RESUMO
BACKGROUND: A major contributor to poor blood pressure (BP) control is nonadherence to therapy, which remains poorly recognized by physicians. The prevention of hypertension-induced changes in arterial wall, namely increased arterial stiffness and peripheral vascular resistance, is a reasoned adequate end-point of hypertension treatment. Indirect measurement of these arterial factors can be derived from the analysis of 24-hour Ambulatory BP Monitoring (24 h-ABPM). This pilot study evaluated the association between antihypertensive therapy adherence and 24 h-ABPM-derived parameters in hypertensive patients. METHODS: We studied 42 hypertensive patients (70±10 years) in chronic antihypertensive therapy. Patients were divided according to the Morisky Medication Adherence Scale (MMAS) in Low-Adher (MMAS <6) and High-Adher (MMAS 6-8) groups. The Ambulatory Arterial Stiffness Index (AASI) and its symmetric calculation (Sym_AASI) were derived from 24 h-ABPM. A bivariate logistic regression analysis was performed to evaluate the predictive value of MMAS for increased AASIs (i.e. above the median). RESULTS: Low-Adher group (n=17) showed higher AASIs compared to High-Adher group (n=25). The two groups were similar in terms of BP burden at the 24 h-ABPM. AASIs were inversely related to MMAS. MMAS resulted a predictor for both increased AASI (O.R. 0.49, 95% CI 0.31-0.76, P<0.01) and increased Sym_AASI (O.R. 0.67, 95% CI 0.47-0.95, P=0.026). After adjustment for PP, age and nocturnal diastolic BP reduction, MMAS persisted as an inverse predictor only of increased AASI. MMAS was also related to the diastolic vs systolic BP correlation coefficient r. CONCLUSIONS: Low adherence to antihypertensive therapy seems to be associated with increased standard AASI. In this setting, AASI could represent an additional information derived from the 24 h-ABPM in hypertensive patient evaluation.
Assuntos
Anti-Hipertensivos/uso terapêutico , Artérias/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Adesão à Medicação , Resistência Vascular , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Anti-Hipertensivos/administração & dosagem , Monitorização Ambulatorial da Pressão Arterial/métodos , Feminino , Humanos , Hipertensão/diagnóstico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Estudos Prospectivos , Análise de Regressão , Medição de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoAssuntos
Corpos Estranhos/diagnóstico por imagem , Aspiração Respiratória/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Idoso de 80 Anos ou mais , Meios de Contraste , Dispneia/etiologia , Corpos Estranhos/complicações , Humanos , Achados Incidentais , Iohexol/análogos & derivados , Masculino , Sons Respiratórios/etiologiaRESUMO
BACKGROUND: A correlation between hyperuricemia and renal target organ damage (TOD) was shown in hypertensive patients, locally mediated by the activation of renin-angiotensin system (RAS). We investigated whether high serum uric acid (UA) levels could negatively affect tubulointerstitial damage in hyperuricemic essential hypertensive patients with normal renal function, on treatment with RAS-blocking drugs. METHODS: We studied 40 patients with World Health Organization stage I-II essential hypertension, 9 with high serum UA levels (hyperuricemic group) and 31 with normal serum UA levels (normouricemic group, either normouricemics, n = 15, or formerly hyperuricemics in chronic allopurinol treatment, n = 16). All patients were on RAS-blocking drugs (either angiotensin-converting enzyme inhibitors or angiotensin II receptors blockers). Evaluation of renal TOD included urinary albumin excretion (UAE), Doppler ultrasound renal resistive index (RRI) and renal volume-to-resistive index ratio (RV/RRI) measurements. RESULTS: Hyperuricemics had significantly higher RRI and lower RV/RRI values than normouricemics. Creatinine clearance and UAE were similar between groups. Linear regression analysis showed that RV/RRI values were inversely related to serum UA levels (r = -0.57, P < 0.01). The logistic regression analysis selected serum UA as an independent predictor of decreased RV/RRI (odds ratio 4.45, 95% CI 1.47-13.45, P = 0.01). CONCLUSIONS: In hyperuricemic hypertensives normal serum UA levels are associated with normal RV/RRI, integrated marker of tubulointerstitial damage and renal arteriolopathy, independently of RAS activation.
