SGLT-2 inhibitors in diabetes: a focus on renoprotection.

Type 2 diabetes mellitus is an important public health problem, with a significant impact on cardiovascular morbidity and mortality and an important risk factor for chronic kidney disease. Various hypoglycemic therapies have proved to be beneficial to clinical outcomes, while others have failed to provide an improvement in cardiovascular and renal failure, only reducing blood glucose levels. Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors, represented by the empagliflozin, dapagliflozin, and canagliflozin, have been showing satisfactory and strong results in several clinical trials, especially regarding the reduction of cardiovascular mortality, reduction of hospitalization due to heart failure, reduction of albuminuria, and long-term maintenance of the glomerular filtration rate. The benefit from SGLT2 inhibitors stems from its main mechanism of action, which occurs in the proximal tubule of the nephron, causing glycosuria, and a consequent increase in natriuresis. This leads to increased sodium intake by the juxtaglomerular apparatus, activating the tubule glomerular-feedback and, finally, reducing intraglomerular hypertension, a frequent physiopathological condition in kidney disease caused by diabetes. In addition, this class of medication presents an appropriate safety profile, and its most frequently reported complication is an increase in the incidence of genital infections. Thus, these hypoglycemic agents gained space in practical recommendations for the management of type 2 diabetes mellitus and should be part of the initial therapeutic approach to provide, in addition to glycemic control, cardiovascular outcomes, and the renoprotection in the long term.

SGLT-2 inhibitors in diabetes: a focus on renoprotection

SUMMARY Type 2 diabetes mellitus is an important public health problem, with a significant impact on cardiovascular morbidity and mortality and an important risk factor for chronic kidney disease. Various hypoglycemic therapies have proved to be beneficial to clinical outcomes, while others have failed to provide an improvement in cardiovascular and renal failure, only reducing blood glucose levels. Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors, represented by the empagliflozin, dapagliflozin, and canagliflozin, have been showing satisfactory and strong results in several clinical trials, especially regarding the reduction of cardiovascular mortality, reduction of hospitalization due to heart failure, reduction of albuminuria, and long-term maintenance of the glomerular filtration rate. The benefit from SGLT2 inhibitors stems from its main mechanism of action, which occurs in the proximal tubule of the nephron, causing glycosuria, and a consequent increase in natriuresis. This leads to increased sodium intake by the juxtaglomerular apparatus, activating the tubule glomerular-feedback and, finally, reducing intraglomerular hypertension, a frequent physiopathological condition in kidney disease caused by diabetes. In addition, this class of medication presents an appropriate safety profile, and its most frequently reported complication is an increase in the incidence of genital infections. Thus, these hypoglycemic agents gained space in practical recommendations for the management of type 2 diabetes mellitus and should be part of the initial therapeutic approach to provide, in addition to glycemic control, cardiovascular outcomes, and the renoprotection in the long term.

TNF-α modulates statin effects on secretion and expression of MCP-1, PAI-1 and adiponectin in 3T3-L1 differentiated adipocytes.

PURPOSE: Systemic inflammatory conditions, as seen in obesity and in the metabolic syndrome, are associated with high plasmatic levels of proatherogenic and prothromboticadipokines and low levels of adiponectin. Inhibitors of HMG-CoA reductase have beneficial effects in reducing cardiovascular events attributed predominantly to its lipid-lowering effects and recent studies suggest that these effects might be due to its anti-inflammatory properties. Based on the pleiotropic properties of simvastatin we studied the effects of this drug on the secretion and expression of adiponectin, PAI-1 and MCP-1 in mature adipocytes under baseline conditions and after an inflammatory stimulation. MATERIALS AND METHODS: The differentiated adipocytes were incubated with 10 µM simvastatin or vehicle and TNF-α 10 ng/mL or vehicle were added to treatment media. After 24h of incubation, the media was harvested and the proteins of interest were analyzed by Multiplex method. Gene expression was analyzed by real time-PCR. RESULTS: The addition of TNF-α increased the expression and secretion of MCP-1 and PAI-1. However, stimulation did not interfere with the secretion of adiponectin, despite having significantly reduced its expression. Our data also demonstrated that simvastatin reduced the expression and secretion of MCP-1, under baseline (770.4 ± 199.9 vs 312.7 ± 113.7 and 1.00 ± 0.14 vs 0.63 ± 0.13, p<0.05, respectively) and inflammatory conditions (14945 ± 228.7 vs 7837.6 ± 847.4 and 24.16 ± 5.49 vs 14.97 ± 2.67, p<0.05, p<0.05, respectively). Simvastatin also attenuated the increase in expression and secretion of PAI-1 induced by TNF-α (16898.6 ± 1663.3 vs 12922.1 ± 843.9 and 5.19 ± 3.12 vs 0.59 ± 0.16, respectively p<0.05), but under baseline conditions had no effect on the expression or secretion of PAI-1. The statin increased the expression of adiponectin under baseline conditions and inflammatory stimulation (1.03 ± 0.08 vs 4.0 ± 0.96 and 0.77 ± 0.19 vs 2.16 ± 0.23, respectively, p<0.05) and also increased the secretion of this adipokine but only with the inflammatory stimulus (5347.7 ± 1789.3 vs 7327.3 ± 753.6, p<0.05). CONCLUSIONS: Our findings suggested that simvastatin counteracted the stimulatory effect of TNF-α on secretion and expression of MCP-1, PAI-1 and adiponectin, implying a potential anti-atherogenic effect during the inflammatory process; these pleitropic effects were more pronounced with HMG-CoA reductase inhibitor.

