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1.
J Thromb Haemost ; 14(11): 2194-2201, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27566988

RESUMO

Essentials Prothrombin and partial thromboplastin time (PT/PTT) measure direct oral anticoagulants (DOACs). PT, PTT and specific tests for DOACs were performed on patients treated for atrial fibrillation. Normal PT/PTT don't exclude DOAC activity and their prolongation doesn't confirm DOAC action. The use of PT or PTT to evaluate DOAC activity could cause dangerous misinterpretations. SUMMARY: Background Prothrombin time (PT) and activated partial thromboplastin time (APTT) have been proposed to measure the effect of oral anti-activated factor X (FXa) or anti-activated FII drugs, respectively. Aims To evaluate the relationships and responsiveness of PT and APTT versus direct oral anticoagulant (DOAC) concentrations measured with specific coagulation tests performed with different platforms in four Italian anticoagulation clinics. Methods Six hundred and thirty-five patients with atrial fibrillation participated in the study: 240 were receiving dabigatran, 264 were receiving rivaroxaban, and 131 were receiving apixaban. Blood was taken at trough and peak within the first month (15-25 days) of treatment. PT, APTT, diluted thrombin time (dTT) calibrated for dabigatran and anti-FXa calibrated for rivaroxaban or apixaban were determined. Results For dabigatran, the correlation between APTT and dTT ranged from r = 0.80 to r = 0.62. For rivaroxaban, the correlation between the anti-FXa assay and PT ranged from r = 0.91 to r = 0.73. For apixaban, the correlation between the anti-FXa assay and PT was lower than for the two other drugs (r = 0.81 to r = 0.54). Despite the above significant correlations, the responsiveness of PT or APTT was relatively poor. A discrepancy between global testing and DOAC plasma concentrations was shown in a considerable proportion of patients, depending on the platform and drug, with values ranging from 6% to 62%. Conclusions Overall, poor responsiveness of the screening tests to DOAC concentrations was observed. PT and APTT normal values cannot exclude DOAC anticoagulant activity, and PT or APTT prolongation is not always associated with DOAC anticoagulant effect as determined with specific tests.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Administração Oral , Antitrombinas/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea/métodos , Calibragem , Dabigatrana/administração & dosagem , Dabigatrana/uso terapêutico , Fator Xa/química , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Itália , Masculino , Pirazóis/administração & dosagem , Pirazóis/uso terapêutico , Piridonas/administração & dosagem , Piridonas/uso terapêutico , Análise de Regressão , Rivaroxabana/administração & dosagem , Rivaroxabana/uso terapêutico , Tempo de Trombina , Resultado do Tratamento
2.
J Thromb Haemost ; 14(11): 2287-2297, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27557753

RESUMO

Essentials Retinal vein occlusion (RVO), characterized by blood hyperviscosity, has an unclear pathogenesis. We aimed to find out if hemorheological profile is altered by oxidative stress in RVO patients. Red blood cell (RBC) oxidative stress is associated to whole blood viscosity and RBC deformability. Reactive oxygen species alter RBC membrane rigidity, playing a key role in RVO pathogenesis. SUMMARY: Background Retinal vein occlusion (RVO) is characterized by vision loss resulting from hypoperfusion and hypoxia of the retina. RVO pathogenesis is not yet fully understood, although blood hyperviscosity has been observed. Erythrocyte deformability plays a key role in determining blood viscosity, and it is critical to microvascular perfusion and oxygen delivery. It has been shown that oxidative stress-induced erythrocyte membrane fluidity alterations are linked to the progression of cardiovascular diseases. Objectives To determine whether erythrocytes from RVO patients show signs of oxidative stress, and whether this condition can modify the hemorheologic profile in these patients. Patients and Methods We analyzed the entire hemorheologic profile and erythrocyte oxidative stress - reactive oxygen species (ROS) production and membrane lipid peroxidation - in 128 RVO patients and 128 healthy subjects, matched for age and sex. Fluorescence anisotropy was used to evaluate the fluidity of erythrocyte membranes. Results In RVO patients, erythrocyte oxidative stress was present and positively correlated with whole blood viscosity and erythrocyte deformability. Multivariate linear regression analysis after adjustment for age, cardiovascular risk factors, medications, leukocyte number and mean corpuscular volume indicated that erythrocyte-derived ROS and erythrocyte lipid peroxidation were significantly and positively correlated with erythrocyte membrane viscosity and deformability. Moreover, in vitro experiments demonstrated that ROS have a key role in erythrocyte membrane fluidity. Conclusions Our findings indicate that erythrocyte oxidative stress plays a key role in the pathogenesis of RVO, and pave the way to new therapeutic interventions.


