Isometric Resistance Training to Manage Hypertension: Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: Hypertension is the primary risk factor for cardiovascular disease and adequate blood pressure control is often elusive. The objective of this work was to conduct a meta-analysis of trial data of isometric resistance training (IRT) studies in people with hypertension, to establish if IRT produced an anti-hypertensive effect. A database search (PubMed, CINAHL, Cochrane Central Register of Controlled Trials, and MEDLINE) identified randomised controlled and crossover trials of IRT versus a sedentary or sham control group in adults with hypertension. RECENT FINDINGS: We included 12 studies (14 intervention groups) in the meta-analyses, with an aggregate of 415 participants. IRT reduced systolic blood pressure (SBP), mean difference (MD) - 7.47 mmHg (95%CI - 10.10, - 4.84), P < 0.01; diastolic blood pressure (DBP) MD - 3.17 mmHg (95%CI - 5.29, - 1.04), P < 0.01; and mean arterial blood pressure (MAP) MD - 7.19 mmHg (95%CI - 9.06, - 5.32), P < 0.0001. Office pulse pressure and resting heart rate was not significantly reduced, neither were 24-h or day-time ambulatory blood pressures (SBP, DBP). Night-time blood pressures, however, were significantly reduced with SBP MD - 4.28 mmHg (95%CI - 7.88, - 0.67), P = 0.02, and DBP MD - 2.22 mmHg (95%CI - 3.55, - 0.88), P < 0.01. IRT does lower SBP, DBP and MAP office and night-time ambulatory SBP and DBP, but not 24-h mean ambulatory blood pressures in people with hypertension.

Rate adaptive pacing in people with chronic heart failure increases peak heart rate but not peak exercise capacity: a systematic review.

Rate adaptive cardiac pacing (RAP) allows increased heart rate (HR) in response to metabolic demand in people with implantable electronic cardiac devices (IECD). The aim of this work was to conduct a systematic review to determine if RAP increases peak exercise capacity (peak VO2) in line with peak HR in people with chronic heart failure. We conducted a systematic literature search from 1980, when IECD and RAP were first introduced, until 31 July 2021. Databases searched include PubMed, Medline, EMBASE, EBSCO, and the Clinical Trials Register. A comprehensive search of the literature produced a total of 246 possible studies; of these, 14 studies were included. Studies and subsequent analyses were segregated according to comparison, specifically standard RAP (RAPON) vs fixed rate pacing (RAPOFF), and tailored RAP (TLD RAPON) vs standard RAP (RAPON). Pooled analyses were conducted for peak VO2 and peak HR for RAPON vs RAPOFF. Peak HR significantly increased by 15 bpm with RAPON compared to RAPOFF (95%CI, 7.98-21.97, P < 0.0001). There was no significant difference between pacing mode for peak VO2 0.45 ml kg-1 min-1 (95%CI, - 0.55-1.47, P = 0.38). This systematic review revealed RAP increased peak HR in people with CHF; however, there was no concomitant improvement in peak VO2. Rather RAP may provide benefits at submaximal intensities by controlling the rise in HR to optimise cardiac output at lower workloads. HR may be an important outcome of CHF management, reflecting myocardial efficiency.

Effect of aerobic and resistance training on inflammatory markers in heart failure patients: systematic review and meta-analysis.

Elevated levels of pro-inflammatory markers are evident in patients with heart failure and are associated with disease severity and prognosis. Exercise training has been shown to reduce circulating levels of pro-inflammatory cytokines and other pro-inflammatory markers in healthy and clinical populations. The aim of the systematic review and meta-analysis was to investigate the effect of aerobic (AT) and resistance training (RT) interventions on circulating concentrations of inflammatory markers; tumour necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), C-reactive protein (CRP), fibrinogen, soluble intercellular adhesion molecule (sICAM) and soluble vascular adhesion molecule (sVCAM) in heart failure patients. We conducted database searches (PubMed, EMBASE and Cochrane Trials Register to 30 June 2017) for exercise-based trials in heart failure, using the following search terms: exercise training, inflammation, tumour necrosis factor-alpha, interleukin 6, C-reactive protein, fibrinogen, soluble intercellular adhesions molecule-1, soluble vascular adhesion molecule-1. Twenty studies, representing 18 independent trials, were included in the review. Pooled data of six studies indicated a minimally favourable effect of exercise training on circulating TNF-α [SMD 0.42 (95% CI 0.15, 0.68), p = 0.002)]. However, together the pooled and descriptive analyses failed to provide strong evidence for a reduction in other pro-inflammatory markers. However, given the complexity of heart failure and the pathways involved in the immune and inflammatory process, large prospective trials considering aetiology, comorbidities and local skeletal muscle inflammation are required to elucidate on the anti-inflammatory effect of exercise in this population.

