El ácido acetilsalicílico reduce la liberación de micropartículas eritrocitarias, monocitarias y de células del músculo liso vascular en pacientes diabéticos / Microparticle shedding by erythrocytes, monocytes and vascular smooth muscular cells is reduced by aspirin in diabetic patients

Introducción y objetivos: La diabetes mellitus está asociada a mayor riesgo de enfermedad cardiovascular y su prevalencia está en aumento. La diabetes mellitus induce estrés metabólico a las células vasculares, lo cual promueve la activación plaquetaria y la disfunción vascular. El grado de activación de las células vasculares se puede medir con el número y el fenotipo de las micropartículas circulantes. El objetivo de este estudio es investigar el efecto de una dosis de ácido acetilsalicílico con acción inhibidora plaquetaria en el número y el tipo de las micropartículas liberadas a la circulación. Métodos: Se inscribió a 43 pacientes diabéticos que recibieron una dosis diaria de 100 mg de ácido acetilsalicílico durante 10 días, con objeto de cubrir el periodo medio de vida de las plaquetas en la circulación. Antes y después del periodo de intervención, se caracterizaron y cuantificaron las micropartículas circulantes mediante citometría de flujo. Resultados: Respecto a los pacientes con diabetes mellitus tipo 2, aquellos con diabetes mellitus tipo 1 presentaron el doble de micropartículas circulantes positivas para factor tisular (derivadas de plaquetas y monocitos) y micropartículas positivas para selectina E de origen endotelial. El tratamiento con ácido acetilsalicílico inhibió significativamente las plaquetas, puesto que la generación de tromboxano derivado de la ciclooxigenasa 1 disminuyó un 99%. Se produjo una reducción significativa de las micropartículas derivadas de eritrocitos, monocitos activados y células de músculo liso tras 10 días de administración de ácido acetilsalicílico. Conclusiones: Estos resultados indican que: a) las células vasculares y hemáticas de los pacientes con diabetes mellitus tipo 1 están expuestas a un mayor estrés continuo, que se refleja en el origen y la cantidad de sus micropartículas; b) el tratamiento con ácido acetilsalicílico inhibe la activación de las células de la pared vascular y la liberación de micropartículas, y c) los efectos del ácido acetilsalicílico son similares en la diabetes mellitus tipos 1 y 2 (AU)

Introduction and objectives: Diabetes mellitus is associated with an enhanced risk for cardiovascular disease and its prevalence is increasing. Diabetes induces metabolic stress on blood and vascular cells, promoting platelet activation and vascular dysfunction. The level of vascular cell activation can be measured by the number and phenotype of microparticles found in the circulation. The aim of this study was to investigate the effect of a platelet-inhibitory dose of aspirin on the number and type of microparticles shed to the circulation. Methods: Forty-three diabetic patients were enrolled in the study and received a daily dose of 100 mg of aspirin for 10 days to cover the average platelet life-span in the circulation. Before and after the intervention period, circulating microparticles were characterized and quantified by flow cytometry. Results: Type 1 diabetic patients had about twice the number of tissue factor-positive circulating microparticles (derived both from platelets and monocytes) and endothelial-derived E-selectin positive microparticles than type 2 diabetic patients. Aspirin therapy significantly inhibited platelets since cyclooxygenase 1 derived thromboxane generation levels were reduced by 99%. Microparticles derived from erythrocytes, activated monocytes, and smooth muscle cells were significantly reduced after 10 days of aspirin administration. Conclusions: These results indicate that: a) vascular and blood cells in type 1 diabetic patients are exposed to more sustained stress shown by their specific microparticle origin and levels; b) aspirin therapy inhibits vascular wall cell activation and microparticle shedding, and c) the effects of aspirin are similar in type 1 and 2 diabetes (AU)

Microparticle Shedding by Erythrocytes, Monocytes and Vascular Smooth Muscular Cells Is Reduced by Aspirin in Diabetic Patients.

