treatment of ischemic heart disease, but vascular restenosis is a main limitation of percutaneous coronary intervention. Our previous work reported that caveolin-1 had a key functional role in intimal hyperplasia, whereas whether Cavin-1 (another important caveolae-related protein) was involved is still unknown. Therefore, we will investigate the effect of Cavin-1 on neointimal formation. METHODS AND RESULTS: Balloon injury markedly reduced Cavin-1 protein and enhanced ubiquitin protein expression accompanied with neointimal hyperplasia in injured carotid arteries, whereas Cavin-1 mRNA had no change. In cultured vascular smooth muscle cells (VSMCs), Cavin-1 was downregulated after inhibition of protein synthesis by cycloheximide, which was distinctly prevented by pretreatment with proteasome inhibitor MG132 but not by lysosomal inhibitor chloroquine, suggesting that proteasomal degradation resulted in Cavin-1 downregulation. Knockdown of Cavin-1 by local injection of Cavin-1 short hairpin RNA (shRNA) into balloon-injured carotid arteries in vivo promoted neointimal formation. In addition, inhibition or overexpression of Cavin-1 in cultured VSMCs in vitro prompted or suppressed VSMC proliferation and migration via increasing or decreasing extracellular signal-regulated kinase phosphorylation and matrix-degrading metalloproteinases-9 activity, respectively. However, under basic conditions, the effect of Cavin-1 on VSMC migration was stronger than on proliferation. Moreover, our results indicated that Cavin-1 regulated caveolin-1 expression via lysosomal degradation pathway. CONCLUSIONS: Our study revealed the role and the mechanisms of Cavin-1 downregulation in neointimal formation by promoting VSMC proliferation, migration, and synchronously enhancing caveolin-1 lysosomal degradation. Cavin-1 may be a potential therapeutic target for the treatment of postinjury vascular remodeling.
Asunto(s)
Angioplastia de Balón/efectos adversos , Traumatismos de las Arterias Carótidas/metabolismo , Caveolina 1/metabolismo , Movimiento Celular , Proliferación Celular , Proteínas de la Membrana/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Neointima , Proteínas de Unión al ARN/metabolismo , Animales , Traumatismos de las Arterias Carótidas/etiología , Traumatismos de las Arterias Carótidas/genética , Traumatismos de las Arterias Carótidas/patología , Arteria Carótida Externa/metabolismo , Arteria Carótida Externa/patología , Células Cultivadas , Modelos Animales de Enfermedad , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Lisosomas/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Proteínas de la Membrana/genética , Músculo Liso Vascular/lesiones , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/patología , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteolisis , Interferencia de ARN , ARN Interferente Pequeño/administración & dosificación , Proteínas de Unión al ARN/genética , Ratas Sprague-Dawley , Transducción de Señal , Factores de Tiempo , Transfección , Remodelación VascularRESUMEN
Numerous studies have reported the relation between pre-procedural C-reactive protein (CRP) levels and the risk of major adverse cardiac events (MACEs) in patients undergoing percutaneous coronary intervention (PCI). However, the results across the studies were inconsistent. The aim of this study was to evaluate the predictive effect of pre-procedural CRP levels and the risk of MACEs in patients undergoing PCI. Longitudinal studies on the association between pre-procedural CRP levels and MACEs were identified by electronic and manual searches. Summary risk ratios (RRs) and 95 % confidence intervals (CI) were calculated employing an inverse variance random-effects model irrespective of between-study heterogeneity. Thirty-three studies involving 34,367 patients with 4119 MACEs were included in this study. High CRP level was associated with increased incidences of MACEs, all-cause death, myocardial infarction, coronary revascularization, and clinical restenosis, with pooled RRs of 1.97 (95 % CI, 1.65, 2.35), 2.88 (95 % CI, 2.15, 3.86), 1.81 (95 % CI, 1.48, 2.21), 1.31 (95 % CI, 1.11, 1.56), and 1.45 (95 % CI, 1.07, 1.96), respectively. Dose-response analysis showed that every 1 mg/L increment in pre-procedural serum CRP level was associated with a significant 12 % increase in the risk of MACEs. In spite of heterogeneity across the included studies, this meta-analysis suggests that pre-procedural serum CRP level is a valuable predictor of MACEs in patients undergoing PCI.
