Accurate Prediction Equations for Ventilatory Thresholds in Cardiometabolic Disease When Gas Exchange Analysis is Unavailable: Development and Validation.

AIMS: To develop and validate equations predicting heart rate (HR) at the first and second ventilatory thresholds (VTs) and an optimized range-adjusted prescription for patients with cardiometabolic disease (CMD). To compare their performance against guideline-based exercise intensity domains. METHODS: Cross-sectional study involving 2,868 CMD patients from nine countries. HR predictive equations for first and second VTs (VT1, VT2) were developed using multivariate linear regression with 975 cycle-ergometer cardiopulmonary exercise tests (CPET). 'Adjusted' percentages of peak HR (%HRpeak) and HR reserve (%HRR) were derived from this group. External validation with 1,893 CPET (cycle-ergometer or treadmill) assessed accuracy, agreement, and reliability against guideline-based %HRpeak and %HRR prescriptions using mean absolute percentage error (MAPE), Bland-Altman analyses, intraclass correlation coefficients (ICC). RESULTS: HR predictive equations (R²: 0.77 VT1, 0.88 VT2) and adjusted %HRR (VT1: 42%, VT2: 77%) were developed. External validation demonstrated superiority over widely used guideline-directed intensity domains for %HRpeak and %HRR. The new methods showed consistent performance across both VTs with lower MAPE (VT1: 7.1%, VT2: 5.0%), 'good' ICC for VT1 (0.81, 0.82) and 'excellent' for VT2 (0.93). Guideline-based exercise intensity domains had higher MAPE (VT1: 6.8%-21.3%, VT2: 5.1%-16.7%), 'poor' to 'good' ICC for VT1, and 'poor' to 'excellent' for VT2, indicating inconsistencies related to specific VTs across guidelines. CONCLUSION: Developed and validated HR predictive equations and the optimized %HRR for CMD patients for determining VT1 and VT2 outperformed the guideline-based exercise intensity domains and showed ergometer interchangeability. They offer a superior alternative for prescribing moderate intensity exercise when CPET is unavailable.

Equations to predict heart rate at ventilatory thresholds were developed and externally validated, offering a new perspective when a cardiopulmonary exercise test is unavailable to accurately determine the aerobic exercise intensity domains. Additionally, an adjusted range for exercise intensity prescription based on the percentage of heart rate reserve (%HRR) was provided, utilizing a large sample from eight countries. The proposed equations and the range-adjusted %HRR significantly outperformed the guideline-directed methods for determining exercise intensity, exhibiting higher accuracy, agreement, and reliability. Exercise intensity prescription based on the percentage of heart rate peak showed higher errors, raising concerns about its clinical applicability. Our study may enhance the efficacy of exercise training and physical activity advice when gas exchange analysis is unavailable, potentially leading to improved clinical outcomes, even in low-resource settings. Employing these approaches in research could facilitate more tailored and consistent interventions, introducing a contemporary perspective for studies comparing exercise intensity prescriptions.

Lifestyle management of hypertension: International Society of Hypertension position paper endorsed by the World Hypertension League and European Society of Hypertension.

Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools.

Physiological responses during walking in men and women with intermittent claudication

ABSTRACT Objective Peak oxygen consumption (VO2peak), anaerobic threshold, walking economy, and cardiovascular responses during walking are used to guide and monitor walking training in patients with peripheral artery disease and intermittent claudication. Women with peripheral artery disease and intermittent claudication present greater impairments than men, and evaluating training markers according to sex for decisions regarding walking prescription in this population is important. This study aimed to compare VO2peak, walking economy, anaerobic threshold, and cardiovascular responses during walking in men and women with peripheral artery disease and intermittent claudication. Methods Forty patients (20 men and 20 women with similar baseline characteristics) underwent a cardiopulmonary treadmill test (3.2km/h and 2% increase in slope every 2 minutes until maximal leg pain). The VO2 and rate-pressure product were assessed. Data from men and women were compared using t-tests. Results There were no significant differences between men and women (VO2peak: 15.0±4.8 versus 13.9±2.9mL∙kg-1∙min-1, p=0.38; walking economy: 9.6±2.7 versus 8.4±1.6mL∙kg-1∙min-1, p=0.09; anaerobic threshold: 10.5±3.2 versus 10.5±2.2mL∙kg-1∙min-1, p=0.98; rate pressure product at 1st stage: 13,465± 2,910 versus 14,445±4,379bpm∙mmHg, p=0.41; and rate pressure product at anaerobic threshold:13,673±3,100 versus 16,390±5,870bpm∙mmHg, p=0.08 and rate pressure product at peak exercise: 21,253±6,141 versus 21,923±7,414bpm∙mmHg, p=0.76, respectively). Conclusion Men and women with peripheral artery disease and similar baseline characteristics presented similar responses to walking, suggesting that decisions regarding walking prescription and monitoring can be made regardless of sex in this specific population.