Effect of exercise training on liver function in adults who are overweight or exhibit fatty liver disease: a systematic review and meta-analysis.

OBJECTIVE: Exercise training has been shown to have beneficial effects on liver function in adults overweight or with fatty liver disease. To establish which exercise programme characteristics were likely to elicit optimal improvements. DESIGN: Systematic review and meta-analysis of randomised, controlled trials. DATA SOURCES: PubMed, CINAHL and Cochrane controlled trials registry searched (1966 to 2 October 2015). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Exercise intervention, with or without dietary intervention, versus usual care in adults undertaking, exercise training, who were overweight, obese or exhibited fatty liver disease (non-alcoholic fatty liver disease or non-alcoholic steatohepatitis). RESULTS: We included 21 randomised controlled trials, totalling 1530 participants. Exercise intervention studies with total exercise programme workload >10 000 kcal produced significant improvements in intrahepatic fat, -3.46% (95% CI -5.20% to -1.73%), p<0.0001, I2=73%; effect size (standardised mean difference, SMD) -1.77 (-3.11 to -0.42), p=0.01, I2=77%. When data from only exercise studies were pooled, there was a reduction in fasting free fatty acids (FFAs) -74.15 µmol/L (95% CI -118.47 to -29.84), p=0.001, I2=67% with a large effect size (SMD) -0.94 (-1.36 to -0.52), p<0.0001, I2=0%. When data from only exercise studies were pooled, there was a significant reduction in insulin MD -1.88 UL (95% CI -3.43 to -0.34), p=0.02, I2=31%. The liver enzymes, alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transpeptidase, were not significantly altered with exercise. CONCLUSIONS: Exercise training reduces intrahepatic fat and FFAs while increasing cardiorespiratory fitness. An aggregate exercise programme energy expenditure (>10 000 kcal) may be required to promote reductions in intrahepatic fat.

Exercise therapy and autonomic function in heart failure patients: a systematic review and meta-analysis.

A large body of evidence exists indicating that autonomic imbalance is characteristic of heart failure, with several parameters of autonomic function associated with adverse clinical outcomes. The aim of this systematic review and meta-analysis was to investigate the effects of exercise training on parameters of autonomic function in patients with heart failure and where possible quantify the size of the effect. We conducted database searches (PubMed, EMBASE and Cochrane Trials Register to 31 March 2017) for exercise-based rehabilitation trials in heart failure; using search terms, exercise training, autonomic function, heart rate recovery, heart rate variability and muscle sympathetic nerve activity. Pooled data indicated a statistically significant increase in heart rate recovery at 1 min (HRR1) in exercise compared to control groups, mean difference 5.90 bpm (95%CI 5.12, 6.69; p < 0.00001). Pooled data also indicated that exercise training improved the short-term heart rate variability (HRV) parameters of root mean square of successive differences between normal heart beats (RMSSD (ms)) [mean difference 10.44 (95%CI 0.60, 20.28, p = 0.04)] and high-frequency normalised units (HFnu) [mean difference 7.72 (95%CI 3.32, 12.12, p = 0.0006), which are predominantly reflective of parasympathetic activity. Analyses also indicated a statistically significant decrease in muscle sympathetic nerve activity (MSNA) bursts/minute (mean difference - 11.09 (95%CI - 16.18, - 6.00; p < 0.0001) and MSNA bursts/100 heart beats (mean difference - 15.44 (95%CI - 20.95, -9.92; p < 0.00001) in exercise groups compared to controls. With improvements in HRR, HRV and MSNA, exercise training appears to facilitate an improvement in parasympathetic tone and reduction in sympathetic activity.

Clinical outcomes to exercise training in type 1 diabetes: A systematic review and meta-analysis.

