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Journal ArticleDOI

Genomic predictors of the maximal O2 uptake response to standardized exercise training programs

TL;DR: These genomic predictors of the response of Vo(2max) to regular exercise provide new targets for the study of the biology of fitness and its adaptation to regular Exercise.
Abstract: Low cardiorespiratory fitness is a powerful predictor of morbidity and cardiovascular mortality. In 473 sedentary adults, all whites, from 99 families of the Health, Risk Factors, Exercise Training...

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Journal ArticleDOI
TL;DR: The addition of CRF for risk classification presents health professionals with unique opportunities to improve patient management and to encourage lifestyle-based strategies designed to reduce cardiovascular risk to meet the American Heart Association’s 2020 goals.
Abstract: Mounting evidence has firmly established that low levels of cardiorespiratory fitness (CRF) are associated with a high risk of cardiovascular disease, all-cause mortality, and mortality rates attributable to various cancers. A growing body of epidemiological and clinical evidence demonstrates not only that CRF is a potentially stronger predictor of mortality than established risk factors such as smoking, hypertension, high cholesterol, and type 2 diabetes mellitus, but that the addition of CRF to traditional risk factors significantly improves the reclassification of risk for adverse outcomes. The purpose of this statement is to review current knowledge related to the association between CRF and health outcomes, increase awareness of the added value of CRF to improve risk prediction, and suggest future directions in research. Although the statement is not intended to be a comprehensive review, critical references that address important advances in the field are highlighted. The underlying premise of this statement is that the addition of CRF for risk classification presents health professionals with unique opportunities to improve patient management and to encourage lifestyle-based strategies designed to reduce cardiovascular risk. These opportunities must be realized to optimize the prevention and treatment of cardiovascular disease and hence meet the American Heart Association's 2020 goals.

1,345 citations

Journal ArticleDOI
TL;DR: The purpose of this document is to update the 1999 ATS/ERS statement on limb muscle dysfunction in COPD with important advances in the understanding of the extent and nature of the structural alterations in limb muscles in patients with COPD.
Abstract: Background: Limb muscle dysfunction is prevalent in chronic obstructive pulmonary disease (COPD) and it has important clinical implications, such as reduced exercise tolerance, quality of life, and even survival. Since the previous American Thoracic Society/European Respiratory Society (ATS/ERS) statement on limb muscle dysfunction, important progress has been made on the characterization of this problem and on our understanding of its pathophysiology and clinical implications.Purpose: The purpose of this document is to update the 1999 ATS/ERS statement on limb muscle dysfunction in COPD.Methods: An interdisciplinary committee of experts from the ATS and ERS Pulmonary Rehabilitation and Clinical Problems assemblies determined that the scope of this document should be limited to limb muscles. Committee members conducted focused reviews of the literature on several topics. A librarian also performed a literature search. An ATS methodologist provided advice to the committee, ensuring that the methodological ...

787 citations

Journal ArticleDOI
TL;DR: Extensive evidence that brain-training interventions improve performance on the trained tasks, less evidence that such interventions improved performance on closely related tasks, and little evidence that training enhances performance on distantly related tasks or that training improves everyday cognitive performance are found.
Abstract: In 2014, two groups of scientists published open letters on the efficacy of brain-training interventions, or "brain games," for improving cognition. The first letter, a consensus statement from an international group of more than 70 scientists, claimed that brain games do not provide a scientifically grounded way to improve cognitive functioning or to stave off cognitive decline. Several months later, an international group of 133 scientists and practitioners countered that the literature is replete with demonstrations of the benefits of brain training for a wide variety of cognitive and everyday activities. How could two teams of scientists examine the same literature and come to conflicting "consensus" views about the effectiveness of brain training?In part, the disagreement might result from different standards used when evaluating the evidence. To date, the field has lacked a comprehensive review of the brain-training literature, one that examines both the quantity and the quality of the evidence according to a well-defined set of best practices. This article provides such a review, focusing exclusively on the use of cognitive tasks or games as a means to enhance performance on other tasks. We specify and justify a set of best practices for such brain-training interventions and then use those standards to evaluate all of the published peer-reviewed intervention studies cited on the websites of leading brain-training companies listed on Cognitive Training Data (www.cognitivetrainingdata.org), the site hosting the open letter from brain-training proponents. These citations presumably represent the evidence that best supports the claims of effectiveness.Based on this examination, we find extensive evidence that brain-training interventions improve performance on the trained tasks, less evidence that such interventions improve performance on closely related tasks, and little evidence that training enhances performance on distantly related tasks or that training improves everyday cognitive performance. We also find that many of the published intervention studies had major shortcomings in design or analysis that preclude definitive conclusions about the efficacy of training, and that none of the cited studies conformed to all of the best practices we identify as essential to drawing clear conclusions about the benefits of brain training for everyday activities. We conclude with detailed recommendations for scientists, funding agencies, and policymakers that, if adopted, would lead to better evidence regarding the efficacy of brain-training interventions.

