Aerobic exercise improves central blood pressure and blood pressure variability among patients with resistant hypertension: results of the EnRicH trial.

Central blood pressure (BP) and BP variability are associated with cardiovascular disease risk. However, the influence of exercise on these hemodynamic parameters is unknown among patients with resistant hypertension. The EnRicH (The Exercise Training in the Treatment of Resistant Hypertension) was a prospective, single-blinded randomized clinical trial (NCT03090529). Sixty patients were randomized to a 12-week aerobic exercise program or usual care. The outcome measures include central BP, BP variability, heart rate variability, carotid-femoral pulse wave velocity, and circulating cardiovascular disease risk biomarkers including high-sensitivity C-reactive protein, angiotensin II, superoxide dismutase, interferon gamma, nitric oxide, and endothelial progenitor cells. Central systolic BP decreased by 12.22 mm Hg (95% CI, -1.88 to -22.57, P = 0.022) as did BP variability by 2.85 mm Hg (95% CI, -4.91 to -0.78, P = 0.008), in the exercise (n = 26) compared to the control group (n = 27). Interferon gamma -4.3 pg/mL (95%CI, -7.1 to -1.5, P = 0.003), angiotensin II -157.0 pg/mL (95%CI, -288.1 to -25.9, P = 0.020), and superoxide dismutase 0.4 pg/mL (95%CI, 0.1-0.6, P = 0.009) improved in the exercise compared to the control group. Carotid-femoral pulse wave velocity, heart rate variability, high-sensitivity C-reactive protein, nitric oxide, and endothelial progenitor cells were not different between groups (P > 0.05). In conclusion, a 12-week exercise training program improved central BP and BP variability, and cardiovascular disease risk biomarkers in patients with resistant hypertension. These markers are clinically relevant as they are associated with target organ damage and increased cardiovascular disease risk and mortality.

The blood pressure response to acute exercise predicts the ambulatory blood pressure response to exercise training in patients with resistant hypertension: results from the EnRicH trial.

Reports suggest that the blood pressure (BP) response to an acute bout of exercise is associated with the BP response to aerobic training in participants with elevated BP. These associations have not been tested among patients with resistant hypertension. This study aimed to determine whether the BP response to acute exercise predicts the 24-h ambulatory BP response to a 12-week exercise training program in patients with resistant hypertension (n = 26, aged 59.3 ± 8.2 years, 24-h ambulatory BP 127.4 ± 12.2/75.6 ± 7.8 mm Hg) who completed the exercise arm of the EnRicH trial. Ambulatory BP measurements were obtained before and after the exercise program to assess the chronic BP response. To assess acute BP changes, resting BP was measured before and 10 min after three exercise sessions in the third week of training and averaged. The resting systolic (9.4 ± 6.7, p < 0.001) and diastolic BP (1.9 ± 3.2, p = 0.005) were reduced after acute exercise. The 24-h systolic (6.2 ± 12.2, p = 0.015) and diastolic BP (4.4 ± 6.1, p = 0.001) were decreased after exercise training. The reductions in systolic BP after acute exercise were associated with the reductions in 24-h systolic BP after exercise training (ß = 0.538, adjusted r2 = 0.260, P = 0.005). The reductions in diastolic BP after acute exercise (ß = 0.453, adjusted r2 = 0.187) and baseline 24-h diastolic BP (ß = -0.459, adjusted r2 = 0. 199) accounted for 38.6% (p = 0.008) of the 24-h diastolic BP response to exercise training. In conclusion, the magnitude of the BP response to acute exercise appears to predict the ambulatory BP response to exercise training among patients with resistant hypertension.

Effect of Exercise Training on Ambulatory Blood Pressure Among Patients With Resistant Hypertension: A Randomized Clinical Trial.