Cholesterol goal attainment in hypertensive patients: the impact of metabolic syndrome components.

BACKGROUND: Hypertension and dyslipidemia are potentially modifiable cardiovascular risk factors. METHODS: We studied hypertensive outpatients regarding goal attainment in controlling dyslipidemia, according to individual cardiovascular risk profile, following the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines. Factors of goal attainment for low-density lipoprotein cholesterol (LDL-C) were determined. RESULTS: Of the 1,202 patients, this study included 886 (73.8% female, 59.9±11.1 years) with available data to determine cardiovascular risk. Overall, 544 (61.4%) had LDL-C within the goal. Individuals with inappropriate LDL-C were older, had higher systolic blood pressure (SBP), and were more likely to have metabolic syndrome, diabetes, and cardiovascular disease (CVD) and were less likely to show a controlled blood pressure. There was a progressive worsening of LDL-C control as the number of components of metabolic syndrome increased. There was also a progressive increase in the percentage of patients with inappropriate LDL-C with the increase in cardiovascular risk. In a logistic regression model including LDL-C inadequacy as a dependent variable, only age, diabetes, and CVD were predictors of inappropriate LDL-C. Moreover, even with correction for demographic and clinical variables, the inappropriate LDL-C was an independent predictor of CVD. CONCLUSIONS: The control of dyslipidemia in hypertensive patients is far from ideal and results are even worse in individuals with CVD.

Hemodinâmica sistêmica e função ventricular esquerda de ratos hipertensos tornados diabéticos / Systemic hemodynamic and left ventricular function of diabetic-induced hypertensive rats

OBJETIVO: Avaliar a indução do diabetes melito tipo 1 (DM1) na hemodinâmica sistêmica e função ventricular de ratos normotensos e hipertensos. MATERIAIS E MÉTODOS: O DM1 foi induzido por estreptozotocina em ratos Wistar (WST), borderline hypertensive rats (BHR) e spontaneously hypertensive rats (SHR). A hemodinâmica sistêmica foi avaliada por termodiluição e a função ventricular, pela preparação de Langendorff. RESULTADOS: A indução de DM1 produziu aumento na pressão arterial de WST e BHR. O DM1 determinou aumento na resistência periférica total no grupo WST e diminuição do débito cardíaco e do volume sistólico nos grupos WST e BHR. Índices de função sistólica foram reduzidos e a rigidez ventricular, apenas nos ratos WST diabéticos. Todos esses efeitos foram mais proeminentes nos ratos WST diabéticos. CONCLUSÃO: O DM1 foi acompanhado por importantes alterações nas funções sistólica e diastólica, levando a uma diminuição nos valores hemodinâmicos sistêmicos que não foram alterados pela hipertensão arterial.

