Development, Validation, and Reproducibility of Food Group-Based Frequency Questionnaires for Clinical Use in Brazil: A Pre-Hypertension and Hypertension Diet Assessment.

The Blood pressure control diet is well described; however, it has not been implemented in clinical care, possibly due to the impracticability of the diet assessment in these contexts. In order to facilitate the dietary assessment, we developed and assessed the validity and reproducibility of two food group-based food frequency questionnaires (FG-FFQs), with a one-week (7-day FG-FFQ) and a one-month (30-day FG-FFQ) period of coverage for patients with pre-hypertension or hypertension. In 2010, 155 men and women, 30-70 years old, were invited to participate in a prospective study in two outpatient clinics in Porto Alegre, southern Brazil. The participants responded to two 30-day, two 7-day FG-FFQ, four 24-h dietary recalls, and underwent demographic, anthropometric, and blood pressure assessments. The validity and reproducibility were assessed using partial correlation coefficients adjusted for sex and age, and the internal validity was tested using the intra-class correlation coefficient. The participants were aged 61 (±10) years and 60% were women. The validity correlation coefficient was higher than r = 0.80 in the 30-day FG-FFQ for whole bread (r = 0.81) and the 7-day FG-FFQ for diet/light/zero soda and industrialized juices (r = 0.84) in comparison to the 24-h dietary recalls. The global internal validity was α = 0.59, but it increased to α = 0.76 when 19 redundant food groups were excluded. The reproducibility was higher than r = 0.80 for pasta, potatoes and manioc, bakery goods, sugar and cocoa, and beans for both versions. The 30-day had a slightly higher validity, both had good internal validity, and the 7-day FG-FFQ had a higher reproducibility.

Effectiveness of Chlorthalidone Plus Amiloride for the Prevention of Hypertension: The PREVER-Prevention Randomized Clinical Trial.

BACKGROUND: Prehypertension is associated with higher cardiovascular risk, target organ damage, and incidence of hypertension. The Prevention of Hypertension in Patients with PreHypertension (PREVER-Prevention) trial aimed to evaluate the efficacy and safety of a low-dose diuretic for the prevention of hypertension and end-organ damage. METHODS AND RESULTS: This randomized, parallel, double-blind, placebo-controlled trial was conducted in 21 Brazilian academic medical centers. Participants with prehypertension who were aged 30 to 70 years and who did not reach optimal blood pressure after 3 months of lifestyle intervention were randomized to a chlorthalidone/amiloride combination pill or placebo and were evaluated every 3 months during 18 months of treatment. The primary outcome was incidence of hypertension. Development or worsening of microalbuminuria, new-onset diabetes mellitus, and reduction of left ventricular mass were secondary outcomes. Participant characteristics were evenly distributed by trial arms. The incidence of hypertension was significantly lower in 372 study participants allocated to diuretics compared with 358 allocated to placebo (hazard ratio 0.56, 95% CI 0.38-0.82), resulting in a cumulative incidence of 11.7% in the diuretic arm versus 19.5% in the placebo arm (P=0.004). Adverse events; levels of blood glucose, glycosylated hemoglobin, creatinine, and microalbuminuria; and incidence of diabetes mellitus were no different between the 2 arms. Left ventricular mass assessed through Sokolow-Lyon voltage and voltage-duration product decreased to a greater extent in participants allocated to diuretic therapy compared with placebo (P=0.02). CONCLUSIONS: A combination of low-dose chlorthalidone and amiloride effectively reduces the risk of incident hypertension and beneficially affects left ventricular mass in patients with prehypertension. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov, www.ensaiosclinicos.gov. Unique identifiers: NCT00970931, RBR-74rr6s.

Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension: results from the PREVER-treatment randomized trial.

OBJECTIVES: To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of stage I hypertension. METHODS: In a randomized, double-blind, controlled trial, 655 participants were followed for 18 months in 21 Brazilian academic centers. Trial participants were adult volunteers aged 30-70 years with stage I hypertension (BP 140-159 or 90-99 mmHg) following 3 months of a lifestyle intervention. Participants were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N = 333) or 50 mg of losartan (N = 322). If BP remained uncontrolled after 3 months, study medication dose was doubled, and if uncontrolled after 6 months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg twice daily) were added as open-label drugs in a progressive fashion. At the end of follow-up, 609 (93%) participants were evaluated. RESULTS: The difference in SBP during 18 months of follow-up was 2.3 (95% confidence interval: 1.2 to 3.3) mmHg favoring chlorthalidone/amiloride. Compared with those randomized to diuretic, more participants allocated to losartan had their initial dose doubled and more of them used add-on antihypertensive medication. Levels of blood glucose, glycosilated hemoglobin, and incidence of diabetes were no different between the two treatment groups. Serum potassium was lower and serum cholesterol was higher in the diuretic arm. Microalbuminuria tended to be higher in patients with diabetes allocated to losartan (28.5 ±â€Š40.4 versus 16.2 ±â€Š26.7 mg, P = 0.09). CONCLUSION: Treatment with a combination of chlorthalidone and amiloride compared with losartan yielded a greater reduction in BP. CLINICAL TRIALS REGISTRATION NUMBER: NCT00971165.

Effects of purple grape juice in the redox-sensitive modulation of right ventricular remodeling in a pulmonary arterial hypertension model.