Asunto(s)
Proteína C-Reactiva/metabolismo , Enfermedades Cardiovasculares/sangre , Intervención Coronaria Percutánea/efectos adversos , Complicaciones Posoperatorias/sangre , Cuidados Preoperatorios/métodos , Biomarcadores/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Humanos , Estudios Longitudinales , Complicaciones Posoperatorias/prevención & control , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: In patients at high risk of atherosclerotic cardiovascular diseases (ASCVDs), residual cardiovascular risk persists despite the achievement of target LDL cholesterol levels with statin therapy. It is still unclear whether adding lipid-modifying agent to statin treatment can further improve clinical outcomes. METHODS: Randomized controlled trials (RCTs) in terms of adding lipid-modifying agent to statin versus statin monotherapy in patients at high risk of ASCVD were identified by electronic and manual searches. Results were expressed as relative risk (RR) with 95% confidence intervals (CIs). RESULTS: Eleven RCTs with 109,244 patients were included in this meta-analysis. Overall, the incidences of major adverse cardiovascular events (MACEs) were 9.70% in the statin combination groups and 9.92% in the statin monotherapy groups. No significant difference was observed in the risk of MACEs either in overall (RR 0.99, 95% CI 0.93-1.05, P=0.76) or subgroup analysis (CETP inhibitor: RR 1.07, 95% CI 0.93-1.23, P=0.37; niacin: RR 1.03, 95% CI 0.85-1.25, P=0.79; n-3 fatty acid: RR 0.98, 95% CI 0.88-1.09, P=0.70; fenofibrate: RR 0.93, 95% CI 0.80-1.09, P=0.38), with the exception of the statin/ezetimibe combination subgroup (RR 0.92, 95% CI 0.87-0.97, P=0.004). Adding lipid-modifying agent to statin significantly increased liver injury risk. Adding ezetimibe to statin did not alter side effect profile. CONCLUSION: Adding niacin, CETP inhibitors, n-3 fatty acid or fibrates to statin therapy has all failed to achieve a clinical benefit. Adding ezetimibe to statin therapy further lowers LDL-cholesterol safely and translates into a clinical benefit in patients at high risk of ASCVD.
Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Metabolismo de los Lípidos/efectos de los fármacos , Lípidos/sangre , Ensayos Clínicos Controlados Aleatorios como Asunto , Enfermedades Cardiovasculares/sangre , Humanos , Factores de RiesgoRESUMEN
INTRODUCTION: The objective of this article is to evaluate the antiproteinuric effect of angiotensin receptor blockers (ARBs) in normotensive patients with proteinuria. MATERIALS AND METHODS: We reviewed randomized controlled trials assessing ARBs treatment in patients with normotension and proteinuria. Data concerning the study design, patient characteristics, and outcomes were extracted. Ratio of means was calculated by using the generalized inverse variance method. RESULTS: Eight trials involving 866 patients were included in this study. Compared with a control group, ARBs group was associated with a significant reduction in urinary protein excretion (ratio of means 0.53, 95% CI 0.44-0.64). Subgroup analysis shows that ARBs therapy resulted in a significant decrease in urinary protein excretion in diabetic patients with microalbuminuria or nondiabetic nephropathy with overt proteinuria (ratio of means 0.57, 95% CI 0.47-0.69 and 0.46, 95% CI 0.26-0.83, respectively), in a Western population or an Asian population (ratio of means 0.61, 95% CI 0.54-0.69 and 0.49, 95% CI 0.37-0.64, respectively), and in patients followed up for one to three months or three to 12 months (ratio of means 0.62, 95% CI 0.54-0.70 and 0.49, 95% CI 0.38-0.63, respectively). CONCLUSIONS: The data suggest that ARBs may have beneficial effects in preventing the progression of proteinuria in normotensive patients with renal disease.