Importance: Limited evidence suggests exercise reduces blood pressure (BP) in individuals with resistant hypertension, a clinical population with low responsiveness to drug therapy. Objective: To determine whether an aerobic exercise training intervention reduces ambulatory BP among patients with resistant hypertension. Design, Settings, and Participants: The Exercise Training in the Treatment of Resistant Hypertension (EnRicH) trial is a prospective, 2-center, single-blinded randomized clinical trial performed at 2 hospital centers in Portugal from March 2017 to December 2019. A total of 60 patients with a diagnosis of resistant hypertension aged 40 to 75 years were prospectively enrolled and observed at the hospitals' hypertension outpatient clinic. Interventions: Patients were randomly assigned in a 1:1 ratio to a 12-week moderate-intensity aerobic exercise training program (exercise group) or a usual care control group. The exercise group performed three 40-minute supervised sessions per week in addition to usual care. Main Outcomes and Measures: The powered primary efficacy measure was 24-hour ambulatory systolic BP change from baseline. Secondary outcomes included daytime and nighttime ambulatory BP, office BP, and cardiorespiratory fitness. Results: A total of 53 patients completed the study, including 26 in the exercise group and 27 in the control group. Of these, 24 (45%) were women, and the mean (SD) age was 60.1 (8.7) years. Compared with the control group, among those in the exercise group, 24-hour ambulatory systolic BP was reduced by 7.1 mm Hg (95% CI, -12.8 to -1.4; P = .02). Additionally, 24-hour ambulatory diastolic BP (-5.1 mm Hg; 95% CI, -7.9 to -2.3; P = .001), daytime systolic BP (-8.4 mm Hg; 95% CI, -14.3 to -2.5; P = .006), and daytime diastolic BP (-5.7 mm Hg; 95% CI, -9.0 to -2.4; P = .001) were reduced in the exercise group compared with the control group. Office systolic BP (-10.0 mm Hg; 95% CI, -17.6 to -2.5; P = .01) and cardiorespiratory fitness (5.05 mL/kg per minute of oxygen consumption; 95% CI, 3.5 to 6.6; P < .001) also improved in the exercise group compared with the control group. Conclusions and Relevance: A 12-week aerobic exercise program reduced 24-hour and daytime ambulatory BP as well as office systolic BP in patients with resistant hypertension. These findings provide clinicians with evidence to embrace moderate-intensity aerobic exercise as a standard coadjutant therapy targeting this patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT03090529.

Physical Activity is Associated With Lower Arterial Stiffness in Patients With Resistant Hypertension.

BACKGROUND: Physical activity is associated with reduced arterial stiffness, although such a relationship has not been reported in those with resistant hypertension. Therefore, this study aimed to determine the association between daily physical activity and arterial stiffness in patients with resistant hypertension. METHODS: Fifty-seven (57) patients with resistant hypertension (50.9% men), aged 58.8±9.4 years, were consecutively recruited. Arterial stiffness was evaluated using carotid-femoral pulse wave velocity (cf-PWV). Daily physical activity was objectively assessed with accelerometers during 7 consecutive days. RESULTS: Patients had a body mass index of 29.0±4.0 kg/m2 (84.3% overweight/obese) and were taking an average 4.5 antihypertensive medications. Overall, the cf-PWV was 9.2±2.4 m/s and the majority of participants (n=41, 71.9%) presented a cf-PWV <10 m/s. The cf-PWV showed an inverse correlation with light-intensity physical activity (r = -0.290, p=0.029) and total daily physical activity (r = -0.287, p=0.030). The correlation between light physical activity and cf-PWV remained significant after adjustment for systolic and diastolic blood pressure, but lost significance when further adjusted for age. CONCLUSIONS: Higher daily levels of light-intensity and total physical activity were associated with lower arterial stiffness. Nonetheless, this association is weak and attenuated or abolished when adjusted for blood pressure and age. These results suggest that physical activity may play an important role as a lifestyle intervention for patients with resistant hypertension. Future studies with larger samples sizes are necessary to confirm this preliminary data.

Prescribing high-intensity interval exercise by rating of perceived exertion in young individuals.