754 citations

Journal ArticleDOI
TL;DR: The prognostic utility of cardiorespiratory fitness compared with obesity and the metabolic syndrome is reviewed, as well as the increase of physical activity /ET for patients with heart failure as a therapeutic strategy, and ET dosing.
Abstract: Sedentary behavior and physical inactivity are among the leading modifiable risk factors worldwide for cardiovascular disease and all-cause mortality. The promotion of physical activity and exercise training (ET) leading to improved levels of cardiorespiratory fitness is needed in all age groups, race, and ethnicities and both sexes to prevent many chronic diseases, especially cardiovascular disease. In this state-of-the-art review, we discuss the negative impact of sedentary behavior and physical inactivity, as well as the beneficial effects of physical activity /ET and cardiorespiratory fitness for the prevention of chronic noncommunicable diseases, including cardiovascular disease. We review the prognostic utility of cardiorespiratory fitness compared with obesity and the metabolic syndrome, as well as the increase of physical activity /ET for patients with heart failure as a therapeutic strategy, and ET dosing. Greater efforts at preventing sedentary behavior and physical inactivity while promoting physical activity, ET, and cardiorespiratory fitness are needed throughout the healthcare system worldwide and particularly in the United States in which the burden of cardiometabolic diseases remains extremely high.

717 citations

Journal ArticleDOI
TL;DR: The idea is that blood flow to the contracting muscle links oxygen in the atmosphere with the contracting muscles where it is consumed in order to link oxygen with the muscle, and the vasodilating factors in the muscle are responsible for these very high flows.
Abstract: This review focuses on how blood flow to contracting skeletal muscles is regulated during exercise in humans The idea is that blood flow to the contracting muscles links oxygen in the atmosphere with the contracting muscles where it is consumed In this context, we take a top down approach and review the basics of oxygen consumption at rest and during exercise in humans, how these values change with training, and the systemic hemodynamic adaptations that support them We highlight the very high muscle blood flow responses to exercise discovered in the 1980s We also discuss the vasodilating factors in the contracting muscles responsible for these very high flows Finally, the competition between demand for blood flow by contracting muscles and maximum systemic cardiac output is discussed as a potential challenge to blood pressure regulation during heavy large muscle mass or whole body exercise in humans At this time, no one dominant dilator mechanism accounts for exercise hyperemia Additionally, complex interactions between the sympathetic nervous system and the microcirculation facilitate high levels of systemic oxygen extraction and permit just enough sympathetic control of blood flow to contracting muscles to regulate blood pressure during large muscle mass exercise in humans

481 citations

References
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Journal ArticleDOI
08 Oct 2009-Nature
TL;DR: This paper examined potential sources of missing heritability and proposed research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.
Abstract: Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far confer relatively small increments in risk, and explain only a small proportion of familial clustering, leading many to question how the remaining, 'missing' heritability can be explained. Here we examine potential sources of missing heritability and propose research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.

7,797 citations


"Genomic predictors of the maximal O..." refers background in this paper

  • ...common chronic diseases or normal human quantitative traits as reported in the GWAS literature over recent years, in which the effect sizes of SNPs rarely exceed 1% (25, 28, 43, 46)....

    [...]

