RESUMO
Accumulating evidence has shown that diabetic patients are increasing in number, and renal and cardiovascular complications are the most common cause of death in diabetic patients. Thus, it would be of considerable value to identify the mechanisms involved in the progression of renal impairment and cardiovascular injury associated with diabetes. Recent evidence also indicated that multifactorial intervention is able to reduce the risk of cardiovascular disease and death among patients with diabetes and microalbuninuria. In this pilot study, we examined the effects of intensified multifactorial intervention, with tight glucose regulation and the use of valsartan and fluvastatin on ambulatory blood pressure (BP) profile, estimated glomerular filtration rate (eGFR), and urinary albumin to creatinine ratio (UACR), in 20 hypertensive patients (16 male and 4 female) with type 2 diabetes mellitus and overt nephropathy. After 12 months of intensified treatment, office BP, fasting plasma glucose (FPG), and low-density lipoprotein cholesterol (LDLC) were significantly decreased compared to baseline (systolic blood pressure (SBP), 130 ± 2 vs. 150 ± 1 mmHg; diastolic blood pressure (DBP), 76 ± 1 vs. 86 ± 1 mmHg; FPG, 117 ± 5 vs. 153 ± 7 mg/dl; LDLC, 116 ± 8 vs. 162 ± 5 mg/dl, P < 0.0001). Also, compared to the baseline values, the daytime and nighttime ambulatory BP and short-term BP variability were significantly decreased after 12 months. Furthermore, while eGFR was not altered (44.3 ± 5.1 vs. 44.3 ± 6.5 ml/min/1.73 m(2), not significant (NS)), UACR showed a significant reduction after 12 months of intensified treatment (1228 ± 355 vs. 2340 ± 381 mg/g-cr, P < 0.05). These results suggest that the intensified multifactorial intervention is able to improve ambulatory BP profile, preserve renal function, and reduce urinary albumin excretion in type 2 diabetic hypertensive patients with overt nephropathy.
Assuntos
Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Rim/fisiopatologia , Albuminúria/urina , Anticolesterolemiantes/farmacologia , Anti-Hipertensivos/farmacologia , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Comorbidade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/etiologia , Ácidos Graxos Monoinsaturados/farmacologia , Feminino , Fluvastatina , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Hipertensão/epidemiologia , Indóis/farmacologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Análise de Regressão , Tetrazóis/farmacologia , Valina/análogos & derivados , Valina/farmacologia , ValsartanaRESUMO
AIMS: In this study, we examined whether addition of an angiotensin II type 1 receptor blocker (ARB), candesartan or valsartan, to conventional antihypertensive treatment could improve blood pressure (BP) variability in hypertensive patients on peritoneal dialysis. METHODS: 45 hypertensive patients on chronic peritoneal dialysis therapy were randomly assigned to the ARB treatment groups either by candesartan (n = 15) or valsartan (n = 15), or the control group (n = 15). At baseline and 6 months after the treatment, 24-hour ambulatory BP monitoring, echocardiography, and measurement of brachial-ankle pulse wave velocity (baPWV) were performed. RESULTS: After the 6 months of treatment, 24-hour ambulatory BP values were similarly decreased in both the control group and ARB groups. However, short-term BP variability assessed on the basis of the standard deviation of 24-hour ambulatory BP was significantly decreased in the ARB groups, but remained unchanged in the control group. Furthermore, parameters of cardiovascular remodeling assessed by natriuretic peptides, echocardiography, and baPWV were significantly improved in the ARB groups but not in the control group. CONCLUSION: ARB treatment and control antihypertensive treatment similarly controlled 24-hour ambulatory BP values in hypertensive patients on peritoneal dialysis. However, ARB treatment is beneficial for the suppression of pathological cardiovascular remodeling with a decrease in BP variability.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Anti-Hipertensivos/farmacologia , Benzimidazóis/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Falência Renal Crônica/terapia , Diálise Peritoneal Ambulatorial Contínua , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Valina/análogos & derivados , Remodelação Ventricular/efeitos dos fármacos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Benzimidazóis/administração & dosagem , Biomarcadores , Compostos de Bifenilo , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/uso terapêutico , Ritmo Circadiano/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Peptídeos Natriuréticos/sangue , Pulso Arterial , Tetrazóis/administração & dosagem , Valina/farmacologia , Valina/uso terapêutico , ValsartanaRESUMO