BACKGROUND: We tested the hypothesis that the 6 to 20 rating of perceived exertion (RPE) is a cost-effective tool similar to heart rate (HR) response to cardiopulmonary exercise test for prescribing and self-regulating high-intensity interval exercise (HIIE). In this context, we analyzed if health-related responses to exercise are similar between HIIE prescribed and self-regulated by RPE (HIIERPE) and HIIE prescribed and regulated by HR response to cardiopulmonary exercise test (HIIEHR). METHODS: Twelve young (21±2 years) sedentary or insufficiently active individuals (weekly levels ˂150 minutes or 75 minutes of moderate- or vigorous-intensity physical activity, respectively) were randomly assigned to perform HIIERPE (25 minutes), HIIEHR (25 minutes) and control session (25 minutes of seated resting). Blood pressure, HR, and arterial stiffness (pulse wave velocity) were measured before, immediately after, and 30 minutes after each intervention. HR, speed, and distance were measured during exercise sessions. 24-hours ambulatory blood pressure was measured after each intervention. RESULTS: Exercise HR, speed, and distance, as well as blood pressure response to exercise were not different between HIIERPE and HIIEHR. Pulse wave velocity reduced (P<0.05) at postintervention in both HIIERPE (0.28±0.17 m/s) and HIIEHR (0.27±0.11 m/s). However, pulse wave velocity at recovery was lower than pre-intervention only during HIIERPE (0.30±0.10 m/s). CONCLUSIONS: These results suggest that RPE is a cost-effective tool for prescribing self-regulating HIIE and improving health-related variables in young individuals.

Cardiac reinnervation affects cardiorespiratory adaptations to exercise training in individuals with heart transplantation.

PURPOSE: The purpose of this study was to investigate the hemodynamic and cardiorespiratory adaptations to exercise in individuals with heart transplantation with evidence of cardiac reinnervation (cardiac reinnervation group) versus without evidence of cardiac reinnervation (no cardiac reinnervation group). METHODS: Sedentary individuals with heart transplantation (age = 45.5 ± 2.2 years; time elapsed since surgery = 6.7 ± 0.7 years) were divided into the cardiac reinnervation (n = 16) and no cardiac reinnervation (n = 17) groups according to their heart rate response to cardiopulmonary exercise testing. The 24-hour ambulatory blood pressure, carotid-femoral pulse wave velocity, and cardiorespiratory fitness were assessed before and after 12 weeks of a thrice-weekly exercise program (five minutes of warm-up, 30 min of endurance exercise, one set of 10-15 reps in five resistance exercises, and five minutes of cool-down). RESULTS: The cardiac reinnervation group had reduced (p < 0.01) 24-hour systolic/diastolic blood pressure (7/9 mm Hg), daytime systolic/diastolic blood pressure (9/10 mm Hg) and nighttime diastolic blood pressure (6 mm Hg) after training. The no cardiac reinnervation group reduced (p < 0.05) only 24-hour (5 mm Hg), daytime (5 mm Hg) and nighttime (6 mm Hg) diastolic blood pressure after training. Hourly analysis showed that the cardiac reinnervation group reduced systolic/diastolic blood pressure for 10/21 h, while the no cardiac reinnervation group reduced systolic/diastolic blood pressure for only 3/11 h. The cardiac reinnervation group also improved both maximal oxygen consumption (10.8%) and exercise tolerance (13.4%) after training, but the no cardiac reinnervation group improved only exercise tolerance (9.9%). Pulse wave velocity did not change in both groups. CONCLUSION: There were greater improvements in ambulatory blood pressure and maximal oxygen consumption in the cardiac reinnervation than the no cardiac reinnervation group. These results suggest that cardiac reinnervation associates with hemodynamic and cardiorespiratory adaptations to exercise training in individuals with heart transplantation.

Inflammatory biomarkers and effect of exercise on functional capacity in patients with heart failure: Insights from a randomized clinical trial.