The Use of Near Infrared Spectroscopy to Evaluate the Effect of Exercise on Peripheral Muscle Oxygenation in Patients with Lower Extremity Artery Disease: A Systematic Review.

OBJECTIVE: Near infrared spectroscopy (NIRS) has been suggested as a new diagnostic tool in patients with lower extremity artery disease (LEAD). The aim of this systematic review was to summarise the impact of exercise therapy on lower limb muscle oxygenation, evaluated by NIRS, in patients with LEAD, and to give an overview on NIRS instruments and methodology. DATA SOURCES: MEDLINE and Embase. REVIEW METHODS: A systematic search was conducted in MEDLINE and Embase, from the earliest date available until 16 March 2020, to identify peer reviewed studies involving the use of NIRS in the evaluation of exercise training on muscle oxygenation in patients with LEAD. Primary outcomes were NIRS derived variables during treadmill exercise. Effect sizes were calculated as standardised mean differences. Assessment of methodological quality was done using a combined checklist from the Cochrane bias and the quality assessment tool for before and after studies without a control group. RESULTS: Eleven original trials were included involving 16 exercise groups and four control groups. Tissue saturation index (TSI) at rest remained unchanged following the exercise interventions. Exercise training increased time to minimum TSI during exercise (range effect sizes: +0.172 to +0.927). In addition, exercise training led to a faster recovery to half and full TSI rest values in most intervention groups (range effect sizes -0.046 to -0.558 and -0.269 to -0.665, respectively). Finally, NIRS data reproducibility and analytic methods were under reported in the included studies. CONCLUSION: The available data suggest that exercise training improves de-oxygenation and re-oxygenation patterns, as measured with NIRS, in patients with LEAD. Whereas NIRS is a promising tool in the evaluation of LEAD, the low number of randomised controlled trials, as well as large heterogeneity in NIRS assessment methods, outcome measures, and instrumentation, warrants more research to better understand the role of muscle oxygenation associated with exercise induced improvements in walking capacity.

Cardiovascular Responses during and after Maximal Walking in Men and Women with Symptomatic Peripheral Artery Disease.

BACKGROUND: Walking is recommended for patients with peripheral arterial disease (PAD). It has been shown that patients with PAD present sharper increases in blood pressure (BP) and heart rate (HR) during maximal walking when compared with healthy subjects. Additionally, women with PAD present a worse physiological profile, and it is possible that they may present higher cardiovascular load during and after a bout of maximal walking than men. Thus, the objective of this study was to compare cardiovascular and autonomic responses during and after maximal walking between men and women with PAD and intermittent claudication (IC). METHODS: Forty patients with PAD and IC (20 men and 20 women) underwent, in random order, 2 sessions: control (standing on treadmill) and exercise (maximal treadmill walking test with Gardner's protocol). During the exercise, HR and BP were measured. Before and after the sessions, cardiovascular variables (BP HR, cardiac output, peripheral vascular resistance, and stroke volume) and autonomic modulation (HR and BP variabilities and baroreflex sensitivity) were assessed. In addition, an ambulatory BP monitoring was recorded after each session. RESULTS: Men and women presented similar maximal walking capacity. During the walking test, HR and systolic BP increased similarly in men and women. After the maximal walking, cardiovascular and autonomic responses did not differ between the genders. In addition, postintervention ambulatory BP parameters were also similar in men and women. Therefore, in men and women, maximal walking similarly reduced clinic systolic BP and stroke volume, and increased HR and total power of HR variability during the recovery period. CONCLUSIONS: Men and women with PAD and IC present similar cardiovascular and autonomic responses during and after maximal walking.

Towards Optimized Care After Bariatric Surgery by Physical Activity and Exercise Intervention: a Review.