Assuntos
Deformação Eritrocítica , Eritrócitos/citologia , Estresse Oxidativo , Oclusão da Veia Retiniana/patologia , Anisotropia , Viscosidade Sanguínea , Estudos de Casos e Controles , Membrana Eritrocítica/metabolismo , Feminino , Hemorreologia , Humanos , Peroxidação de Lipídeos , Masculino , Análise Multivariada , Espécies Reativas de Oxigênio/metabolismo , Fatores de Risco , Estresse Mecânico , Viscosidade
4.
Thromb Haemost ; 112(1): 196-204, 2014 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-24573342

RESUMO

An increase of endothelial progenitor cells (EPCs) among acute myocardial infarction (AMI) patients participating in a cardiac rehabilitation (CR) program has been reported, but no data on the impact of adherence to lifestyle recommendations provided during a CR program on EPCs are available. It was our aim to investigate the effect of adherence to lifestyle recommendations on EPCs, inflammatory and functional parameters after six months of a CR program in AMI patients. In 110 AMI patients (90 male/20 female; mean age 57.9 ± 9.4 years) EPCs, high sensitivity C-reactive protein (hsCRP), N-terminal pro-brain natriuretic peptide (NT-ProBNP) levels, and cardiopulmonary testings were determined at the end of the CR (T1) and at a six-month follow-up (T2). At T2 we administered a questionnaire assessing dietary habits and physical activity. At T2, we observed a decrease of EPCs (p<0.05), of hsCRP (p=0.009) and of NT-ProBNP (p<0.0001). Patient population was divided into three categories by Healthy Lifestyle (HL) score (none/low, moderate and high adherence to lifestyle recommendations). We observed a significant association between adherence to lifestyle recommendations, increase in EPCs and exercise capacity between T1 and T2 (Δ EPCs p for trend <0.05; ΔWatt max p for trend=0.004). In a multivariate logistic regression analyses, being in the highest tertile of HL score affected the likelihood of an increase of EPC levels at T2 [OR (95% confidence interval): 3.36 (1.0-10.72) p=0.04]. In conclusion, adherence to lifestyle recommendations provided during a CR program positively influences EPC levels and exercise capacity.


Assuntos
Células Progenitoras Endoteliais/fisiologia , Infarto do Miocárdio/reabilitação , Cooperação do Paciente/estatística & dados numéricos , Doença Aguda , Idoso , Proteína C-Reativa/metabolismo , Comportamento Alimentar , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Infarto do Miocárdio/epidemiologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Avaliação de Programas e Projetos de Saúde , Comportamento de Redução do Risco , Inquéritos e Questionários
5.
Thromb Haemost ; 109(5): 846-53, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23494003

RESUMO

Reticulated platelets (RP) are newly-formed platelets with a greater mass, a residual amount of RNA and an increased prothrombotic potential. No studies investigating the association between RP and the risk of cardiovascular death in acute coronary syndrome (ACS) patients are available. In the frame of the AMI-Florence 2 study, we investigated RP in 229 (154 M/ 75 F) ACS patients (125 ST-elevation myocardial infarction [STEMI]; 104 Non-STEMI/Unstable Angina). RP were measured by using the Sysmex XE-2100 haematology analyzer and were expressed as the percentage of RP out of the total optical platelet count (immature platelet fraction; IPF) and as the percentage of RP highly fluorescent (H-IPF). At one-year follow-up, 22 out of 229 patients (9.6%) died from cardiovascular causes. Higher values of IPF (p=0.05) and H-IPF (p=0.006) were detected in dead compared to alive patients. A receiver operating characteristics curve analysis identified IPF ≥3.3% and H-IPF ≥0.9% as optimal cut-off values to predict cardiovascular death. At the multivariate model adjusted for the Global Registry of Acute Coronary Events (GRACE) risk score, the association between RP and cardiovascular death remained significant for both IPF [OR (95%CI) : 4.15 (1.24-13.91) p=0.02] and H-IPF [OR (95%CI): H-IPF 5.03 (1.38-18.38) p=0.01]. In conclusion, RP are independent predictors of cardiovascular death and may be useful in improving risk stratification for ACS patients. Future prospective studies to evaluate the role of RP in determining cardiovascular events are warranted.