INTRODUCTION AND OBJECTIVES: Diabetes mellitus is associated with an enhanced risk for cardiovascular disease and its prevalence is increasing. Diabetes induces metabolic stress on blood and vascular cells, promoting platelet activation and vascular dysfunction. The level of vascular cell activation can be measured by the number and phenotype of microparticles found in the circulation. The aim of this study was to investigate the effect of a platelet-inhibitory dose of aspirin on the number and type of microparticles shed to the circulation. METHODS: Forty-three diabetic patients were enrolled in the study and received a daily dose of 100mg of aspirin for 10 days to cover the average platelet life-span in the circulation. Before and after the intervention period, circulating microparticles were characterized and quantified by flow cytometry. RESULTS: Type 1 diabetic patients had about twice the number of tissue factor-positive circulating microparticles (derived both from platelets and monocytes) and endothelial-derived E-selectin positive microparticles than type 2 diabetic patients. Aspirin therapy significantly inhibited platelets since cyclooxygenase 1 derived thromboxane generation levels were reduced by 99%. Microparticles derived from erythrocytes, activated monocytes, and smooth muscle cells were significantly reduced after 10 days of aspirin administration. CONCLUSIONS: These results indicate that: a) vascular and blood cells in type 1 diabetic patients are exposed to more sustained stress shown by their specific microparticle origin and levels; b) aspirin therapy inhibits vascular wall cell activation and microparticle shedding, and c) the effects of aspirin are similar in type 1 and 2 diabetes.

Evolution of lipid profiles after bariatric surgery.

BACKGROUND: The most commonly encountered dyslipidemia in obese individuals is characterized by a cluster of interrelated plasma lipid and lipoprotein abnormalities including hypertriglyceridemia, low HDL cholesterol values, and increased small, dense LDL cholesterol particles. The aim of this study was to assess the changes in lipid profiles at baseline (pre-operatively) and at follow-up (6, 12, and 18 months) after a laparoscopic Roux-en-Y gastric bypass (LRYGBP). A retrospective observational study was performed involving all patients who consecutively underwent a LRYGBP between January 1, 2007 and December 31, 2009. Fasting lipids sub-fractions (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides) were measured and HOMA-IR calculated pre-operatively and at follow-up post-LRYGBP. Pearson's correlation coefficients were used to assess the relationship between excess weight loss (EWL) and lipid sub-fractions. ANOVA was used to assess the differences between each lipid sub-fraction at various time-points. METHODS: One hundred twenty eight (N = 128) medical charts were reviewed, and those containing data on lipid fractions at the three follow-up time-points were analyzed. One hundred fourteen patients (N = 114), 84 of whom were women (73.7%), were finally included in the study. RESULTS: Total cholesterol, LDL cholesterol, triglycerides, and HOMA-IR were significantly reduced after LRYGBP (P < 0.0005 for all). Inversely, HDL cholesterol disclosed a significant rise (P < 0.0005). Noteworthy significant associations between lipid subfractions and EWL were detected overall (P < 0.0005 for all). A gender effect was found since female patients displayed a milder association than male patients (P < 0.0005). CONCLUSIONS: LRYGBP-induced weight loss improves the lipid profile while reducing insulin resistance, with male patients showing a better profile than female patients.

Prevalence of cardiovascular disease and risk factors in a type 2 diabetic population of the North Catalonia diabetes study.

PURPOSE: The purpose of the study was to evaluate the prevalence of cardiovascular disease (CVD), cardiovascular risk factors (CVRFs), and their control in patients with type 2 diabetes mellitus (T2DM) at primary care settings from the North Catalonia Diabetes Study (NCDS). DATA SOURCES: In this multicentre cross-sectional descriptive study, data were collected from a random sample of 307 patients with T2DM. The prevalence of CVD, CVRF, metabolic syndrome (MS), coronary heart disease (CHD) risk at 10 years (Framingham Point Scores), and CVRF control was evaluated. MS and lipid profiles were established according to Adult Treatment Panel III criteria. CONCLUSIONS: CVD prevalence was 22.0% (CHD: 18.9% and peripheral ischemia: 4.5%) and more frequent in men. The prevalence of selected CVRF was: hypertension: 74.5%; dyslipidemia: 77.7%; smoking: 14.9%; obesity 44.9%, and familial CVD: 38.4%. Three or more CVRFs, including T2DM, were observed in 91.3%. MS prevalence was 68.7%. Framingham score was 10.0%, higher in men than in women. CVD prevalence was related to: age, number of CVRFs, duration of diabetes, familial history of CVD, waist circumference, hypertension, lipid profile, kidney disease, and Framingham score, but not to MS by itself. Correct lipid profiles and blood pressure were only observed in 18.9% and 24.0%, respectively, whereas platelet aggregation inhibitors were only recorded in 16.1% of the patient cohort. MS presence was not an independent risk factor of CVD in our study. IMPLICATIONS FOR PRACTICE: The high prevalence of CVD and an inadequate control of CVRF, which were apparent in the NCDS population, would suggest that advanced practice nurses should consider incorporating specific cardiovascular assessment in their routine care of persons with T2DM.

Association between sleep-disordered breathing, aminoterminal pro-brain natriuretic peptide (NT-proBNP) levels and insulin resistance in morbidly obese young women.