Although there is growing evidence on the importance of physical activity and exercise intervention after bariatric surgery, it remains to be clarified as to why and how post-operative exercise intervention should be implemented. In this narrative and practically oriented review, it is explained why exercise interventions and physical activity are important after bariatric surgery, how to prescribe exercise and monitor physical activity and how and when physical fitness, muscle strength, fat (-free) mass and bone mineral density could be assessed during follow-up. It is suggested that the inclusion of physical activity and exercise training in the clinical follow-up trajectory could be of great benefit to bariatric surgery patients, since it leads to greater improvements in body composition, bone mineral density, muscle strength and physical fitness.

The Impact of Supervised Exercise Training on Traditional Cardiovascular Risk Factors in Patients With Intermittent Claudication: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with intermittent claudication (IC) are at increased risk of cardiovascular (CV) morbidity and mortality. Whereas extensive evidence supports the beneficial effects of supervised exercise training (SET) on walking capacity, little is known about the effect of SET on the CV risk profile of IC patients. Therefore, the aim was to evaluate the effects of SET on CV risk factors in IC patients by using meta-analysis techniques. METHODS: A systematic search in the electronic databases MEDLINE, EMBASE, CINAHL, and CENTRAL was conducted from the earliest date available until October 2, 2018. Randomised and non-randomised controlled trials lasting ≥ four weeks and investigating the effect of SET on CV risk factors in IC patients were included. Traditional CV risk factors were studied as primary outcomes; pain free walking distance (PFWD) and maximum walking distance (MWD) were included as secondary outcomes. Data were pooled using random effects models with summary data reported as weighted means and 95% confidence interval (CIs). RESULTS: Fifteen trials were included, involving 18 study groups (nine walking, four resistance, two aerobic training, and three combined groups), totalling 725 patients (mean age 66.3 years; mean ankle brachial index, 0.64). Exercise reduced systolic blood pressure (-5.8 mmHg; CI -9.89 to 1.67, p < .01) whereas all other CV risk factors (i.e., body weight, body mass index, diastolic blood pressure, and blood lipids) remained statistically unaltered. Exercise also improved PFWD (+132 m; CI 70-194, p < .001) and MWD (+183 m; CI 98-268, p < .001). CONCLUSION: This meta-analysis supports the beneficial effects of SET on walking capacity. Little evidence for an improvement of the CV risk profile was found following exercise in patients with IC. However, given the scarcity of data, high quality RCTs that include an assessment of CV risk factors are urgently required to determine the effect of exercise therapy in the secondary prevention of CV disease of IC patients.

Aerobic Interval vs. Continuous Training in Patients with Coronary Artery Disease or Heart Failure: An Updated Systematic Review and Meta-Analysis with a Focus on Secondary Outcomes.

BACKGROUND: In a previous meta-analysis including nine trials comparing aerobic interval training with aerobic continuous training in patients with coronary artery disease, we found a significant difference in peak oxygen uptake favoring aerobic interval training. OBJECTIVE: The objective of this study was to (1) update the original meta-analysis focussing on peak oxygen uptake and (2) evaluate the effect on secondary outcomes. METHODS: We conducted a systematic review with a meta-analysis by searching PubMed and SPORTDiscus databases up to March 2017. We included randomized trials comparing aerobic interval training and aerobic continuous training in patients with coronary artery disease or chronic heart failure. The primary outcome was change in peak oxygen uptake. Secondary outcomes included cardiorespiratory parameters, cardiovascular risk factors, cardiac and vascular function, and quality of life. RESULTS: Twenty-four papers were identified (n = 1080; mean age 60.7 ± 10.7 years). Aerobic interval training resulted in a higher increase in peak oxygen uptake compared with aerobic continuous training in all patients (1.40 mL/kg/min; p < 0.001), and in the subgroups of patients with coronary artery disease (1.25 mL/kg/min; p = 0.001) and patients with chronic heart failure with reduced ejection fraction (1.46 mL/kg/min; p = 0.03). Moreover, a larger increase of the first ventilatory threshold and peak heart rate was observed after aerobic interval training in all patients. Other cardiorespiratory parameters, cardiovascular risk factors, and quality of life were equally affected. CONCLUSION: This meta-analysis adds further evidence to the clinically significant larger increase in peak oxygen uptake following aerobic interval training vs. aerobic continuous training in patients with coronary artery disease and chronic heart failure. More well-designed randomized controlled trials are needed to establish the safety of aerobic interval training and the sustainability of the training response over longer periods.

