Severe thermal and major traumatic injury results in elevated plasma concentrations of total heme that are associated with poor clinical outcomes and systemic immune suppression.

Background: Traumatic and thermal injuries result in a state of systemic immune suppression, yet the mechanisms that underlie its development are poorly understood. Released from injured muscle and lysed red blood cells, heme is a damage associated molecular pattern with potent immune modulatory properties. Here, we measured plasma concentrations of total heme in over 200 traumatic and thermally-injured patients in order to examine its relationship with clinical outcomes and post-injury immune suppression. Methods: Blood samples were collected from 98 burns (≥15% total body surface area) and 147 traumatically-injured (injury severity score ≥8) patients across the ultra-early (≤1 hour) and acute (4-72 hours) post-injury settings. Pro-inflammatory cytokine production by lipopolysaccharide (LPS) challenged whole blood leukocytes was studied, and plasma concentrations of total heme, and its scavengers haptoglobin, hemopexin and albumin measured, alongside the expression of heme-oxygenase-1 (HO-1) in peripheral blood mononuclear cells (PBMCs). LPS-induced tumour necrosis factor-alpha (TNF-α) production by THP-1 cells and monocytes following in vitro heme treatment was also examined. Results: Burns and traumatic injury resulted in significantly elevated plasma concentrations of heme, which coincided with reduced levels of hemopexin and albumin, and correlated positively with circulating levels of pro and anti-inflammatory cytokines. PBMCs isolated from trauma patients 4-12 and 48-72 hours post-injury exhibited increased HO-1 gene expression. Non-survivors of burn injury and patients who developed sepsis, presented on day 1 with significantly elevated heme levels, with a difference of 6.5 µM in heme concentrations corresponding to a relative 52% increase in the odds of post-burn mortality. On day 1 post-burn, heme levels were negatively associated with ex vivo LPS-induced TNF-α and interleukin-6 production by whole blood leukocytes. THP-1 cells and monocytes pre-treated with heme exhibited significantly reduced TNF-α production following LPS stimulation. This impairment was associated with decreased gene transcription, reduced activation of extracellular signal-regulated kinase 1/2 and an impaired glycolytic response. Conclusions: Major injury results in elevated plasma concentrations of total heme that may contribute to the development of endotoxin tolerance and increase the risk of poor clinical outcomes. Restoration of the heme scavenging system could be a therapeutic approach by which to improve immune function post-injury.

Are equine-assisted services beneficial for military veterans with post-traumatic stress disorder? A systematic review and meta-analysis.

BACKGROUND: Equine-assisted services (EAS) involves the use of horses within therapy, learning or horsemanship sessions and has been used with military veterans suffering from post-traumatic stress disorder (PTSD). This study systematically reviewed existing research on the use of EAS in the treatment of PTSD in military veterans and evaluated its effectiveness. METHODS: A systematic review was performed, in May 2023, with searches and data extraction carried out from three separate databases (PubMed, JSTOR and Science Direct) related to testing the effect of EAS on PTSD outcomes in veterans. A risk of bias assessment of included studies was conducted and meta-analysis of outcomes performed when two or more studies reported the same outcomes. Other effects of EAS on veterans' health were also discussed. RESULTS: A total of 13 studies were identified based on our inclusion and exclusion criteria with 11 originating from the US and the remaining two from Australia and Israel. There were 344 participants amongst all of the studies with a mean age of 47 years and a male:female ratio of 19:6. Eight out of the 13 studies reported PTSD scores, as measured by either PTSD Checklist for DSM-5 (PCL-5) or PCL-Veteran/-Military versions (PCL-V/-M), and results suggested a reduction in PTSD score after EAS treatment of 22.6%. A meta-analysis confirmed that EAS favored a significantly lower PTSD score after treatment, with a mean difference of 12.46, 95% CI [9.03,15.88], p < 0.00001. However, only one study had low risk of bias whilst all the rest of the studies had some concerns to high risk of bias. CONCLUSIONS: EAS appeared to have a positive influence on PTSD symptoms in military veterans, significantly reducing PTSD severity scores. Other benefits of EAS may be peer support, social integration, learning new skills and bonding. However, the results of this systematic review must be interpreted with caution as almost all of the studies were of low quality. Therefore, further rigorous research is required with larger participants to be able to draw conclusions about the benefits of EAS on PTSD severity.

Influence of scar age, laser type and laser treatment intervals on paediatric burn scars: a systematic review and meta-analysis.