Assuntos
Hipertensão/tratamento farmacológico , Hiperuricemia/complicações , Sistema Renina-Angiotensina/efeitos dos fármacos , Adulto , Idoso , Alopurinol/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estudos Transversais , Feminino , Humanos , Hipertensão/sangue , Hipertensão/complicações , Hiperuricemia/sangue , Hiperuricemia/tratamento farmacológico , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Ácido Úrico/sangueRESUMO
OBJECTIVE: The aim of the present study was to investigate whether the improvement of pulmonary capillary wedge pressure (PCWP) non-invasively assessed with tissue Doppler imaging is able to predict prognosis and cardiac-related mortality in patients with heart failure (HF), as previously demonstrated for NT-proBNP. METHODS: We prospectively studied 23 patients (74 +/- 10 y; 17 M, 6 F) with acute HF. NT-proBNP and PCWP were measured at admission and discharge. NT-proBNP concentrations were determined by a chemiluminescent immunoassay kit. PCWP was assessed using the ratio of transmitral E velocity to the early diastolic mitral annulus velocity (E'), with the formula PCWP = 1.9 + 1.24 (E/E'). Patients were divided in two groups according to the clinical end-point based on cardiac death and hospital readmission for HF. RESULTS: After a mean follow-up of 230 days, 10 patients reached the end-point (group A), while 13 patients resulted event-free (group B). In group B, NT-proBNP values significantly decreased (3816 +/- 7424 vs. 6799 +/- 10537 pg/mL, P < 0.01) and PCWP improved (17 +/- 7 vs. 23 +/- 12 mmHg, P < 0.01). The decrease in both NT-proBNP and PCWP values was able to identify the majority of patients (77%) with an event-free survival at follow-up, whereas 70% of patients who reached the end-point had discordant changes in NT-proBNP and PCWP (chi2 = 5.06, P < 0.05). CONCLUSIONS: The combination of a biochemical marker such as NT-proBNP and a new indicator of LV filling pressure (E/E') allows to estimate the prognostic impact of standard medical therapy even in a small group of HF patients.
Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Ecocardiografia Doppler em Cores/métodos , Insuficiência Cardíaca/fisiopatologia , Valva Mitral/diagnóstico por imagem , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Pressão Propulsora Pulmonar/fisiologia , Pressão Ventricular/fisiologia , Idoso , Feminino , Seguimentos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Imunoensaio/métodos , Medições Luminescentes , Masculino , Valva Mitral/fisiopatologia , Prognóstico , Estudos Prospectivos , Precursores de Proteínas , Curva ROC , Índice de Gravidade de DoençaAssuntos
Colonoscopia , Angiografia Coronária , Tomada de Decisões , Idoso de 80 Anos ou mais , Humanos , Masculino , Síncope/etiologiaAssuntos
Transtornos Relacionados ao Uso de Cocaína/complicações , Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Hemoptise/etiologia , Adulto , Análise Química do Sangue , Gasometria , Broncoscopia/métodos , Seguimentos , Hemoptise/diagnóstico , Hemoptise/terapia , Humanos , Masculino , Recidiva , Medição de Risco , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: We studied whether the measurement of intrarenal vascular resistance by Doppler ultrasonography, capable of investigating renal interstitial compartment, allows the early detection of chronic tubulointerstitial nephropathy (TIN). METHODS: 30 normotensive and 28 hypertensive (I-II OMS) patients with a clinical history suggestive of chronic TIN and normal renal function were enrolled. 40 healthy volunteers served as controls. Patients were considered TIN-negative or TIN-positive after investigating tubular function by urine concentrating and acidification tests. Renal sonographic parameters and renal resistive index (RRI) were obtained by duplex scanner. Glomerular filtration rate/effective renal plasmatic flow ratio was investigated by sequential renal scintigraphy in TIN-negative and TIN-positive patients; (99m)Tc-DMSA scintigraphy was also performed in TIN-positive patients. RESULTS: RRI values of TIN-positive normotensive and hypertensive patients were significantly higher (p < 0.01 for both) than those of TIN-negative patients and of controls. RRI values resulted to be linearly related to uricemia (r = 0.88, p < 0.0001) only in normotensive patients. RRI values also resulted to be linearly related to filtration ratio values (r = 0.60, p < 0.0001). (99m)Tc-DMSA scintigraphy confirmed interstitial renal damage (grade 1 and 2). CONCLUSION: RRI measurement allows the early identification of both normotensive and hypertensive patients with chronic TIN and signs of tubular dysfunction, when renal function is still preserved.