Assuntos
Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/mortalidade , Angina Instável/sangue , Angina Instável/mortalidade , Plaquetas , Infarto do Miocárdio/sangue , Infarto do Miocárdio/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Distribuição de Qui-Quadrado , Feminino , Humanos , Itália , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Contagem de Plaquetas , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Sistema de Registros , Fatores de Risco , Fatores de Tempo
6.
Eur J Clin Nutr ; 67(2): 190-5, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23299714

RESUMO

BACKGROUND/OBJECTIVES: Khorasan wheat (Kamut) is an ancient grain with widely acclaimed beneficial effects on human health. The objective was to characterise Kamut and to examine the effect of a replacement diet with their products on cardiovascular risk parameters. SUBJECTS/METHODS: We conducted a randomized, single-blinded cross-over trial with two intervention phases on 22 healthy subjects (14 females; 8 males). The participants were assigned to consume products (bread, pasta and crackers) made either from Kamut or control semi-whole-grain wheat for 8 weeks in a random order. An 8-week washout period was implemented between the interventions. Laboratory analyses were performed both at the beginning and at the end of each intervention phase. RESULTS: At a general linear model for repeated measurements adjusted for several confounders, consumption of Kamut products showed a significant reduction of metabolic risk factors such as total cholesterol (mean reduction: -8.46 mg/dl; -4%), low-density lipoprotein cholesterol (-9.82 mg/dl; -7.8%) and blood glucose. Similarly, redox status was significantly improved only after the Kamut intervention phase, as measured by a reduction in both thiobarbituric acid reactive substances (-0.17 nmol/ml; -21.5%;) and carbonyl levels (-0.16 nmol/ml; -17.6%). The replacement diet with Kamut products also resulted in a significant increase of serum potassium and magnesium. Circulating levels of key pro-inflammatory cytokines (interleukin (IL)-6, IL-12, tumour necrosis factor-α and vascular endothelial growth factor) were significantly reduced after the consumption of Kamut products. CONCLUSIONS: The present results suggest that a replacement diet with Kamut products could be effective in reducing metabolic risk factors, markers of both oxidative stress and inflammatory status.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dieta , Comportamento Alimentar , Inflamação/prevenção & controle , Estresse Oxidativo , Triticum , Adulto , Glicemia/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Colesterol/sangue , LDL-Colesterol/sangue , Estudos Cross-Over , Citocinas/sangue , Feminino , Humanos , Inflamação/sangue , Inflamação/complicações , Mediadores da Inflamação/sangue , Magnésio/sangue , Masculino , Pessoa de Meia-Idade , Oxirredução , Potássio/sangue , Carbonilação Proteica , Fatores de Risco , Método Simples-Cego , Especificidade da Espécie , Triticum/classificação
7.
Clin Hemorheol Microcirc ; 55(2): 271-6, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-23089883

RESUMO

Peripheral arterial disease (PAD), is a common manifestation of systemic atherosclerosis. Advances on the development of such vascular disease have described with a number of novel risk factors. Hyperviscosity, due to alterations of blood cells and plasma components, may play a role on the pathogenesis of the disease. Aim of this study was to evaluate the possible association between hemorheological variables and PAD. The hemorheological variables [whole blood viscosity (WBV), erythrocyte deformability index (DI), plasma viscosity (PLV)] were analyzed in 90 patients and in 180 healthy subjects. WBV and PLV were measured by a Rotational Viscosimeter and DI by a filtrometer. DI and PLV were significantly different in patients as compared to controls. To investigate the possible association between these parameters and the disease we divided the study population into tertiles. At the univariate analysis, we found a significant association between the highest tertiles of PLV, of DI and the disease. A model adjusted for traditional risk factors showed an association between highest tertiles of PLV and PAD. After adjustment for confounding parameters highest tertiles of PLV remained to be significantly associated with the disease. Our data indicate that an alteration of plasma viscosity may modulate the predisposition to PAD.