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Proteinuria/tratamiento farmacológico , Adulto , Creatinina/sangre , Creatinina/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Angiotensin converting enzyme inhibitors (ACEIs) have been linked to reduced risk of new-onset diabetes, but the evidence was insufficient. OBJECTIVE AND METHODS: The aim of this study was to evaluate the effect of ACEIs on the development of new-onset type 2 diabetes. Randomized controlled trials (RCTs) about ACEIs and new-onset diabetes were identified by electronic and manual searches. RESULTS: Nine RCTs with 92,404 patients (72,128 non-diabetic patients at baseline) were included in this study. Compared with control group, incidence of new-onset diabetes was significantly reduced in the ACEIs group [OR 0.80, (0.71, 0.91)], irrespective of achieved blood pressure levels at the follow-up. ACEIs therapy was associated with significant reduction in the risk of new-onset diabetes compared with beta-blockers/diuretics [OR 0.78, (0.65, 0.93)], placebo [OR 0.79, (0.64, 0.96)], or calcium channel blockers [OR 0.85, (0.73, 0.99)]. ACEIs treatment was associated with significant reduction in the risk of new-onset diabetes in patients with hypertension [OR 0.80, (0.68, 0.93)], coronary artery disease (CAD) or cardiovascular disease [OR 0.83, (0.68, 1.00)], or heart failure [OR 0.22, (0.10, 0.47)]. Among patients with impaired glucose tolerance or impaired fasting glucose, ramipril did not significantly reduce the incidence of diabetes [OR 0.91, (0.79, 1.05)], but significantly increased regression to normoglycemia. CONCLUSION: ACEIs have beneficial effects in preventing new-onset diabetes. ACEIs provide additional benefits of lowering the risk of new-onset diabetes in patients with hypertension, CAD or other cardiovascular disease.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/prevención & control , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/tratamiento farmacológico , Intolerancia a la Glucosa/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto/métodosRESUMEN
The mechanisms and mediators underlying common renal impairment after myocardial infarction (MI) are still poorly understood. The present study aimed to test the hypothesis that angiotensin II type 1 receptor blockers (ARBs) provides renoprotective effects after MI by preventing augmented intrarenal renin-angiotensin-system (RAS)-induced podocyte injury. Sprague-Dawley rats that underwent ligation of their coronary arteries were treated with losartan (20 mg/kg/d) or vehicle for 3 or 9 weeks. Renal function, histology and molecular changes were assessed. The current study revealed that MI-induced glomerular podocyte injury was identified by increased immunostaining for desmin and p16(ink4a), decreased immunostaining for Wilms' tumor-1 and podocin mRNA expression, and an induced increase of blood cystatin C at both 3 and 9 weeks. These changes were associated with increased intrarenal angiotensin II levels and enhanced expressions of angiotensinogen mRNA and angiotensin II receptor mRNA and protein. These changes were also associated with decreased levels of insulin-like growth factor (IGF-1) and decreased expressions of IGF-1 receptor (IGF-1R) protein and mRNA and phosphorylated(p)-Akt protein at 9 weeks, as well as increased expressions of 8-hydroxy-2'-deoxyguanosine at both time points. Treatment with losartan significantly attenuated desmin- and p16(ink4a)-positive podocytes, restored podocin mRNA expression, and decreased blood cystatin C levels. Losartan also prevented RAS activation and oxidative stress and restored the IGF-1/IGF-1R/Akt pathway. In conclusion, ARBs prevent the progression of renal impairment after MI via podocyte protection, partially by inhibiting the activation of the local RAS with subsequent enhanced oxidative stress and an inhibited IGF-1/IGF-1R/Akt pathway.