Assuntos
Hipertensão/complicações , Rim/irrigação sanguínea , Nefrite Intersticial/diagnóstico , Resistência Vascular , Adulto , Doença Crônica , Feminino , Taxa de Filtração Glomerular , Humanos , Capacidade de Concentração Renal , Túbulos Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Cintilografia , Fluxo Plasmático Renal Efetivo , Ácido Dimercaptossuccínico Tecnécio Tc 99m , Ultrassonografia DopplerRESUMO
Angiotensin (Ang) II is now recognized to be a mediator of a wide variety of inflammatory processes. This study investigated renin-angiotensin system (RAS) components and a number of inflammatory mediators in left ventricular biopsies from 2-vessel disease unstable angina (UA) (n=43) and stable angina (SA) (n=15) patients undergoing coronary bypass surgery. Biopsy samples from 6 patients undergoing valve replacement for mitral stenosis served as controls. UA patients were randomly assigned to angiotensin-converting enzyme (ACE)-inhibitor (ramipril), AT1 antagonist (valsartan), or placebo and treated during the 5 days preceding coronary bypass surgery, performed from 6 to 9 days after coronary angiography. During coronary angiography coronary blood flow was measured and samples were obtained from aorta and coronary sinus for determination of Ang I and Ang II gradients. The hearts of UA patients produced Ang II in a greater amount than in SA patients (P<0.01). UA biopsy samples showed numerous DR+ cells, identified as lymphocytes, macrophages, and endothelial cells. Reverse-transcriptase polymerase chain reaction showed overexpression of AGTN, ACE, and AT1-R genes, as well as upregulation of TNF-alpha, IL-6, IFN-gamma, and iNOS genes (P<0.01), with no differences between nonischemic and potentially ischemic areas. AGTN, ACE, and cytokine genes were mainly localized on endothelial cells. Ramipril and valsartan markedly decreased the expression levels of TNF-alpha, IL-6, and iNOS, and, to a lesser extent, of IFN-gamma genes, but did not affect the number of DR+ cells, with no significant difference between the 2 treatments. These results show that locally generated Ang II amplifies the immunomediated inflammatory process of coronary microvessels occurring in unstable angina.
Assuntos
Angina Instável/fisiopatologia , Angiotensina II/fisiologia , Valina/análogos & derivados , Vasculite/fisiopatologia , Adulto , Idoso , Angina Pectoris/complicações , Angina Pectoris/tratamento farmacológico , Angina Pectoris/imunologia , Angina Pectoris/fisiopatologia , Angina Pectoris/cirurgia , Angina Instável/complicações , Angina Instável/tratamento farmacológico , Angina Instável/imunologia , Angina Instável/cirurgia , Angiotensina II/biossíntese , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Quimases , Terapia Combinada , Angiografia Coronária , Ponte de Artéria Coronária , Circulação Coronária , Citocinas/biossíntese , Citocinas/genética , Citocinas/fisiologia , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Microcirculação/efeitos dos fármacos , Pessoa de Meia-Idade , Estenose da Valva Mitral/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , Cuidados Pré-Operatórios , RNA Mensageiro/biossíntese , Ramipril/farmacologia , Ramipril/uso terapêutico , Sistema Renina-Angiotensina/genética , Sistema Renina-Angiotensina/fisiologia , Serina Endopeptidases/biossíntese , Serina Endopeptidases/genética , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Valina/farmacologia , Valina/uso terapêutico , Valsartana , Vasculite/tratamento farmacológicoRESUMO
Mechanical factors play a key role in activation of cardiac growth factor response in hemodynamic overload, and both cooperate in myocardial remodeling. The present study was performed to investigate whether a different growth factor response is activated in the right and left ventricles in aortocaval fistula and its effects on regional myocardial adaptation. Relations between regional growth factor expression (angiotensin II, insulin-like growth factor-I, and endothelin-1), myocyte shape changes, and collagen deposition were investigated at mRNA and peptide levels in adult pigs after the creation of an aortocaval fistula distal to the renal arteries (n=15) and in sham-operated animals (n=15). The role of angiotensin II was investigated by the administration of angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist. In the left ventricle, pure volume overload was accompanied by persistent increase of insulin-like growth factor-I mRNA expression, peptide concentration (2.2-fold versus sham at 3 months, P<0.05), and significant increase of myocyte length (+29% at 3 months, P<0.05). Conversely, the mixed pressure-volume overload faced by the right ventricle resulted in significant regional overexpression of all growth factors investigated (angiotensin II, insulin-like growth factor-I, and endothelin-1), with corresponding increase of myocyte diameter and length and collagen deposition (+117% at 3 months). Collagen accumulation in the right ventricle as well as the increase in right ventricular end-diastolic pressure at the 3-month observation were inhibited by angiotensin II antagonism. The left and right ventricles respond differently to aortocaval fistula, and local growth factor expression is closely related to the regional myocardial adaptation.
