Hypolipidemic treatment under special conditions: posttransplant and/or immunosupressive therapy

There are limited data regarding the use of hypolipidemic agents concomitantly with immunosuppressive drugs. Best evidence is provided for the use of statins and cyclosporine. In terms of pharmacodynamics, these two drugs have different substrates. In respect to pharmacokinetics, statins usually do not modify serum concentrations of cyclosporine, however when combined with any statin a careful monitoring of cyclosporine levels is recommended, due to a narrow therapeutic window of the immunosupressive agent. Conversely, cyclosporine does affect the area under the curve for many statins, by inhibiting the CYP450 3A4, thus increasing systemic exposure to statins. Pravastatin appears to be the safest compound, once it is glucuronized. The area under the curve for the other statins (simvastatin, lovastatin, atorvastatin, cerivastatin, and rosuvastatin) can be increased in variable degrees according to the site of metabolization, liver extraction by OATP-C transporter, biliary secretion, renal excretion, and drug extrusion by the MDR system.Existem dados limitados sobre o uso concomitante de agentes hipolipemiantes e drogas imunosupressoras. As melhores evidências provêm do uso de estatinas e ciclosporina. Em termos farmacodinâmicos, estas duas drogas têm substratos diferentes. No tocante a farmacocinética, as estatinas não modificam as concentrações plasmáticas de ciclosporina. Entretanto, quando combinada a qualquer estatina, um controle rigoroso dos níveis de ciclosporina é recomendado, levando-se em conta o seu estreito intervalo terapêutico. Ciclosporina afeta a área sob a curva de muitas estatinas, pela inibição do CYP450 3A4, aumentando a exposição sistêmica dessas drogas. Pravastatina se apresenta como o composto de maior segurança, uma vez que é glucuronidado. A área sob a curva para as outras estatinas (sinvastatina, lovastatina, atorvastatina, cerivastatina e rosuvastatina) pode aumentar em graus variáveis de acordo com o seu sítio de metabolização, extração hepática pelo OATP-transportador, secreção biliar, excreção renal, e extrusão da droga pelo sistema MDR.UNIFESP-EPM Setor de Lípides, Aterosclerose e Biologia VascularUNIFESP, EPM, Setor de Lípides, Aterosclerose e Biologia VascularSciEL

High-Sensitivity C-Reactive Protein and Cardiovascular Disease Across Countries and Ethnicities

Despite substantial differences in ethnicities, habits, cultures, the prevalence of traditional cardiovascular risk factors and affordable therapies, atherosclerosis remains the major cause of death in developing and developed countries. However, irrespective of these differences, inflammation is currently recognized as the common pathway for the major complications of atherosclerosis, stroke, and ischemic heart disease. A PubMed search was conducted for “high-sensitivity C-reactive protein” (hs-CRP) in combination with the terms race, ethnicity, gender, prevalence, geographic, epidemiology, cardiovascular, obesity, diabetes, hypertension, cholesterol, smoking, ischemic heart disease, stroke, and mortality. This review includes the articles that pertained to the topic and additional articles identified from the reference lists of relevant publications. This review describes the marked differences in cardiovascular mortality across countries and ethnicities, which may be attributed to inequalities in the prevalence of the classic risk factors and the stage of cardiovascular epidemiological transition. However, hs-CRP appears to contribute to the prognostic information regarding cardiovascular risk and mortality even after multiple adjustments. Considering the perception of cardiovascular disease as an inflammatory disease, the more widespread use of hs-CRP appears to represent a valid tool to identify people at risk, independent of their ancestry or geographic region. In conclusion, this review reports that the complications associated with vulnerable atherosclerotic plaques are triggered by the major mechanisms of dyslipidemia and inflammation; whereas both mechanisms are influenced by classic risk factors, hs-CRP contributes additional information regarding cardiovascular events and mortality

Effects of simvastatin/ezetimibe on microparticles, endothelial progenitor cells and platelet aggregation in subjects with coronary heart disease under antiplatelet therapy

It is not known whether the addition of ezetimibe to statins adds cardiovascular protection beyond the expected changes in lipid levels. Subjects with coronary heart disease were treated with four consecutive 1-week courses of therapy (T) and evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133; CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was examined by flow-mediated dilation. Comparisons between therapies revealed differences in lipids (T2 and T3T1 and T4, P=0.001). Decreased platelet aggregation was observed after aspirin (arachidonic acid, T1<T3 and T4, P=0.034) and clopidogrel (adenosine, T3 and T4<T1 and T2, P<0.0001) therapy. Simvastatin/ezetimibe diphosphate did not change platelet aggregation, the amount of circulating endothelial and platelet microparticles, or endothelial progenitor cells. Cardiovascular protection following therapy with simvastatin/ezetimibe seems restricted to lipid changes and improvement of endothelial function not affecting the release of microparticles, mobilization of endothelial progenitor cells or decreased platelet aggregation.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MedicinaUNIFESP, EPM, Depto. de MedicinaSciEL

