Renato Gorga Bandeira de Mello

Sleep duration and mortality in the elderly : a systematic review with meta-analysis

Objective The purpose of our study was to evaluate the association between short and long sleep duration and all-cause and cardiovascular mortality among elderly individuals. Design Systematic review and meta-analysis of population-based cohort studies. Setting Articles were retrieved from international and national electronic databases. Study selection Studies were identified in PubMed, EMBASE, LILACS (Latin American and Caribbean Health Sciences Literature), IBECS (Bibliographic Index on Health Sciences from Spain) and CAPES (PhD thesis repository) between 1980 and 2015. Studies which met all criteria were eligible: participants aged 60 years or over, assessment of sleep duration as 24 h, nighttime or daytime sleep, evaluation of all-cause or cause-specific mortality, population-based cohort studies conducted on representative samples. There was no language restriction and studies published as abstracts were excluded. Data extraction Data were analysed using the Comprehensive Meta-Analysis software (V.3.3.070), and summary estimates (relative risk (RR), 95% CI) were calculated using a random effects model. Heterogeneity and consistency were evaluated through Cochrans Q and the I2 statistics, respectively, and sensitivity analyses were conducted. Primary and secondary outcome measures All-cause and cardiovascular mortality. Results Overall, 27 cohort studies were selected, comprising >70 000 elderly individuals, and followed up from 3.4 to 35 years. In the pooled analysis, long and short sleep duration were associated with increased all-cause mortality (RR 1.33; 95% CI 1.24 to 1.43 and RR 1.07; 95% CI 1.03 to 1.11, respectively), compared with the reference category. For cardiovascular mortality, the pooled relative risks were 1.43 (95% CI 1.15 to 1.78) for long sleep, and 1.18 (95% CI 0.76 to 1.84) for short sleep. Daytime napping ≥30 min was associated with risk of all-cause mortality (RR 1.27; 95% CI 1.08 to 1.49), compared with no daytime sleep, but longer sleep duration (≥2.0 h) was not (RR 1.34; 95% CI 1.95 to 1.90). Conclusions Among elderly individuals, long and short sleep duration are associated with increased risk for all-cause mortality. Long sleep duration is associated with cardiovascular mortality.

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.

Home Blood Pressure Monitoring Is Better Predictor of Cardiovascular Disease and Target Organ Damage than Office Blood Pressure: A Systematic Review and Meta-Analysis

The available, albeit rare, evidence indicates the superiority of home- over office blood pressure monitoring (HBPM vs OBP) to predict cardiovascular (CV) outcomes. We performed a systematic review to update the efficacy of HBPM vs OBP as predictors of all-cause mortality, CV death, and target organ damage. Two reviewers independently performed the literature search in various databases. A meta-analysis with a fixed-effect model was conducted, and the heterogeneity and inconsistency indices were assessed. The search identified 291 articles, of which 10 were eligible for inclusion in the study, and five articles published in 2012 were included in the meta-analysis. A previous meta-analysis showed the superiority of HBPM over OBP to predict all-cause mortality, CV mortality, and CV events. The meta-analysis of articles published in 2012 identified that HBPM was also a better predictor of proteinuria than OBP. In conclusion, the results of our systematic review and meta-analysis confirm that HBPM is a better predictor of CV outcomes and target organ damage than OBP.

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.

Preventing the Progression of Prehypertension to Hypertension: Role of Antihypertensives

Recent guidelines for the diagnosis and management of hypertension reversed the historical trend to recommend lower blood pressure (BP) thresholds to diagnose hypertension in high-risk individuals, such as patients with diabetes and elderly patients. The decision to raise the BP thresholds for diagnosis of hypertension in patients with diabetes was mostly based on the findings of the ACCORD trial. Nonetheless, the results of the ACCORD trial are within the predicted benefit to prevent coronary artery disease and stroke by meta-analysis of randomized controlled trials (RCT), particularly in regard to the prevention of stroke. The Eighth Joint National Committee (JNC 8) did not address prehypertension. There are many RCT done in individuals with prehypertension and concomitant cardiovascular disease showing the benefit of treatment of these patients. Trials exploring the efficacy of interventions to prevent cardiovascular disease in individuals with prehypertension free of cardiovascular disease would be hardly feasible in face of the low absolute risk of these individuals. Considering the risks of prehypertension for cardiovascular disease and the fast progression to hypertension of a large proportion of individuals with prehypertension, it is worth to consider drug treatment for individuals with prehypertension. RCT showed that the progression to hypertension can be partially halted by BP-lowering agents. These and ongoing clinical trials are herein revised. Prehypertension may be a window of opportunity to prevent hypertension and its cardiovascular consequences.

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

Overweight and abdominal obesity association with all-cause and cardiovascular mortality in the elderly aged 80 and over: A cohort study

ObjectiveTo evaluate the association between overweight and abdominal obesity with all-cause and cardiovascular mortality in the elderly aged 80 and over.DesignA prospective cohort study.SettingA population-based study of community-dwelling very elderly adults in a city in southern Brazil.Participants236 very elderly adults, number that represents 85% of the population aged 80 and over living in the city in the period (mean age 83.4 ± 3.2).MeasurementsOverweight and abdominal obesity were assessed using recommended cut-off points for body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR) and waist-height ratio (WHtR). The association between these anthropometric measurements and all-cause and cardiovascular mortality were independently estimated by Cox proportional hazards model. Kaplan-Meier was used to assess survival time.ResultsIncreased WC (>80cm F and >94cm M) and WHtR (>0.53 F and >0.52 M) were associated with lower all-cause mortality, but only WHtR remained associated even after controlling for residual confounding (HR 0.55 CI95% 0.36-0.84; p<0.001). Additionally increased WC was independently associated with lower mortality from cardiovascular diseases (HR 0.57 CI95% 0.34-0.95; p<0.030). BMI and WHR did not show significant independent association with mortality in the main analysis.ConclusionGreater abdominal fat accumulation, as estimated by WC and WHtR, presented an association with lower allcause and cardiovascular mortality in the elderly aged 80 and over, but not by BMI and WHR.