Assuntos
Substâncias de Crescimento/biossíntese , Ventrículos do Coração/metabolismo , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Direita/metabolismo , Adaptação Fisiológica , Angiotensina II/biossíntese , Angiotensina II/genética , Angiotensina II/fisiologia , Animais , Volume Cardíaco , Colágeno/análise , Endotelina-1/biossíntese , Endotelina-1/genética , Feminino , Substâncias de Crescimento/genética , Ventrículos do Coração/química , Ventrículos do Coração/fisiopatologia , Hemodinâmica , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Direita/patologia , Hipertrofia Ventricular Direita/fisiopatologia , Fator de Crescimento Insulin-Like I/biossíntese , Fator de Crescimento Insulin-Like I/genética , Masculino , RNA Mensageiro/metabolismo , SuínosRESUMO
This study investigated whether the myocardium is involved in the acute inflammatory reaction associated with bursts of unstable angina (UA). We looked for the presence of activated DR+ inflammatory cells and the expression patterns, localization, and immunostaining identification of genes for cytokines (IL-1beta, TNF-alpha, IL-6, and IFN-gamma), MCP-1, and iNOS in the left ventricle biopsies from 2-vessel disease anginal patients, 24 with UA and 12 with stable angina (SA), who underwent coronary bypass surgery. Biopsy specimens from 6 patients with mitral stenosis who underwent valve replacement were examined as control hearts (CHs). Plasma levels of IL-2 soluble receptor (sIL-2R) were measured as a marker of systemic immune reaction. In CHs, DR+ cells were undetectable, and cytokine and iNOS mRNA expression were negligible. UA patients had higher sIL-2R levels than SA patients (P<0.01), and their biopsy specimens showed both numerous DR+ cells identified as lymphocytes, macrophages, endothelial cells, and elevated expression levels of cytokine and iNOS genes (from 2.4- to 6.1-fold vs SA; P<0.01). Cytokine and iNOS genes and proteins were localized in endothelial cells without involvement of myocytes. IL-1beta and MCP-1 mRNAs were nearly undetectable. No significant differences were found in the number of DR+ cells, levels of cytokine, and iNOS genes between potentially ischemic and nonischemic left ventricle areas. In SA specimens, DR+ cells were very rare and only mRNAs for TNF-alpha and iNOS genes were overexpressed versus CHs. These results indicated that an acute immunomediated inflammatory reaction, essentially involving coronary microvessels, is demonstrable in UA patients.