The aim of the present study was to examine the relationships between the anti-hypertensive effects, autonomic function, and health-related quality of life (HRQOL) following treatment of hypertensive subjects with angiotensin receptor blockers (ARBs) in hypertensives. Nineteen patients with hypertension were assigned randomly to daily treatment with ARBs. After 16 weeks of treatment, blood pressure (BP) and 24 h the ratio of low frequency to high frequency component (LF/HF), an index of sympathovagal balance were decreased by ARBs. The HRQOL scores improved during the study. In this study, ARB therapy was associated with an improvement in BP, autonomic function, and HRQOL.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea/efeitos dos fármacos , Ritmo Circadiano , Hipertensão/tratamento farmacológico , Qualidade de Vida , Idoso , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Benzimidazóis/uso terapêutico , Benzoatos/uso terapêutico , Compostos de Bifenilo , Ritmo Circadiano/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/fisiopatologia , Imidazóis/uso terapêutico , Losartan/uso terapêutico , Masculino , Pessoa de Meia-Idade , Sistema Nervoso Simpático/efeitos dos fármacos , Telmisartan , Tetrazóis/uso terapêutico , Resultado do Tratamento , Valina/análogos & derivados , Valina/uso terapêutico , ValsartanaRESUMO
Blood pressure (BP) variability is calculated as the standard deviation of ambulatory BP. Blood pressure variability is associated with the cardiovascular morbidity; however whether it is related to target organ damage is controversial. In this study we examined a possible relationship between the BP variability and left ventricular hypertrophy (LVH), and between BP variability and brachial-ankle pulse wave velocity (baPWV). The present study was conducted on 111 consecutive Japanese hypertensive patients who were hospitalized for the educational program in our hospital under stable sodium chloride intake (6 g/day). Blood pressure measurements were at 30-minute intervals all day. In a multivariable analysis adjusted with confounding factor, LVH was associated with 24-hour systolic BP (SBP), 24 hour diastolic BP (DBP), daytime SBP, daytime DBP, nighttime SBP, and nighttime DBP. Additionally, nighttime DBP variability was related to LVH. By the same method, baPWV as a dependent variable was related to 24-hour SBP and nighttime SBP. Furthermore, nighttime SBP variability was concerned with baPWV. The LVH was associated with not only BP level but also with nighttime DBP variability. The baPWV was also related not only to BP level but also to nighttime SBP variability.
Assuntos
Índice Tornozelo-Braço , Determinação da Pressão Arterial/métodos , Pressão Sanguínea , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Idoso , Monitorização Ambulatorial da Pressão Arterial/métodos , Ritmo Circadiano , Feminino , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertrofia Ventricular Esquerda/diagnóstico , Hipertrofia Ventricular Esquerda/etiologia , Pacientes Internados , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
We examined risk factors for coronary heart disease (CHD) by ambulatory blood pressure (BP) monitoring in 72 diabetic hypertensives who were hospitalized for the educational program. The patients were divided into two groups (CHD group, 19 subjects; and non-CHD group, 53 subjects) along with or without co-existing CHD. On ambulatory BP monitoring, no significant differences were found between the groups regarding BP values through the day. However, the CHD group had a significantly greater BP variability than non-CHD group. The result of logistic regression analysis demonstrated that nighttime systolic BP variability was an independent risk factor for CHD.