Background In patients with heart failure, inflammation has been associated with worse functional capacity, but it is uncertain whether it could affect their response to exercise training. We evaluated whether inflammatory biomarkers are related to differential effect of exercise on the peak oxygen uptake (V˙O2) among patients with heart failure. Design Open, parallel group, randomized controlled trial. Methods Patients with heart failure and ejection fraction ≤0.4 were randomized into exercise training or control for 12 weeks. Patients were classified according to: 1) inflammatory biomarkers blood levels, defined as 'low' if both interleukin-6 and tumor necrosis factor-alpha blood levels were below median, and 'high' otherwise; and 2) galectin-3 blood levels, which also reflect pro-fibrotic processes. Results Forty-four participants (50 ± 7 years old, 55% men, 25% ischemic) were allocated to exercise training ( n = 28) or control ( n = 16). Exercise significantly improved peak V˙O2 among participants with 'low' inflammatory biomarkers (3.5 ± 0.9 vs. -0.7 ± 1.1 ml/kg per min, p = 0.006), as compared with control, but not among those with 'high' inflammatory biomarkers (0.4 ± 0.6 vs. -0.2 ± 0.7 ml/kg per min, p = 0.54, p for interaction = 0.009). Similarly, exercise improved peak V˙O2 among participants with below median (2.4 ± 0.8 vs. -0.3 ± 0.9 ml/kg per min, p = 0.032), but not among those with above median galectin-3 blood levels (0.3 ± 0.7 vs. -0.7 ± 1.0 ml/kg per min, p = 0.41, p for interaction = 0.053). Conclusion In patients with heart failure, levels of biomarkers that reflect pro-inflammatory and pro-fibrotic processes were associated with differential effect of exercise on functional capacity. Further studies should evaluate whether exercise training can improve clinical outcomes in patients with heart failure and low levels of these biomarkers.

Circulating miR-1 as a potential biomarker of doxorubicin-induced cardiotoxicity in breast cancer patients.

Cardiotoxicity is associated with the chronic use of doxorubicin leading to cardiomyopathy and heart failure. Identification of cardiotoxicity-specific miRNA biomarkers could provide clinicians with a valuable prognostic tool. The aim of the study was to evaluate circulating levels of miRNAs in breast cancer patients receiving doxorubicin treatment and to correlate with cardiac function. This is an ancillary study from "Carvedilol Effect on Chemotherapy-induced Cardiotoxicity" (CECCY trial), which included 56 female patients (49.9±3.3 years of age) from the placebo arm. Enrolled patients were treated with doxorubicin followed by taxanes. cTnI, LVEF, and miRNAs were measured periodically. Circulating levels of miR-1, -133b, -146a, and -423-5p increased during the treatment whereas miR-208a and -208b were undetectable. cTnI increased from 6.6±0.3 to 46.7±5.5 pg/mL (p<0.001), while overall LVEF tended to decrease from 65.3±0.5 to 63.8±0.9 (p=0.053) over 12 months. Ten patients (17.9%) developed cardiotoxicity showing a decrease in LVEF from 67.2±1.0 to 58.8±2.7 (p=0.005). miR-1 was associated with changes in LVEF (r=-0.531, p<0.001). In a ROC curve analysis miR-1 showed an AUC greater than cTnI to discriminate between patients who did and did not develop cardiotoxicity (AUC = 0.851 and 0.544, p= 0.0016). Our data suggest that circulating miR-1 might be a potential new biomarker of doxorubicin-induced cardiotoxicity in breast cancer patients.

Systemic effects of controlled exposure to diesel exhaust: a meta-analysis from randomized controlled trials.