Assuntos
Doença Arterial Periférica/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Viscosidade Sanguínea , Estudos de Casos e Controles , Estudos de Coortes , Deformação Eritrocítica , Feminino , Hemorreologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
8.
J Hum Hypertens ; 26(12): 723-30, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21993489

RESUMO

In essential hypertension, increased renal resistive index (RRI) is associated to a reduction of renal function and microalbuminuria, and to renal tubulo-interstitial damage. A tubulo-interstitial inflammatory infiltration was found in experimental models of hypertension, and serum high-sensitive C-reactive protein (hsCRP) levels correlated with urinary markers of tubulo-interstitial damage in humans. We studied the relationship between RRI and serum hsCRP in hypertensives with preserved renal function, without microalbuminuria. We investigated hypertensive patients without diabetes, renal failure, microalbuminuria or major inflammatory disease. Serum levels of hsCRP were assayed. RRI was calculated by intrarenal Doppler ultrasound and considered pathologic when ≥0.70 or >95% of upper confidence limit expected for age decade. The renal volume-to-resistive index ratio (RV/RRI) was also calculated. We evaluated 85 patients (57±14 years, 61 males). Patients with pathologic RRI (n=21) were older and had significantly higher hsCRP levels (4.70±2.30 vs 2.93±2.09 mg l(-1), P<0.01) compared with patients with normal RRI, as well as patients with decreased RV/RRI (n=43). HsCRP was directly related with RRI (r=0.41, P<0.001) and inversely with RV/RRI (r=-0.35, P<0.001). HsCRP proved to be a significant predictor of both pathologic RRI and decreased RV/RRI, even after adjustment. In essential hypertension low-grade inflammation is associated with tubulo-interstitial damage evaluated by Doppler ultrasonography.


Assuntos
Hipertensão/fisiopatologia , Inflamação/fisiopatologia , Túbulos Renais/fisiopatologia , Rim/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Comorbidade , Estudos Transversais , Hipertensão Essencial , Feminino , Humanos , Hipertensão/sangue , Hipertensão/epidemiologia , Inflamação/sangue , Inflamação/epidemiologia , Rim/diagnóstico por imagem , Túbulos Renais/diagnóstico por imagem , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Ultrassonografia Doppler
9.
Eur J Phys Rehabil Med ; 47(4): 543-9, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21508911

RESUMO

BACKGROUND: Back pain is a significant problem due to the high healthcare utilization, rising costs of care and low effectiveness of many current treatments. AIM: Aim of this study was to determine the effects of a community-based Adapted Physical Activity (APA) program focused on chronic, non-specific back pain. DESIGN: Open-label intervention study. SETTING: Community. POPULATION: All patients admitted to Empoli Rehabilitation Department for non-specific back pain for at least three months, were considered for APA. Exclusion criteria were: "red flags", difficulty/disability in basic daily living activities, severe/acute medical conditions, acute pain, psychiatric disease or cognitive impairment, severe visuoauditory deficit. Overall, 650 persons were enrolled. METHODS: The APA program, including strength and flexibility training and exercises for improving posture was delivered for 12 months, with 1-hour group classes three times per week. RESULTS: Overall 261 (40.2%) subjects completed the 12-month APA program and were compared to the 310 (47.7%) who were screened but failed to initiate or complete the study. There were no significant differences in baseline demographic and clinical characteristics between groups. Patients who followed the APA program reported significantly improved health status and significant back pain improvement, compared with those who did not adhere to the program. In the logistic regression analysis adjusted for age and gender, a distance from home to gymnasium greater than the median for the study population (2.6 km) was the only baseline characteristic significantly associated with an increased risk of non-adherence (OR 1.44, 95%CI 1.01-2.13; P=0.04). CONCLUSION: This study suggests that a community-based APA program can improve back pain and health status in persons with chronic, non-specific low back pain. CLINICA REHABILITATION IMPACT: These findings highlight the potential for new approaches to manage chronic disease and disability by facilitating a healthy lifestyle and promoting physical activity through implementation of community-based exercise programs.