AIMS: To establish the relationship between exercise training and clinical outcomes in people with type I diabetes. METHODS: Studies were identified through a MEDLINE search strategy, Cochrane Controlled Trials Registry, CINAHL, SPORTDiscus and Science Citation Index. The search strategy included a mix of key concepts related to trials of exercise training in people with type 1 diabetes; glycaemic control. Searches were limited to prospective randomized or controlled trials of exercise training in humans with type 1 diabetes lasting 12  weeks or more. RESULTS: In exercised adults there were significant improvements in body mass Mean Difference (MD): -2.20 kg, 95% Confidence Interval (CI) -3.79-0.61, p = .007; body mass index (BMI) MD: -0.39 kg/m2, 95% CI -0.75-0.02, p = .04; Peak VO2 MD: 4.08 ml/kg/min, 95% CI -2.18-5.98, p < .0001; and, low-density lipoprotein cholesterol (LDL) MD: -0.21 mmol/L, 95% CI -0.33-0.08, p = .002. In exercised children there were significant improvements in insulin dose MD: -0.23 IU/kg, 95% CI -0.37-0.09, p = .002; waist circumference MD: -5.40 cm, 95% CI -8.45 to -2.35, p = .0005; LDL MD: -0.31 mmol/L, 95% CI -0.55 to -0.06, p = .02; and, triglycerides MD: -0.21 mmol/L, 95% CI -0.42 to -0.01, p = .04. There were no significant changes in glycosylated haemoglobin (HbA1C%), fasting blood glucose, resting heart rate, resting systolic blood pressure or high density lipoproteins in either group. CONCLUSIONS: Exercise training improves some markers of type 1 diabetes severity; particularly body mass, BMI, Peak VO2 and LDL in adults and insulin dose, waist circumference, LDL and triglycerides in children.

The effect of exercise training on clinical outcomes in patients with the metabolic syndrome: a systematic review and meta-analysis.

BACKGROUND: Purpose: to establish if exercise training improves clinical outcomes in people with metabolic syndrome (MetS). Registered with PROSPERO international prospective register of systematic reviews ( https://www.crd.york.ac.uk/PROSPERO/Identifier:CRD42017055491 ). DATA SOURCES: studies were identified through a MEDLINE search strategy (1985 to Jan 12, 2017), Cochrane controlled trials registry, CINAHL and SPORTDiscus. STUDY SELECTION: prospective randomized or controlled trials of exercise training in humans with metabolic syndrome, lasting 12 weeks or more. RESULTS: We included 16 studies with 23 intervention groups; 77,000 patient-hours of exercise training. In analyses of aerobic exercise studies versus control: body mass index was significantly reduced, mean difference (MD) -0.29 (kg m-2) (95% CI -0.44, -0.15, p < 0.0001); body mass was significantly reduced, MD -1.16 kg (95% CI -1.83, -0.48, p = 0.0008); waist circumference was significantly reduced MD -1.37 cm (95% CI -2.02, -0.71, p < 0.0001), peak VO2 was significantly improved MD 3.00 mL kg-1 min-1 (95% CI 1.92, 4.08, p < 0.000001); systolic blood pressure and diastolic blood pressure were significantly reduced, MD -2.54 mmHg (95% CI -4.34, -0.75, p = 0.006), and, MD -2.27 mmHg (95% CI -3.47, -1.06, p = 0.0002) respectively; fasting blood glucose was significantly reduced MD -0.16 mmol L-1 (95% CI -0.32, -0.01, p = 0.04); triglycerides were significantly reduced MD -0.21 mmol L-1 (95% CI -0.29, -0.13, p < 0.00001); and low density lipoprotein was significantly reduced MD -0.03 mmol L-1 (95% CI -0.05, -0.00, p = 0.02). In analyses of combined exercise versus control: waist circumference, MD -3.80 cm (95% CI -5.65, -1.95, p < 0.0001); peak VO2 MD 4.64 mL kg-1 min-1 (95% CI 2.42, 6.87, p < 0.0001); systolic blood pressure MD -3.79 mmHg (95% CI -6.18, -1.40, p = 0.002); and high density lipoprotein (HDL) MD 0.14 (95% CI 0.04, 0.25, p = 0.009) were all significantly improved. We found no significant differences between outcome measures between the two exercise interventions. CONCLUSIONS: Exercise training improves body composition, cardiovascular, and, metabolic outcomes in people with metabolic syndrome. For some outcome measures, isolated aerobic exercise appears optimal.