OBJECTIVE: To analyze the effects of type-1 diabetes mellitus (DM1) induction on systemic hemodynamic and ventricular function of normotensive and hypertensive rats. MATERIALS AND METHODS: DM1 was induced by streptozotocin in Wistar rats (WST), borderline hypertensive rats (BHR) and spontaneously hypertensive rats (SHR). The systemic hemodynamic was evaluated by thermodilution and ventricular function by Langendorff preparation. RESULTS: DM1-induction increased tail arterial pressure of WST and BHR. DM1 also increased total peripheral resistance in WST and decrease in cardiac output stroke volume in WST and BHR. Systolic function indexes were reduced and ventricular stiffness increased in all WST-diabetic rats. All of these effects were more prominent on diabetic WST rats. CONCLUSION: The DM1 in rats was accompanied by important changes in both systolic and diastolic heart function leading to significant changes in the systemic hemodynamics that were not significantly enhanced by hypertension.

Controle da pressão arterial em pacientes sob tratamento anti-hipertensivo no Brasil: Controlar Brasil / Control of arterial pressure in patients undergoing anti-hypertensive treatment in Brazil: Controlar Brazil

FUNDAMENTO: O controle da pressão arterial (PA) é fundamental na hipertensão arterial (HA). OBJETIVO: Conhecer o porcentual de pacientes exigindo metas específicas de controle da PA, atendidos em consultórios no Brasil. MÉTODOS: Cada pesquisador, em número de 291, deveria avaliar, por medida convencional da PA, em cinco dias consecutivos, os dois primeiros pacientes atendidos. Determinou-se o número de hipertensos tratados por, pelo menos, quatro semanas, e com controle da pressão arterial, de acordo com as metas desejadas para o grupo de risco a que pertenciam. RESULTADOS: Foram avaliados 2.810 pacientes, em 291 centros. Os indivíduos obedeceram à seguinte distribuição, por grupo: A (HA estágios 1 e 2, risco adicional baixo e médio) = 1.054 (37,51 por cento); B (HA e PA limítrofe, risco adicional alto) = 689 (24,52 por cento); C (HA e PA limítrofe risco adicional muito alto, incluindo diabéticos) = 758 (26,98 por cento) e D (HA com nefropatia e proteinúria > 1 g/l) = 309 (11 por cento). As médias de PA na população foram: 138,9 ± 17,1 e 83,1 ± 10,7 mmHg. Fatores relacionados ao menor controle da PA: idade, circunferência abdominal, diabete, tabagismo e doença coronariana. Os porcentuais de controle da PA em cada um dos grupos foram, respectivamente: 61,7; 42,5; 41,8 e 32,4. CONCLUSÃO: O baixo controle da PA segundo as metas predefinidas, como explicitado nos resultados, reforça a necessidade de medidas que promovam melhores taxas de controle.

BACKGROUND: Blood pressure (BP) control is crucial in arterial hypertension (AH). OBJECTIVE: To determine the percentage of patients requiring specific BP control goals treated in medical offices throughout Brazil. METHODS: Each researcher, from a total number of 291, had to evaluate, through conventional BP measurement performed during five consecutive days, the two first patients treated on that day. We determined the number of hypertensive patients treated for at least four weeks who presented BP control, according to the goals established for the risk group they belonged to. RESULTS: A total of 2,810 patients were assessed in 291 centers. The individuals were divided in groups as follows: A (AH stages 1 and 2, low and moderate additional risk) = 1,054 (37.51 percent); B (AH and borderline BP, high additional risk ) = 689 (24.52 percent); C (AH and borderline BP, very high additional risk, including diabetic patients) = 758 (26.98 percent) and D (AH with nephropathy and proteinuria > 1 g/l) = 309 (11 percent). The BP means in the population were: 138.9 ± 17.1 and 83.1 ± 10.7 mmHg. Factors associated with a worse BP control were: age, abdominal circumference, diabetes, smoking and coronary disease. The BP control percentages in each of the groups were, respectively: 61.7; 42.5; 41.8 and 32.4 percent. CONCLUSION: The low BP control according to the predefined goals, as demonstrated in the results, reinforces the necessity to establish measures to promote better control rates.

[Control of arterial pressure in patients undergoing anti-hypertensive treatment in Brazil: Controlar Brazil]. / Controle da pressão arterial em pacientes sob tratamento anti-hipertensivo no Brasil: Controlar Brasil.