Background: Laser therapy has emerged to play a valuable role in the treatment of paediatric burn scars; however, there is heterogeneity in the literature, particularly concerning optimal timing for initiation of laser therapy. This study aims to investigate the effect of factors such as scar age, type of laser and laser treatment interval on burn scar outcomes in children by meta-analysis of previous studies. Methods: A literature search was conducted across seven databases in May 2022 to understand the effects of laser therapy on burn scar outcomes in paediatric patients by metanalysis of standardized mean difference (SMD) between pre- and post-laser intervention. Meta-analyses were performed using the Comprehensive Meta-Analysis software version 4.0. Fixed models were selected when there was no significant heterogeneity, and the random effects model was selected for analysis when significant heterogeneity was identified. For all analyses, a p-value < 0.05 was considered significant. Results: Seven studies were included in the meta-analysis with a total of 467 patients. Laser therapy significantly improved Vancouver Scar Scale (VSS)/Total Patient and Observer Scar Assessment Scale (Total POSAS), vascularity, pliability, pigmentation and scar height of burn scars. Significant heterogeneity was found between the studies and thus subgroup analyses were performed. Early laser therapy (<12 months post-injury) significantly improved VSS/POSAS scores compared to latent therapy (>12 months post-injury) {SMD -1.97 [95% confidence interval (CI) = -3.08; -0.87], p < 0.001 vs -0.59 [95%CI = -1.10; -0.07], p = 0.03} as well as vascularity {SMD -3.95 [95%CI = -4.38; -3.53], p < 0.001 vs -0.48 [95%CI = -0.66; -0.30], p < 0.001}. Non-ablative laser was most effective, significantly reducing VSS/POSAS, vascularity, pliability and scar height outcomes compared to ablative, pulse dye laser and a combination of ablative and pulse dye laser. Shorter treatment intervals of <4 weeks significantly reduced VSS/POSAS and scar height outcomes compared to intervals of 4 to 6 weeks. Conclusions: Efficacy of laser therapy in the paediatric population is influenced by scar age, type of laser and interval between laser therapy application. The result of this study particularly challenges the currently accepted initiation time for laser treatment. Significant heterogeneity was observed within the studies, which suggests the need to explore other confounding factors influencing burn scar outcomes after laser therapy.

The influence of classical music on learning and memory in rats: a systematic review and meta-analysis.

During the learning process, music can activate important neural areas in the brain, promoting the retention of information and memory formation. However, studies testing music effects on memory had found different improvements, which could be due to the methodological differences across studies. Thus, the purpose of this article was to systematically review the literature and meta-analyze the effects of music on Rattus norvegicus' explicit memory (Maze tests) only in controlled investigations. The seven studies included led to a very homogeneous analysis (I2 = 0%), confirming the consistency of the significant standardized mean difference (SMD) between the memory of animals exposed and not exposed to music (SMD 0.60 (95% CI 0.38; 0.83, p < 0.001)). Exploratory analysis suggests music benefits on memory can be acquired when begun at any age, when tested with the three types of mazes evaluated, with exposure lasting from 8 to 83 days and when the age on test day was either under 30 days or over 30 days. To expand the actual understanding of music effects on memory, future studies should investigate different types of music and animal species, with different sex and health conditions, at different time points.

Type of delivery and perinatal outcomes in pregnant women diagnosed with COVID-19: A systematic review and meta-analysis.

BACKGROUND: There is paucity in the literature that provides a comprehensive and evidence-based conclusion regarding this topic. OBJECTIVE: To compare perinatal outcomes of vaginal and caesarean section delivery in women diagnosed with COVID-19 by meta-analysis of literature. SEARCH STRATEGY: The search was conducted on MEDLINE, EMBASE, LILACS, CINAHL, Scopus, Web of Science and Cochrane Database of Systematic Reviews by 25th May 2022. SELECTION CRITERIA: The inclusion criteria involved pregnant women diagnosed with COVID-19 who underwent caesarean section and those who had vaginal deliveries. DATA COLLECTION AND ANALYSIS: The included studies were meta-analyzed for various outcomes including: Gestational age, maternal intensive care unit admission, maternal death, prematurity, newborn birth weight, newborn intensive care unit admission, Apgar scores, newborn death, and newborn vertical transmission of COVID-19. The meta-analysis was conducted using Comprehensive Meta-Analysis (CMA) software, version 3.3.070. MAIN RESULTS: The meta-analyses included 2,566 deliveries (866 caesarean sections and 1,700 vaginal deliveries) and identified that caesarean section was significantly associated with increased prematurity (OR 2.5 [1.7; 3.6], p < 0.001), lower birth weight (-118 g [-170; -66], p < 0.001), and a higher need for maternal (OR 9.54 [5.22; 17.43], p < 0.01) and neonatal intensive care unit intervention (OR 3.67 [2.71; 4.96], p < 0.01) compared to vaginal delivery. CONCLUSION: COVID-19 infection alone should not be an indication for caesarean section as there is insufficient evidence that caesarean section reduces mortality, improves birth conditions, or prevents vertical transmission. Additionally, caesarean section is associated with poorer perinatal outcomes compared to vaginal delivery.