Aerobic Training Intensity for Improved Endothelial Function in Heart Failure Patients: A Systematic Review and Meta-Analysis.

Objective. Flow-mediated dilation (FMD) is widely utilised to assess endothelial function and aerobic exercise improves FMD in heart failure patients. The aim of this meta-analysis is to quantify the effect of aerobic training intensity on FMD in patients with heart failure. Background. A large number of studies now exist that examine endothelial function in patients with heart failure. We sought to add to the current literature by quantifying the effect of the aerobic training intensity on endothelial function. Methods. We conducted database searches (PubMed, Embase, ProQuest, and Cochrane Trials Register to June 30, 2016) for exercise based rehabilitation trials in heart failure, using search terms exercise training, endothelial function, and flow-mediated dilation (FMD). Results. The 13 included studies provided a total of 458 participants, 264 in intervention groups, and 194 in nonexercising control groups. Both vigorous and moderate intensity aerobic training significantly improved FMD. Conclusion. Overall both vigorous and moderate aerobic exercise training improved FMD in patients with heart failure.

Effect of exercise on diastolic function in heart failure patients: a systematic review and meta-analysis.

Diastolic dysfunction contributes to the development and progression of heart failure. Conventional echocardiography and tissue Doppler imaging are widely utilised in clinical research providing a number of indices of diastolic function valuable in the diagnosis and prognosis of heart failure patients. The aim of this meta-analysis was to quantify the effect of exercise training on diastolic function in patients with heart failure. Exercise training studies that investigate different indices of diastolic function in patients with heart failure have reported that exercise training improves diastolic function in these patients. We sought to add to the current literature by quantifying, where possible, the effect of exercise training on diastolic function. We conducted database searches (PubMed, EBSCO, EMBASE, and Cochrane Trials Register to 31 July 2016) for exercise based rehabilitation trials in heart failure, using the search terms 'exercise training, diastolic function and diastolic dysfunction'. Data from six studies, with a total of 266 heart failure with reduced ejection fraction (HFrEF) participants, 144 in intervention groups and 122 in control groups, indicated a significant reduction in the ratio of early diastolic transmitral velocity (E) to early diastolic tissue velocity (E') (E/E' ratio) with exercise training, exercise vs. control mean difference (MD) of -2.85 (95% CI -3.66 to -2.04, p < 0.00001). Data from five studies in heart failure with preserved ejection fraction (HFpEF) patients, with a total of 204 participants, 115 in intervention groups and 89 in control groups, also demonstrated a significant improvement in E/E' in exercise vs. control MD of -2.38 (95% CI -3.47 to -1.28, p < 0.0001).

Effect of exercise training on endothelial function in heart failure patients: A systematic review meta-analysis.

OBJECTIVE: Endothelial dysfunction contributes to the development and progression of cardiovascular disease and heart failure (HF) and is associated with an increased risk of mortality. Flow-mediated dilation (FMD) is widely utilised to assess endothelial function and is improved with exercise training in heart failure patients. The aim of this meta-analysis is to quantify the effect of exercise training in patients with heart failure. BACKGROUND: A large number of studies now exist that have examined endothelial function in patients with heart failure. We sought to add to the current literature by quantifying the effect of exercise training on endothelial function. METHODS: We conducted database searches (PubMed, EMBASE, PROQUEST and Cochrane Trials Register to June 2016) for exercise based rehabilitation trials in heart failure, using search terms exercise training, endothelial function, flow-mediated dilation (FMD) and endothelial progenitor cells (EPCs). RESULTS: The 16 included studies provided a total of 529 participants, 293 in an intervention and 236 in controls groups. FMD was improved with exercise training in exercise vs. control, SMD of 1.08 (95%CI 0.70 to 1.46, p<0.00001). CONCLUSION: Overall exercise training improved endothelial function, assessed via FMD, and endothelial progenitor cells in heart failure patients.

Remote ischaemic conditioning in the context of type 2 diabetes and neuropathy: the case for repeat application as a novel therapy for lower extremity ulceration.