Book
30 Aug 2004
TL;DR: This report is the first report of the Surgeon General on physical activity and health, and strong evidence is shown to indicate that regular physical activity will provide clear and substantial health gains.
Abstract: : This report is the first report of the Surgeon General on physical activity and health. For more than a century, the Surgeon General of the Public Health Service has focused the nation's attention on important public health issues. Reports from Surgeons General on the adverse health consequences of smoking triggered nationwide efforts to prevent tobacco use. Reports on nutrition, violence, and HIV/AlDS - to name but a few - have heightened America's awareness of important public health issues and have spawned major public health initiatives. This new report, which is a comprehensive review of the available scientific evidence about the relationship between physical activity and health status, follows in this notable tradition. Scientists and doctors have known for years that substantial benefits can be gained from regular physical activity. The expanding and strengthening evidence on the relationship between physical activity and health necessitates the focus this report brings to this important public health challenge. Although the science of physical activity is a complex and still-developing field, we have today strong evidence to indicate that regular physical activity will provide clear and substantial health gains. In this sense, the report is more than a summary of the science - it is a national call to action.

5,107 citations

Journal ArticleDOI
TL;DR: Evidence is provided that the remaining heritability is due to incomplete linkage disequilibrium between causal variants and genotyped SNPs, exacerbated by causal variants having lower minor allele frequency than the SNPs explored to date.
Abstract: SNPs discovered by genome-wide association studies (GWASs) account for only a small fraction of the genetic variation of complex traits in human populations. Where is the remaining heritability? We estimated the proportion of variance for human height explained by 294,831 SNPs genotyped on 3,925 unrelated individuals using a linear model analysis, and validated the estimation method with simulations based on the observed genotype data. We show that 45% of variance can be explained by considering all SNPs simultaneously. Thus, most of the heritability is not missing but has not previously been detected because the individual effects are too small to pass stringent significance tests. We provide evidence that the remaining heritability is due to incomplete linkage disequilibrium between causal variants and genotyped SNPs, exacerbated by causal variants having lower minor allele frequency than the SNPs explored to date.

3,759 citations


"Genomic predictors of the maximal O..." refers background in this paper

  • ...common chronic diseases or normal human quantitative traits as reported in the GWAS literature over recent years, in which the effect sizes of SNPs rarely exceed 1% (25, 28, 43, 46)....

    [...]

Journal ArticleDOI
12 Apr 1995-JAMA
TL;DR: Men who maintained or improved adequate physical fitness were less likely to die from all causes and from cardiovascular disease during follow-up than persistently unfit men.
Abstract: Objective. —To evaluate the relationship between changes in physical fitness and risk of mortality in men. Design. —Prospective study, with two clinical examinations (mean interval between examinations, 4.9 years) to assess change or lack of change in physical fitness as associated with risk of mortality during follow-up after the subsequent examination (mean follow-up from subsequent examination, 5.1 years). Setting. —Preventive medicine clinic. Study Participants. —Participants were 9777 men given two preventive medical examinations, each of which included assessment of physical fitness by maximal exercise tests and evaluation of health status. Main Outcome Measures. —All-cause (n=223) and cardiovascular disease (n=87) mortality. Results. —The highest age-adjusted all-cause death rate was observed in men who were unfit at both examinations (122.0/10 000 man-years); the lowest death rate was in men who were physically fit at both examinations (39.6/10000 man-years). Men who improved from unfit to fit between the first and subsequent examinations had an age-adjusted death rate of 67.7/10 000 man-years. This is a reduction in mortality risk of 44% (95% confidence interval, 25% to 59%) relative to men who remained unfit at both examinations. Improvement in fitness was associated with lower death rates after adjusting for age, health status, and other risk factors of premature mortality. For each minute increase in maximal treadmill time between examinations, there was a corresponding 7.9% (P=.001) decrease in risk of mortality. Similar results were seen when the group was stratified by health status, and for cardiovascular disease mortality. Conclusions. —Men who maintained or improved adequate physical fitness were less likely to die from all causes and from cardiovascular disease during follow-up than persistently unfit men. Physicians should encourage unfit men to improve their fitness by starting a physical activity program. (JAMA. 1995;273:1093-1098)

1,980 citations


"Genomic predictors of the maximal O..." refers result in this paper

  • ...This approach has been validated in several studies (2, 21)....

    [...]

Journal ArticleDOI
TL;DR: By combining genome-wide association data from 8,130 individuals with type 2 diabetes and 38,987 controls of European descent and following up previously unidentified meta-analysis signals, 12 new T2D association signals are identified with combined P < 5 × 10−8.
Abstract: By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P<5x10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.

1,785 citations

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