BACKGROUND: Blood pressure (BP) control is crucial in arterial hypertension (AH). OBJECTIVE: To determine the percentage of patients requiring specific BP control goals treated in medical offices throughout Brazil. METHODS: Each researcher, from a total number of 291, had to evaluate, through conventional BP measurement performed during five consecutive days, the two first patients treated on that day. We determined the number of hypertensive patients treated for at least four weeks who presented BP control, according to the goals established for the risk group they belonged to. RESULTS: A total of 2,810 patients were assessed in 291 centers. The individuals were divided in groups as follows: A (AH stages 1 and 2, low and moderate additional risk) = 1,054 (37.51%); B (AH and borderline BP, high additional risk ) = 689 (24.52%); C (AH and borderline BP, very high additional risk, including diabetic patients) = 758 (26.98%) and D (AH with nephropathy and proteinuria > 1 g/l) = 309 (11%). The BP means in the population were: 138.9 +/- 17.1 and 83.1 +/- 10.7 mmHg. Factors associated with a worse BP control were: age, abdominal circumference, diabetes, smoking and coronary disease. The BP control percentages in each of the groups were, respectively: 61.7; 42.5; 41.8 and 32.4%. CONCLUSION: The low BP control according to the predefined goals, as demonstrated in the results, reinforces the necessity to establish measures to promote better control rates.

Uric acid as a factor in the metabolic syndrome.

Hyperuricemia is a prevalent finding in patients presenting metabolic syndrome, although its clinical meaning is still controversial and often underestimated. Men and women have different serum urate levels at all ages, and the impact of hyperuricemia in cardiovascular and renal outcomes is generally associated with a worse prognosis in women. Recent studies also have called attention to another perspective on hyperuricemia, indicating that it may be not only a consequence of insulin resistance states but also a significant predictor of the development of metabolic syndrome. This review discusses recent evidence related to the clinical significance of hyperuricemia in both sexes and the potential benefits of lowering serum uric acid levels.

[Systemic hemodynamic and left ventricular function of diabetic-induced hypertensive rats]. / Hemodinâmica sistêmica e função ventricular esquerda de ratos hipertensos tornados diabéticos.

OBJECTIVE: To analyze the effects of type-1 diabetes mellitus (DM1) induction on systemic hemodynamic and ventricular function of normotensive and hypertensive rats. MATERIALS AND METHODS: DM1 was induced by streptozotocin in Wistar rats (WST), borderline hypertensive rats (BHR) and spontaneously hypertensive rats (SHR). The systemic hemodynamic was evaluated by thermodilution and ventricular function by Langendorff preparation. RESULTS: DM1-induction increased tail arterial pressure of WST and BHR. DM1 also increased total peripheral resistance in WST and decrease in cardiac output stroke volume in WST and BHR. Systolic function indexes were reduced and ventricular stiffness increased in all WST-diabetic rats. All of these effects were more prominent on diabetic WST rats. CONCLUSION: The DM1 in rats was accompanied by important changes in both systolic and diastolic heart function leading to significant changes in the systemic hemodynamics that were not significantly enhanced by hypertension.

Continuous positive airway pressure therapy improves hypoadiponectinemia in severe obese men with obstructive sleep apnea without changes in insulin resistance.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with several conditions that could facilitate the onset of cardiovascular and metabolic dysfunctions. Continuous positive airway pressure (CPAP) therapy has been shown to improve cardiovascular morbidity and mortality related to OSA, but the mechanisms underlying this association are not fully understood. OBJECTIVE: The aim of the present study was to evaluate whether sleep apnea contributes to insulin resistance and inflammatory marker alterations and to evaluate the benefits of nasal CPAP therapy in severe obese patients with OSA. METHODS: Plasma inflammatory cytokines and the homeostasis model assessment of insulin resistance index (HOMA-IR, Insulin Sensitivity Index [ISI]) were measured in severe obese male with OSA (n = 16) and compared with body mass index (BMI)-matched male controls without OSA (n = 13). Seven patients with severe sleep apnea (apnea-hypopnea index >30 events/h) were reevaluated after 3 months of nasal CPAP therapy. RESULTS: OSA patients had a significantly lower adiponectin levels than obese controls (8.7 +/- 1.18 ng/mL vs. 15.0 +/- 2.55 ng/mL, P = 0.025). HOMA-IR, ISI, tumor necrosis factor-alpha (TNF-alpha, C-reactive protein (CRP), and interleukin-6 (IL-6) levels were not different between groups. Although insulin resistance index and BMI values did not change after 3 months of nCPAP therapy, adiponectin levels increased (P = 0.036) and the levels of TNF-alpha tended to decrease (P = 0.065). Changes in adiponectin levels during nCPAP therapy were positively correlated with an improvement in minimum oxygen saturation (r = 0.773; P = 0.041) and negatively correlated with changes in TNF-alpha levels (r = -0.885; P = 0.008). CONCLUSIONS: nCPAP therapy reverses hypoadiponectinemia levels present in obese men with OSA, probably through reductions in hypoxia and inflammation activity.

