Physical exercise: a polypill against chronic kidney disease.

We are currently facing a pandemic of physical inactivity that might contribute to the growing prevalence of chronic kidney disease (CKD). Here, we summarize currently available evidence on the association between physical activity and CKD, and also review the effects of exercise intervention in affected patients. Physical activity/exercise might act as a polypill against CKD, preventing its development or even exerting beneficial effects once it is established (i.e. improvements in patients' physical fitness and cardiovascular risk, as well as in kidney function). Exercise benefits are also found at advanced CKD stages or in patients under hemodialysis. The biological mechanisms behind the clinical evidence are also discussed. An active lifestyle appears as a cornerstone in CKD prevention and management.

Physical activity, chronic kidney disease, and cardiovascular risk: A study in half a million adults.

OBJECTIVE: There is a growing prevalence of chronic kidney disease (CKD), a condition associated with a higher cardiovascular disease (CVD) risk. We assessed the association between self-reported physical activity (PA) and CKD and also studied whether PA attenuates CKD-associated CVD risk. METHODS: A cohort of Spanish adults (18-64 years) participated in this nationwide study. Participants were categorized at baseline as being either inactive (performing no PA), regularly, or insufficiently active (meeting or not, respectively, international PA recommendations) and were followed for up to 5 years. The presence of CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2 ) and major CVD risk factors (diabetes, hypercholesterolemia, hypertension, obesity) was determined at baseline and at follow-up. RESULTS: 517 917 participants (44 ± 9 years, 67% male, CKD prevalence = 7%) were studied at baseline, with prospective analyses (median follow-up = 2 years, range = 2-5) in a subcohort of 264 581 individuals. Compared to physical inactivity, cross-sectional analyses at baseline showed that regular PA (odds ratio = 0.80; 95% confidence interval = 0.79-0.81), but not insufficient PA (1.02; 0.99-1.04) was associated with lower CKD prevalence. However, prospective analyses failed to confirm this association (p > 0.1). In turn, CKD was associated with a higher prevalence of hypertension (+3%) and diabetes (+5%) at baseline and with a greater incidence of hypertension at follow-up (+37%). Among those participants with CKD, regular PA was associated with a lower prevalence (-45% to -7%) and incidence (-38% to -4%) of all CVD risk factors. CONCLUSION: Although PA might not reduce incident CKD in the middle term (~2 years), it can attenuate the CVD risk linked to this condition.

Poor self-reported sleep is associated with risk factors for cardiovascular disease: A cross-sectional analysis in half a million adults.

BACKGROUND: Sleep is known to affect cardiovascular health, but some controversy exists on the independent association between different sleep characteristics (duration, restfulness, difficulties falling asleep) and specific risk factors for cardiovascular disease (CVD). We aimed to assess the association between self-reported sleep characteristics and the likelihood of major CVD risk factors. METHODS: Totally, 521,364 Spanish workers (32% female, 44 ± 9 years [18-64]) insured by an occupational risk prevention company participated in this nationwide cross-sectional study. Participants' sleep was considered 'poor' if they reported having ≥1 of the following conditions: excessively short (<6 h/d) or long (>9 h/d) sleep, unrestful sleep, or difficulties to fall asleep. We assessed the independent association between aforementioned sleep characteristics and the prevalence of hypertension, diabetes, hypercholesterolaemia, obesity and physical inactivity. RESULTS: Poor sleep (reported by 33% of participants) was associated with a higher likelihood of presenting all CVD risk factors individually, particularly physical inactivity (which prevalence was ~3-fold higher in the poor sleep group compared with participants reporting no sleep abnormality). In separate analyses, all the different sleep characteristics were associated with the likelihood of ≥2 CVD risk factors. Participants with optimal sleep, normal sleep duration, no difficulties falling sleep and restful sleep showed a lower total CVD risk score than their peers with poor sleep, short sleep duration, difficulties falling sleep and unrestful sleep, respectively (all p < .001). CONCLUSIONS: Poor sleep was associated with a higher likelihood of presenting major CVD risk factors. These findings might support the importance of monitoring and improving sleep patterns for primary CVD prevention.

What are the effects of exercise training in childhood cancer survivors? A systematic review.