Asunto(s)
Antagonistas de Receptores de Angiotensina/farmacología , Losartán/farmacología , Infarto del Miocardio/tratamiento farmacológico , Podocitos/efectos de los fármacos , Insuficiencia Renal/prevención & control , Sistema Renina-Angiotensina/efectos de los fármacos , Antagonistas de Receptores de Angiotensina/uso terapéutico , Animales , Senescencia Celular , Expresión Génica/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Riñón/efectos de los fármacos , Riñón/patología , Riñón/fisiopatología , Losartán/uso terapéutico , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Infarto del Miocardio/complicaciones , Estrés Oxidativo , Podocitos/fisiología , Ratas , Ratas Sprague-Dawley , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Insuficiencia Renal/etiología , Volumen Sistólico/efectos de los fármacosRESUMEN
BACKGROUND: Whether an addition of OAC to double antiplatelet therapy for patients with an indication of chronic oral anticoagulation undergoing PCI-S may improve clinical outcomes is still debated. This meta-analysis aimed to update and re-compare the benefits and risks of triple antithrombotic therapy (TT) with double anti-platelet therapy (DAPT) after in patients who requiring oral anticoagulation after percutaneous coronary interventions with stenting (PCI-s). METHODS: Ten reports of observational retrospective or prospective studies were retrieved, including a total of 6296 patients, follow-up period ranging from 1 year to 2 years. RESULTS: Baseline characteristics were similar in both groups. The main finding of this study is the overall incidence of major adverse cardiovascular events (MACE), myocardial infarction (MI) and stent thrombosis was comparable between two groups. Patients with TT was associated with significant reduction in ischemic stroke (OR: 0.27; 95%CI: 0.13 - 0.57; P = 0.0006) as compared to DAPT. We reaffirmed triple therapy significantly increased the risk of major bleeding (OR: 1.47; 95%CI: 1.22 - 1.78; P < 0.0001) and minor bleeding (OR: 1.55; 95%CI: 1.07 - 2.24; P = 0.02). CONCLUSIONS: Triple therapy is more efficacious in reducing the occurrence of ischemic stroke in PCI-s patients with an indication of chronic oral anticoagulation (OAC), compared with DAPT. However, it significantly increased major and minor risk of bleeding. It is imperative that further prospective randomized controlled trials are required to defne the best therapeutic strategy for patients with an indication of chronic OAC undergoing PCI-s.
Asunto(s)
Anticoagulantes/uso terapéutico , Fibrinolíticos/administración & dosificación , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/administración & dosificación , Stents , Anciano , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sesgo de PublicaciónRESUMEN
BACKGROUND: Angiotensin receptor blockers (ARBs) have been linked to reduced risk of new-onset diabetes, but the evidence was insufficient. OBJECTIVE AND METHODS: The aim of this study was to evaluate the effect of ARBs on the development of new-onset type 2 diabetes. Randomized controlled trials (RCTs) about ARBs and new-onset diabetes were identified by electronic and manual searches. RESULTS: Eleven RCTs with 79,773 patients (59,862 non-diabetic patients at baseline) were included in this study. Compared with control group, incidence of new-onset diabetes was significantly reduced in ARBs group [OR 0.79, (0.74, 0.84)] and various categories of ARBs subgroup. ARBs were associated with significant reduction in the risk of new-onset diabetes compared with placebo [OR 0.83, (0.78, 0.89)], beta-blocker [OR 0.73, (0.62, 0.87)], calcium channel blocker [OR 0.76, (0.68, 0.85)] and non-ARB [OR 0.57, (0.36, 0.91)]. ARBs were associated with significant reduction in the risk of new-onset diabetes in patients with hypertension [OR 0.74, (0.68, 0.81)], heart failure [OR 0.70, (0.50, 0.96)], impaired glucose tolerance [OR 0.85, (0.78, 0.92)] or cardiocerebrovascular diseases [OR 0.84, (0.72, 0.97)]. Compared with control group, incidence of new-onset diabetes was significantly reduced in ARBs group, irrespective of achieved blood pressure level. ARBs were associated with a lower incidence of new-onset diabetes in Western population [OR 0.81, (0.76, 0.85)] and Japanese population [OR 0.61, (0.48, 0.79)]. CONCLUSION: There is sufficient evidence that ARBs have beneficial effect in preventing new-onset type 2 diabetes. ARBs should be considered in patients with high risk of developing diabetes.
Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Diabetes Mellitus Tipo 2/prevención & control , Intolerancia a la Glucosa/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: It has been well established that cilostazol has anti-proliferative effect against in-stent restenosis. However, it remains unclear whether cilostazol can prevent the progression of carotid atherosclerosis. METHODS AND RESULTS: We performed a meta-analysis of all relevant randomized controlled trials (RCTs) to evaluate the effect of cilostazol on the progression of carotid intima-media thickness (IMT). Five RCTs with 698 patients [597 subjects with type 2 diabetes mellitus (T2DM)] were included in this study. Cilostazol was associated with a significant reduction in the progression of carotid IMT (WMD, -0.08mm, 95% CI -0.13, -0.04; P=0.00003). Subgroup analysis shows that cilostazol monotherapy or addition to dual antiplatelet therapy (aspirin and clopidogrel) was superior to placebo (WMD, -0.04mm, 95% CI -0.05, -0.03; P<0.00001), no antiplatelet medication (WMD, -0.12mm, 95% CI -0.21, -0.03; P=0.008), aspirin monotherapy (WMD, -0.06mm, 95% CI -0.12, 0.00; P=0.04) or dual antiplatelet therapy (WMD, -0.16mm, 95% CI -0.30, -0.02; P=0.03) in preventing the progression of carotid IMT. Cilostazol resulted in a significant decrease in total cholesterol (WMD -8.47mg/dl, 95% CI -14.18, -2.75; P=0.004) and LDL-C (WMD -8.25mg/dl, 95% CI -14.15, -2.36; P=0.006) and favorable trends in reducing triglyceride (WMD -15.83mg/dl, 95% CI -32.14, 0.48; P=0.06). CONCLUSION: It suggests that cilostazol may have beneficial effects in preventing the progression of carotid atherosclerosis and improving pro-atherogenic lipid profile, especially in patients with T2DM. Whether the anti-atherosclerotic effect of cilostazol is independent of improving pro-atherogenic dyslipidemia is worth further investigation.
Asunto(s)
Enfermedades de las Arterias Carótidas/tratamiento farmacológico , Grosor Intima-Media Carotídeo , Inhibidores de Fosfodiesterasa 3/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Tetrazoles/uso terapéutico , Anciano , Enfermedades de las Arterias Carótidas/diagnóstico , Enfermedades de las Arterias Carótidas/patología , Cilostazol , Progresión de la Enfermedad , Quimioterapia Combinada , Medicina Basada en la Evidencia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Fosfodiesterasa 3/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Tetrazoles/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVES: The study compared the predictive value of admission plasma glucose (APG) and first fasting plasma glucose (FPG) in stratifying patients meriting an oral glucose tolerance test (OGTT). DESIGN AND METHODS: Characteristics of APG, FPG and OGTT 2-hour glucose as well as other blood measurements, physical examinations and medical information were assessed in 994 patients without known diabetes. RESULTS: The prevalences of diabetes and impaired glucose tolerance were 24.6% and 37.9%, according to an OGTT, respectively. The first FPG demonstrated stronger predictive value in diagnosing diabetes than APG did both in overall and in patients with less clinical value. Compared to the first FPG, APG provided less value to coronary artery disease, hypertension and high-sensitivity C-reactive protein for diabetes screening. CONCLUSIONS: The first FPG exerted more predictive value than APG did and was still a preferable reference prior to APG in stratifying patients for undiagnosed diabetes by an OGTT.