Based treatment algorithm for essencial hypertension with olmesartan medoxomil.

BACKGROUND: The national and international guidelines emphasize the importance of the effective treatment of arterial hypertension. Nevertheless, low levels of control are observed, as well as low attainment of the recommended goals, indicating that it is important to plan and implement better treatment strategies. OBJECTIVE: To evaluate the efficacy of a based treatment algorithm with olmesartan medoxomil. METHODS: This is an open, national, multicentric and prospective study of 144 patients with primary arterial hypertension, stages 1 and 2, naïve to treatment or after a 2-to-3 week washout period for those in whom treatment was ineffective. The use of olmesartan medoxomil was assessed in a treatment algorithm divided into 4 phases: (i) monotherapy (20 mg), (ii-iii) associated to à hydrochlorothiazide (20/12.5 mg and 40/25 mg) and (iv) addition of amlodipine besylate (40/25 mg + 5 mg). RESULTS: At the end of the phased-treatment, 86% of the study subjects attained the goal of BP < 130/85 mmHg. Maximum reductions in SAP and DAP were -44.4 mmHg and -20.0 mmHg, respectively. The rate of systolic responders (SAP >or= 20 mmHg) and of diastolic responders (DAP >or= 10 mmHg) was 87.5% and 92.4%, respectively. CONCLUSION: The study was based on a treatment regimen that was similar to the therapeutic approach in daily clinical practice and showed that the use of olmesartan medoxomil in monotherapy or in association with hydrochlorothiazide and amlodipine was effective in the attainment of the recommended goals for hypertension stage 1 and 2 hypertensive individuals.

Tratamento da hipertensão arterial com olmesartana medoxomila em escalonamento / Based treatment algorithm for essencial hypertension with olmesartan medoxomil

FUNDAMENTO: As diretrizes nacionais e internacionais enfatizam a importância do tratamento eficaz da hipertensão arterial. Apesar disso, verificam-se baixos índices de controle e alcance das metas preconizadas, indicando que é importante planejar e implementar melhores estratégias de tratamento. OBJETIVO: Avaliar a eficácia de um tratamento, em escalonamento de doses, tendo como base a olmesartana medoxomila. MÉTODOS: Este é um estudo aberto, nacional, multicêntrico e prospectivo, de 144 pacientes com hipertensão arterial primária nos estágios 1 e 2, virgens de tratamento ou após período de washout de duas a três semanas para aqueles em tratamento ineficaz. Avaliou-se o uso da olmesartana medoxomila num algoritmo de tratamento, em quatro fases: (i) monoterapia (20 mg), (ii-iii) associada à hidroclorotiazida (20/12,5 mg e 40/25 mg) e (iv) adição de besilato de anlodipino (40/25 mg + 5 mg). RESULTADOS: Ao fim do tratamento, em escalonamento, 86 por cento dos sujeitos de pesquisa alcançaram a meta de pressão arterial (PA) < 130/85 mmHg. Ocorreram reduções na pressão arterial sistólica (PAS) e na pressão arterial diastólica (PAD) de, no máximo, -44,4 mmHg e -20,0 mmHg, respectivamente. A taxa dos respondedores sistólicos (PAS > 20 mmHg) foi de 87,5 por cento e diastólicos (PAD > 10 mmHg) de 92,4 por cento. CONCLUSÃO: O estudo se baseou em um esquema de tratamento semelhante à abordagem terapêutica da prática clínica diária e mostrou que o uso da olmesartana medoxomila, em monoterapia ou em associação a hidroclorotiazida e anlodipino, foi eficaz para o alcance de meta para hipertensos dos estágios 1 e 2.