Electrocardiogram sensitivity in left ventricular hypertrophy according to gender and cardiac mass

BACKGROUND: Several factors are known to interfere with electrocardiogram (ECG) sensitivity when diagnosing Left Ventricular Hypertrophy (LVH), with gender and cardiac mass being two of the most important ones OBJECTIVE: To evaluate the influence of gender on the sensitivity of some of the criteria used to detect LVH, according to the progression of ventricular hypertrophy degree. METHODS: According to gender and the degree of LVH at the echocardiogram, the patients were divided in three groups: mild, moderate and severe LVH. ECG sensitivity to detect LVH was assessed between men and women, according to the LVH degree. RESULTS: Of the 874 patients, 265 were males (30.3%) and 609, females (69.7%). The [(S + R) X QRS], Sokolow-Lyon, Romhilt-Estes, Perugia and strain criteria showed high discriminatory power in the diagnosis of LVH between men and women in the three groups with LVH, with a superior performance in the male population and highlighting the importance of the [(S + R) X QRS] and Perugia scores. Conclusion: The diagnostic sensitivity of the ECG increases with the cardiac mass. The examination is more sensitive in men, highlighting the importance of the [(S + R) X QRS] and Perugia scores. CONCLUSION: The diagnostic sensitivity of the ECG increases with the cardiac mass. The examination is more sensitive in men, highlighting the importance of the [(S + R) X QRS] and Perugia scores.FUNDAMENTO: Sabe-se que vários fatores interferem na sensibilidade do Eletrocardiograma (ECG) no diagnóstico da Hipertrofia Ventricular Esquerda (HVE), sendo o gênero e a massa cardíaca alguns dos principais. OBJETIVO: Avaliar a influência do sexo na sensibilidade de alguns dos critérios utilizados para a detecção de HVE, de acordo com a progressão do grau de hipertrofia ventricular. MÉTODOS: De acordo com o gênero e com o grau de HVE ao ecocardiograma, os pacientes foram divididos em três grupos: HVE leve, moderada e severa. Avaliou-se a sensibilidade do ECG para detectar HVE entre homens e mulheres, conforme o grau de HVE. RESULTADOS: Dos 874 pacientes, 265 eram homens (30,3%) e 609, mulheres (69,7%). Os critérios [(S + R) X QRS], Sokolow-Lyon, Romhilt-Estes, Perúgia e padrão strain mostraram alto poder discriminatório no diagnóstico de HVE entre homens e mulheres nos três grupos de HVE, com desempenho superior na população masculina e destaque para os escores [(S + R) X QRS] e Perúgia. CONCLUSÃO: A sensibilidade diagnóstica do ECG é maior com o aumento da massa cardíaca. O exame é mais sensível entre homens, destacando-se os escores [(S + R) X QRS] e Perúgia.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Circulating microparticles and central blood pressure according to antihypertensive strategy

OBJECTIVES: This prospective, randomized, open-label study aimed to compare the effects of antihypertensive treatment based on amlodipine or hydrochlorothiazide on the circulating microparticles and central blood pressure values of hypertensive patients. METHODS: The effects of treatments on circulating microparticles were assessed during monotherapy and after the consecutive addition of valsartan and rosuvastatin followed by the withdrawal of rosuvastatin. Each treatment period lasted for 30 days. Central blood pressure and pulse wave velocity were measured at the end of each period. Endothelial, monocyte, and platelet circulating microparticles were determined by flow cytometry. Central blood pressure values and pulse wave velocity were recorded at the end of each treatment period. RESULTS: No differences in brachial blood pressure were observed between the treatment groups throughout the study. Although similar central blood pressure values were observed during monotherapy, lower systolic and diastolic central blood pressure values and early and late blood pressure peaks were observed in the amlodipine arm after the addition of valsartan alone or combined with rosuvastatin. Hydrochlorothiazide-based therapy was associated with a lower number of endothelial microparticles throughout the study, whereas a higher number of platelet microparticles was observed after rosuvastatin withdrawal in the amlodipine arm. CONCLUSIONS: Despite similar brachial blood pressure values between groups throughout the study, exposure to amlodipine was associated with lower central blood pressure values after combination with valsartan, indicating a beneficial interaction. Differences between circulating microparticles were modest and were mainly influenced by rosuvastatin withdrawal in the amlodipine arm

Evaluación de la hipertensión arterial resistente por monitoreo residencial de la presión arterial