Influence of scar age, laser type and laser treatment intervals on adult burn scars: A systematic review and meta-analysis.

AIM: The study aims to identify whether factors such as time to initiation of laser therapy following scar formation, type of laser used, laser treatment interval and presence of complications influence burn scar outcomes in adults, by meta-analysis of previous studies. METHODS: A literature search was conducted in May 2022 in seven databases to select studies on the effects of laser therapy in adult hypertrophic burn scars. The study protocol was registered with PROSPERO (CRD42022347836). RESULTS: Eleven studies were included in the meta-analysis, with a total of 491 patients. Laser therapy significantly improved overall VSS/POSAS, vascularity, pliability, pigmentation and scar height of burn scars. Vascularity improvement was greater when laser therapy was performed >12 months (-1.50 [95%CI = -2.58;-0.42], p = 0.01) compared to <12 months after injury (-0.39 [95%CI = -0.68; -0.10], p = 0.01), the same was true for scar height ((-1.36 [95%CI = -2.07; -0.66], p<0.001) vs (-0.56 [95%CI = -0.70; -0.42], p<0.001)). Pulse dye laser (-4.35 [95%CI = -6.83; -1.86], p<0.001) gave a greater reduction in VSS/POSAS scores compared to non-ablative (-1.52 [95%CI = -2.24; -0.83], p<0.001) and ablative lasers (-0.95 [95%CI = -1.31; -0.59], p<0.001). CONCLUSION: Efficacy of laser therapy is influenced by the time lapse after injury, the type of laser used and the interval between laser treatments. Significant heterogeneity was observed among studies, suggesting the need to explore other factors that may affect scar outcomes.

Cardiovascular telerehabilitation improves functional capacity, cardiorespiratory fitness and quality of life in older adults: A systematic review and meta-analysis.

INTRODUCTION: The aim was to identify whether cardiovascular telerehabilitation programs (CV-T-REHAB) can improve functional capacity, cardiorespiratory fitness and quality of life (QoL) to the same extent of presential rehabilitation (CV-P-REHAB) in older adults, by meta-analysis of previous studies. METHODS: Literature search was conducted in October 2020 in four databases to select controlled trials of CV-T-REHAB effects on functional capacity (six-minute walk test [6MWT]), cardiorespiratory fitness (maximal oxygen consumption [V˙O2max]), and QoL in older adults (> 50 years) and included new articles in April 2022. RESULTS: CV-T-REHAB improved 6MWT (11.14 m [CI95% = 8.03; 14.26], p < 0.001), V˙O2max (1.18 ml/kg/min [CI95% = 0.70; 1.66], p < 0.001), and QoL (standardized mean difference [SMD] = 0.36 [CI95% = 0.05; 0.67], p = 0.02). CV-T-REHAB increased V˙O2max to a greater extent than CV-P-REHAB (1.08 ml/kg/min [0.39; 1.76], p = 0.002). Although the 6MWT and V˙O2max analyses proved consistent and homogeneous, the QoL analysis showed considerable inconsistency (I2 = 92.90%), suggesting the need for studies exploring the effect of CV-T-REHAB on QoL in this population. Part of the heterogeneity was explained by age differences, as CV-T-REHAB improved QoL in adults >65 years, but not in adults <64 years. CONCLUSION: CV-T-REHAB improved cardiorespiratory fitness to a level equal to or higher than CV-P-REHAB and improved functional capacity and QoL; being mainly effective for QoL in older adults >65 years. Thus, CV-T-REHAB can be a good alternative, when not the best option and might be considered especially for individuals with limited access to participate in face-to-face programs.

Metabolomic Response throughout 16 Weeks of Combined Aerobic and Resistance Exercise Training in Older Women with Metabolic Syndrome.