INTRODUCTION: Ambient air pollution is associated with adverse cardiovascular events. This meta-analysis aimed to investigate the short-term association between air pollution and cardiovascular effects on healthy volunteers. METHODS: We searched databases to identify randomized trials with controlled human exposures to either of two models for studying ambient particulate matter: diesel-exhaust or concentrated ambient particles. Estimates of size effect were performed using standardized mean difference (SMD). Heterogeneity was assessed with I2 statistics. Outcomes were vascular function estimated by forearm blood flow (FBF), blood pressure, heart rate, and blood analysis. RESULTS: Database searches yielded 17 articles (n = 342) with sufficient information for meta-analyses. High levels of heterogeneity for the some outcomes were analyzed using random-effects model. The pooled effect estimate showed that short-term exposure to air pollution impaired FBF response from 2.7 to 2.5 mL/100 mL tissue/min (SMD 0.404; p = .006). There was an increase in 5000 platelet/mm3 following pollution exposure (SMD 0.390; p = .050) but no significant differences for other outcomes. CONCLUSION: Controlled human exposures to air pollution are associated with the surrogates of vascular dysfunction and increase in platelet count, which might be related to adverse cardiovascular events. Given the worldwide prevalence of exposure to air pollution, these findings are relevant for public health. KEY MESSAGES Controlled exposure to air pollution impairs vasomotor response, which is a surrogate for adverse cardiovascular events. This is the first meta-analysis from randomized clinical trials showing short-term association between air pollution and cardiovascular effects on healthy volunteers. Given the worldwide prevalence of exposure to air pollution, this finding is important for public health.

Effects of reducing exposure to air pollution on submaximal cardiopulmonary test in patients with heart failure: Analysis of the randomized, double-blind and controlled FILTER-HF trial.

BACKGROUND: Air pollution exposure could mitigate the health benefits of exercise in patients with heart failure (HF). We tested the effects of a respiratory filter on HF patients exposed to air pollution during exercise. METHODS AND RESULTS: Ancillary analysis of the FILTER-HF trial, focused on the exercise outcomes. In a randomized, double-blind, 3-way crossover design, 26 HF patients and 15 control volunteers were exposed to clean air, unfiltered dilute diesel engine exhaust (DE), or filtered DE for 6min during a submaximal cardiopulmonary testing in a controlled-exposure facility. Prospectively collected data included six-minute walking test [6mwt], VO2, VE/VCO2 Slope, O2Pulse, pulmonary ventilation [VE], tidal volume, VD/Vt, oxyhemoglobin saturation and CO2-rebreathing. Compared to clean air, DE adversely affected VO2 (11.0±3.9 vs. 8.4±2.8ml/kg/min; p<0.001); 6mwt (243.3±13.0 vs. 220.8±13.7m; p=0.030); and O2Pulse (8.9±1.0 vs. 7.8±0.7ml/beat; p<0.001) in HF patients. Compared to DE, filtration reduced the particulate concentration from 325±31 to 25±6µg/m(3), and was associated with an increase in VO2 (10.4±3.8ml/kg/min; p<0.001 vs. DE) and O2Pulse (9.7±1.1ml/beat; p<0.001 vs. DE) in patients with HF. Filtration was associated with higher VE and CO2-rebreathing in both groups. VE/VCO2 Slope was higher among patients with HF. CONCLUSION: DE adversely affects exercise capacity in patients with HF. A simple respiratory filter can reduce the adverse effects of pollution on VO2 and O2Pulse. Given the worldwide prevalence of exposure to traffic-related air pollution, these findings are relevant for public health especially in this highly susceptible population. The filter intervention holds great promise that needs to be tested in future studies.

Respiratory Filter Reduces the Cardiovascular Effects Associated With Diesel Exhaust Exposure: A Randomized, Prospective, Double-Blind, Controlled Study of Heart Failure: The FILTER-HF Trial.