OBJECTIVE: Sleep-disordered breathing (SDB) is often encountered in morbid obesity (MO) in conjunction with insulin resistance (IR) and several cardio-vascular risk factors. Aminoterminal pro-brain natriuretic peptide (NT-proBNP) is a promising marker for left ventricular dysfunction (LVD) in MO. The aim of this study was to look for possible correlations between SDB, IR, heart structure and function indexes and NT-proBNP levels in MO female subjects. MATERIALS AND METHODS: Cross-sectional study involving 110 MO (44.5+/-0.7 kg m(-2)) apparently healthy, young (37.8+/-1.0 y.o.) female patients. NT-proBNP was measured using an ELISA kit (Roche). Echo-cardiograms were performed to quantify left ventricular ejection fraction values (LVEF), cardiac output (CO), left ventricular mass (LVM), left atria size (LA) and left ventricular filling pressures (the E/Em ratio). The Berlin Questionnaire (BQ) was used to assess the risk of SDB. IR and sensitivity were assessed using the HOMA index and adiponectin measurements, respectively. RESULTS: All patients had a normal LVEF (>50%). Hypertension and Type 2 diabetes mellitus prevalences were 34.5 and 4.5% (respectively). Log-transformed NT-proBNP levels correlated with BQ categories (P<0.0005), creatinine (P<0.001), age (P<0.05), LVM (P<0.001), CO (P<0.001), LA (P<0.0005) and E/Em (P<0.01). NT-proBNP levels, LVD and LVM increased significantly along with BQ scores (P<0.0001). Stepwise multiple regression analysis identified BQ and log-transformed HOMA as independent variables predicting as much as 48.0% of log-transformed NT-proBNP's variability (dependent variable). CONCLUSIONS: NT-proBNP levels are independently predicted by SDB and IR in asymptomatic MO women. Additionally, SDB worsens along with LVH and diastolic dysfunction. Larger prospective studies are warranted.

Aminoterminal pro-brain natriuretic peptide (NT-proBNP) and sleep-disordered breathing in morbidly obese females: a cross-sectional study.

Sleep-disordered breathing (SDB) is often encountered in morbid obesity (MO) in conjunction with insulin resistance (IR). Aminoterminal pro-brain natriuretic peptide (NT-proBNP) is a promising marker for left ventricular dysfunction (LVD) in MO. We sought to explore the factors that may influence the relationships of SDB and IR with NT-proBNP in MO women. We performed a cross-sectional pilot study involving 110 asymptomatic MO (44.5+/-0.7 kg/m2) young women. SDB risk was assessed using a modified version of the Berlin Questionnaire (BQ). IR was assessed using the homeostasis model assessment (HOMA) index and adiponectin levels. LVD was assessed using NT-proBNP and echocardiograms. In this study, NT-proBNP levels and LVD increased significantly along the BQ strata. Multiple regression analysis identified BQ and log-transformed HOMA as the independent variables predicting as much as 48.0% of the variability of logNT-proBNP. In conclusion, NT-pro-BNP levels are independently predicted by SDB and IR in asymptomatic MO women. Larger prospective studies are warranted.

Correlation between insulin resistance surrogates and echocardiographic findings in asymptomatic patients with morbid obesity: a cross-sectional study.

OBJECTIVE: To assess the relationship between insulin resistance (IR) and left ventricular diastolic dysfunction (LVDD) in asymptomatic patients with morbid obesity (MO). METHODS: The study cohort consisted of 231 patients (165 women and 66 men) with MO (mean body mass index [BMI] of 46.0 kg/m2) and a control group of 93 age-and sex-matched apparently healthy control subjects (56 women and 37 men; mean BMI of 24.1 kg/m2). Tissue Doppler imaging echocardiography was used to provide measurements of ejection fraction, LVDD (peak early tissue Doppler velocity/peak late tissue Doppler velocity or Em/Am ratio), left ventricular mass (LVM), and left ventricular hypertrophy (LVH). Adiponectin levels, the homeostasis model assessment index, and the ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL) were used as surrogate markers of IR. RESULTS: The ejection fraction was normal and similar in the patient and control groups. LVDD (Em/Am ratio <1.0) and LVH prevalences were 52% and 30%, respectively, in the group with MO (significantly higher than in the control group; P<0.0005). The patients with MO displayed higher IR on the basis of all 3 surrogate markers (P<0.0005, respectively). Log-transformed adiponectin showed the strongest correlations with LVM and Em/Am ratios; log-transformed homeostasis model assessment index and TG/HDL ratio displayed less robust yet significant correlations. Stepwise multiple linear regression analysis identified hypertension and the TG/HDL ratio as independent predictors of 35.5% of the variance of LVDD. In contrast, LVM was mainly predicted by BMI, hypertension, and sex. CONCLUSION: LVH and LVDD are highly prevalent in asymptomatic patients with MO. IR is significantly correlated with both variables. Furthermore, LVDD is independently predicted by the presence of hypertension and the TG/HDL ratio. The prognostic implications of these findings warrant further studies.