BACKGROUND: The national and international guidelines emphasize the importance of the effective treatment of essenssial hypertension. Nevertheless, low levels of control are observed, as well as low attainment of the recommended goals, indicating that it is important to plan and implement better treatment strategies. OBJECTIVE: To evaluate the efficacy of a based treatment algorithm with olmesartan medoxomil. METHODS: This is an open, national, multicentric and prospective study of 144 patients with primary arterial hypertension, stages 1 and 2, naïve to treatment or after a 2-to-3 week washout period for those in whom treatment was ineffective. The use of olmesartan medoxomil was assessed in a treatment algorithm divided into 4 phases: (i) monotherapy (20 mg), (ii-iii) associated to à hydrochlorothiazide (20/12.5 mg and 40/25 mg) and (iv) addition of amlodipine besylate (40/25 mg + 5 mg). RESULTS: At the end of the phased-treatment, 86 percent of the study subjects attained the goal of BP < 130/85 mmHg. Maximum reductions in SAP and DAP were -44.4 mmHg and -20.0 mmHg, respectively. The rate of systolic responders (SAP > 20 mmHg) and of diastolic responders (DAP > 10 mmHg) was 87.5 percent and 92.4 percent, respectively. CONCLUSION: The study was based on a treatment regimen that was similar to the therapeutic approach in daily clinical practice and showed that the use of olmesartan medoxomil in monotherapy or in association with hydrochlorothiazide and amlodipine was effective in the attainment of the recommended goals for hypertension stage 1 and 2 hypertensive individuals.

Effect of continuous positive airway pressure therapy on hypothalamic-pituitary-adrenal axis function and 24-h blood pressure profile in obese men with obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) increases the risk of cardiovascular events. Sympathetic nervous system and hypothalamic-pituitary-adrenal (HPA) axis activation may be the mechanism of this relationship. The aim of this study was to evaluate HPA axis and ambulatory blood pressure monitoring in obese men with and without OSAS and to determine whether nasal continuous positive airway pressure therapy (nCPAP) influenced responses. Twenty-four-hour ambulatory blood pressure monitoring and overnight cortisol suppression test with 0.25 mg of dexamethasone were performed in 16 obese men with OSAS and 13 obese men controls. Nine men with severe apnea were reevaluated 3 mo after nCPAP therapy. Body mass index and blood pressure of OSAS patients and obese controls were similar. In OSAS patients, the percentage of fall in systolic blood pressure at night (P = 0.027) and salivary cortisol suppression postdexamethasone (P = 0.038) were lower, whereas heart rate (P = 0.022) was higher compared with obese controls. After nCPAP therapy, patients showed a reduction in heart rate (P = 0.036) and a greater cortisol suppression after dexamethasone (P = 0.001). No difference in arterial blood pressure (P = 0.183) was observed after 3 mo of nCPAP therapy. Improvement in cortisol suppression was positively correlated with an improvement in apnea-hypopnea index during nCPAP therapy (r = 0.799, P = 0.010). In conclusion, men with OSAS present increased postdexamethasone cortisol levels and heart rate, which were recovered by nCPAP.

Abdominal obesity is associated with potassium depletion and changes in glucose homeostasis during diuretic therapy.

The activation of the renin-angiotensin system (RAS) is an important mechanism that contributes to hypertension in obese individuals. Thiazide diuretics also activate the RAS in response to volume contraction and can lead to a decrease in serum potassium values and glucose metabolism abnormalities. To evaluate the impact of abdominal obesity on potassium depletion and glucose homeostasis in hypertensive patients receiving thiazide therapy, the authors studied 329 hypertensive patients without known diabetes or impaired renal function. Patients were stratified into 2 major groups according to whether they used thiazide diuretic therapy, and each group was further divided in 2 subgroups according to the presence of abdominal obesity. The authors demonstrated that obese patients receiving diuretic therapy had lower plasma potassium levels and higher glucose values compared with nonobese patients receiving diuretic therapy. In conclusion, abdominal obesity predisposes to potassium depletion during diuretic therapy in association with effects on glucose homeostasis.

Blood pressure and cardiorenal responses to antihypertensive therapy in obese women.