OBJECTIVES: The goal of this study was to test the effects of a respiratory filter intervention (filter) during controlled pollution exposure. BACKGROUND: Air pollution is considered a risk factor for heart failure (HF) decompensation and mortality. METHODS: This study was a double-blind, randomized to order, controlled, 3-way crossover, single-center clinical trial. It enrolled 26 patients with HF and 15 control volunteers. Participants were exposed in 3 separate sessions to clean air, unfiltered diesel exhaust exposure (DE), or filtered DE. Endpoints were endothelial function assessed by using the reactive hyperemia index (RHi), arterial stiffness, serum biomarkers, 6-min walking distance, and heart rate variability. RESULTS: In patients with HF, DE was associated with a worsening in RHi from 2.17 (interquartile range [IQR]: 1.8 to 2.5) to 1.72 (IQR: 1.5 to 2.2; p = 0.002) and an increase in B-type natriuretic peptide (BNP) from 47.0 pg/ml (IQR: 17.3 to 118.0 pg/ml) to 66.5 pg/ml (IQR: 26.5 to 155.5 pg/ml; p = 0.004). Filtration reduced the particulate concentration (325 ± 31 µg/m(3) vs. 25 ± 6 µg/m(3); p < 0.001); in the group with HF, filter was associated with an improvement in RHi from 1.72 (IQR: 1.5 to 2.2) to 2.06 (IQR: 1.5 to 2.6; p = 0.019) and a decrease in BNP from 66.5 pg/ml (IQR: 26.5 to 155.5 pg/ml) to 44.0 pg/ml (IQR: 20.0 to 110.0 pg/ml; p = 0.015) compared with DE. In both groups, DE decreased the 6-min walking distance and arterial stiffness, although filter did not change these responses. DE had no effect on heart rate variability or exercise testing. CONCLUSIONS: To our knowledge, this trial is the first to show that a filter can reduce both endothelial dysfunction and BNP increases in patients with HF during DE. Given these potential benefits, the widespread use of filters in patients with HF exposed to traffic-derived air pollution may have beneficial public health effects and reduce the burden of HF. (Effects of Air Pollution Exposure Reduction by Filter Mask on Heart Failure; NCT01960920).

Effects of short-term heated water-based exercise training on systemic blood pressure in patients with resistant hypertension: a pilot study.

High blood pressure (BP) increases the risk of cardiovascular diseases, and its control is a clinical challenge. Regular exercise lowers BP in patients with mild-to-moderate hypertension. No data are available on the effects of heated water-based exercise in hypertensive patients. Our objective was to evaluate the effects of heated water-based exercise on BP in patients with resistant hypertension. We tested the effects of 60-min heated water-based exercise training three times per week in 16 patients with resistant hypertension (age 55±6 years). The protocol included walking and callisthenic exercises. All patients underwent 24-h ambulatory blood pressure monitoring (ABPM) before and after a 2-week exercise program in a heated pool. Systolic office BP was reduced from 162 to 144 mmHg (P<0.004) after heated-water training. After the heated-water exercise training during 24-h ABPM, systolic BP decreased from 135 to 123 mmHg (P=0.02), diastolic BP decreased from 83 to 74 mmHg (P=0.001), daytime systolic BP decreased from 141 to 125 mmHg (P=0.02), diastolic BP decreased from 87 to 77 mmHg (P=0.009), night-time systolic BP decreased from 128 to 118 mmHg (P=0.06), and diastolic BP decreased from 77 to 69 mmHg (P=0.01). In addition, BP cardiovascular load was reduced significantly during the 24-h daytime and night-time period after the heated water-based exercise. Heated water-based exercise reduced office BP and 24-h daytime and night-time ABPM levels. These effects suggest that heated water-based exercise may have a potential as a new therapeutic approach to resistant hypertensive patients.

Mode of death on Chagas heart disease: comparison with other etiologies. a subanalysis of the REMADHE prospective trial.

BACKGROUND: Sudden death has been considered the main cause of death in patients with Chagas heart disease. Nevertheless, this information comes from a period before the introduction of drugs that changed the natural history of heart failure. We sought to study the mode of death of patients with heart failure caused by Chagas heart disease, comparing with non-Chagas cardiomyopathy. METHODS AND RESULTS: We examined the REMADHE trial and grouped patients according to etiology (Chagas vs non-Chagas) and mode of death. The primary end-point was all-cause, heart failure and sudden death mortality; 342 patients were analyzed and 185 (54.1%) died. Death occurred in 56.4% Chagas patients and 53.7% non-Chagas patients. The cumulative incidence of all-cause mortality and heart failure mortality was significantly higher in Chagas patients compared to non-Chagas. There was no difference in the cumulative incidence of sudden death mortality between the two groups. In the Cox regression model, Chagas etiology (HR 2.76; CI 1.34-5.69; p = 0.006), LVEDD (left ventricular end diastolic diameter) (HR 1.07; CI 1.04-1.10; p<0.001), creatinine clearance (HR 0.98; CI 0.97-0.99; p = 0.006) and use of amiodarone (HR 3.05; CI 1.47-6.34; p = 0.003) were independently associated with heart failure mortality. LVEDD (HR 1.04; CI 1.01-1.07; p = 0.005) and use of beta-blocker (HR 0.52; CI 0.34-0.94; p = 0.014) were independently associated with sudden death mortality. CONCLUSIONS: In severe Chagas heart disease, progressive heart failure is the most important mode of death. These data challenge the current understanding of Chagas heart disease and may have implications in the selection of treatment choices, considering the mode of death. TRIAL REGISTRATION: ClinicalTrials.gov NCT00505050 (REMADHE).

