Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment)

ABSTRACT: The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD) or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55-1.88]; P=1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with ≥80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (≈21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy.

Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension: The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment).

The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD) or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55-1.88]; P=1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with ≥80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (≈21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01643434.

The influence of dietary and supplemental calcium on postprandial effects of a high-fat meal on lipaemia, glycaemia, C-reactive protein and adiponectin in obese women.

Non-fasting hypertriacylglycerolaemia is a risk factor for CVD and the amount of fat in a meal seems to be the main factor influencing postprandial lipaemia. Although several studies suggest that Ca can increase faecal fat excretion, it is not known whether Ca can decrease postprandial TAG. This study aimed to evaluate the influence of dietary Ca (DC) and supplemental Ca (SC) on lipaemia, glucose metabolism, C-reactive protein (CRP) and adiponectin during postprandial period in obese women challenged with a high-fat meal. In this cross-over controlled trial, sixteen obese women aged 20-50 years were randomly assigned to receive three test meals (approximately 2900 kJ; 48 % fat): high DC (547 mg DC), high SC (HSCM; 500 mg SC-calcium carbonate) and low Ca (42 mg DC). Blood samples were collected in the fasting period and at minutes 120 and 240 after meals to evaluate total cholesterol and fractions, TAG, glucose, insulin, high-sensitivity CRP and adiponectin. Serum levels of TAG and insulin increased significantly after all test meals. Only after HSCM total cholesterol did not present a significant increase and LDL-cholesterol had a significant decrease. Postprandial glucose, HDL-cholesterol, CRP and adiponectin did not present significant changes after the three test meals. The comparative analysis of the effects of the three test meals on serum lipids, glucose, insulin, CRP and adiponectin revealed no significant meal-by-time interaction. These results suggest that in obese women challenged with a high-fat meal DC and SC do not interfere with postprandial lipaemia, glucose metabolism, CRP and adiponectin.

Short-term Effects of Green Tea on Blood Pressure, Endothelial Function, and Metabolic Profile in Obese Prehypertensive Women: A Crossover Randomized Clinical Trial.

BACKGROUND: Green tea consumption has been inversely associated with cardiovascular disease (CVD) in epidemiological studies. Although some interventional trials suggest that green tea has beneficial effects on CVD risk factors, such as hypertension and obesity, others have failed to show such benefits. AIMS: To evaluate the short-term effects of green tea on blood pressure, endothelial function, metabolic profile, and inflammatory activity in obese prehypertensive women. METHODS: This study was a crossover, randomized, double-blind, placebo-controlled clinical trial. Participants were randomly allocated to receive daily 3 capsules containing either 500 mg of green tea extract (GTE) or a matching placebo for 4 weeks, with a washout period of 2 weeks between treatments. Each GTE capsule contained 260 mg of polyphenols. At the beginning and at the end of each treatment, participants were submitted to evaluation of blood pressure (ambulatory blood pressure monitoring, ABPM), endothelial function (Endo-PAT 2000 and cellular adhesion molecules), nutritional parameters, metabolic profile, and biomarkers of inflammation. RESULTS: Twenty women age 41.1 ± 8.4 years completed the study. After 4 weeks of GTE supplementation in comparison with placebo, there was a significant decrease (p < 0.05) in systolic blood pressure at 24 hours (-3.61 ± 1.23 vs 1.05 ± 1.34 mmHg), daytime (-3.61 ± 1.26 vs 0.80 ± 1.57 mmHg), and nighttime (-3.94 ± 1.70 vs 1.90 ± 1.66 mmHg). Changes in diastolic blood pressure and in all other parameters did not present a significant difference between GTE and placebo. CONCLUSION: The findings of this study suggest that in obese prehypertensive women, short-term daily intake of GTE may decrease blood pressure.

Antihypertensive treatment improves microvascular rarefaction and reactivity in low-risk hypertensive individuals.

OBJECTIVE: To test whether long-term antihypertensive treatment with metoprolol succinate (a ß1-adrenoceptor blocker) or olmesartan medoxomil (an angiotensin II AT1-receptor blocker) reverses microvascular dysfunction in hypertensive patients. METHODS: This study included 44 hypertensive outpatients and 20 age and sex-matched healthy controls. We used skin capillaroscopy to measure capillary density and recruitment at rest and during PORH. Endothelium-dependent vasodilation of skin microcirculation was evaluated with a LDPM system in combination with ACh iontophoresis, PORH, and LTH. RESULTS: Pretreatment capillary density in hypertensive patients was significantly reduced compared with controls (71.3 ± 1.5 vs. 80.6 ± 1.8 cap/mm²; p < 0.001), as was PORH (71.7 ± 1.5 vs. 79.5 ± 2.6 cap/mm²; p < 0.05). After treatment for six months, capillary density increased to 75.4 ± 1.1 cap/mm² (p < 0.01) at rest and 76.8 ± 1.1 cap/mm² during PORH. During LTH, CVC in perfusion units (PU)/mmHg was similar in patients (1.71 [1.31-2.12]) and controls (1.60 [1.12-1.91]) and increased significantly (1.82 [1.30-2.20]) after treatment. Maximal CVC during PORH was reduced in hypertensive patients (0.30 [0.22-0.39]) compared to controls (0.39 [0.31-0.49], p < 0.001) and increased (0.41 [0.29-0.51], p < 0.001) after treatment. CONCLUSIONS: Capillary rarefaction and microvascular endothelial dysfunction in hypertensive patients responded favorably to long-term pharmacological treatment.