Assuntos
Angina Instável/metabolismo , Vasos Coronários/química , Mediadores da Inflamação/análise , Adulto , Angina Instável/patologia , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Complexo CD3/análise , Quimiocina CCL2/genética , Vasos Coronários/patologia , Citocinas/análise , Citocinas/genética , Feminino , Expressão Gênica , Antígenos HLA-DR/análise , Humanos , Imuno-Histoquímica , Hibridização In Situ , Inflamação/imunologia , Inflamação/patologia , Linfócitos/imunologia , Linfócitos/patologia , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/patologia , Óxido Nítrico Sintase/análise , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
UNLABELLED: The role of angiotensin II in pressure overload is still debated because notwithstanding its effects on myocyte contractility angiotensin II is not an obligatory factor for the development of hypertrophy. To define the role of angiotensin II in acute pressure overload we studied the effects of AT1 blockade (valsartan 80mg per day) on myocardial contractility, cardiac growth factor gene expression, and myocardial hypertrophy in aortic banded (60mmHg) pigs. Acute pressure overload caused an abrupt reduction of myocardial contractility, measured by the end-systolic stiffness constant, and a sharp increase in end-systolic stress which rapidly normalized (within 12h) in the placebo group. In AT1-blocked animals end-systolic stiffness constant remained significantly depressed up to 24h and end-systolic stress was still elevated up to 48h (both P<0.05 vs placebo). In both groups confocal microscopy revealed that granular staining of angiotensin II in cardiomyocyte cytoplasm disappeared after 30min of pressure overload. AT1 blockade abolished following cardiac overexpression of angiotensinogen and endothelin-1 genes as shown in RT-PCR studies and the consequent angiotensin II and endothelin-1 release in the coronary circulation. Conversely, insulin-like growth factor-I and ACE mRNA overexpression, as well as the onset of left ventricular mass increase, were not significantly affected by AT1 blockade. IN CONCLUSION: (1) mechanical stress releases preformed angiotensin II from myocyte in vivo; (2) the AT1 blockade abolishes cardiac angiotensin II and endothelin-1 production with delayed recovery of myocardial contractility; whereas (3) the overexpression of insulin-like growth factor-I gene and the development of myocardial hypertrophy are not angiotensin II-mediated effects.
Assuntos
Angiotensina II/metabolismo , Angiotensinogênio/biossíntese , Endotelina-1/biossíntese , Regulação da Expressão Gênica , Coração/metabolismo , Miocárdio/metabolismo , Receptores de Angiotensina/fisiologia , Valina/análogos & derivados , Antagonistas de Receptores de Angiotensina , Angiotensinogênio/genética , Animais , Estenose da Valva Aórtica/fisiopatologia , Cateterismo Cardíaco , Citoplasma/química , Modelos Animais de Doenças , Endotelina-1/genética , Fator de Crescimento Insulin-Like I/biossíntese , Fator de Crescimento Insulin-Like I/genética , Microscopia Confocal , Miocárdio/citologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptor Tipo 1 de Angiotensina , Sistema Renina-Angiotensina/fisiologia , Estresse Mecânico , Suínos , Sístole , Tetrazóis/farmacologia , Valina/farmacologia , ValsartanaRESUMO
Renal endothelin-1 participates in sodium and water handling, and its urinary excretion is increased in sodium-retentive states. We compared the cortical and medullary renal expression of prepro-endothelin-1, endothelin-converting enzyme-1, and endothelin type A and type B receptors in patients who underwent nephrectomy after normal (108 mmol/d NaCl; n=6) or low (20 mmol/d NaCl; n=6) sodium diet and investigated whether sodium exerts a direct role on endothelin receptor binding in vitro. With normal sodium diet prepro-endothelin-1 mRNA was 3-fold higher in renal medulla than in cortex (P<0.01), whereas endothelin-converting enzyme-1 mRNA was equally distributed. Endothelin-1 receptor density was 2-fold higher in renal medulla than in cortex (P<0.05). Type B was the main receptor subtype in both regions. In the renal cortex, low sodium diet caused a 194% increase in prepro-endothelin-1 mRNA (P<0.05), whereas endothelin-converting enzyme-1 type B and type A receptors remained unchanged. In contrast, in the renal medulla the increase in prepro-endothelin-1 mRNA (+30%, P<0.05) was associated with a selective increase in type B receptor for both mRNA expression (+37%, P<0.05) and binding density (+55%, P<0.05). Increasing in vitro sodium concentrations between 154 and 308 mmol/L significantly enhanced type B receptor density (P<0.05) and affinity (P<0.05). In conclusion, during low sodium diet, renal prepro-endothelin-1 synthesis increases mainly in the renal cortex (where no changes in receptors occur), whereas type B receptor is selectively enhanced in the renal medulla. The range of sodium concentrations that are physiologically present in vivo in the renal medulla selectively modulate type B receptor density and affinity.