Hilton Chaves

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

BackgroundBlood 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.MethodsThis 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.DiscussionThe 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 RegistrationClinical Trials NCT00970931.

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.

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.

I posicionamento brasileiro em hipertensão arterial e diabetes mellitus

The association between AH and DM was first described in the 70s, observed in both sexes and at any age range. The prevalence of hypertension is two to three-fold higher in diabetics than in the general population5, and about 70% of diabetics are hypertensive3,6. A meta-analysis of 102 prospective studies and 698,782 individuals showed that the presence of DM increases by two-fold the risk of coronary artery disease (CAD), cerebrovascular accident (CVA) and CV death. According to this meta-analysis, 10% of CV deaths in developed countries can be attributed to the presence of DM7.

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

BackgroundCardiovascular 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/designThis 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.DiscussionThe 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 numberClinicalTrials.gov: NCT00971165

Effect of Brain Derived Neurotrophic Factor, In Relation to Diet and Lifestyle Factors, for Prevention of Neuropsychiatric and Vascular Diseases and Diabetes

Background: Brain-derived neurotrophic factor (BDNF) is a major neurotrophin which may have promise to be a nutraceutical of this decade. It has a documented role in neurogenesis, angiogenesis, and neuronal survival. BDNF can have beneficial effects on several cardio-metabolic and neuro-psychiatric disorders, indicating that it is important in brain- body interactions. Diet and lifestyle factors may also have an influence on BDNF levels. In this review, we examine the beneficial role of BDNF on risk factors of vascular diseases, type 2 diabetes mellitus and anxiety disorders. Methods: In- ternet search and discussion with peer colleagues. Results: Majority of the BDNF (70-80%) is derived from dendrite of neurons but it is also present in other body tissues. BDNF controls the food intake and appetite as well as lipid and glu- cose metabolism. Sedentary behavior and tobacco intake may be associated with BDNF deficiency. Lower serum concen- tration of BDNF and higher vascular endothelial growth factor (VEGF) concentrations were associated with increased risk of incident stroke/TIA. BDNF may serve as an intermediate biomarker for subclinical vascular disease and may also have biological potential to serve as a therapeutic target for primary and secondary prevention of vascular diseases, as well as clinical and subclinical vascular brain disease. BDNF deficiency has been observed in association with anxiety, depres- sion, insomnia, dementia, insulin resistance, type 2 diabetes and vascular diseases. The phenotypes associated with insulin resistance are at increased risk for developing cognitive decline and neuro-degeneration resulting in vascular dementia, and depression as well as diabetes mellitus and metabolic syndrome, which are risk factors for CVDs. BDNF may be ad- ministered as nutraceutical due to its protective influence on BDNF concentrations, insulin receptors and hypothalamic dysfunction leading to beneficial effects on cardiovascular risk and neuropsychological dysfunction. It is proposed that omega-3 fatty acids and moderate physical activity may enhance BDNF release. Conclusions: It is possible that circulat- ing BDNF deficiency is a risk factor for obesity, CVDs and diabetes as well as risk factor for neuropsychiatric diseases. BDNF administration may modify the risk of clinical and subclinical stroke, depression, and dementia as well as of obe- sity and type 2 diabetes.

The association between socioeconomic characteristics and consumption of food items among brazilian industry workers

Background. Dietary pattern plays a causative role in the rising of noncommunicable diseases. The SESI (Serviço Social da Indústria) study was designed to evaluate risk factors for noncommunicable diseases. We aimed to describe food items consumed by Brazilian workers and to assess their association with socioeconomic status. Methods. Cross-sectional study was carried out among Brazilian industrial workers, selected by multistage sampling, from 157 companies. Interviews were conducted at the work place using standardized forms. Results. 4818 workers were interviewed, aged 35.4 ± 10.7 years, 76.5% were men. The workers had an average of 8.7 ± 4.1 years of schooling and 25.4 ± 4.1 kg/m2 of BMI. Men and individuals with less than high school education were less likely to consume dairy products, fruits, and vegetables daily, even after control for confounding factors. Men consumed rice and beans daily more often than women. In comparison to workers aged 50–76 years, those under 30 years old consumed less fruits and green leafy vegetables daily. Conclusion. The food items consumed by Brazilian workers show that there are insufficient consumption according to the guidelines of healthy foods, particularly of dairy products, vegetables, and fruits.