Hypertonic saline solution for prevention of renal dysfunction in patients with decompensated heart failure.

BACKGROUND: Renal dysfunction is associated with increased mortality in patients with decompensated heart failure. However, interventions targeted to prevention in this setting have been disappointing. We investigated the effects of hypertonic saline solution (HSS) for prevention of renal dysfunction in decompensated heart failure. METHODS: In a double-blind randomized trial, patients with decompensated heart failure were assigned to receive three-day course of 100mL HSS (NaCl 7.5%) twice daily or placebo. Primary end point was an increase in serum creatinine of 0.3mg/dL or more. Main secondary end point was change in biomarkers of renal function, including serum levels of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin-NGAL and the urinary excretion of aquaporin 2 (AQP2), urea transporter (UT-A1), and sodium/hydrogen exchanger 3 (NHE3). RESULTS: Twenty-two patients were assigned to HSS and 12 to placebo. Primary end point occurred in two (10%) patients in HSS group and six (50%) in placebo group (relative risk 0.3; 95% CI 0.09-0.98; P=0.01). Relative to baseline, serum creatinine and cystatin C levels were lower in HSS as compared to placebo (P=0.004 and 0.03, respectively). NGAL level was not statistically different between groups, however the urinary expression of AQP2, UT-A1 and NHE3 was significantly higher in HSS than in placebo. CONCLUSIONS: HSS administration attenuated heart failure-induced kidney dysfunction as indicated by improvement in both glomerular and tubular defects, a finding with important clinical implications. HSS modulated the expression of tubular proteins involved in regulation of water and electrolyte homeostasis.

Heart rate response to exercise and cardiorespiratory fitness of young women at high familial risk for hypertension: effects of interval vs continuous training.

Exercise training is an effective intervention for treating and preventing hypertension, but its effects on heart rate (HR) response to exercise and cardiorespiratory fitness (CRF) of non-hypertensive offspring of hypertensive parents (FH+) has not been studied. We compared the effects of three times per week equal-volume high-intensity aerobic interval (AIT) and continuous moderate-intensity exercise (CME) on HR response to exercise and CRF of FH+. Forty-four young FH+ women (25.0 ± 4.4 years) randomized to control (CON; n = 12), AIT (80-90% of VO(2MAX); n = 16), or CME (50-60% of VO(2MAX); n = 16) performed a graded exercise test (GXT) before and after 16 weeks of follow-up to evaluate HR response to exercise and several parameters of CRF. Resting, maximal, and reserve HR did not change after the follow-up in all groups. HR recovery (difference between HR(MAX) and HR at 1 minute of GXT recovery phase) improved only after AIT (11.8 ± 4.9 vs. 20.6 ± 5.8 bpm, p < 0.01). Both exercise programmes were effective for improving CRF parameters, but AIT was more effective than CME for improving oxygen consumption at the respiratory compensation point (VO(2RCP); 22.1% vs. 8.8%, p = 0.008) and maximal effort (VO(2MAX); 15.8% vs. 8.0%, p = 0.036), as well as tolerance time (TT) to reach anaerobic threshold (TT(AT); 62.0 vs. 37.7, p = 0.048), TT(RCP) (49.3 vs. 32.9, p = 0.032), and TT(MAX) (38.9 vs. 29.2, p = 0.042). Exercise intensity was an important factor in improving HR recovery and CRF of FH+women. These findings may have important implications for designing exercise-training programmes for the prevention of an inherited hypertensive disorder.