An emerging treatment modality for reducing damage caused by ischaemia-reperfusion injury is ischaemic conditioning. This technique induces short periods of ischaemia that have been found to protect against a more significant ischaemic insult. Remote ischaemic conditioning (RIC) can be administered more conveniently and safely, by inflation of a pneumatic blood pressure cuff to a suprasystolic pressure on a limb. Protection is then transferred to a remote organ via humoral and neural pathways. The diabetic state is particularly vulnerable to ischaemia-reperfusion injury, and ischaemia is a significant cause of many diabetic complications, including the diabetic foot. Despite this, studies utilising ischaemic conditioning and RIC in type 2 diabetes have often been disappointing. A newer strategy, repeat RIC, involves the repeated application of short periods of limb ischaemia over days or weeks. It has been demonstrated that this improves endothelial function, skin microcirculation, and modulates the systemic inflammatory response. Repeat RIC was recently shown to be beneficial for healing in lower extremity diabetic ulcers. This article summarises the mechanisms of RIC, and the impact that type 2 diabetes may have upon these, with the role of neural mechanisms in the context of diabetic neuropathy a focus. Repeat RIC may show more promise than RIC in type 2 diabetes, and its potential mechanisms and applications will also be explored. Considering the high costs, rates of chronicity and serious complications resulting from diabetic lower extremity ulceration, repeat RIC has the potential to be an effective novel advanced therapy for this condition.

The effect of resistance training on clinical outcomes in heart failure: A systematic review and meta-analysis.

OBJECTIVES: To quantify the change in effect sizes, for selected clinical outcome measures, in people with heart failure, from resistance exercise, either in isolation, or in combination with aerobic training. BACKGROUND: Most exercise training data in heart failure, relates to aerobic exercise, we sought to provide current evidence for the benefits of resistance training in this population. METHODS: We conducted a MEDLINE search (1985 to May 1, 2016), for exercise based rehabilitation trials in heart failure, using search terms 'resistance training, combined training, left ventricular dysfunction, peak VO2, cardio-myopathy and systolic heart dysfunction'. RESULTS: The 27 included studies provided a total of 2321 participants, 1172 in an intervention and 1149 in either sedentary controls or aerobic exercise only groups, producing over 31,263 patient-hours of training. Mortality, hospitalization, resting blood pressure and Left ventricular fraction were all unchanged with resistance or combined aerobic and resistance training. Peak VO2 was improved in combined exercise vs. control MD of 1.43ml·kg(-1)·min(-1) (95% CI 0.63, 2.23, p=0.0004; and in resistance vs. control MD 3.99ml·kg(-1)·min(-1) (95% CI 1.47, 6.51, p=0.002). Quality of Life (MLwHFQ) was improved in combined vs. control MD -8.31 (95% CI -14.3, -2.33, p=0.006). Six-minute walk distance was improved combined exercise vs. control, MD 13.49m (95% CI 1.13, 25.84, p=0.03); and resistance vs. control MD 41.77m (95% CI 21.90, 61.64, p<0.0001): SMD 1.25 (95%CI 0.53, 1.98, p=0.0007). CONCLUSIONS: Resistance only or combined training improves peak VO2, quality of life and walking performance in heart failure patients.

Clinically meaningful blood pressure reductions with low intensity isometric handgrip exercise. A randomized trial.

There exists no examination of what is the minimum anti-hypertensive threshold intensity for isometric exercise training. Twenty two normotensive participants were randomly assigned to training intensities at either 5 % or 10 % of their maximal contraction. Twenty participants completed the study. Clinical meaningful, but not statistically significant, reductions in systolic blood pressure were observed in both 5 % and 10 % groups -4.04 mm Hg (95 % CI -8.67 to +0.59, p=0.08) and -5.62 mm Hg (95 % CI -11.5 to +0.29, p=0.06) respectively after 6 weeks training. No diastolic blood pressure reductions were observed in either 5 % -0.97 mm Hg (95 % CI -2.56 to +0.62, p=0.20) or 10 % MVC +1.8 mm Hg (95 % CI -1.29 to +4.89, p=0.22) groups respectively after training. In those unable to complete isometric exercise at the traditional 30 % intensity, our results suggest there is no difference between 5 and 10 % groups and based on the principle of regression to the mean, this could mean both interventions induce a similar placebo-effect.