Assuntos
Terapia por Exercício/métodos , Dor Lombar/reabilitação , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Distribuição de Qui-Quadrado , Feminino , Humanos , Itália , Dor Lombar/psicologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Medição da Dor , Postura/fisiologia , Amplitude de Movimento Articular , Análise de Regressão , Treinamento Resistido , Adulto Jovem
10.
J Intern Med ; 269(1): 107-17, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20831630

RESUMO

OBJECTIVE: The relationship between physical activity and cognitive function is intriguing but controversial. We performed a systematic meta-analysis of all the available prospective studies that investigated the association between physical activity and risk of cognitive decline in nondemented subjects. METHODS: We conducted an electronic literature search through MedLine, Embase, Google Scholar, Web of Science, The Cochrane Library and bibliographies of retrieved articles up to January 2010. Studies were included if they analysed prospectively the association between physical activity and cognitive decline in nondemented subjects. RESULTS: After the review process, 15 prospective studies (12 cohorts) were included in the final analysis. These studies included 33,816 nondemented subjects followed for 1-12 years. A total of 3210 patients showed cognitive decline during the follow-up. The cumulative analysis for all the studies under a random-effects model showed that subjects who performed a high level of physical activity were significantly protected (-38%) against cognitive decline during the follow-up (hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.54-0.70; P < 0.00001). Furthermore, even analysis of low-to-moderate level exercise also showed a significant protection (-35%) against cognitive impairment (HR 0.65, 95% CI 0.57-0.75; P < 0.00001). CONCLUSION: This is the first meta-analysis to evaluate the role of physical activity on cognitive decline amongst nondemented subjects. The present results suggest a significant and consistent protection for all levels of physical activity against the occurrence of cognitive decline.


Assuntos
Transtornos Cognitivos/prevenção & controle , Atividade Motora , Adulto , Idoso , Idoso de 80 Anos ou mais , Demência/prevenção & controle , Exercício Físico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Sensibilidade e Especificidade
11.
Nutr Metab Cardiovasc Dis ; 21(1): 11-7, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19819117

RESUMO

BACKGROUND AND AIM: Platelet nitric oxide (NO) synthesis is compromised in patients with acute coronary syndrome (ACS), and platelet NO availability may be critically relevant in determining the extent of thrombosis in ACS patients. It has been demonstrated that an impaired responsiveness to the antiaggregatory effects of NO may affect platelet dysfunction in diabetic patients with ACS. Since NO availability may be genetically determined, we have investigated the role of endothelial nitric oxide synthase (eNOS) gene in influencing platelet aggregability in relation to the presence (n=247) or absence (n=883) of type 2 diabetes in ACS patients. METHODS AND RESULTS: We have genotyped 1130 consecutive high risk ACS patients on dual antiplatelet therapy, previously investigated in relation to platelet function. eNOS 4a allele frequency was significantly higher in diabetic vs. non-diabetic patients (p=0.02). In non-diabetic patients the eNOS 4a allele significantly modulated platelet aggregability in response to arachidonic acid (AA), but not to collagen and adenosine diphosphate (ADP) stimulus, after Bonferroni correction for multiple testing. After adjustment for age, gender, smoking habit, hypertension and ejection fraction ≤40%, the eNOS 4a allele remained significantly and independently associated with platelet aggregability in response to AA stimulus [ß (SE)=0.17 (0.07), p=0.01]. When platelet aggregation values were considered according to the presence or absence of high residual platelet reactivity (RPR) eNOS 4a, but not -786C and 894T, allele was significantly associated with RPR by AA stimulus. The haplotype reconstruction analysis for eNOS gene showed that the -786C/894G/4a and -786C/894G/4b haplotypes significantly influenced platelet aggregation after AA stimulus. CONCLUSIONS: Our study indicates that eNOS 4a allele, may be a determinant of higher platelet aggregability and residual platelet reactivity in non-diabetic ACS patients.


Assuntos
Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/genética , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Óxido Nítrico Sintase Tipo III/genética , Agregação Plaquetária/genética , Agregação Plaquetária/fisiologia , Síndrome Coronariana Aguda/complicações , Difosfato de Adenosina/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Ácido Araquidônico/farmacologia , Estudos de Coortes , Colágeno/farmacologia , Diabetes Mellitus Tipo 2/complicações , Endotélio Vascular/patologia , Feminino , Genótipo , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , Polimorfismo Genético/genética
12.
Pharmacogenomics J ; 11(3): 199-206, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20351750