Asunto(s)
Glucemia/análisis , Enfermedades Cardiovasculares/diagnóstico , Diabetes Mellitus/diagnóstico , Ayuno/sangre , Glucosa/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Proteína C-Reactiva/análisis , Bases de Datos Factuales , Diabetes Mellitus/epidemiología , Ayuno/metabolismo , Femenino , Glucosa/análisis , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Persona de Mediana Edad , Examen Físico , Valor Predictivo de las Pruebas , Prevalencia , Curva ROC , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: It remains unclear whether lowering postprandial glucose by alpha-glucosidase inhibitors (alpha-GIs) can prevent the progression of carotid intima-media thickness (IMT). METHODS AND RESULTS: We performed a meta-analysis of all relevant randomized controlled trials (RCTs) to evaluate the effect of alpha-GIs on the progression of carotid IMT. Five RCTs with 411 patients were included in this study. Alpha-GIs therapy was associated with a significant reduction in the annual progression of carotid IMT (WMD, -0.06 mm/year, 95% CI -0.11, -0.01; P=0.02) and the progression in carotid IMT at the end of follow-up (WMD, -0.07 mm, 95% CI -0.12, -0.02; P=0.003). In subgroup analysis, alpha-GIs therapy was associated with a significant reduction in the annual progression of carotid IMT in patients with type 2 diabetes mellitus (T2DM) (WMD, -0.08 mm/year, 95% CI -0.10, -0.06; P<0.00001), and in the progression of carotid IMT in patients with impaired glucose tolerance (IGT) at the end of follow-up (WMD, -0.03 mm, 95% CI -0.05, -0.01; P=0.01). Alpha-GIs treatment was associated with significant increase in HDL-C (WMD 1.56 mg/dl, 95% CI 0.09, 3.03; P=0.04) and decrease in basal immunoreactive insulin as well as had favorable trends towards reducing HbA1c, triglyceride and diastolic blood pressure. CONCLUSION: It suggests that alpha-GIs therapy may be an effective strategy in preventing the progression of carotid IMT in patients with IGT or T2DM. It partially contributes to the improvement in atherogenic metabolic parameters induced by alpha-GIs. More studies, especially large multi-centre RCTs, are still warranted to further clarify the anti-atherosclerotic effect of alpha-GIs.
Asunto(s)
Aterosclerosis/tratamiento farmacológico , Arterias Carótidas/patología , Grosor Intima-Media Carotídeo , Inhibidores Enzimáticos/farmacología , Inhibidores de Glicósido Hidrolasas , Anciano , Presión Sanguínea , Enfermedades de las Arterias Carótidas/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
OBJECTIVES: The study aimed to investigate the predictive value of the combination of high-sensitivity C-reactive protein (hs-CRP) and apolipoprotein B (apoB)/apoA-1 ratio for the outcomes of coronary angiography (CAG), echocardiography and oral glucose tolerance tests (OGTTs). DESIGN AND METHODS: Hs-CRP, apoB, apoA-1, and the profiles of CAG, echocardiography and OGTTs as well as traditional risk factors were measured in 1757 cardiology patients. RESULTS: Hs-CRP or apoB/apoA-1 ratio was significantly correlated with the presence and severity of angiographic profiles, the levels of left ventricular (LV) ejection fraction, LV mass and LV mass index, and the presence of abnormal glucose metabolism. The combination of hs-CRP and apoB/apoA-1 ratio had greater correlation with abnormal glucose metabolism than its individual components in patients with normal fasting glucose, and was an independent predictor for coronary artery disease. CONCLUSIONS: The combination of hs-CRP and apoB/apoA-1 ratio may be a strong predictor for coronary artery disease and abnormal glucose metabolism.