Predicting blood flow responses to rhythmic handgrip exercise from one second isometric contractions.

The aim of this work was to predict blood flow responses to rhythmic handgrip exercise from one second isometric contractions. Seven healthy men were studied. Each subject performed a single 1 s handgrip contraction at 10 %, 20 % and 40 % of the maximum handgrip strength. We then repeatedly summed hyperaemic responses from single contractions to predict hyperaemic response to a prolonged bout of rhythmic exercise. There was similarity between steady state brachial blood flow velocity (BBV) extrapolated from single handgrip contractions and during 2 min of rhythmic exercise for 20 % (10.0+/-3.8 cm/s vs. 10.2+/-2.6 cm/s, r=0.93, p=0.003) and 40 % of maximum contractions (14.2+/-5.5 cm/s vs. 15.6+/-3.4 cm/s, r=0.88, p=0.009), but not for 10 % (7.5+/-4.1 cm/s vs. 5.7+/-3.3 cm/s, r=0.94, p=0.018). BBV progressively rose substantially higher during rhythmic contractions than peak BBV observed during single contractions at matched intensity. Respective peak BBV during single contractions and steady state BBV rhythmic contractions were 4.4+/-2.1 and 5.7+/-3.3 cm.s(-1) at 10 % forearm strength (p=0.14), 5.6+/-2.4 and 10.2+/-2.8 cm.s(-1) at 20 % (p=0.002), and 7.0+/-2.5 and 15.6+/-3.6 cm.s(-1) at 40 % (p=0.003). In conclusion, there is similarity between the summated blood flow velocity calculated from a single 1 s muscle contraction and the steady state blood flow velocity response of rhythmic exercise.

Repeat remote ischaemic pre-conditioning for improved cardiovascular function in humans: A systematic review.

BACKGROUND: Single exposure to remote ischaemic pre-conditioning (RIPC) has been shown to be effective in reducing major adverse events during cardiac surgery. We evaluated the efficacy of repeated exposure RIPC to elicit improvements in cardiovascular function. METHODS: A systematic search was conducted up until May 1st, 2015, using the following databases: EMBASE, PubMed (Medline), Web of Science and the Cochrane Central Registry of Controlled Trials (CENTRAL). Data was extracted and synthesized from published studies of repeat RIPC. RESULTS: Data from seven studies showed evidence of improvements in vascular function and anti-hypertensive effects of systolic, diastolic and mean arterial blood pressure following repeat RIPC. Currently existing work justifies a systematic review but not data pooling of individual study data. Repeat RIPC has also produced evidence of improvements in endothelial dependent vasodilation, but not non-endothelial dependent vasodilation, cutaneous vascular conductance or cardiorespiratory fitness. CONCLUSION: Repeated RIPC exposure has produced evidence of improvements in endothelial dependent vasodilation, ulcer healing and blood pressure but no benefit in non-endothelial dependent vasodilation, cutaneous vascular conductance or cardiorespiratory fitness. The optimal delivery of RIPC remains unclear, but at least 3 or preferably 4, 5 min exposures appears to be most beneficial, at least for reducing blood pressure. Aside from those undertaking cardiac surgery, other study populations with endothelial dysfunction may benefit from repeat exposure to RIPC.

An updated view of leptin on implantation and pregnancy: a review.

The hormone leptin, which is thought to be primarily produced by adipose tissue, is a polypeptide that was initially characterized by its ability to regulate food intake and energy metabolism. Leptin appears to signal the status of body energy stores to the brain, resulting in the regulation of food intake and whole-body energy expenditure. Subsequently, it was recognized as a cytokine with a wide range of peripheral actions and is involved in the regulation of a number of physiological systems including reproduction. In the fed state, leptin circulates in the plasma in proportion to body adiposity in all species studied to date. However other factors such as sex, age, body mass index (BMI), sex steroids and pregnancy may also affect leptin levels in plasma. In pregnant mice and humans, the placenta is also a major site of leptin expression. Leptin circulates in biological fluids both as free protein and in a form that is bound to the soluble isoform of its receptor or other binding proteins such as one of the immunoglobulin superfamily members Siglec-6 (OB-BP1). Although the actions of leptin in the control of reproductive function are thought to be exerted mainly via the hypothalamic-pituitary-gonadal axis, there have also been reports of local direct effects of leptin at the peripheral level, however, these data appear contradictory. Therefore, there is a need to summarize the current status of research outcomes and analyze the possible reasons for differing results and thus provide researchers with new insight in designing experiments to investigate leptin effect on reproduction. Most importantly, our recent experimental data suggesting that reproductive performance is improved by decreasing concentrations of peripheral leptin was unexpected and cannot be explained by hypotheses drawn from the experiments of excessive exogenous leptin administration to normal animals or ob/ob mice.