Effects of high-intensity aerobic interval training vs. moderate exercise on hemodynamic, metabolic and neuro-humoral abnormalities of young normotensive women at high familial risk for hypertension.

Exercise training has an important role in the prevention and treatment of hypertension, but its effects on the early metabolic and hemodynamic abnormalities observed in normotensive offspring of hypertensive parents (FH+) have not been studied. We compared high-intensity interval (aerobic interval training, AIT) and moderate-intensity continuous exercise training (CMT) with regard to hemodynamic, metabolic and hormonal variables in FH+ subjects. Forty-four healthy FH+ women (25.0+/-4.4 years) randomized to control (ConFH+) or to a three times per week equal-volume AIT (80-90% of VO(2MAX)) or CMT (50-60% of VO(2MAX)) regimen, and 15 healthy women with normotensive parents (ConFH-; 25.3+/-3.1 years) had their hemodynamic, metabolic and hormonal variables analyzed at baseline and after 16 weeks of follow-up. Ambulatorial blood pressure (ABP), glucose and cholesterol levels were similar among all groups, but the FH+ groups showed higher insulin, insulin sensitivity, carotid-femoral pulse wave velocity (PWV), norepinephrine and endothelin-1 (ET-1) levels and lower nitrite/nitrate (NOx) levels than ConFH- subjects. AIT and CMT were equally effective in improving ABP (P<0.05), insulin and insulin sensitivity (P<0.001); however, AIT was superior in improving cardiorespiratory fitness (15 vs. 8%; P<0.05), PWV (P<0.01), and BP, norepinephrine, ET-1 and NOx response to exercise (P<0.05). Exercise intensity was an important factor in improving cardiorespiratory fitness and reversing hemodynamic, metabolic and hormonal alterations involved in the pathophysiology of hypertension. These findings may have important implications for the exercise training programs used for the prevention of inherited hypertensive disorder.

Glycemia and prognosis of patients with chronic heart failure--subanalysis of the Long-term Prospective Randomized Controlled Study Using Repetitive Education at Six-Month Intervals and Monitoring for Adherence in Heart Failure Outpatients (REMADHE) trial.

BACKGROUND: Heart failure and diabetes often occur simultaneously in patients, but the prognostic value of glycemia in chronic heart failure is debatable. We evaluated the role of glycemia on prognosis of heart failure. METHODS: Outpatients with chronic heart failure from the Long-term Prospective Randomized Controlled Study Using Repetitive Education at Six-Month Intervals and Monitoring for Adherence in Heart Failure Outpatients (REMADHE) trial were grouped according to the presence of diabetes and level of glycemia. All-cause mortality/heart transplantation and unplanned hospital admission were evaluated. RESULTS: Four hundred fifty-six patients were included (135 [29.5%] female, 124 [27.2%] with diabetes mellitus, age of 50.2 +/- 11.4 years, and left-ventricle ejection fraction of 34.7% +/- 10.5%). During follow-up (3.6 +/- 2.2 years), 27 (5.9%) patients were submitted to heart transplantation and 202 (44.2%) died; survival was similar in patients with and without diabetes mellitus. When patients with and without diabetes were categorized according to glucose range (glycemia < or = 100 mg/dL [5.5 mmol/L]), as well as when distributed in quintiles of glucose, the survival was significantly worse among patients with lower levels of glycemia. This finding persisted in Cox proportional hazards regression model that included gender, etiology, left ventricle ejection fraction, left ventricle diastolic diameter, creatinine level and beta-blocker therapy, and functional status (hazard ratio 1.45, 95% CI 1.09-1.69, P = .039). No difference regarding unplanned hospital admission was found. CONCLUSION: We report on an inverse association between glycemia and mortality in outpatients with chronic heart failure. These results point to a new pathophysiologic understanding of the interactions between diabetes mellitus, hyperglycemia, and heart disease.