Test-Retest Reliability of Maximal and Submaximal Gas Exchange Variables in Patients With Coronary Artery Disease.

PURPOSE: Gas exchange variables derived from cardiopulmonary exercise tests (CPETs) need to be reliable for evaluating interventions and clinical decision making. Whereas peak oxygen uptake ((Equation is included in full-text article.)O2) has shown to be a highly reliable parameter in patients with coronary artery disease (CAD), little is known about the reproducibility of these parameters in patients with CAD. Therefore, the purpose of this study was to confirm the reliability of peak (Equation is included in full-text article.)O2 and to investigate the reliability of submaximal CPET variables in patients with CAD. METHODS: Eighty-five patients with CAD (57.6 ± 8.5 years; 79 males) performed 2 CPETs within 10 days before starting a rehabilitation program. Reliability of peak and submaximal exercise variables was assessed by using intraclass correlation coefficients (ICC), coefficients of variation, Pearson correlation coefficients, paired t tests, and Bland-Altman plots. RESULTS: Maximal and submaximal exercise parameters showed adequate reliability. Overall, there was a good correlation across both testing occasions (r = 0.63-0.95; P < .05 for all). Peak (Equation is included in full-text article.)O2 (ICC, 0.95; 95% CI, 0.92-0.97) demonstrated excellent reliability. Of the submaximal exercise variables, oxygen uptake efficiency slope (OUES) was as reliable as peak (Equation is included in full-text article.)O2 (ICC, 0.97; 95% CI, 0.95-0.98). The ventilation/carbon dioxide production ((Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2) slope showed very good test-retest reliability (ICC, 0.87; 95% CI, 0.80-0.91) and the (Equation is included in full-text article.)O2/work rate slope showed good reliability (ICC, 0.76; 95% CI, 0.64-0.85). CONCLUSIONS: Both peak (Equation is included in full-text article.)O2 and OUES show excellent test-retest reliability. Accordingly, in the case of no or unreliable peak (Equation is included in full-text article.)O2 data, we suggest using OUES to evaluate cardiorespiratory fitness in patients with CAD.

Evidence for the role of isometric exercise training in reducing blood pressure: potential mechanisms and future directions.

Hypertension, or the chronic elevation in resting arterial blood pressure (BP), is a significant risk factor for cardiovascular disease and estimated to affect ~1 billion adults worldwide. The goals of treatment are to lower BP through lifestyle modifications (smoking cessation, weight loss, exercise training, healthy eating and reduced sodium intake), and if not solely effective, the addition of antihypertensive medications. In particular, increased physical exercise and decreased sedentarism are important strategies in the prevention and management of hypertension. Current guidelines recommend both aerobic and dynamic resistance exercise training modalities to reduce BP. Mounting prospective evidence suggests that isometric exercise training in normotensive and hypertensive (medicated and non-medicated) cohorts of young and old participants may produce similar, if not greater, reductions in BP, with meta-analyses reporting mean reductions of between 10 and 13 mmHg systolic, and 6 and 8 mmHg diastolic. Isometric exercise training protocols typically consist of four sets of 2-min handgrip or leg contractions sustained at 20-50 % of maximal voluntary contraction, with each set separated by a rest period of 1-4 min. Training is usually completed three to five times per week for 4-10 weeks. Although the mechanisms responsible for these adaptations remain to be fully clarified, improvements in conduit and resistance vessel endothelium-dependent dilation, oxidative stress, and autonomic regulation of heart rate and BP have been reported. The clinical significance of isometric exercise training, as a time-efficient and effective training modality to reduce BP, warrants further study. This evidence-based review aims to summarize the current state of knowledge regarding the effects of isometric exercise training on resting BP.

Usefulness of cardiopulmonary exercise testing to predict the development of arterial hypertension in adult patients with repaired isolated coarctation of the aorta.