This systematic review aimed to summarize evidence on the effects of physical exercise interventions in childhood cancer survivors (CCS) who had finished anticancer therapy ≥ 1 year before the study. Relevant articles were identified in the electronic databases PubMed, Web of Science, and SPORTDiscus (from inception to June 27, 2019). The PEDro scale was used to assess methodological quality. Twelve studies including 109 CCS met all inclusion criteria and were included in the systematic review. The quality of the included studies was overall low. Physical exercise improved endothelial function, reduced waist circumference, and waist-to-hip ratio and increased physical activity levels. Preliminary evidence was found regarding benefits on brain volume and structure after exercise interventions in childhood brain tumor survivors. Only two studies reported exercise-related adverse events. Physical exercise seems to be safe and effective for improving several health markers in CCS, but further high-quality research and especially randomized controlled trials are needed to confirm these results.

Exercise training effects on natural killer cells: a preliminary proteomics and systems biology approach.

BACKGROUND: Regular exercise, particularly moderate-intensity continuous training (MICT), can improve immune function. Natural killer (NK) cells, a subset of lymphocytes that react to infections, are the most responsive innate immune cells to exercise, but the mechanisms underlying this are poorly understood. A type of exercise training that is gaining popularity in recent years is high-intensity interval training (HIIT), but how it affects NK cells is largely unknown. In fact, intense exercise has been traditionally viewed as a potential stressor to immune homeostasis. The purpose of this study was to determine in healthy, previously untrained adults (N=8 [3 male; 40±6 years]) the effects of an intervention consisting of 4-week MICT followed by 4-week HIIT on NK cells as compared with a pre-training (baseline) state. METHODS: Participants were studied at three time points: baseline, mid-intervention (after MICT), and post-intervention (after HIIT). Main assessments included cytotoxicity assays, flow-cytometry analysis of NK cell surface markers, and interrogation of the cellular proteome using a systems biology approach. RESULTS: A significant time effect was found for NK cell cytotoxicity (p<0.001), which was increased ~10-fold at both midand post-intervention versus baseline. No significant intervention effect was found for NK surface receptor expression, except for CXCR3 determined as mean fluorescence intensity (p=0.044, although with no significant differences in post hoc pairwise comparisons). The proteins showing a higher differential expression (Log2 fold-change > 10 and false discovery rate [FDR] q-value < 0.001) were COP9 signalosome subunit 3 (COPS3), DnaJ heat shock protein family member B11 (DNAJB11), histidyl-TRNA synthetase 1 (HARS), NIMA related kinase 9 (NEK9), nucleoporin 88 (NUP88), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), regulator of chromosome condensation 2 (RCC2), TAO kinase 3 (TAOK3), transducin beta like 2 (TBL2), and ring finger protein 40 (RNF40). All were upregulated at mid-intervention compared with baseline, with the exception of HARS, which was downregulated. Four enriched pathways (FDR p<25%) were found: two related to transmembrane transport and cellular composition (downregulated at mid-intervention vs baseline), and two related to oxidation- reduction reactions (regulated at post-intervention versus baseline). CONCLUSION: A progressive exercise intervention of MICT followed by HIIT induces a remarkable improvement in NK function compared with the untrained state, although at the mechanistic level the pathways involved seem to differ over time during the intervention.

Mortality from mental disorders and suicide in male professional American football and soccer players: A meta-analysis.

OBJECTIVE: To determine the risk of mortality from mental disorders and suicide in professional sports associated with repeated head impacts. METHODS: A systematic search was performed in PubMed, Web of Science, Scopus, and SPORTDiscus (since inception to June 8, 2021) to find studies comparing the incidence of mortality from mental disorders or suicide in former or active professional athletes of sports characterized by repeated head impacts vs athletes with no such exposure or the general non-athletic population. RESULTS: Seven retrospective studies of moderate-to-high quality that included data from boxers and from basketball, ice hockey, soccer, and National Football League (NFL) players, respectively (total = 27 477 athletes, 100% male) met all inclusion criteria. Former male NFL players (n = 13 217) had a lower risk of mortality from mental disorders (standard mortality rate [SMR] = 0.30; 0.12-0.77; p = 0.012) and suicide (SMR = 0.54; 0.37-0.78; p < 0.001) than the general population. This finding was also corroborated in male soccer players (n = 13,065; SMR = 0.55; 0.46-0.67; p < 0.001). Male athletes participating in sports associated with repeated head impacts (n = 18,606) had also a lower risk of all-cause, cardiovascular disease (CVD), and cancer mortality (all p < 0.01) than the general population. CONCLUSIONS: Participation of male athletes in American football or soccer at the professional level might confer a certain protective effect against mortality from mental disorders or suicide, besides its association with a lower risk of all-cause, CVD, or cancer-related mortality.