Assuntos
Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Doença das Coronárias/epidemiologia , Complicações do Diabetes/complicações , Hipertensão/complicações , Idoso , Doença das Coronárias/fisiopatologia , Estudos Transversais , Complicações do Diabetes/fisiopatologia , Feminino , Humanos , Hipertensão/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
The purpose of this study was to examine the possible difference in the 24-hr BP profile--including short-term BP variability, assessed as the standard deviation--between diabetic and non-diabetic hypertensives. We measured 24-hr ambulatory BP in 11 diabetic hypertensives (diabetic HT) and 10 non-diabetic hypertensives (non-diabetic HT) who were hospitalized for the educational program in our hospital and were under stable salt intake. Renal function and sleep apnea were also estimated. There were no significant differences in 24-hr systolic BP (141 mmHg vs. 135 mmHg, ns), daytime systolic BP (143 mmHg vs. 138 mmHg, ns), and nighttime systolic BP (135 mmHg vs. 130 mmHg, ns) between diabetic HT and non-diabetic HT. The values of 24-hr HR (69.7 beats/min vs. 65.2 beats/min, ns) and 24-hr HR variability (9.9 beats/min vs. 10.1 beats/min, ns) were also similar between the groups. Interestingly, diabetic HT had a significantly greater 24-hr systolic and diastolic BP variability than non-diabetic HT (18.2 mmHg vs. 14.5 mmHg, p < 0.05; 11.5 mmHg vs. 9.6 mmHg, p < 0.05, respectively). The values for creatinine clearance, urinary protein excretion, and apnea-hypopnea index were similar between the groups. Bivariate linear regression analysis demonstrated that fasting blood glucose was the primary determinant of 24-hr diastolic BP variability (r = 0.661, p < 0.01). Multiple stepwise regression analysis revealed that fasting blood glucose was a significant and independent contributor to 24-hr systolic BP variability (r = 0.501, p < 0.05). Taken together, these results demonstrate that BP variability is increased in diabetic hypertensives. Furthermore, it is possible that an elevation of fasting blood glucose may contribute to the enhanced BP variability in hypertensives.
Assuntos
Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea , Complicações do Diabetes , Hipertensão/complicações , Hipertensão/fisiopatologia , Idoso , Glicemia/metabolismo , Ritmo Circadiano , Diástole , Jejum/sangue , Feminino , Humanos , Hipertensão/diagnóstico , Modelos Lineares , Masculino , Pessoa de Meia-Idade , SístoleRESUMO
The purpose of this study was to examine a possible difference in the 24-h blood pressure (BP) profile between hypertensives with diabetic nephropathy (DN) and those with non-diabetic glomerulopathy (non-DN). We measured 24-h ambulatory BP in 34 type 2 DN and 34 non-DN patients who were hospitalized for the educational program in our hospital. There were no significant differences in 24-h and daytime systolic BP between DN (143 vs. 136 mmHg, NS for 24-h systolic BP) and non-DN (143 vs. 138 mmHg, NS for daytime systolic BP). Although both groups disclosed blunted nocturnal decrease in BP and were classified as "non-dipper" type, DN patients had a significantly higher nighttime systolic BP than patients with non-DN (142 vs. 132 mmHg, p = 0.0217). BP and heart rate (HR) variabilities were also estimated, and patients with DN showed a reduced nighttime HR variability than those with non-DN (4.8 vs. 6.6 beats/min, p = 0.0115). DN patients had an increase in urinary protein excretion (3.0 vs. 1.4 g/day, p = 0.0095) and a decrease in serum albumin concentration (3.1 vs. 3.7 mg/dl, p < 0.0001). Furthermore, urinary protein excretion was significantly correlated with nighttime systolic BP (r = 0.480, p = 0.0031) but not with nighttime HR variability. Taken together, these results demonstrate that the circadian rhythms of BP and HR are affected by underlying diseases and suggest that an elevated nighttime BP level may contribute to the enhanced urinary protein excretion in hypertensives with DN.
Assuntos
Pressão Sanguínea , Nefropatias Diabéticas/fisiopatologia , Glomerulonefrite/fisiopatologia , Frequência Cardíaca , Hipertensão Renal/fisiopatologia , Falência Renal Crônica/fisiopatologia , Nefroesclerose/fisiopatologia , Idoso , Monitorização Ambulatorial da Pressão Arterial , Ritmo Circadiano , Estudos Transversais , Feminino , Humanos , Hipertensão Renal/complicações , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , ProteinúriaRESUMO
Presently hypertensive patients with chronic kidney disease (CKD) particularly diabetic nephropathy are increasing in number, and cardiovascular and renal complications are the most common cause of death in these patients. The control of blood pressure (BP) is an important issue in cardiovascular and renal protection in hypertensive patients with CKD. Although hypertension is usually diagnosed based on measurements of BP recorded during a visit to a physician, that is, office BP, several studies have shown that target organ damage and prognosis are more closely associated with ambulatory BP than with office BP. It should be important to achieve the target absolute BP levels in hypertensive patients obtained either by office or home measurements or by ambulatory recordings for the cardiovascular and renal protection. Noninvasive techniques for measuring ambulatory BP have allowed BP to be monitored during both day and night. Additionally, ambulatory BP monitoring can provide information on circadian BP variation and short-term BP variability, which is suggested to be associated with cardiovascular and renal morbidity and mortality. This review will briefly summarize the emerging concept of anti-hypertensive therapy based on ambulatory BP profile in hypertensive patients with CKD.