A pilot study on the relation between dietary calcium and clinical parameters in renal transplant recipients.

OBJECTIVE: This aim of this study was to evaluate the association between dietary calcium and variables that include body mass index, abdominal obesity, metabolic profile, and blood pressure levels in renal transplant patients. DESIGN: A cross-sectional study was conducted. SETTING: Eligible patients were recruited from renal transplant outpatient clinics at Pedro Ernesto University Hospital, Rio de Janeiro, Brazil. PATIENTS: A total of 40 men and 34 women aged >18 years who had received kidney transplants in the past ≥12 months were included in this study. INTERVENTION: All patients underwent clinical, dietary, anthropometric, and biochemical evaluation. RESULTS: Participants were classified into the following 2 groups on the basis of their mean dietary calcium intake: group A (<600 mg/day) and group B (≥600 mg/day). Patients in group B presented significantly lower levels of waist circumference and waist-to-hip ratio as compared with those in group A (P = .04 and P = .005, respectively), after adjusting for confounding variables such as energy intake, gender, age, physical activity, time since transplantation, and prednisone dose. After controlling for potential confounders, including energy intake and physical activity, subjects in group B had a lower odds ratio for prevalent abdominal obesity as compared with those in group A (odds ratio, 0.17; 95% confidence interval, 0.03 to 0.94; P = .04). Body mass index was significantly lower in patients with higher calcium intake; however, this difference did not reach statistical significance after adjustments for confounding factors. Metabolic profile and blood pressure levels were similar in both groups. CONCLUSION: The findings of the present study suggest that a higher dietary calcium intake may be associated with lower abdominal adiposity in renal transplant patients.

Efeito do urapidil sobre a pressão arterial, hemodinâmica renal, metabolismo lipídico e glicídico / The effect of urapidil on blood pressure, renal hemodynamics, lipid and glucose metabolism

PURPOSE--To evaluate the effects of urapidil on blood pressure (BP), renal hemodynamics and lipid and glucose metabolism, in patients with mild-to-moderate uncomplicated essential hypertension. METHODS--Fifteen hypertensive patients, aged 38-64 year-old were studied by ambulatory blood pressure monitoring system (ABPM). It was also evaluated: 1) the creatinine clearance; 2) the effective renal plasma flow by use of a single plasma sample after injection of orthoiodohippurate; 3) the serum triglycerides, cholesterol, and HDL-cholesterol; 4) blood levels of glucose and insulin. The urapidil dose ranged from 60 to 180 mg/day, according to the individual response. RESULTS--The values after four weeks washout-placebo and active treatment with urapidil showed: the systolic/diastolic BP was reduced from 157.7 +/- 6/108.0 +/- 2 on placebo to 140.4 +/- 4/97.3 +/- 3 mmHg (p < 0.05/p < 0.01) after urapidil, respectively, whereas heart rate was unchanged. The percentage of elevated systolic and diastolic BP values during 24h (BP load) was reduced from 60.9 to 54.4 and from 60.8 to 50.3, respectively. Effective renal plasma flow, glomerular filtration rate, filtration fraction and renal vascular resistance were unaltered by treatment. Significant increase in HDL-cholesterol was observed (from 39.5 +/- 3.6 on placebo vs 49.2 +/- 4.8 mg/dl (p < 0.01) after urapidil. Total cholesterol, LDL-cholesterol and triglycerides levels were not modified with treatment. Circulating plasma glucose and insulin remained unchanged. CONCLUSION--Urapidil is an effective antihypertensive agent without deleterious effect on renal hemodynamics, lipid and glucose metabolism.

Objetivo − Avaliar os efeitos do urapidil sobre a pressão arterial, hemodinâmica renal, metabolismo lipídico e glicídico em portadores de hipertensão arterial sistêmica primária leve a moderada. Métodos − Foram analisados 15 pacientes hipertensos, com idades entre 38 e 64 anos, utilizando-se a técnica da monitorização ambulatorial da pressão arterial (MAPA) em 24h, avaliando-se, também, os clearances de creatinina e do hipuran radioativo, espectrofotometria de cristal sólido e as dosagens do colesterol e triglicérides séricos, do HDL-colesterol, da glicemia e insulina. As doses de urapidil variaram de 60 a 180mg/dia, administradas 2 ou 3 vezes, de acordo com cada caso. A avaliação durou pelo menos 6 semanas. Resultados − Os parâmetros analisados após 4 semanas de washout-placebo e tratamento com urapidil revelaram: 1) redução significante das pressões sistólica e diastólica (157,7±6 e 108±2 na fase placebo para 140,4±4 e 97,3±3mmHg, p<0,05; p<0,01, respectivamente); 2) o fluxo plasmático renal efetivo, ritmo de filtração glomerular, fração de filtração e resistência vascular renal não sofreram mudanças significantes; 3) aumento significante na concentração sérica das HDLcolesterol (39,5±3,6 para 49,2±4,8mg/dl, p<0,01), sem modificações nos níveis séricos do colesterol total, LDL colesterol e triglicérides; 4) as curvas glicêmicas e insulínicas não se alteraram. Conclusão − O urapidil reduziu a pressão arterial sem promover alterações na hemodinâmica renal, metabolismo lipídico e glicídico