Effectiveness of low-dose diuretics for blood pressure reduction to optimal values in prehypertension: a randomized clinical trial

Background: To determine the effectiveness of low-dose diuretic therapy to achieve an optimal level of blood pressure (BP) in adults with prehypertension. Methods: The PREVER-prevention trial was a randomized, parallel, double-blinded, placebo-controlled trial, with 18 months of follow-up, conducted at 21 academic medical centers in Brazil. Of 1772 individuals evaluated for eligibility, 730 volunteers with prehypertension who were aged 30–70 years, and who did not reach optimal blood pressure after 3 months of lifestyle intervention, were randomized to a fixed association of chlorthalidone 12.5 mg and amiloride 2.5 mg or placebo once a day. The main outcomes were the percentage of participants who achieved an optimal level of BP. Results: A total of 372 participants were randomly allocated to diuretics and 358 to placebo. After 18 months of treatment, optimal BP was noted in 25.6% of the diuretic group and 19.3% in the placebo group (P < 0.05). The mean net reduction in SBP and DBP for the diuretic group compared with placebo was 2.8 mmHg (95% CI 1.1 to 4.5) and 1.1 mmHg (95% CI −0.09 to 2.4), respectively. Most participants in the active treatment group (74.5%) and in the placebo group (80.7%) continued to have BP in the prehypertension range or progressed to hypertension. Conclusion: Low-dose diuretic therapy increased the probability of individuals with prehypertension to achieve optimal BP but most of those treated continued to have a BP in the prehypertension range or progressed to having overt hypertension.

Editorial Nutritional Modulators in Chronic Heart Failure

Chronic Heart failure (HF) may be associated with cardiac cachexia characterized with weight loss as well as with nutritional deficiency [1-4]. The increased oxidative stress in chronic HF attempts to consume various nutrients present in the cardiomyocyte as well as endogenous antioxidants. Vitamin C, E and beta carotene, as well as coenzyme Q10 are potential antioxidants for protection against oxidative stress developed in HF patients [1-5]. The increase in homocysteine due to oxidative stress, is antagonized by vitamins; B6, B12 and folic acid. The decrease in magnesium and potassium due to long term diuretic therapy in HF which can predispose arrhythmiogenesis, leading to rhythm disturbances and sudden cardiac death [3-5]. L-carnitine, cysteins and taurine amino acids are also reduced in chronic HF and their supplementation may be protective [6-8]. It seems that these nutrients can be administered as nutraceuticals among these patients with chronic HF. Apart from above micronutrients, calcium, selenium, zinc, thiamine, vitamin D and omega-3 fatty acids may play a more important role than previously thought [1-9]. Increased concentration of aldosterone and chronic use of loop diuretics increase urinary excretion of calcium and magnesium, leading to arrhythmias and secondary hyperparathyroidism, which in turn depletes calcium from bone and drives calcium into cells, causing further increase in oxidative stress [8-12]. Vitamin D deficiency, can enhance the damage, which now appears ubiquitous in northern

Workplace staff canteen is associated with lower blood pressure among industry workers

Purpose A staff canteen in the workplace can offer a healthier diet, which may lower the blood pressure (BP). The purpose of this paper is to evaluate whether the presence of staff canteen in the workplace is associated with consumption of healthy food and lower systolic and diastolic BP. Design/methodology/approach A cross-sectional study was conducted, randomly selecting workers through a multistage sampling, stratified by company size in Brazil. Demographic, socioeconomic, and life style characteristics were evaluated, and weight, height, and BP were measured. Statistical analysis used generalized linear models, controlling for design effect and confounding factors, to assess the association between BP and staff canteen and the intake of food items. Findings In total, 4.818 workers, aged 35.4±10.7 years, 76.5 percent men, with 8.7±4.1 years of formal education were enrolled. Prevalence of hypertension was 24.7 percent (p-value <0.001) among workers from industries with staff canteen vs 30.6 percent among those with no staff canteen. Workers of industries with staff canteen consumed higher proportion of fruits, green leafy vegetables, and milk than workers of industries without canteen, and had lower systolic and diastolic BP, independently of the frequency of intake. Practical implications Workers of industries with staff canteen consumed a healthier diet, and had lower systolic and diastolic BP, and lower prevalence of hypertension than workers from workplaces without staff canteen. Originality/value This study was the first carried out among workers of industries reporting that the presence of a staff canteen in the workplace is associated with lower systolic and diastolic BP and prevalence of hypertension.