Increases in longevity and obesity have led to a higher prevalence of Metabolic Syndrome (MetS) and several chronic conditions, such as hypertension. The prevalence of MetS and hypertension increases with advancing age and their detrimental effects on health can be attenuated by physical activity. Combined aerobic and resistance exercise training (CT) is recommended to maintain good health in older adults and is known to generate important metabolic adaptations. In this study we performed a metabolomics analysis, based on Hydrogen Nuclear Magnetic Resonance (1H NMR), to investigate the kinetics of changes in metabolism in non-physically active older women with MetS in response to 16 weeks of CT. A subset of women with MetS were selected from a larger randomized trial (that included men and women without MetS), with 12 participants on CT and 13 from the Control Group (CG). CT comprised walking/running at 63% of VO2max, three times/week, and resistance training (RT), consisting of 15 repetitions of seven exercises at moderate intensity, twice/week. Serum metabolomic profile was analysed at baseline (0W), 4 (4W), 8 (8W), 12 (12W) and 16 weeks (16W) for CT or CG. Cardiorespiratory fitness, RT load, blood pressure, body composition, lipid and glycaemic profile were also assessed. After 16 weeks CT increased cardiorespiratory fitness (13.1%, p < 0.05) and RT load (from 48% in the lat pulldown to 160% in the leg press, p < 0.05), but there were no changes in MetS parameters, such as body composition (Body Mass, Body Mass Index (BMI), body fat percentage and waist circumference), blood pressure, lipid and glycaemic profile. However, we identified potential higher substrate to the tricarboxylic acid cycle (increase in 2-Oxobutyrate from 0W (0.0029 ± 0.0009) to 4W (0.0038 ± 0.0011) and 8W (0.0041 ± 0.0015), p < 0.05), followed by alterations (different from 0W, p < 0.05) in the production of ketone bodies (3-Hydroxybutyrate, 0W (0.0717 ± 0.0377) to 16W (0.0397 ± 0.0331), and Acetoacetate, 0W (0.0441 ± 0.0240) to 16W (0.0239 ± 0.0141)), which together might explain the known improvement in fatty acid oxidation with exercise. There was also a late increase in ornithine at 16W of CT. Further studies are needed to investigate the association between these metabolic pathways and clinical outcomes in this population.

Comparison between frail and non-frail older adults' gut microbiota: A systematic review and meta-analysis.

BACKGROUND: Emerging evidence suggests that the intestinal microbiota (IM) undergoes remodelling as we age, and this impacts the ageing trajectory and mortality in older adults. The aim was to investigate IM diversity differences between frail and non-frail older adults by meta-analysing previous studies. METHODS: The protocol of this systematic review with meta-analysis was registered on PROSPERO (CRD42021276733). We searched for studies comparing IM diversity of frail and non-frail older adults indexed on PubMed, Embase, Cochrane, and Web of Science in November 2021. RESULTS: We included 11 studies with 1239 participants, of which 340 were meta-analysed. Frailty was defined by a variety of criteria (i.e. Fried Scale, European Consensus on Sarcopenia). There were no differences in the meta-analyses between the frail and non-frail groups for species richness index (SMD = -0.147; 95% CI = -0.394, 0.100; p = 0.243) and species diversity index (SMD = -0.033; 95% CI = -0.315, 0.250; p = 0.820). However, we identified almost 50 differences between frail and non-frail within the relative abundance of bacteria phyla, families, genera, and species in the primary studies. CONCLUSIONS: The evidence to prove that there are differences between frail and non-frail IM diversity by meta-analysis is still lacking. The present results suggest that further investigation into the role of specific bacteria, their function, and their influence on the physiopathology of frailty is needed.

Comprehensive Time-Course Effects of Combined Training on Hypertensive Older Adults: A Randomized Control Trial.