RESUMO

Several polymorphisms in genes that encode platelet components (receptors or enzymes), or cytochrome P450 enzyme isoforms, involved in clopidogrel metabolism, have been proposed as possible mechanisms for nonresponsiveness to clopidogrel. Among them, a great deal of attention has been focused on the loss-of-function CYP2C19(*)2 (or 681 G > A) polymorphism. We performed a meta-analysis of all the prospective studies that have been published, which analyze the role of such a polymorphism in recurrent cardiovascular events in patients with coronary artery disease (CAD) being treated with clopidogrel. Studies were searched in MedLine, Embase, Web of Science, The Cochrane Systematic Review Database, Google Scholar and bibliographies of retrieved articles up to January 2010. The principal underlying hypothesis was that the presence of the (*)2 variant allele of the polymorphism would be associated with an increased risk of clinical recurrence. Data were available for a total of 8043 patients from seven cohort prospective studies, who were followed for a period of time ranging from 6 months to 8.3 years. The summary risk ratios (RRs) for the prospective cohort studies included showed a significant association between the CYP2C19(*)2 polymorphism and an increased risk of major adverse cardiovascular events in the follow-up (RR: 1.96 (1.14-3.37); P = 0.02). When studies evaluating stent thrombosis (n = 4) for a total of 4975 patients were considered, the presence of the variant allele was associated with an increased risk of stent thrombosis (RR: 3.82 (2.23-6.54); P = 0.0001). The current meta-analysis, carried out on nearly 8000 patients with CAD undergoing clopidogrel treatment, shows that the CYP2C19(*)2 polymorphism is associated with an increased risk of major adverse cardiovascular events and stent thrombosis.


Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Doenças Cardiovasculares/induzido quimicamente , Doença da Artéria Coronariana/tratamento farmacológico , Trombose/induzido quimicamente , Ticlopidina/análogos & derivados , Adolescente , Adulto , Idoso , Clopidogrel , Citocromo P-450 CYP2C19 , Estudos de Associação Genética , Genótipo , Humanos , Pessoa de Meia-Idade , Polimorfismo Genético , Recidiva , Fatores de Risco , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Ticlopidina/farmacocinética , Estados Unidos
13.
Nutr Metab Cardiovasc Dis ; 21(10): 776-82, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20554169

RESUMO

BACKGROUND AND AIM: Previous studies have shown that increased levels of C-reactive protein (CRP) predict cardiovascular events, including stroke, myocardial infarction and death from cardiovascular causes. Previous studies have also shown that increased levels of CRP are strong predictors of the progression of pre-existing carotid artery plaques. However, whether CRP is involved in the development of new plaques, that may or may not be associated with clinical events, in subjects with clean carotid arteries has been scarcely investigated. METHODS AND RESULTS: 486 "InCHIANTI" Study participants (200 men and 286 women, 72% aged 65 years and over) free from carotid artery plaques at baseline, also underwent carotid artery scan three years later. We tested the association of baseline characteristics, cardiovascular risk factors and inflammatory markers with the development of new carotid artery plaques. Older participants were significantly more likely to develop new plaques. Independent of age, the relative risks of developing new plaques associated with heavy smoking and family history of atherosclerosis were 1.7 (95%CI 1.5-1.9) and 1.9 (95%CI 1.2-3.1), respectively. Participants with high (>3 µg/mL) and moderate (≥1 and ≤3 µg/mL) CRP levels had a relative risk of 2.2 (95%CI 1.9-2.6) and 1.9 (95%CI 1.6-2.3) respectively, when compared with subjects with low (<1 µg/mL) CRP levels. Surprisingly, risk factors such as hypertension, diabetes, dyslipidemia and overweight/obesity were not significant predictors of the development of new carotid artery plaques. CONCLUSIONS: High CRP levels independently predict the development of new plaques in older persons with carotid arteries free from atherosclerotic lesions.


Assuntos
Proteína C-Reativa/análise , Artérias Carótidas/patologia , Estenose das Carótidas/patologia , Fatores Etários , Idoso , Aterosclerose/genética , Doenças Cardiovasculares/sangue , Estenose das Carótidas/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Prospectivos , Risco , Fatores Sexuais , Fumar
14.
Eur J Vasc Endovasc Surg ; 40(5): 549-58, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20709579