Anthropometric and fitness normative values for young karatekas.

To provide information regarding the anthropometric and fitness profile of young karatekas and to study its evolution with age. Data from top-level karatekas were included in the analysis: 97 athletes in the U14 category (12-13 years old), 238 in cadet (14-15 years old), 261 in junior (16-17 years old) and 177 in U21 (18-20 years old), which makes a total of 773 athlete data sets. Karatekas underwent anthropometric (weight, height, body mass index and body fat percentage) and fitness (sit and reach, 20-m shuttle run, standing long jump, overhead 3-kg ball throw, 10x5-m shuttle run, and plate-tapping) assessments during the training camps organized by the Spanish National Karate Federation between 1999 and 2016. Male karatekas were taller and heavier, and performed better than females in all the fitness dimensions assessed, except for flexibility and speed of upper limb movements. The obtained cardiovascular and lower-body muscular values indicated that karatekas in this study were placed between the 80th and the 90th percentile when compared with the general population. The results of the agility, coordination and speed of upper limb movements, and flexibility tests showed that the karatekas obtained much higher scores than those observed in age-matched populations. Young karatekas show a high fitness level in comparison with the general population, especially with regards to aerobic performance, lower-body muscular power and upper-limb movement speed. Reference values of anthropometric and fitness dimensions are provided in order to be used by coaches, conditioning trainers and sport scientists when testing young male and female karatekas.

Reply: Letter to the Editor: Exercise Interventions and Cardiovascular Health in Childhood Cancer: A Meta-Analysis.

Dear EditorWe sincerely appreciate the nice comments by Drs. P.V. da Costa Ghignatti and R. Pereira de Lima 1 concerning our recent meta-analysis assessing the effects of physical exercise interventions on cardiovascular endpoints in childhood cancer survivors 2. They are quite right to remain that even non-significant improvements in cardiorespiratory fitness (CRF) might be clinically relevant. Indeed, we still do not know if CRF increments of a theoretically low magnitude (i. e., <1 metabolic equivalent) might have a prognostic value in the context of pediatric cancer and treatment-associated cardiotoxicity. We also agree that unsupervised exercise interventions are unlikely to be as effective as tailored programs, especially because the latter allow for intensity to being adequately controlled and thus gradually increased. It is indeed our opinion, after long years of experience working with children with cancer as well as with other debilitated clinical populations, that there is always room for physiological improvement and ideally loads should be gradually improved instead of remaining stable.

Exercise Interventions and Cardiovascular Health in Childhood Cancer: A Meta-analysis.

This study analyzed the effects of physical exercise interventions on cardiovascular endpoints in childhood cancer survivors. Relevant articles were systematically searched in PubMed, CINAHL, and Web of Science databases (since inception to 11th September 2019). We performed a meta-analysis (random effects) to determine the mean difference (expressed together with 95% confidence intervals) between pre- and post-intervention values for those cardiovascular endpoints reported in more than three studies. Twenty-seven studies (of which 16 were controlled studies) comprising 697 participants were included. Only three studies reported adverse events related to exercise interventions. Exercise resulted in an increased performance on the 6-minute walk distance test (mean difference=111 m, 95% confidence interval=39-183, p=0.003) and a non-significant trend (mean difference=1.97 ml∙kg-1∙min-1, 95% confidence interval=-0.12-4.06, p=0.065) for improvement in peak oxygen uptake. Furthermore, left ventricular ejection fraction was preserved after exercise interventions (mean difference=0.29%, 95% confidence interval=-1.41-1.99, p=0.738). In summary, exercise interventions might exert a cardioprotective effect in childhood cancer survivors by improving - or attenuating the decline of - physical capacity and cardiovascular function. Further studies, particularly randomized controlled trials, are needed to confirm these benefits.

Lifestyle and cardiovascular risk in working young adults: insights from a nationwide Spanish cohort.