The aim was to identify whether 16 weeks of combined training (Training) reduces blood pressure of hypertensive older adults and what the key fitness, hemodynamic, autonomic, inflammatory, oxidative, glucose and/or lipid mediators of this intervention would be. Fifty-two individuals were randomized to either 16 weeks of Training or control group who remained physically inactive (Control). Training included walking/running at 63% of V˙O2max, three times per week, and strength training, consisting of one set of fifteen repetitions (seven exercises) at moderate intensity, twice per week. Both groups underwent a comprehensive health assessment at baseline (W0) and every four weeks, for 16 weeks total. p-value ≤ 0.05 was set as significant. Training did not reduce blood pressure. It increased V˙O2max after eight weeks and again after 16 weeks (~18%), differently from the Control group. At 16 weeks, Training increased strength (~8%), slightly reduced body mass (~1%), and reduced the number of individuals with metabolic syndrome (~7%). No other changes were observed (heart rate, carotid compliance, body composition, glycemic and lipid profile, inflammatory markers and oxidative profile, vasoactive substances, heart rate variability indices). Although Training increased cardiorespiratory fitness and strength, Training was able to reduce neither blood pressure nor a wide range of mediators in hypertensive older adults, suggesting other exercise interventions might be necessary to improve overall health in this population. The novelty of this study was the time-course characterization of Training effects, surprisingly demonstrating stability among a comprehensive number of health outcomes in hypertensive older adults, including blood pressure.

Acute burn injuries associated with long-term mortality: a systematic review and meta-analysis.

BACKGROUND: Emerging evidence suggests that the pathophysiological impact of acute burn injuries may have chronic health consequences. We conducted a systematic review and meta-analysis to investigate the association between burn injuries and long-term mortality in patients surviving to initial discharge from hospital. METHODS: Medline and Embase databases were searched on 22 October 2021. Studies were eligible for inclusion if they compared long-term mortality amongst burn survivors to non-injured controls from the general population. When the same output metrics related to mortality were reported, meta-analyses were undertaken using a random effects model. Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tool. RESULTS: Following an extensive literature search, six studies (seven articles) were identified for inclusion. They were predominantly based in high-income countries, with each comparing burns' survivors to matched non-injured controls from the general population. The four studies included in the meta-analysis had a combined unadjusted odds ratio of 2.65 (1.84 - 3.81; 95 % confidence interval) and adjusted mortality rate ratio of 1.59 (1.31 - 1.93; 95 % confidence interval). Thus, burn survivors demonstrated greater mortality rates when compared to their non-injured counterparts. Similar findings were illustrated in the remaining studies not included in the meta-analysis, with the exception of one study which found no significant difference between the two groups. CONCLUSIONS: Our review suggests that acute burn injuries may be associated with greater long-term mortality rates (unadjusted and adjusted). The underlying mechanism is unclear and further work is required to establish the role of certain factors such as biological ageing processes, to improve outcomes for burn patients.

Acute low- compared to high-load resistance training to failure results in greater energy expenditure during exercise in healthy young men.

The objective of the present study was to verify the energy expenditure (EE), energy system contributions and autonomic control during and after an acute low-load or high-load resistance training (RT) protocol to momentary failure (MF) in young adults. Eleven young men (22 ± 3 yrs, 71.8 ± 7.7 kg; 1.75 ± 0.06 m) underwent a randomized crossover design of three knee extension acute protocols: a low-load RT [30% of their maximal strength (1RM); RT30] or a high-load RT (80% of 1RM; RT80) protocol, with all sets being performed to MF; or a control session (Control) without exercise. Participants were measured for EE, energy system contributions, and cardiac autonomic control before, during, and after each exercise session. Exercise EE was significantly higher for RT30 as compared to RT80. Furthermore, post measurements of blood lactate levels and the anaerobic lactic system contribution were significantly greater for RT30 as compared to RT80. In addition, parasympathetic restoration was lower for RT30 as compared to RT80. In conclusion, a low-load (30% 1RM) RT session produced higher EE during exercise than a high-load (80% 1RM) RT session to MF, and may be a good option for fitness professionals, exercise physiologists, and practitioners when choosing the optimal RT protocol that provides more EE, especially for those who want or need to lose weight.

Exercise Training Does Improve Cardiorespiratory Fitness in Post-Bariatric Surgery Patients.

Although exercise is recognized as an important component of the management for patients following bariatric surgery (BS), its effectiveness on cardiorespiratory fitness (CRF) is still unclear. To investigate this relationship between BS and CRF, a systematic review was conducted in the MEDLINE database. The literature search included studies involving exercise training in patients following BS. A total of 306 studies were identified, 7 met the criteria and were included in the meta-analysis. Exercise training was found to result in a moderate and significant increase in VO2max (SMD = 0.430, 95% CI 0.157; 0.704, p = 0.002) following BS. The results from this meta-analysis indicate that exercise training can significantly improve CRF. Further research is needed to determine the ideal training duration and exercise training parameters for patients following BS.

Acute, short-, and long-term effects of different types of exercise in central arterial stiffness: a systematic review and meta-analysis.