BACKGROUND: Ambulatory blood pressure monitoring (ABPM) is considered the gold standard for the diagnostic confirmation of resistant hypertension (RH). However, home blood pressure monitoring (HBPM) has been considered an option, because of its lower cost and greater comfort. OBJECTIVE: To compare the values obtained by HBPM with those obtained by ABPM in the identification of patients with resistant hypertension. METHODS: A total of 51 consecutive patients with resistant hypertension were selected. All were adults of both genders and were undergoing treatment in an outpatient referral clinic from January 2007 to September 2009. Casual office blood pressure (BP), 24-hour ABPM, and HBPM were performed according to current guidelines, with a maximum two-week interval between the methods. RESULTS: The comparison of ABPM (mean daytime) with HBPM showed a good correlation between them, both for systolic blood pressure (SBP) and for diastolic blood pressure (DBP): SBP r = 0.70, CI = 0.51-0.82, DBP r = 0.69, CI = 0.52-0.81. RH was confirmed by ABPM in 33 patients and by HBPM in 37, with no significant difference between the methods. CONCLUSION: According to the results obtained, we conclude that HBPM is a method that can be used as an alternative to ABPM for the diagnostic confirmation of RH.FUNDAMENTO: El monitoreo ambulatorio de la presión arterial (MAPA) es considerado el gold standard para la confirmación diagnóstica de la hipertensión arterial resistente (HAR). Mientras tanto, el monitoreo residencial de la presión arterial (MRPA) ha sido considerado una opción, por su costo menor y mayor confort. OBJETIVO: Comparar los valores obtenidos por la MRPA con los obtenidos por la MAPA en la identificación de pacientes hipertensos resistentes. MÉTODOS: Fueron seleccionados consecutivamente 51 pacientes hipertensos resistentes, adultos de ambos sexos, en tratamiento ambulatorio de referencia, de ene/2007-set/2009. La medida de la presión arterial (PA) casual de consultorio, MAPA de 24 horas y MRPA fueron realizadas según las directrices vigentes, con intervalo máximo de dos semanas entre los métodos. RESULTADOS: Al comparar la MAPA (media de vigilia) y MRPA, fue obtenida buena correlación entre ambas, tanto para la presión arterial sistólica (PAS) como para la diastólica (PAD): PAS r = 0,70, IC = 0,51-0,82; PAD r = 0,69, IC = 0,52-0,81. La HAR fue confirmada por la MAPA en 33 pacientes y por la MRPA en 37 de esos, no habiendo diferencia significativa entre los dos métodos. CONCLUSIÓN: De acuerdo con los resultados obtenidos, se concluye que la MRPA es un examen que puede ser utilizado como alternativa a la MAPA para la confirmación diagnóstica de la HAR.FUNDAMENTO: A monitorização ambulatorial da pressão arterial (MAPA) é considerada o padrão-ouro para a confirmação diagnóstica da hipertensão arterial resistente (HAR). No entanto, a monitorização residencial da pressão arterial (MRPA) tem sido considerada uma opção, pelo seu custo menor e maior conforto. OBJETIVO: Comparar os valores obtidos pela MRPA com os obtidos pela MAPA na identificação de pacientes hipertensos resistentes. MÉTODOS: Foram selecionados consecutivamente 51 pacientes hipertensos resistentes, adultos de ambos os sexos, em tratamento ambulatorial de referência, de jan/2007 a set/2009. A medida da pressão arterial (PA) casual de consultório, MAPA de 24 horas e MRPA foram realizadas conforme as diretrizes vigentes, com intervalo máximo de duas semanas entre os métodos. RESULTADOS: Ao comparar a MAPA (média de vigília) e MRPA, foi obtida boa correlação entre ambas, tanto para a pressão arterial sistólica (PAS) quanto para a diastólica (PAD): PAS r = 0,70, IC = 0,51-0,82; PAD r = 0,69, IC = 0,52-0,81. A HAR foi confirmada pela MAPA em 33 pacientes e pela MRPA em 37 desses, não havendo diferença significante entre os dois métodos. CONCLUSÃO: De acordo com os resultados obtidos, conclui-se que a MRPA é um exame que pode ser utilizado como alternativa à MAPA para a confirmação diagnóstica da HAR.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Inflammatory environment and immune responses to oxidized LDL are linked to systolic and diastolic blood pressure levels in hypertensive subjects

Universidade Federal de São Paulo, Dept Med, Div Cardiol, BR-04039030 São Paulo, BrazilUniv São Paulo, Dept Immunol, São Paulo, BrazilNatl Inst Complex Fluids, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Cardiol, BR-04039030 São Paulo, BrazilWeb of Scienc

Pharmacokinetic interactions between clopidogrel and rosuvastatin: Effects on vascular protection in subjects with coronary heart disease

Universidade Federal de São Paulo, Dept Med, Div Cardiol, São Paulo, BrazilUniv São Paulo, Inst Phys, Natl Inst Complex Fluids, São Paulo, BrazilGaleno Lab, Campinas, SP, BrazilUniversidade Federal de São Paulo, Dept Med, Div Cardiol, São Paulo, BrazilWeb of Scienc