OBJECTIVE: Blood pressure (BP) and target organ responses to antihypertensive drugs are not well established in hypertensive obese patients. This study is aimed at evaluating the effects of obesity and adiposity distribution patterns on these responses. METHODS: 49 hypertensive obese women were designated to different groups according to waist to hip ratio measurements--37 with troncular and 12 with peripheral obesity. Patients were treated for 24-weeks on a stepwise regimen with cilazapril alone or a cilazapril/hydrochlorothiazide/amlodipine combination therapy to achieve a BP lower than 140/90 mmHg. Ambulatory blood pressure monitoring (ABPM), echocardiography, and albuminuria were assessed before and after the intervention. RESULTS: After 24 weeks, weight loss was less than 2% in both groups. ABPM targets were achieved in 81.5% of patients upon a combination of 2(26.5%) or 3(55.1%) drugs. Similar reductions in daytime-SBP/DBP: -22.5/-14.1(troncular obesity)/-23.6/-14.9 mmHg (peripheral obesity) were obtained. Decrease in nocturnal-SBP was greater in troncular obesity patients. Upon BP control, microalbuminuria was markedly decreased, while only slight decrease in left ventricular mass was observed for both groups. CONCLUSIONS: In the absence of weight loss, most patients required combined antihypertensive therapy to control their BP, regardless of their body fat distribution pattern. Optimal target BP and normal albuminuria were achieved in the group as a whole and in both obese patient groups, while benefits to cardiac structure were of a smaller magnitude.

Blood pressure and cardiorenal responses to antihypertensive therapy in obese women

OBJECTIVE: Blood pressure(BP) and target organ responses to antihypertensive drugs are not well established in hypertensive obese patients. This study is aimed at evaluating the effects of obesity and adiposity distribution patterns on these responses. METHODS: 49 hypertensive obese women were designated to different groups according to waist to hip ratio measurements - 37 with troncular and 12 with peripheral obesity. Patients were treated for 24-weeks on a stepwise regimen with cilazapril alone or a cilazapril/hydrochlorothiazide/amlodipine combination therapy to achieve a BP lower than 140/90mmHg. Ambulatory blood pressure monitoring (ABPM), echocardiography, and albuminuria were assessed before and after the intervention. RESULTS: After 24 weeks, weight loss was less than 2 percent in both groups. ABPM targets were achieved in 81.5 percent of patients upon a combination of 2(26.5 percent) or 3(55.1 percent) drugs. Similar reductions in daytime-SBP/DBP: -22.5/-14.1(troncular obesity) / -23.6/-14.9mmHg (peripheral obesity) were obtained. Decrease in nocturnal-SBP was greater in troncular obesity patients. Upon BP control, microalbuminuria was markedly decreased, while only slight decrease in left ventricular mass was observed for both groups. CONCLUSIONS: In the absence of weight loss, most patients required combined antihypertensive therapy to control their BP, regardless of their body fat distribution pattern. Optimal target BP and normal albuminuria were achieved in the group as a whole and in both obese patient groups, while benefits to cardiac structure were of a smaller magnitude.

As respostas pressórica e de órgãos-alvo mediante o tratamento anti-hipertensivo medicamentoso, não estão bem estabelecidas em pacientes obesos hipertensos. O presente estudo tem por objetivo avaliar as repercussões da obesidade e da distribuição de gordura corporal sobre estas respostas. MÉTODOS: Foram avaliadas 49 mulheres obesas hipertensas, separadas em subgrupos com distribuição troncular (n = 37) e periférica (n = 12) de gordura, de acordo com a distribuição cintura/quadril. As pacientes foram tratadas por 24 semanas com um regime anti-hipertensivo escalonado, iniciando-se com cilazapril e adicionando-se na seqüência, hidroclortiazida e amlodipina, com alvo pressórico inferior a 140 x 90 mmHg. Foram realizados MAPA, ecocardiograma e microalbuminuria antes e após o tratamento. RESULTADOS: Depois de 24 semanas observou-se perda de peso inferior a 2 por cento em ambos os subgrupos. O controle pressórico à MAPA pode ser observado em 81,5 por cento das pacientes mediante a combinação de duas (26,5 por cento) ou três (55,1 por cento) drogas. Foram obtidas reduções similares nas medidas de PAS/PAD diurnas: -22,5/-14,1(obesas tronculares)/-23,6/-14,9 mmHg (obesas periféricas), enquanto se observou nas obesas tronculares redução maior na PAS noturna. Mediante o controle pressórico, houve redução acentuada da microalbuminúria nos dois subgrupos. Por outro lado, observou-se em ambos, apenas discreta redução na massa ventricular. CONCLUSÕES: Na ausência de perda significativa de peso, e independentemente da distribuição de gordura corporal, a maioria das pacientes obesas necessitou terapia anti-hipertensiva combinada a fim de obter controle pressórico. Em ambos os subgrupos foram alcançados níveis adequados de pressão arterial e redução satisfatória da microalbuminúria, ao passo que os benefícios para a regressão estrutural cardíaca foram menores.