INTRODUCTION AND OBJECTIVES: This study aimed to describe the cardiovascular risk profile of working young adults from Spain and its association with lifestyle. METHODS: Participants (18-30 years) were recruited from a nationwide cohort of economically active adults insured by a large occupational risk prevention company, with data obtained from routine medical assessments. The participants were categorized as having an "unhealthy" cardiovascular risk profile based on the presence of prediabetes/diabetes, prehypertension/hypertension, or hypercholesterolemia, or a "healthy" profile if these conditions were completely absent. The association with lifestyle factors (weight, physical activity, sleeping characteristics, alcohol consumption, smoking) was assessed. RESULTS: A total of 78 421 young adults (27±2 years, 36% female) were evaluated at baseline. The "unhealthy" cardiovascular risk profile was prevalent (18%) and inversely associated (OR, 0.64; 95%CI, 0.57-0.80) with an optimal lifestyle (normal weight, regular physical activity, no drinking/smoking, and good sleep). The latter condition was found in only 3.5% of the participants. On the other hand, prospective analyses in 44 776 participants (median follow-up=2 [range 2-5] years) showed that 2.0% transitioned from a "healthy" to an "unhealthy" profile. Being physically active (OR, 0.95; 95%CI, 0.81-0.99) and having a normal weight (OR, 0.61; 95%CI, 0.51-0.70) were associated with a lower likelihood of this transition. No consistent associations were found for other lifestyle factors. CONCLUSIONS: The prevalence of cardiovascular risk factors is high in economically active young Spanish adults. An unhealthy cardiovascular risk profile is inversely associated with an optimal lifestyle, but the latter is highly infrequent in this population.

Association between self-reported sleep characteristics and cardiovascular risk factors: Weight status and physical activity matter.

We analysed the association between self-reported sleep characteristics and the prevalence of major cardiovascular disease (CVD) risk factors attending to the potential effect of physical activity (PA) and weight status. A large cohort of Spanish workers (n = 527,662; 32% female, 44 ± 9yrs) participated in this cross-sectional study. We assessed participants' self-reported indicators of sleep quantity (short [<6 h/d], normal [6-9 h/d] or long [>9 h/d]) and quality (unrestful or restful, and difficulties or not falling asleep) as well as the presence of major CVD risk factors (diabetes, hypertension and hypercholesterolemia); and categorised participants based on PA ("inactive", "insufficiently active" or "regularly active") and weight status (normal weight, overweight or obesity). Impairments in any sleep quantity or quality indicator, respectively, were significantly (p < 0.05) associated with the prevalence of at least one CVD risk factor. Yet, being physically active and having normal weight markedly attenuated these associations. Thus, individuals with poor sleep quantity or quality but who were physically active and had normal weight showed no different risk of hypertension or diabetes than those with normal sleep characteristics, albeit the former still presented a higher risk of hypercholesterolemia if they reported short sleep (+5% vs. normal duration, p = 0.047), unrestful sleep (+9% vs. restful, p < 0.001) or having difficulties to fall asleep (+48% vs. no difficulties, p < 0.001). The present findings support the need for maintaining optimal PA levels and weight status in order to minimise the CVD risk associated with poor sleep quantity or quality.HighlightsBoth sleep quantity and quality are associated with the prevalence of hypertension, diabetes, and hypercholesterolemia.Being physically active and having normal weight markedly reduces the cardiovascular risk associated with poor sleep quantity/quality.Having poor sleep quantity/quality while being also inactive and overweight/obese predisposes to a higher cardiovascular risk.

Obesity, cardiovascular risk, and lifestyle: cross-sectional and prospective analyses in a nationwide Spanish cohort.

AIMS: To assess whether overweight and obesity are independently associated with cardiometabolic health [as categorized based on the presence/absence of cardiovascular disease (CVD) risk factors (diabetes, hypercholesterolaemia, or hypertension)], and the role of lifestyle on this association. METHODS AND RESULTS: A nationwide cohort of Spanish adults (18-64 years) was studied using a cross-sectional design and prospective observational design. Lifestyle-related factors (physical activity, sleeping characteristics, alcohol drinking, and smoking) were registered, and participants were classified as having an 'unhealthy' or 'healthy' cardiometabolic status attending to the presence or absence, respectively, of ≥1 CVD risk factor. A number of 596 111 participants (44 ± 9 years, 67% male) were studied at baseline, with prospective analyses in a subcohort [n = 302 061; median follow-up, 2 years (range, 2 to 5)]. Compared to normal weight, overweight and obesity were associated with a higher prevalence [odds ratio, 1.67 (95% confidence interval, 1.61-1.67) and 2.70 (2.69-2.78), respectively] and incidence [1.62 (1.59-1.67) and 2.70 (2.63-2.78)] of an unhealthy cardiometabolic status. Meeting physical activity guidelines reduced the odds of an unhealthy cardiometabolic status at baseline [0.87 (0.85-0.88)] among individuals with overweight/obesity, as well as of transitioning from a healthy status to an unhealthy status during the follow-up [0.87 (0.84-0.94)]. No significant associations were found for the remainder of lifestyle factors. CONCLUSION: Overweight and obesity are independently associated with an unhealthy cardiometabolic status. Regular physical activity attenuates not only the prevalence but also the incidence of CVD risk factors.