RESUMO

OBJECT: The pathogenesis of carotid artery stenosis (CAS) as well as the mechanisms underlying the different localisation of the atherosclerotic lesions remains poorly understood. We used microarray technology to identify novel systemic mediators that could contribute to CAS pathogenesis. Moreover, we compared gene-expression profile of CAS with that of patients affected by abdominal aortic aneurysm (AAA), previously published by our group. METHODS AND RESULTS: By global gene-expression profiling in a pool of 10 CAS patients and 10 matched controls, we found 82 genes differentially expressed. Validation study in pools used for profiling and replication study in larger numbers of CAS patients (n = 40) and controls (n = 40) of 14 genes by real-time polymerase chain reaction (RT-PCR) confirmed microarray results. Fourteen out of 82 genes were similarly expressed in AAA patients. Gene ontology analysis identified a statistically significant enrichment in CAS of differentially expressed transcripts involved in immune response and oxygen transport. Whereas alteration of oxygen transport is a common tract of the two localisations, alteration of immune response in CAS and of lipid metabolic process in AAA represents distinctive tracts of the two atherosclerotic diseases. CONCLUSIONS: We describe the systemic gene-expression profile of CAS, which provides an extensive list of potential molecular markers.


Assuntos
Estenose das Carótidas/genética , Perfilação da Expressão Gênica , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Abdominal/genética , Estenose das Carótidas/sangue , Estenose das Carótidas/fisiopatologia , Estenose das Carótidas/cirurgia , Feminino , Humanos , Masculino , Análise em Microsséries , Pessoa de Meia-Idade
16.
Eur J Med Genet ; 53(5): 299-302, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20538085

RESUMO

The Fibrillin-1 gene (FBN1; chromosome 15q21.1) encodes a major glycoprotein component of the extracellular matrix. Mutations in FBN1, TGFBR1, TGFBR2 are known to cause Marfan syndrome (MIM 154700), a pleiotropic disorder. In the present study, we describe five novel missense FBN1 mutations in five Marfan patients that have the peculiarity to activate two contemporary mutational mechanisms: a missense mutation and exon skipping.


Assuntos
Substituição de Aminoácidos , Síndrome de Marfan , Proteínas dos Microfilamentos/genética , Mutação de Sentido Incorreto , Adulto , Criança , Éxons , Feminino , Fibrilina-1 , Fibrilinas , Heterozigoto , Humanos , Masculino , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade
17.
Transplant Proc ; 42(4): 1156-7, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20534248

RESUMO

INTRODUCTION: Renal transplant recipients are at increased risk of cardiovascular morbidity and mortality. We assessed platelet reactivity and reticulated platelets (RPs) in 90 recipients, 51 (56.6%) of whom were not receiving acetylsalicylic acid (ASA) therapy (group A) and 39 (43.3%) who were receiving ASA therapy, 100 mg (group B), and in 60 healthy controls (group C). METHODS: Reticulated platelets were measured using a hematology automated analyzer (XE-2100; Sysmex Corp, Kobe, Japan) and were expressed as the percentage of RPs in the total optical platelet count (immature platelet fraction [IPF]), as the percentage of highly fluorescent RPs, and as the absolute number of RPs (IPF#). Platelet function was assessed using optical aggregometry (platelet aggregation) induced using 1 mmol/L of arachidonic acid, 2 or 10 micromol/L of adenosine diphosphate, or 2 microg/mL of collagen. RESULTS: Group A demonstrated significantly higher values of RP compared with group B or group C. Group B demonstrated a substantially higher percentage of RPs compared with group C, which was significant only for the IPF parameter. Multiple regression analysis demonstrated that IPF and IPF# were significantly and positively related to collagen-induced platelet aggregation. CONCLUSION: We documented the presence of higher concentrations of RPs in transplant recipients compared with a control population, and a significant association between RPs and platelet function.


Assuntos
Plaquetas/efeitos dos fármacos , Transplante de Rim/fisiologia , Inibidores da Agregação Plaquetária/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Adulto , Idoso , Aspirina/uso terapêutico , Automação , Resistência a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefelometria e Turbidimetria , Adulto Jovem
18.
Transplant Proc ; 42(4): 1381-2, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20534308