INTRODUCTION: The independent predictor of cardiovascular mortality, central arterial stiffness (CAS), is modulated by exercise depending on type of exercises, arteries assessed, sample features and time to exposure. Thus, this study aim to determine the endurance, resistance and combined exercise effects on CAS over time in humans. EVIDENCE ACQUISITION: MEDLINE database for studies published between January 1st, 1990 and February 3rd, 2015. Studies measuring the effects of exercise on CAS, measured by aortic pulse wave velocity or carotid arterial compliance measured by ultrasound were included. Two independent reviewers extracted the 56 studies meta-analyzed and allocated among type of exercise and time effects categories: acute (10 minutes to 24 hours post-exercise session effect), short-term (interventional studies testing basal CAS from 1 to 24 weeks of exercise) and long-term (cross-sectional studies comparing trained and untrained individuals). EVIDENCE SYNTHESIS: We calculated standard difference in means 95% CIs, applying random or fixed-effects models, according to presence or absence of true heterogeneity, respectively. Endurance exercise reduced CAS in short and long-term analysis (-0.42 [-0.53 to -0.31] and -0.62 [-0.95 to -0.29], respectively), however it did not modify CAS acutely; higher magnitude of reduction occurred in normal weight individuals, with longer duration, higher weekly frequency and continuous (rather than interval) protocols. Resistance exercise increases CAS acutely (0.30 [0.01 to 0.58]) and after long-term (0.47 [0.19 to 0.75]), while short-term resistance exercise did not modify CAS significantly. No significant effect was found for short-term combined exercises and there was not enough number of studies for acute and long-term effects to be meta-analysed. CONCLUSIONS: Endurance and resistance exercise have opposite long-term effects, being beneficial and deleterious, respectively, while the combined exercise showed to be innocuous.

Resistance Training Prevents Muscle Loss Induced by Caloric Restriction in Obese Elderly Individuals: A Systematic Review and Meta-Analysis.

It remains unclear as to what extent resistance training (RT) can attenuate muscle loss during caloric restriction (CR) interventions in humans. The objective here is to address if RT could attenuate muscle loss induced by CR in obese elderly individuals, through summarized effects of previous studies. Databases MEDLINE, Embase and Web of Science were used to perform a systematic search between July and August 2017. Were included in the review randomized clinical trials (RCT) comparing the effects of CR with (CRRT) or without RT on lean body mass (LBM), fat body mass (FBM), and total body mass (BM), measured by dual-energy X-ray absorptiometry, on obese elderly individuals. The six RCTs included in the review applied RT three times per week, for 12 to 24 weeks, and most CR interventions followed diets of 55% carbohydrate, 15% protein, and 30% fat. RT reduced 93.5% of CR-induced LBM loss (0.819 kg [0.364 to 1.273]), with similar reduction in FBM and BM, compared with CR. Furthermore, to address muscle quality, the change in strength/LBM ratio tended to be different (p = 0.07) following CRRT (20.9 ± 23.1%) and CR interventions (−7.5 ± 9.9%). Our conclusion is that CRRT is able to prevent almost 100% of CR-induced muscle loss, while resulting in FBM and BM reductions that do not significantly differ from CR.

Time-course of health-related adaptations in response to combined training in hypertensive elderly: immune and autonomic modulation interactions

This article is a methodological description of a randomized clinical trial (ClinicalTrials.gov U1111-1181-4455) aiming to evaluate the time-course (monthly) and associations between blood pressure changes and other health-related adaptations in response to exercise training in hypertensive elderly. Methods: The patients will be randomized to a control or combined training group interventions (aerobic and resistance exercise), with monthly assessments in four months. Although, the changes in baseline blood pressure is the primary clinical outcome, the secondary outcomes include: body composition, cardiorespiratory fitness, muscle strength, arterial stiffness, baroreceptor sensitivity, cardiovascular autonomic modulation, inflammatory markers, oxidative stress, growth factors, tissue remodeling markers, metabolic profile, renal function, cognitive function and quality of life. Results: To support the understanding of the blood pressure changes in hypertensive elderly, a time-course of exercise-induced adaptations including cardiovascular and immunological adaptations are fundamental for research in this field. Conclusion: To investigate the time-course of combined training-induced adaptations including all the diverse aspects of health in hypertensive elderly a well-controlled protocol design is necessary, mainly to clarify the relationship between cardiovascular and immunological exercise-induced adaptations.(AU)