This study (n = 596 111, with 302 061 participants followed for ∼2 years) indicates that overweigh and obesity are independently associated with the prevalence and incidence of major cardiovascular disease (CVD) risk factors (hypertension, diabetes, and hypercholesterolaemia). Individuals with metabolically healthy overweight/obesity are more likely to develop CVD risk factors in the short-to-middle term than their peers with normal weight even after accounting for lifestyle. Regular physical activity is the only lifestyle factor that seems to be inversely and independently associated with the prevalence and incidence of the studied CVD risk factors among individuals with overweight/obesity.

Obesity and the risk of cardiometabolic diseases.

The prevalence of obesity has reached pandemic proportions, and now approximately 25% of adults in Westernized countries have obesity. Recognized as a major health concern, obesity is associated with multiple comorbidities, particularly cardiometabolic disorders. In this Review, we present obesity as an evolutionarily novel condition, summarize the epidemiological evidence on its detrimental cardiometabolic consequences and discuss the major mechanisms involved in the association between obesity and the risk of cardiometabolic diseases. We also examine the role of potential moderators of this association, with evidence for and against the so-called 'metabolically healthy obesity phenotype', the 'fatness but fitness' paradox or the 'obesity paradox'. Although maintenance of optimal cardiometabolic status should be a primary goal in individuals with obesity, losing body weight and, particularly, excess visceral adiposity seems to be necessary to minimize the risk of cardiometabolic diseases.

Effects of physical exercise on physical function in older adults in residential care: a systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND: Physical exercise is effective at attenuating ageing-related physical decline in general, but evidence of its benefits for older adults in residential care, who often have functional dependency, multimorbidity, and polypharmacy, is inconclusive. We aimed to establish the effects of exercise interventions on the physical function of this population. METHODS: For this systematic review and network meta-analysis, we searched PubMed, Web of Science, Cochrane Library, Rehabilitation & Sports Medicine Source, and SPORTDiscus to identify randomised controlled trials assessing the effects of exercise interventions (vs usual care) on physical function (ie, functional independence, physical performance, and other related measures, such as muscle strength, balance, or flexibility) in adults aged 60 years or older living in residential care. Relevant studies published in English or Spanish up to Jan 12, 2023, were included in the systematic review. The quality of studies was assessed using the Tool for the Assessment of Study Quality and Reporting in Exercise (TESTEX) score. A network meta-analysis was performed for physical function-related outcomes reported in at least ten studies, with subanalyses for specific intervention (ie, exercise type, training volume, and study duration) and participant (eg, having cognitive impairment or dementia, pre-frail or frail status, and being functionally dependent) characteristics. The study protocol was registered on PROSPERO (CRD42021247809). FINDINGS: 147 studies (11 609 participants, with mean ages ranging from 67 years [SD 9] to 92 years [2]) were included in the systematic review, and were rated as having overall good quality (median TESTEX score 9 [range 3-14]). In the meta-analysis (including 105 studies, n=7759 participants), exercise interventions were associated with significantly improved overall physical function, with a standardised mean difference [SMD] of 0·13 (95% credible interval [CrI] 0·04-0·21), which was confirmed in all analysed subpopulations. The strongest association was observed with 110-225 min per week of exercise, and the greatest improvements were observed with 170 min per week (SMD 0·36 [95% CrI 0·20-0·52]). No significant differences were found between exercise types. Subanalyses showed significant improvements for almost all analysed physical function-related outcomes (Barthel index, five-times sit-to-stand test, 30-s sit-to-stand test, knee extension, hand grip strength, bicep curl strength, Short Physical Performance Battery, 6-min walking test, walking speed, Berg balance scale, and sit-and-reach test). Large heterogeneity was found between and within studies in terms of population and intervention characteristics. INTERPRETATION: Exercise interventions are associated with improved physical function in older adults in residential care, and should, therefore, be routinely promoted in long-term care facilities. FUNDING: None. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.