The effects of purple grape juice (PGJ) pretreatment in signaling proteins involved in cardiac remodeling in rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) were investigated. Male Wistar rats (control, MCT, PGJ, and MCT + PGJ groups) were treated for 6 weeks with water or PGJ (10 mL·kg(-1)·d(-1)) by gavage. In the third week, they were administered a single dose of MCT (60 mg/kg i.p.). Pulmonary vascular resistance was determined by echocardiography, and hemodynamic analysis was performed in the right ventricle (RV). Hydrogen peroxide (H2O2) concentration and lipid peroxidation were quantified and thioredoxin-1 (Trx-1), p-ERK1/2/ERK1/2, p-Akt/Akt, p-JNK/JNK, and cleaved caspase-3 were detected at RV by Western blot. Pretreatment with PGJ attenuated pulmonary vascular resistance and improved hemodynamic parameters in MCT-induced PAH. PGJ and MCT groups exhibited increased H2O2 levels, which were reduced to baseline in MCT + PGJ. ERK1/2 phosphorylation showed the same profile of H2O2 changes. No changes in p-JNK/JNK and p-Akt/Akt expressions were found. An enhanced cleaved caspase-3 immunodetection was induced by the model, which was reversed in the MCT + PGJ group and associated with increased Trx-1 and reduced lipid peroxidation. Improvement in functional parameters mediated by PGJ pretreatment may be associated with the induction of Trx-1, influencing the expression of proteins involved in RV remodeling.

Association of the time course of pulmonary arterial hypertension with changes in oxidative stress in the left ventricle.

1. This study investigates the time course of pulmonary arterial hypertension (PAH) due to monocrotaline (MCT) and its association with cardiac function and oxidative stress markers in the left ventricle (LV). 2. Male Wistar rats were divided into six groups: 7 days, 21 days, and 31 days for both control and MCT groups. Following echocardiographic analysis, the heart was removed. The LV was separated and homogenized to analyze oxidized-to-total glutathione ratio and thioredoxin reductase (TrxR) activity as well as hydrogen peroxide (H(2) O(2) ) and ascorbic acid levels. 3. There was significant (P < 0.01) cardiac and right ventricle (RV) hypertrophy and pulmonary congestion in the MCT 21 day and 31 day groups. Echocardiography showed a change in the flow wave of the pulmonary artery at 21 days after MCT treatment. There was an increase in the LV ejection time (P < 0.05) at 31 days after MCT. The LV H(2)O(2) concentration was increased (P < 0.05) in the MCT 21 day and MCT 31 day groups compared with controls. There was a reduction (P < 0.05) in the LV ascorbic acid concentration and an increase (P < 0.05) in TrxR activity in the MCT 31 day rats. 4. Our findings showed RV changes due to pulmonary hypertension at 21 days after MCT injection. There was a correlation between the degree of dysfunction and the morphometry of the heart chambers, along with impairment of the antioxidant/pro-oxidant balance in the LV 31 days after the beginning of the protocol. This study suggests that LV changes follow RV dysfunction subsequent to pulmonary hypertension.

Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial.

BACKGROUND: Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage. METHODS: This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution. DISCUSSION: The early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil. TRIAL REGISTRATION: Clinical Trials NCT00970931.

A comparison between diuretics and angiotensin-receptor blocker agents in patients with stage I hypertension (PREVER-treatment trial): study protocol for a randomized double-blind controlled trial.

BACKGROUND: Cardiovascular disease is the leading cause of death in Brazil, and hypertension is its major risk factor. The benefit of its drug treatment to prevent major cardiovascular events was consistently demonstrated. Angiotensin-receptor blockers (ARB) have been the preferential drugs in the management of hypertension worldwide, despite the absence of any consistent evidence of advantage over older agents, and the concern that they may be associated with lower renal protection and risk for cancer. Diuretics are as efficacious as other agents, are well tolerated, have longer duration of action and low cost, but have been scarcely compared with ARBs. A study comparing diuretic and ARB is therefore warranted. METHODS/DESIGN: This is a randomized, double-blind, clinical trial, comparing the association of chlorthalidone and amiloride with losartan as first drug option in patients aged 30 to 70 years, with stage I hypertension. The primary outcomes will be variation of blood pressure by time, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new subclinical atherosclerosis and sudden death. The study will last 18 months. The sample size will be of 1200 participants for group in order to confer enough power to test for all primary outcomes. The project was approved by the Ethics committee of each participating institution. DISCUSSION: The putative pleiotropic effects of ARB agents, particularly renal protection, have been disputed, and they have been scarcely compared with diuretics in large clinical trials, despite that they have been at least as efficacious as newer agents in managing hypertension. Even if the null hypothesis is not rejected, the information will be useful for health care policy to treat hypertension in Brazil. CLINICAL TRIALS REGISTRATION NUMBER: ClinicalTrials.gov: NCT00971165.

Modulation of monocrotaline-induced cor pulmonale by grape juice.

The study was designed to test whether the ingestion grape juice (GJ) could modulate monocrotaline (MCT)-induced Cor pulmonale resulting from antioxidant properties. Three-week-old male Wistar rats received GJ (10 mL/kg/day) by gavage for 6 weeks. A single injection of MCT (60 mg/kg body weight intraperitoneally) was administered at the end of the third week. Animals were divided in four groups: control, MCT, GJ, and GJ + MCT. MCT promoted a significant increase in right ventricle (36%) and lung (70%) weight to body weight ratio. There was an increase in the right systolic (38%) as well as in the end diastolic (70%) ventricular pressures. MCT caused a significant decrease in lung endothelial nitric oxide synthase (20%) but increase in lipid peroxidation (13%) and catalase (43%). MCT-induced decrease in the endothelial nitric oxide synthase and increase in the right ventricular end diastolic pressure were prevented by GJ, whereas right systolic ventricular pressure and lung weight to body weight ratio were corrected only partially. MCT-induced increase in heart and right ventricle to body weight ratios was not changed by GJ. GJ blunted MCT-induced increase in lipid peroxidation but had no effect on the changes in catalase and superoxide dismutase activities. GJ appears to offer some protection against MCT-induced Cor pulmonale and right ventricle function changes.