RESUMO
OBJECTIVE: Previous studies have shown increases in ambulatory short-term blood pressure (BP) variability to be related to cardiovascular disease. In this study, we examined whether an angiotensin II type 1 receptor blocker losartan would improve ambulatory short-term BP variability in hypertensive patients on hemodialysis. METHODS: Forty hypertensive patients on hemodialysis therapy were randomly assigned to the losartan treatment group (n=20) or the control treatment group (n=20). At baseline and 6 and 12 months after the treatment, 24-h ambulatory BP monitoring was performed. Echocardiography and measurements of brachial-ankle pulse wave velocity (baPWV) and biochemical parameters were also performed before and after therapy. RESULTS: After 6- and 12-months of treatment, nighttime short-term BP variability, assessed on the basis of the coefficient of variation of ambulatory BP, was significantly decreased in the losartan group, but remained unchanged in the control group. Compared with the control group, losartan significantly decreased left ventricular mass index (LVMI), baPWV, and the plasma levels of brain natriuretic peptide and advanced glycation end products (AGE). Furthermore, multiple regression analysis showed significant correlations between changes in LVMI and changes in nighttime short-term BP variability, as well as between changes in LVMI and changes in the plasma levels of AGE. CONCLUSION: These results suggest that losartan is beneficial for the suppression of pathological cardiovascular remodeling though its inhibitory effect on ambulatory short-term BP variability during nighttime.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Losartan/uso terapêutico , Diálise Renal , Remodelação Ventricular/efeitos dos fármacos , Adiponectina/sangue , Idoso , Tornozelo/irrigação sanguínea , Biomarcadores/sangue , Artéria Braquial/fisiopatologia , Ritmo Circadiano , Feminino , Produtos Finais de Glicação Avançada/sangue , Humanos , Hipertensão/diagnóstico por imagem , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/fisiopatologia , Lipoproteínas LDL/sangue , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Análise de Regressão , Fatores de Tempo , Resultado do Tratamento , UltrassonografiaRESUMO
We previously cloned a novel molecule interacting with angiotensin II (Ang II) type 1 receptor protein (ATRAP) and showed it to be an endogenous inhibitor of Ang II type 1 receptor signaling in cardiovascular cells. In this study, we tested a hypothesis that the balance of tissue expression of ATRAP and Ang II type 1 receptor is regulated in a tissue-specific manner during the development of hypertension and related cardiac hypertrophy. Concomitant with blood pressure increase and cardiac hypertrophy in spontaneously hypertensive rats, there was a constitutive decrease in the ratio of cardiac expression of ATRAP to Ang II type 1 receptor. However, treatment with olmesartan, an Ang II type 1 receptor-specific antagonist, either at a depressor or subdepressor dose, recovered the suppressed cardiac ATRAP to Ang II type 1 receptor ratio, which was accompanied by a decrease in Ang II type 1 receptor density, an inhibition of p38 mitogen-activated protein kinase activity, and a regression of cardiac hypertrophy. Furthermore, Ang II stimulation suppressed the ATRAP to Ang II type 1 receptor ratio with hypertrophic responses in both the cardiomyocytes and rat hearts. These findings show a tissue-specific regulatory balancing of the expression of ATRAP and Ang II type 1 receptor during the development of hypertension and cardiac remodeling and further suggest that the upregulation of the tissue ATRAP to Ang II type 1 receptor ratio may be one of the therapeutic benefits of olmesartan beyond its blood pressure-lowering effect.