Individual patient meta-analysis of exercise training effects on systemic brain natriuretic peptide expression in heart failure.

BACKGROUND: Brain natriuretic peptide (BNP) predicts exercise performance and exercise training may modulate BNP and its N-terminal portion (NT-pro-BNP), we therefore conducted an individual patient analysis of exercise training effects on BNP and NT-pro-BNP. AIMS: To use an individual patient meta-analysis to relate changes in BNP, NT-pro-BNP, and peak VO(2); to link these changes to volume parameters of exercise training programmes (intensity etc.); and to identify patient characteristics likely to lead to greater improvements in BNP, NT-pro-BNP, and peak VO(2). DESIGN: Individual patient meta-analysis. METHODS: A systematic search was conducted of Medline (Ovid), Embase.com, Cochrane Central Register of Controlled Trials, and CINAHL (until July 2008) to identify randomized controlled trials of aerobic and/or resistance exercise training in systolic heart failure patients measuring BNP and/or NT-pro-BNP. Primary outcome measures were change in BNP, NT-pro-BNP, and peak VO2. Subanalyses were conducted to identify (1) patient groups that benefit most and (2) exercise programme parameters enhancing favourable changes in primary outcome measures. RESULTS: Ten randomized controlled studies measuring BNP or NT-pro-BNP met eligibility criteria, authors provided individual patient data for 565 patients (313 exercise and 252 controls). Exercise training had favourable effects on BNP (-28.3%, p < 0.0001), NT-pro-BNP (-37.4%, p = < 0.0001), and peak VO(2) (17.8%, p < 0.0001). The analysis showed a significant change in primary outcome measures; moreover, change in BNP (r = -0.31, p < 0.0001) and NT-pro-BNP (r = -0.22, p < 0.0001) were correlated with peak VO(2) change. CONCLUSION: Exercise training has favourable effects on BNP, NT-pro-BNP, and peak VO(2) in heart failure patients and BNP/NT-pro-BNP changes were correlated with peak VO(2) changes.

Systematic review of the effect of aerobic and resistance exercise training on systemic brain natriuretic peptide (BNP) and N-terminal BNP expression in heart failure patients.

BACKGROUND: BNP and the N-terminal portion (NT-pro-BNP) have emerged as powerful tools in the diagnosis and prognosis of heart failure on acute presentation. The aim of this work was to systematically review the effect of exercise training on BNP and NT-pro-BNP levels in patients with left ventricular dysfunction. METHODS: A systematic search was conducted of Medline (Ovid) (1950-July 2008), Embase.com (1974-current), Cochrane Central Register of Controlled Trials, CINAHL (1981-current) and Web of Science (2000-current) to identify randomized controlled trials of aerobic and/or resistance exercise training in heart failure patients that measured BNP and/or pro-BNP. Primary outcome measures were changes in BNP and NT-pro-BNP. Secondary outcomes were changes in functional capacity and energy expenditure, measures of study quality were also recorded. RESULTS: Nine randomized controlled studies measuring BNP or NT-pro-BNP met our eligibility criteria. Exercise training had a favourable effect on BNP (mean difference -79 pg/ml 95% C.I. -141 to - 17 pg/ml, P=0.01) and NT-pro-BNP (mean difference -621 pg/ml, 95% C.I. -844 to -398 pg/ml, P=<0.00001). Moreover the trials that showed a significant change in NT-pro-BNP all had a weekly exercise energy expenditure of more than 400 Kcal. CONCLUSION: Data from nine published studies, suggest exercise training has a favorable effect on BNP and NT-pro-BNP in heart failure patients.