Bedside Ultrasound of Quadriceps to Predict Rehospitalization and Functional Decline in Hospitalized Elders

Objective To evaluate the capacity of total anterior thigh thickness, quadriceps muscle thickness, and quadriceps contractile index, all measured by bedside ultrasound, to predict rehospitalization, functional decline, and death in elderly patients 3 months after hospital discharge. To evaluate intra and interobserver reproducibility of the dominant thigh evaluation method by point of care ultrasound. Methods Cohort study of patients aged 65 years or more admitted to a medium complexity unit in a teaching hospital in southern Brazil. Comprehensive geriatric assessment and ultrasound evaluation of the dominant thigh of each participant were performed. After 3 months of hospital discharge, telephone contact was made to evaluate the outcomes of rehospitalization or death and functional decline—assessed by the 100 points Barthel scale and defined as a decrease of five or more points. Results 100 participants were included. There was no statistically significant difference between intraobserver measurements in the GEE method analysis (p > 0.05), and the mean bias obtained in Bland–Altman plots was close to zero in all four analyses performed, suggesting good intra and interobserver agreement. There was a significant correlation between the echographic measurements (quadriceps thickness and contractile index) and gait speed, timed up and go, and handgrip tests. There was a significant association between contractile index (quadriceps thickness over total anterior thigh thickness multiplied by 100) lower than 60% and functional decline (relative risk 1.35; CI 95% 1.10–1.65; p = 0.003) as well as between the thickness of the quadriceps and rehospitalization or death, in both individuals with preserved walking capacity and in bedridden elders (relative risk 1.34; CI 95% 1.02–1.75; p = 0.04). Conclusion The ultrasonographic method to evaluate thigh thickness was easily applicable and reproducible. The thickness of the quadriceps could predict rehospitalization or death, even in those patients without walking capacity—unable to perform gait speed and timed up and go tests. Additionally, the contractile index was associated with functional decline after 3 months of hospital discharge. This is a promising result, which highlights the bedside ultrasound of the quadriceps as a potential tool for the prognosis evaluation of bedridden hospitalized elderly patients.

Effects of concurrent and aerobic exercises on postexercise hypotension in elderly hypertensive men

ABSTRACT Despite the fact that simultaneous performance of resistance and aerobic exercises (i.e., concurrent exercise) has become a standard exercise prescription for the elderly, no information is available on its effects on post‐exercise hypotension (PEH) in elderly men with hypertension. Purpose: To compare the effects of different types of exercise on PEH in elderly men with hypertension. Methods: Twenty elderly men with essential hypertension participated in three crossover interventions, in random order, and on separate days: a non‐exercise control session at seated rest, aerobic exercise performed for 45 min, and 45 min of concurrent resistance and aerobic exercise consisted of 4 sets of 8 repetitions at 70% 1RM of resistance exercise followed by aerobic exercise on treadmill. After each session, blood pressure (BP) was measured continuously for 1 h in the laboratory and for 24 h under ambulatory conditions. Results: During the first hour in laboratory, diastolic BP was lower after aerobic (−5 mm Hg) and concurrent exercise (−6 mm Hg) in comparison with Control. Day‐time diastolic BP was significantly lower after aerobic exercise (−7 mm Hg) when compared to the control. No significant differences were found among the three experimental sessions for night‐time and 24‐hour diastolic BP, as well as day‐time, night‐time and 24‐hour systolic BP. Conclusion: Concurrent exercise produced acute PEH similar to aerobic exercise but such effect did not last as long as aerobic exercise in elderly patients with essential hypertension. HighlightsA single session of aerobic or concurrent exercise reduces blood pressure in elderly individuals with hypertension.Different exercise interventions acutely reduce blood pressure even for patients who have well‐controlled blood pressure.Aerobic exercise performed alone is more effective than concurrent exercise to reduce blood pressure.

Alternative Physical Therapy Protocol Using a Cycle Ergometer During Hospital Rehabilitation of Coronary Artery Bypass Grafting: a Clinical Trial

OBJECTIVE To compare the efficacy of a cycle ergometer-based exercise program to a standard protocol on the increment of the maximum distance walked during the six-minute walk test in the postoperative rehabilitation of patients submitted to coronary artery bypass grafting. METHODS A controlled clinical trial pilot, blinded to the outcome, enrolled subjects who underwent coronary artery bypass grafting in a hospital from Southern Brazil. Subjects were designated for the standard physical rehabilitation protocol or to an alternative cycle ergometer-based protocol through simple random sampling. The primary outcome was the difference in the maximum distance walked in the six-minute walk test before and after the allocated intervention. RESULTS Twenty-four patients were included in the analysis, 10 in the standard protocol and 14 in the alternative protocol group. There was an increment in the maximum distance walked in both groups, and borderline superiority in the intervention group comparing to the control group (312.2 vs. 249.7; P=0.06). CONCLUSION There was an increase in the maximum distance walked in the alternative protocol compared to the standard protocol. Thus, it is postulated that the use of a cycle ergometer can be included in physical rehabilitation in the hospital phase of postoperative coronary artery bypass grafting. However, randomized studies with larger sample size should be conducted to assess the significance of these findings.