Angiotensin-converting enzyme polymorphism gene and evolution of nephropathy to end-stage renal disease.

Genetic polymorphisms of the renin-angiotensin system (RAS) have been implicated in the pathogenesis of nephropathy and end-stage renal disease (ESRD). The association between angiotensin-converting enzyme (ACE) gene polymorphism and nephropathy evolution was studied. A random sample of 161 subjects from the Nephrology Department (of Hospital de Sant Pau) were divided into two groups: (i) 117 with end-stage renal disease; (ii) 44 with established nephropathy; and (iii) control groups of 129 subjects. The ACE gene polymorphism was performed by using polymerase chain reaction. High DD genotype presentation was observed in the two groups of subjects with nephropathy (46.12 and 61.37%, respectively vs 35.66% in controls; P < 0.0482), and also, a decrease was observed in the II genotype (6.4 and 4.54%, respectively vs 13.17% in controls, P < 0.0404). Glomerular filtration rate (GFR) was evaluated after 44 months of follow up. An important decrease of GFR was observed in patients with DD polymorphism versus other genotypes (initial, 32.3 +/- 7.9 and at 44 months, 18.35 +/- 3.3 mL/min vs 31.4 +/- 11.9 and 11.7 +/- 3.2 mL/min; P < 0.039). In a non-longitudinal study of patients in ESRD, patients with an ACE-DD genotype had a lower period of time between diagnosis of nephropathy and ESRD than patients with other genotypes (10.45 +/- 9.32 vs 19.5 +/- 8.4 years; P < 0.034). In conclusion, the ACE gene that controls RAS response may influence the development and progression of nephropathy to ESRD. Patients who develop several types of nephropathy have a higher risk of severe evolution if they have a profile of ACE-DD genotype.

Endothelial nitric oxide synthase gene polymorphism in dialysis patients.

Nitric oxide is an important factor in the regulation of vasodilator tone. In vascular cells, NO is synthesized by endothelial nitric oxide synthase, a key enzyme of the endogenous vasodilator system. Some studies have described the interaction between NO and the other factors that promote vasodilatation in vascular smooth muscular cells. Some of those factors are angiotensin-converting enzyme (ACE), transforming growth factor beta (TGF beta), and endothelial oxide nitric synthase (eNOS). Polymorphism that can alter the expression or the function of the eNOS protein has been identified in the eNOS gene in the promoter and codification zones. We studied the Glu298Asp variant of the eNOS gene in 52 hemodialysis (HD) patients, 22 peritoneal dialysis (PD) patients, and 93 healthy controls. Identification of the Glu298Asp variant in exon 7 was performed by enzymatic amplification and restriction fragment length polymorphism (RFLP) analysis. The frequencies of eNOS genotypes in the control group were GG, 39.8%; GT, 43%; and TT, 17.2%. In HD patients, the frequencies were GG, 40.3%; GT, 38.7%; and TT, 21.7%. In PD patients, they were GG, 41.6%; GT, 50%; and TT, 8.6%. No significant differences were seen between the control group and the dialysis patients, or between the HD and the PD patients.

Protein oxidative stress in dialysis patients.

Inflammatory status is observed in patients with chronic renal failure (CRF). The relationship between oxygen free radical production and dialysis could play an important role in protein oxidation. Carbonyl protein plasma level is an important tool in the study of protein stress, and it is related to the arterial intima thickness in the atherosclerosis process. We studied protein oxidative stress in 21 peritoneal dialysis (PD) patients and 42 hemodialysis (HD) patients as compared with 32 undialyzed patients with CRF. Carbonyl protein plasma levels were measured in nanomoles per milligram protein by the ELISA method (Winterbourn et al). Dialysis patients had a higher protein carbonyl content than did CRF patients (0.1265 +/- 0.04 nmol/mg vs. 0.1594 +/- 0.03 nmol/mg, p < 0.0002). Patients on PD had a lower level than patients on HD (0.1452 +/- 0.03 nmol/mg vs. 0.1665 +/- 0.04, p < 0.004). Glucose administration in PD is known to be able to increase glucose degradation products (GDPs) and advanced glycosylation end-products (AGEs) with high carboxylic and oxidative stress. In our study, the carbonyl protein level was higher in HD patients than in PD patients, perhaps because more protein oxidative stress is associated with hemodialysis technique or because the PD patients had greater residual renal function.