BACKGROUND: Patients who underwent surgery for aortic coarctation (COA) have an increased risk of arterial hypertension. We aimed at evaluating (1) differences between hypertensive and non-hypertensive patients and (2) the value of cardiopulmonary exercise testing (CPET) to predict the development or progression of hypertension. METHODS: Between 1999 and 2010, CPET was performed in 223 COA-patients of whom 122 had resting blood pressures of <140/90 mmHg without medication, and 101 were considered hypertensive. Comparative statistics were performed. Cox regression analysis was used to assess the relation between demographic, clinical and exercise variables and the development/progression of hypertension. RESULTS: At baseline, hypertensive patients were older (p=0.007), were more often male (p=0.004) and had repair at later age (p=0.008) when compared to normotensive patients. After 3.6 ± 1.2 years, 29/120 (25%) normotensive patients developed hypertension. In normotensives, VE/VCO2-slope (p=0.0016) and peak systolic blood pressure (SBP; p=0.049) were significantly related to the development of hypertension during follow-up. Cut-off points related to higher risk for hypertension, based on best sensitivity and specificity, were defined as VE/VCO2-slope ≥ 27 and peak SBP ≥ 220 mmHg. In the hypertensive group, antihypertensive medication was started/extended in 48/101 (48%) patients. Only age was associated with the need to start/extend antihypertensive therapy in this group (p=0.042). CONCLUSIONS: Higher VE/VCO2-slope and higher peak SBP are risk factors for the development of hypertension in adults with COA. Cardiopulmonary exercise testing may guide clinical decision making regarding close blood pressure control and preventive lifestyle recommendations.

A genetic predisposition score for muscular endophenotypes predicts the increase in aerobic power after training: the CAREGENE study.

BACKGROUND: It is widely accepted that genetic variability might explain a large part of the observed heterogeneity in aerobic capacity and its response to training. Significant associations between polymorphisms of different genes with muscular strength, anaerobic phenotypes and body composition have been reported. Muscular endophenotypes are positively correlated with aerobic capacity, therefore, we tested the association of polymorphisms in twelve muscular related genes on aerobic capacity and its response to endurance training. METHODS: 935 Coronary artery disease patients (CAD) who performed an incremental exercise test until exhaustion at baseline and after three months of training were included. Polymorphisms of the genes were detected using the invader assay. Genotype-phenotype association analyses were performed using ANCOVA. Different models for a genetic predisposition score (GPS) were constructed based on literature and own data and were related to baseline and response VO(2) scores. RESULTS: Carriers of the minor allele in the R23K polymorphism of the glucocorticoid receptor gene (GR) and the ciliary neurotrophic factor gene (CNTF) had a significantly higher increase in peakVO(2) after training (p < 0.05). Carriers of the minor allele (C34T) in the adenosine monophosphate deaminase (AMPD1) gene had a significantly lower relative increase (p < 0.05) in peakVO(2). GPS of data driven models were significantly associated with the increase in peakVO(2) after training. CONCLUSIONS: In CAD patients, suggestive associations were found in the GR, CNTF and the AMPD1 gene with an improved change in aerobic capacity after three months of training. Additionally data driven models with a genetic predisposition score (GPS) showed a significant predictive value for the increase in peakVO(2).

The CAREGENE study: genetic variants of the endothelium and aerobic power in patients with coronary artery disease.

OBJECTIVES: Aerobic phenotypes show a wide variability to similar aerobic training stimuli, which can be partly attributed to heritability. Endothelial function affects aerobic power. Various physiological pathways may influence the endothelial function. Therefore, we aimed to examine whether polymorphisms of the eNos gene, the CAT gene, the VEGF gene, the GPX1 gene, the subunit P22 phox of the NAD(P)H-odixase gene, the PPAR-alpha gene, and the PGC-alpha gene are associated with aerobic power or with its response to physical training in patients with coronary artery disease (CAD). METHODS: 935 biologically unrelated Caucasian patients with CAD who had exercised until exhaustion during graded bicycle testing at baseline and after completion of 3 months of training were included in the CAREGENE study (Cardiac Rehabilitation and GENetics of exercise performance). Polymorphisms were detected using the invader assay and MassARRAY technology. Haplotype analysis was performed on the polymorphisms of the eNos gene, the VEGF gene and the NAD(P)H-oxidase gene. RESULTS: Physical training significantly increased aerobic power by 24.2 +/- 0.6% (P < 0.001). Associations of P < 0.05 were found between aerobic power and the eNOS 273C>T variant and the catalase -262C>T variant and aerobic power response. Haplotypes of the eNOS polymorhisms were predictive of aerobic power and its response to training (P < 0.05). After Bonferroni correction of multiple testing no significant differences remained. CONCLUSION: We believe that genetic factors are very important in the explanation of the great variability of aerobic power and its response. However, after Bonferroni-correction, differences in these polymorphisms remained no longer statistically significant.