RESUMO

Cardiovascular disease (CVD) is the main cause of morbidity and mortality in renal transplant recipients. The incidence of CVD in this setting is approximately 5-fold greater than in age- and and gender-matched subjects. This excess cardiovascular risk is not completely explained by traditional cardiac risk factors. It has been well documented that these patients show greatly increased prevalence of both fasting and postmethionine-loading hyperhomocysteinemia (hHcy) compared with the general population. An immunosuppressive therapy based on everolimus has been demonstrated to reduce the incidence major adverse coronary events at 4 years compared with azathioprine among heart transplant recipients. In contrast, scarce data are available on the impact of everolimus on emerging risk factors, such as homocysteine (Hcy), in renal transplant recipients. The aim of this study was to evaluate the possible impact of everolimus compared with other immunosuppressive regimes among 132 stable recipients, including 91 men and 41 women who were at least 1 year after transplant with stable renal function and no clinical evidence of acute or chronic renal graft rejections. We compared 31 subjects on everolimus immunosuppressive therapy (group A) versus 101 on immunosuppressive therapy based on cyclosporine, steroids, and mycophenolate. The Hcy levels were significantly lower among group A patients compared with group B: 16.5 +/- 5 micromol/L vs 21.2 +/- 11 micromol/L; P < .005. Hyper-Hcy, defined as Hcy levels >15 micromol/L, was diagnosed in 18 out of 31 patients (51%) of group A and in 82 out of 101 patients (81%) of group B. This preliminary study demonstrates a favorable impact of everolimus on a marker of atherothrombosis which is associated with a worse vascular prognosis.


Assuntos
Homocisteína/sangue , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Sirolimo/análogos & derivados , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Quimioterapia Combinada , Everolimo , Feminino , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/fisiologia , Masculino , Complicações Pós-Operatórias/prevenção & controle , Sirolimo/uso terapêutico
19.
Transplant Proc ; 42(4): 1383-4, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20534309

RESUMO

Renal transplant recipients (RTRs) are at increased risk of cardiovascular complications. An altered hemorheological profile may determine both cardiovascular complications and progression of renal failure in RTRs. We performed this study to evaluate the rheologic status in 239 RTRs at least 12 months after transplantation with stable and normal renal function compared with 90 control subjects. In RTRs, a significantly higher hematocrit-adjusted, but not native, whole blood viscosity was found (P < .0001). Moreover, plasma viscosity and red blood cell deformability were significantly higher in patients than in control subjects (P < .0001), whereas no difference in erythrocyte aggregation between patients and control subjects was observed (P = .5). Fibrinogen, but not hematocrit, significantly increased in RTRs (P = .001). This preliminary study provides evidence of an altered hemorheologic profile in RTRs.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Transplante de Rim/fisiologia , Adolescente , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Feminino , Hemorreologia , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Medição de Risco , Estatísticas não Paramétricas
20.
J Thromb Haemost ; 8(1): 121-8, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19874469

RESUMO

BACKGROUND: Deep vein thrombosis (DVT) is a major complication in intensive care units (ICU) but dedicated guidelines on its management are still lacking. OBJECTIVES AND METHODS: This study investigated the effect of a 1-year educational program for the implementation of DVT prophylaxis on the incidence of inferior limb DVT in a mixed-bed ICU that admits high-risk surgical and trauma patients, investigated during a first retrospective phase [126 patients, SAPS II score 42 (28-54)] and a following prospective phase [264 patients, SAPS II score II 41 (27-55)]. The role of baseline and time-dependent DVT risk factors in DVT occurrence was also investigated during the prospective phase. RESULTS: The educational program on implementation of DVT prophylaxis was associated with a significant decrease in DVT incidence from 11.9% to 4.5% (P < 0.01) and in the mean length of ICU stay (P < 0.01). Combined with pharmacological prophylaxis, the use of elastic compressive stockings significantly also increased in the prospective phase (P < 0.01). The duration of mechanical ventilation, vasopressor administration and neuromuscular block were significantly different between DVT-positive and DVT-negative patients (P < 0.01). Multivariate analysis identified neuromuscular block as the strongest independent predictor for DVT incidence. CONCLUSION: One-year ICU-based educational programs on implementation of DVT prophylaxis were associated with a significant decrease in the incidence of DVT and also in the length of stay in ICU.


Assuntos
Educação Médica Continuada , Fibrinolíticos/uso terapêutico , Hematologia/educação , Unidades de Terapia Intensiva , Dispositivos de Compressão Pneumática Intermitente , Meias de Compressão , Trombose Venosa/prevenção & controle , Adulto , Idoso , Terapia Combinada , Currículo , Feminino , Humanos , Incidência , Itália/epidemiologia , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Bloqueio Neuromuscular/efeitos adversos , Guias de Prática Clínica como Assunto , Prevalência , Avaliação de Programas e Projetos de Saúde , Estudos Prospectivos , Respiração Artificial/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia , Vasoconstritores/efeitos adversos , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia
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