Asunto(s)
Apolipoproteína A-I/sangre , Apolipoproteínas B/sangre , Proteína C-Reactiva/metabolismo , Enfermedad de la Arteria Coronaria/diagnóstico , Anciano , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/metabolismo , Ecocardiografía/métodos , Femenino , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa/métodos , Humanos , Hipertensión/sangre , Hipertensión/metabolismo , Lípido A/sangre , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/metabolismo , Valor Predictivo de las Pruebas , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The development of coronary collaterals is crucial to survival through acute ischemia. Mild to moderate loss of renal function has been suggested to play a role in this event, but evidential data are scarce. The aim of this study was to investigate the relationship between mild to moderate renal insufficiency and coronary collateral development in patients with chronic total coronary artery occlusion. METHODS AND RESULTS: A total of 83 patients with mild to moderate loss of renal function (30 mL/min/1.73 m(2) ≤ eGFR < 90 mL/min/1.73 m(2)) with chronic total coronary artery occlusion were included in our study. The collateral circulation was graded according to Rentrop classification and the function of collateral circulation was graded according to Werner collateral connection (CC) grades. Compared to patients with good collateral circulation (Rentrop = 2,3), eGFR was found to be lower in those patients with poor coronary collateral circulation (Rentrop = 0,1) (63.30 ± 10.51 vs. 54.13 ± 10.56, P = 0.02). eGFR was also found to be lower in poorly functioning coronary collateral circulation (CC = 0,1) than in efficiently functioning coronary collateral circulation (CC = 2) (55.22 ± 9.98 vs. 66.28 ± 9.16, P = 0.03). Multiple logistic regression analysis showed that low eGFR was independently associated with poor coronary collateral circulation (Rentrop = 0,1, 95% CI, 0.09-1.09, P = 0.044) and poor function of coronary collateral circulation (CC = 0,1, 95% CI, 0.02-0.17, P = 0.02). CONCLUSIONS: Lower eGFR is associated with poorer coronary collateral vessel development in patients experiencing mild to moderate renal insufficiency. Moreover, eGFR represents an independent factor affecting coronary collateral vessel development.
Asunto(s)
Circulación Colateral , Circulación Coronaria , Oclusión Coronaria/complicaciones , Insuficiencia Renal/complicaciones , Anciano , Angiografía Coronaria , Oclusión Coronaria/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
AIM: The aim of this study is to characterize the glucometabolic state of patients undergoing elective coronary angiography (CA) in a subpopulation in China. METHODS AND RESULTS: This study recruited 896 patients undergoing elective CA for the evaluation of suspected coronary artery disease (CAD). Oral glucose tolerance tests (OGTTs) performed in patients without previously known diabetes revealed that 173 (19.2%) had newly diagnosed diabetes and 281 (31.5%) had impaired glucose regulation. The prevalence of abnormal glucose metabolism (AGM) was significant difference among three groups of CA diagnosis, including normal coronary, nonsignificant stenosis and CAD. Overall, the proportion of patients with type 2 diabetes increased from 22.0% at baseline to 41.2% post-OGTT analysis. In total, 270 (59.5%) patients with AGM would have remained undetected if OGTTs had not been performed. Patients with CAD, hypertension, dyslipidemia, obesity and high C-reactive protein levels were at high risk of AGM. CONCLUSIONS: AGM is common and underestimated by FPG testing alone in patients undergoing elective CA. OGTTs should be routinely performed to assess the glucometabolic state of patients undergoing elective CA, especially in patients with high risks of AGM. Detecting the state of AGM in CA individuals may provide strategies to reduce the progression of AGM and associated complications.
Asunto(s)
Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Glucosa/metabolismo , Anciano , Pueblo Asiatico , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/metabolismo , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
AIMS: To evaluate the effectiveness of transcutaneous electrical nerve stimulation (TENS) on diabetic peripheral neuropathy (DPN). METHODS: Randomized controlled trials (RCTs) comparing TENS with routine care, pharmacological interventions or placebo devices on patients with symptomatic DPN, were identified by electronic and manual searches. Studies were selected and available data were extracted independently by two investigators. Meta-analysis was performed by RevMan 4.2.8 software. RESULTS: Three RCTs involving 78 patients were included in this study. The reductions in mean pain score were significantly greater in TENS group than in placebo TENS group in 4 weeks and 6 weeks follow-up [4 weeks, SMD-5.37, 95% CI (-6.97, -3.77); 6 weeks, SMD-1.01, 95% CI (-2.01, -0.01)], but not in 12 weeks follow-up [SMD-1.65, 95% CI (-4.02, 0.73)]. TENS therapy was associated with significantly subjective improvement in overall neuropathic symptoms in 12 weeks follow-up [WMD-0.18, 95% CI (-0.32, -0.051)]. No TENS-related adverse events were registered in TENS group. CONCLUSIONS: TENS therapy may be an effective and safe strategy in treatment of symptomatic DPN. Due to small sample and short-term treatment duration, large multi-centre RCTs are needed to further evaluate the long-term effect of TENS on DPN.